Kidney Disease Free Forever

Beat Kidney Disease

The ebook teaches you how to beat kidney disease in a way that no big pharm company wants you to know. The biggest companies make their money when people like you, with kidney disease come in and wonder if there is any way that they can be cured. The medical industry profits off of these sorts of people, because most people do not know that there is a way around the mass-produced medical industry. With the information in this ebook guide you will be able to restore your help without using drugs that end up hurting your kidneys even more. You will be able to avoid surgery, or having to use dialysis just to survive. You can also improve your quality of life if you are already on dialysis or end stage renal failure. This book was born of years of research from Duncan Capicchiano, ND. All of his research, findings, and suggestions are available to you! Read more here...

The Kidney Disease Solution Overview

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Polycystic Kidney Disease A Disease of Ca2 Channels

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, occurring in 1 in 1000 people and accounting for 10 of end-stage renal disease worldwide. It is characterised by the presence of multiple fluid-filled cysts that occur throughout the tubules of both kidneys. These cysts are already present in the fetus and develop progressively through life, eventually resulting in renal failure in 45 of affected individuals between 40 and 60 years of age. Hypertension is common and many patients also have cysts in other organs, most notably the liver. ADPKD is a genetically heterogeneous disease and has been mapped to chromosome 16p13.3 (PKD1) and chromosome 4q21-23 (PKD2) a third gene is also known to exist. Mutations in PKD1 are the most frequent cause of the disease, but 15 of cases are associated with mutations in PKD2. The latter encodes a 968 amino acid protein that has six putative transmembrane domains with cytosolic N and C termini (Fig. 9.12)...

N178 Other acute renal failure N179 Acute renal failure unspecified

Chronic renal failure Excludes chronic renal failure with hypertension ( I12.0 ) N18.0 End-stage renal disease N18.8 Other chronic renal failure N18.9 Chronic renal failure, unspecified Unspecified renal failure Excludes renal failure with hypertension ( I12.0 ) uraemia of newborn ( P96.0 )

Drugs Used In The Treatment Of Anemia Associated With Chronic Renal Failure

Anemia may occur in patients with chronic renal failure as the result of the inability of the kidney to produce ery-thropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia. Two examples of drugs used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp).

Imaging of Hemodialysis Access Fistulas

Hemodialysis Shunt

Recognition of the cause of impaired access function is important to prevent complete thrombosis of the dialysis fistula. The role of MRA in imaging of these fistulas has been evaluated in various studies 18-21 . Although CE MRA is less sensitive to disturbed flow compared to conventional nonenhanced techniques (PC and TOF MRA), flow Fig. 11a. b. Postsurgical CE MRA study in a patient with dialysis access fistula of the lower arm in which insufficient flow was present for adequate dialysis. MIP reconstruction of two consecutive CE 3D MRA datasets (Gd-BOPTA, 0.1 mmol kg acquisition time per dataset 4 sec) demonstrates first (a) early enhancement of the fistula vein (arrowin a) and (b) increasing drainage into collateral veins (arrowheads in b). After surgical occlusion of the collateral veins sufficient flow was achieved Images courtesy of Dr. G. Schneider related artifacts may still be present under the extreme flow conditions that can occur in dialysis fistulas (flow rates may range...

ET Antagonists in Heart Failure Renal Failure and Diabetes Mellitus

Selective ETA antagonists have prevented the progression of diabetic nephropathy in rat models (84). In an acute, randomized, placebo-controlled, double-blind, four-way crossover study, the selective ETa (BQ-123) and ETb (BQ-788) receptor antagonists were given alone and in combination to patients with chronic renal failure (85). The ETa receptor blocker lowered blood pressure and induced renoprotective effects in the chronic renal failure patients. Because the ETB receptor has renal vasodilatory action, combined ETa ETb receptor blockade did not confer these renal benefits, although it did lower blood pressure. On the basis of the experimental and clinical data reported above, a clinical trial has recently been initiated in diabetic nephropathy using an ETa selective receptor blocker. The results of this study, when available, will allow further conclusions on the potential of inhibition of the endothelin system to stop progression of this critical complication of diabetes mellitus.

Hemodialysisrelated outbreaks

In the USA, more than 340 000 patients are on dialysis or have a kidney transplant, with costs estimated at 17 billion per year 31 . The invasive nature of hemodialysis lends itself to outbreaks. Infection is the major cause of death in 15-30 of dialysis patients, with vascular access-related infections being a contributing cause 32 . There have been numerous disease outbreaks originating in hemodialysis centers, as described below (Table 17.3). In hemodialysis, a dialysis machine and a special filter called a dialyzer are used to reduce waste and fluids from the blood of patients with endstage renal disease. A cohort study was carried out in Columbia, South America, to investigate 13 dialysis patients at one dialysis center who were found to be HIV-positive 34 . In 1993, testing of dialysis center patients confirmed a cluster of HIV seroconversions. A cohort study was conducted to determine risk factors for infection. The HIV seroconversion rate was found to be higher among patients...

Other chronic tubulointerstitial nephritis

Chronic tubulo-interstitial nephritis, unspecified interstitial nephritis NOS Tubulo-interstitial nephritis, not specified as acute or chronic Interstitial nephritis NOS Pyelitis NOS Pyelonephritis NOS N14.0 Analgesic nephropathy N14.1 Nephropathy induced by other drugs, medicaments and biological substances N14.2 Nephropathy induced by unspecified drug, medicament or biological substance N14.3 Nephropathy induced by heavy metals N14.4 Toxic nephropathy, not elsewhere classified Other renal tubulo-interstitial diseases N15.0 Balkan nephropathy Balkan endemic nephropathy N15.1 Renal and perinephric abscess N15.8 Other specified renal tubulo-interstitial diseases N15.9 Renal tubulo-interstitial disease, unspecified Infection of kidney NOS

Puberty In Chronic Renal Failure

Disorders of puberty commonly accompany chronic renal failure and require age-appropriate medical management. Although centrally mediated precocious puberty, which is reversed by renal transplantation, has been reported (46), the most characteristic feature of chronic renal failure in boys is delayed puberty with retarded bone age (1). The delayed puberty usually progresses slowly to completion during dialysis, whereas transplantation accelerates maturation unless complicated by poor graft function and or high-dose glucocorticoids (47). Because puberty involves the unleashing by the hypothalamus of pulsatile GnRH secretion that subsequently entrains pituitary gonadotropin secretion, the delayed puberty is further evidence of neuroendocrine dysfunction in uremia. This is consistent with experimental models of chronic renal failure, which show a predominant defect in the regulation of hypothalamic GnRH secretion (12). In concert, these findings raise the issue of gonadotropin or...

Reproductive Endocrinology Of Chronic Renal Failure

Men with chronic renal failure have consistent reduction in circulating testosterone, accompanied by moderate elevations in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin-a (1,12). The pathophysiological interpretation of these changes is complex. Prima facie elevated blood gonadotropin and inhibin concentrations, together with moderate reduction in sperm and testosterone production, are indicative of primary (testicular) hypogonadism. Nevertheless, the modest elevations in peptide hormones, despite markedly impaired peptide clearance, together with direct evidence of hypothalamic dysregulation of pulsatile LH and FSH secretion (13), suggest important defects in hypothalamic-pituitary regulation of gonadotropin secretion as well. This functional state of partial gonadotropin deficiency has interesting but largely unexplored therapeutic implications for adjuvant hormonal treatment. The hormonal changes of renal failure become evident with even moderate...

With Continuous Ambulatory Peritoneal Dialysis

The rate of peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD) is decreasing, down from 2.8 to 0.8 episodes per year (4). S. aureus and coagulase-negative staphylococci account for 50-80 of CAPD peritonitis cases. Streptococci cause approx 10 , of these infections and Gram-negative bacilli are isolated in another 20 of cases. Infections with mycobacteria and fungi are rare but cause serious complications. Sources of peritonitis associated with CAPD include contamination of the catheter during implantation, manipulation of the dialysate tubing, the dialysate fluid itself, and possible bowel perforation. Most often, the peritoneum is infected by organisms that invade along the catheter tract. Lack of proper sterile technique is a major risk factor. The Advisory Committee on Peritonitis Management of the International Society for Peritoneal Dialysis has published guidelines for treatment of these infections on the Internet. These are available at http...

Studying Kidney Function

The whole kidney can be studied by examination of the kidney in relation to a reference substance. For example, the chemical inulin goes through the nephron without any alteration, so its excretion can be compared with other substances If more of another substance appears in the urine in proportion to the inulin, the substance must have been excreted from the blood into the urine and secreted. If less is present, some material must have been reabsorbed from the tubule into the blood. This is called the clearance technique, and it is widely used to predict kidney function in health and disease. For less sophisticated testing, substances such as certain dyes that can be taken orally and are excreted by the kidney can be used to measure the rate of excretion. Radioopaque substances, substances that will appear on X rays, can be used to detect overt kidney malfunction.

Acute renal failure

Critically ill patients who have acute renal failure as a component of their multiple organ failure have significantly different requirements in terms of renal support from patients with isolated acute or chronic renal failure. An inherently unstable cardiovascular system, the need for continued infusion of large volumes of fluid to combat the extravasation of circulating volume through leaky capillaries and the use of potent inotropic and va-sopressor drugs mean that these patients are often unable to tolerate the rapid fluid and ionic shifts associated with intermittent haemodialysis techniques, which may precipitate cardiovascular collapse. Peritoneal dialysis is also of limited value in the ICU as it does not have the capacity to maintain homeostasis in hypermetabolic patients or remove fluid rapidly enough when required. In addition, it is often not possible in patients after abdominal surgery and those with abdominal sepsis. Therefore, continuous haemofiltration (a process...

Salt Blood Pressure and Kidney

Diabetic Nephropathy

Early period of high salt diet in salt-sensitive hypertensives. Generally, when salt loading after the low salt diet starts to be given, urinary Na excretion gradually increases, leading to the elevation of BP by Na retention. In turn, Na excretion reaches and further exceeds the Na intake (so-called 'escape') by pressure natriuresis, and finally returns to the equal level to the net Na intake. The delayed escape of natriuresis caused the greater Na retention in salt-sensitive patients than in non-salt-sensitive ones, resulting in the greater elevation of BP. Supporting it, the salt loading-induced rise in BP was accompanied with the greater increment of cardiac output (CO) in salt-sensitive patients 2 . The increase in BP was positively correlated with retained Na and increase in CO. Therefore, the impaired renal function for Na excretion plays an important role in salt-induced hypertension in humans. Guyton 5 proposed that all types of hypertension basically have the impaired renal...

An Overview of Blood Pressure Regulation Associated with the Kidney

Goldblatt Kidney Model

Recent clinical and experimental studies have demonstrated that the blockade of the RAS produced an improvement of symptoms and survival rate of patients with congestive heart failure. We examined the role of vasopressin in congestive heart failure induced by rapid right ventricular pacing in dogs. In the dogs with impaired cardiac function, effective RBF and GFR were decreased mainly due to reduction of cardiac output. In these dogs, plasma renin activity, norepinephrine and vasopressin were all elevated. Murakami et al. 58 provided interesting data by studying the dogs with impaired cardiac function. They compared the acute effects of an ACE inhibitor and an angiotensin type 1 receptor antagonist on cardiac output and RBF. Interestingly, these two types of drugs showed distinct effects captopril increased both cardiac output and RBF, however, losartan increased RBF but failed to alter cardiac output. Furthermore, Matsumoto et al. 59 found a synergistic action with an ACE inhibitor...

Role Of Hyperglycemia In The Development Of Complications Evidence To Date

Nephropathy or by three or more insulin injections) or to conventional therapy (one or two daily insulin injections). The subjects were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. The trial demonstrated conclusively that control of clinical hyperglycemia, as evidenced by a reduction in HbA,c, reduced retinopathy by 75 , nephropathy by 54 , and neuropathy by 60 . There was also a 41 reduction in macrovascular disease, but this was not statistically significant because of the low number of events. The Stockholm Diabetes Intervention Study (SDIS) also evaluated the benefit of glycemic control in type 1 subjects. In this trial, 43 subjects were randomized to intensified conventional treatment (ICT) and 48 subjects randomized to standard treatment (ST). Subjects were followed for 10 years while vascular complications, treatment side effects, well-being, and risk factors for complications were studied....

The Physical Laws Obeyed by the Blood and Blood Vessels

The axioms of the classical continuum mechanics are listed in Table 1. This includes the laws of conservation of mass and energy, the Newton's laws of motion, the immutable constitutive equations of the materials, the invariability of the zero-stress state of solids, the constancy of mechanical properties of solids, and the constancy of material composition of solids. Classically, these were considered as universal truth. Much of our modern civilization was developed on the basis of these axioms. Airplanes, ships, telescopes, microscopes, artificial heart valves, and kidney dialysis machines were designed on the basis of these classical axioms.

Factors Influencing Outcome from ARF

Many investigators have found death from ARDS to be primarily related to the degree of organ dysfunction 24, 29,46 . Doyle et al. 2 found that multiple organ failure (MOF), liver disease, and sepsis were the main factors contributing to death. Other important prognostic factors include age 28, 29, 47 and the development of acute renal failure 48 . The prognostic value of the degree of hypoxemia is not well established. Luhr et al. 37 emphasized that the degree of hypoxemia was unimportant in terms of mortality prediction. Likewise, Valta et al. 36 reported that the PaO2 FiO2 ratio at the onset of ARDS was similar in survivors and nonsur-vivors.

Tissue Remodeling Fibrosis

Tial fibrosis are greater than from control individuals (102), and patients with idiopathic interstitial pulmonary fibrosis show evidence of mast cell degranulation and elevated mast cell numbers (103). In the kidney tissue of patients with IgA nephropathy, mast cell numbers correlate with the degree of interstitial fibrosis and creatinine clearance. In these kidney tissues, mast cells express tryptase and bFGF (104), which may be partially responsible for the fibrosis observed. The mast cell appears to be the dominant source of bFGF in some patients with pulmonary fibrosis (105). Similarly, patients with pulmonary fibrosis associated with scleroderma show higher numbers of mast cells and quantities of histamine and tryptase in bronchoalveolar lavage fluid than patients with normal chest roentgenograms (106). Mast cells also are found in intimate contact with myofibroblasts in keloid scars, suggesting they may play a role in fibroblast activation and scar formation (107). Thus, it...

Suggested Readings

Recombinant human erythropoietin in anemic subjects with end-stage renal disease results of phase III multicenter clinical trial. Am Intern Med 1989 111 992. Sinai-Trieman L, Salusky I, et al. The use of subcutaneous recombinant erythropoi-etin in children undergoing continuous cycling peritoneal dialysis. J Pediatr 1989 114 550.

Bloodpressure Control

Comment Hypertension is a significant risk factor for many of the complications of diabetes, playing a role in the development of retinopathy, nephropathy, and cardiovascular disease. Because cardiovascular disease is the most significant contributor to the morbidity and mortality in patients with type 2 diabetes, aggressive regulation of blood pressure is advised. A recent clinical advisory from the National High Blood Pressure Education program (7) indicates that the coexistence of diabetes and hypertension warrants a lower blood pressure goal (135 80) than for the patient with hypertension who does not have diabetes (140 90). ACE inhibitors, and perhaps angiotensin-receptor blockers, offer many advantages in the treatment of hypertension in the patient with diabetes. There is evolving research examining the role of these agents in vascular reactivity, endothelial function, and fibrinolysis that may underlie the recent exciting observation from the MICRO-HOPE study of a protective...

Immunoinformatics in improving transplantation outcomes

Renal failure is an increasing problem around the world, with a rising incidence largely due to the rising incidence of type 2 diabetes. Although dialysis is a short-term solution, renal transplantation remains the optimum solution both for restoring quality of life and for increasing life expectancy of patients. A major limitation to renal transplantation is the supply of donor kidneys. Although success rates from renal transplantation continue to improve, a significant number of donor kidneys continue to be lost due to rejection or recurrent disease. Consequently, a significant number of renal transplant recipients require a second or subsequent graft. The ability to improve the graft success rate and thereby reduce the number of patients requiring multiple grafts would both improve patient outcomes and increase availability of donor kidneys for primary recipients. To further demonstrate the applicability of an immunoinformatic approach to organ transplantation we performed a study...

The Practice of Clinical Neurotransplantation

The survival and integration of transplanted nerve cells depends on their plastic growth capacities at the stage of maturation in which they have not yet fully developed their complex neurite connections and bio-electrical interactions. In the brain developmental period each type of nerve cells has its own time window of birth and its own pace of maturation. The transplantation of entire brain sub-regions might thus easily result in one cell type surviving and another, more mature, cell type failing to do so. Consequently, a large brain part may survive transplantation as a tissue mass, but it can or will not easily develop its normal organisation in the recipient brain, nor develop the proper connections with, or within, the damaged neuronal systems of the brain. In other words, neurotransplantation strategies in human patients add new cells of particular types (cell suspensions), or place fragments of immature brain structures (minced tissue) but cannot aim to replace entire brain...

Affinitychromatography on heparincross linked columns

Heparin-agarose affinity chromatography has been used to isolate LF from human milk whey in a single chromatographic step (Blackberg & Hernell, 1980). Al-Mashikhi and Nakai (1987) have used heparin-sepharose affinity chromatography to isolate LF from cheddar cheese whey. In this procedure, whey is dialyzed against 0.05M NaCl in 0.005 M sodium barbital-HCl buffer, pH 7.4. Whey solution is applied to a heparin-agarose column equilibrated with the above dialysis buffer. Protein is eluted at a flow rate of 48 ml h using a continuous gradient of 0.05M to 1.0 M NaCl constituted in the dialysis buffer. Fractions are collected and absorbance is read at 280 nm. Rejman et al. (1989) used this method to isolate bLF from mammary secretions collected during the nonlactating period. About 1600 absorbance units (280 nm) of whey protein were efficiently separated by the heparin-agarose column (packed with 2.0 x 16.5 cm of Affi-Gel heparin agarose from Bio-Rad) into four absorbance peaks. LF was...

Largescale production of hybridomas

Monoclonal antibodies can be produced in dialysis tubing, where the antibody yields are up to 1 mg ml (standard culture supernatant is up to 5 p,g ml). A high concentration of cells (107 ml) in 10 ml of medium supplemented with 10 FCS is placed in a dialysis tube (pore size 12000-14000) and then into an 800-ml tissue culture flask The flask is fed with RPMI-1640 medium containing 2 FCS and 2 primatone (Kraft, Norwich, NY, USA) and placed in a rotator in a C02 incubator (17). A similar system using dialysis tubing fixed inside a roller bottle was described by Pannell and Milstein in 1992 (18). The yield of 1-2 mg ml obtained with this method is good. The reader is referred to Andersen and Gruenberg (19) and von Wedel (20) for more information on other large-scale production methods.

Cardiovascular Complications In Diabetes

The coexistence of diabetes and hypertension causes a very high risk for the development of macrovascular and microvascular complications. In patients with diabetes, 30 to 75 of complications can be attributed to hypertension (12). Risk for cardiovascular disease increases significantly when hypertension coexists with diabetes mellitus (13,14). Moreover, hypertension has a greater impact on cardiovascular diseases in diabetic as compared with nondiabetic subjects (15). Diabetic patients have a higher incidence of coronary artery disease, congestive heart failure, and left ventricular hypertrophy when hypertension is present. The incidence of other macrovascular complications, such as stroke and peripheral vascular disease, also increases significantly when hypertension exists in diabetic patients. Moreover, in addition to macrovascular complications, hypertension accelerates the risk of microvascular complications. Diabetic nephropathy (16,17), retinopathy (18-20), and neuropathy (21)...

Metabonomics in Disease Diagnosis

In addition to characterization of disease states, NMR-based metabonomic analysis offers an efficient means to monitor the response of patients to drug therapy or other therapeutic interventions. For example, in a study of patients with end-stage renal failure, the response of patients to hemodialysis was monitored. Plasma samples were obtained from healthy subjects and from patients with renal failure immediately preceding and following hemodialy-sis. Samples were analyzed by NMR spectroscopy and mapped with pattern-recognition methods. Samples obtained from the majority of patients following hemodialysis were observed to map more closely to the cluster of samples obtained from healthy subjects than those samples obtained prior to dialysis therapy, with the exception of one patient who responded badly to the therapy and mapped separately to all other samples 13 . Thus, this methodology can be used to select appropriate therapies for patients.

Promoting an Optimal Response to Therapy

RISK FOR INEFFECTIVE TISSUE PERFUSION RENAL. When the patient is taking a drug that is potentially toxic to the kidneys, the nurse must carefully monitor fluid intake and output. In some instances, the nurse may need to perform hourly measurements of the urinary output. Periodic laboratory tests are usually ordered to monitor the patient's response to therapy and to detect toxic drug reactions. Serum creatinine levels and BUN levels are checked frequently during the course of therapy to monitor kidney function. If the BUN exceeds 40 mg dL or if the serum creatinine level exceeds 3 mg dL, the primary health care provider may discontinue the drug therapy or reduce the dosage until renal function improves.

Physiological Side Effects of Cellular Implants

So far, patients who have received pig organ or tissue transplants (Nasto 1997 Stoye et al. 1998 Heneine et al. 1998) or who have undergone dialysis using pig kidneys (Patience et al. 1998) have shown no signs of porcine virus-induced pathogenesis. Clinical studies with porcine embryonic mes-encephalic dopaminergic grafts in the brain should always include long-term, post-operative screening on the expression of PERVs in serum samples (Isacson and Breakefield 1997). Possible consequences for the patient when hazardous viruses do show up have hardly been considered in the neurotransplantation field. If it affects just the patient, it is to be regarded simply as a side effect. If it becomes a highly transmittable, life-threatening disease, it could require, in extreme cases, the isolation of the person receiving the xenotransplant.

Intermediate Kca Channels

Clotrimazole is currently in clinical trials for the treatment of sickle cell disease (Brugnara et al., 1996). This disease is caused by a single point mutation in the haemoglobin molecule, which renders it less soluble in the deoxyge-nated form. Consequently, it precipitates out of solution within the cell more readily. When this happens, the erythrocyte is no longer sufficiently distensible to pass through the small capillaries so that the sickled cells block the microvasculature and cause local tissue hypoxia. Such a sickle cell crisis is extremely painful and, because the sickled cells are more fragile and have a shorter life, may lead to chronic anaemia. Kidney failure may result if sickled erythrocytes block the renal vasculature. The sickle attacks are triggered by hypoxia, by protons, and by elevated temperature, all of which cause dehydration of the red blood cell and thus an increase in the haemoglobin concentration, which precipitates sickling. IK channels contribute to...

Intervertebral Disc Degeneration

Intervertebral Disc Gas

Also present with high T2 signal in the disc space. One such scenario occurs when there is complete loss of disc height at a given disc level associated with segmental instability, which results in a pseudoarthrosis of the adjoining endplates. The result is similar to the Baastrup's phenomenon, in which fluid is noted at the friction point between adjacent spinous processes. Other causes of pseudoarthrosis, such as when an unstable fracture complicates ankylosing spondylitis or spinal fusion, can also simulate infectious discitis (Fig. 2). Additional rare mimics include neuropathic (Charcot) spine and dialysis-related spondyloarthropathy (11). In some cases, disc biopsy is needed to exclude infection, which can be performed using either fluoroscopic or CT guidance.

Clinical features

Acidotic breathing - hyperventilation, deep breathing - may develop in severely ill patients who are shocked, hypoglycaemic, hyperparasitaemic or in renal failure. This is usually due to lactic acidosis, and lactic acid concentrations in both blood and CSF are raised. Perfusion is improved by correcting hypovolaemia.

Cellular Identity of the Donor Cell

Similarly, there is mounting evidence suggesting the donor cell type might influence the phenotype of cloned mice. When cumulus cells were used as nuclear donors, many cloned mice became obese (Tamashiro et al. 2002). In contrast, mice derived from sertoli cells of the same genetic background did not become obese, but instead died prematurely with some signs of tumorigenesis and kidney failure (Ogonuki et al. 2002). Our own analysis of placental transcriptional profiles from cloned mice revealed abnormalities in gene expression that were common to all cloned animals. However, we also detected gene expression abnormalities that were present in all animals cloned from cumulus cells but that were not found in animals cloned from ES cells, which had their own set of common abnormalities that were not found in cumulus clones (Humpherys et al. 2002). Together, these results suggest there may be incomplete cell-type specific reprogramming of the donor nucleus, and that these cell-type...

Common abnormalities

Systemic hypertension is common, particularly in the elderly, has no specific symptoms but, if untreated, can lead to death or morbidity from heart disease, cerebrovascular accident or renal failure. Clinical assessment of the hypertensive patient has three aims

Adverse Reactions

The skeletal muscle relaxants are used with caution in patients with a history of cerebrovascular accident, cerebral palsy, parkinsonism, or seizure disorders and during pregnancy (Pregnancy Category C) and lactation. Carisoprodol is used with caution in patients with severe liver or kidney disease and during pregnancy (category unknown) and lactation. Cyclobenzaprine is used cautiously in patients with cardiovascular disease and during pregnancy (Pregnancy Category B) and lactation. Dantrolene is a Pregnancy Category C drug and is used with caution during pregnancy. See Chapter 25 for information on diazepam.

Eosinophils Outside The Lung

Peritoneal invasion with a variety of fungal organisms can occur in patients receiving continuous ambulatory peritoneal dialysis (CAPD) and in some cases is associated with an eosinophilic infiltrate (Ampel et al. 1988 Lee et al. 1997 Nankivell et al. 1991). The cell wall fraction from H. capsulatum induced peritoneal eosinophilia through an IL-5 dependent mechanism. In a murine model of infection with H. capsulatum or inoculation with H. capsulatum derived beta-glucan, leukotrienes were demonstrated to play and important role in the recruitment of eosinophils and other inflammatory cells (Medeiros et al. 2004, 2004 Sa-Nunes et al. 2004).

The MiniPERM Bioreactor

Miniperm Bioreactor

The MiniPERM bioreactor is our method of choice for the high-density culture of hybridoma cells (Fig. 1). The modular system, consisting of a 40-mL disposable culture chamber and a 550-mL reusable nutrient module separated by a dialysis membrane (12.5 kDa molecular weight cutoff), allows for the production of a low-volume, high-density cell population with a correspondingly high antibody yield.

Medical Complications of Glucose Intolerance and Diabetes Mellitus

Finally, many diabetic patients suffer a great deal from microvascular-and macrovascular-induced nephropathy, which can cause hypertension, proteinuria, and a decrease in the glomerular filtration rate, leading to renal failure. Indeed, diabetic nephropathy accounts for approximately 25 of end-stage renal failure cases in the United States (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2000) and is a leading cause of morbidity and mortality in diabetic patients.

Preoperative Considerations Patient Selection

A medical history should focus on the patient's urologic history along with surgical risks and concomitant medical problems. Urologic history should include a history of sexually transmitted diseases, kidney stones, trauma, previous catheterizations, genitourinary cancer, renal insufficiency, neurologic disease, and neurogenic bladder. Medical conditions that may influence bladder functioning include diabetes and neurologic diseases. Surgical risks predominantly are the result of renal failure, coronary artery disease, and cerebrovascular disease. Medicines containing a-sympathomimetics, including over-the-counter cold remedies, enhance bladder outlet obstruction. A family history should focus on a history of urologic cancer, and a social history should focus on risks for cancer such as smoking and occupational exposure.

Differential diagnosis

Systemic lupus erythematosus and other connective tissue disorders. The symmetric joint inflammation of RA and SLE may be indistinguishable. However, in SLE, erosions do not develop, and the joint disease is commonly accompanied by such manifestations of SLE as fever, serositis, nephritis, dermatitis, cytopenias, and antinuclear antibody (ANA) and anti-DNA seropositivity. Other connective tissue disorders, such as scleroderma and the vasculitides, may present with an RA-like polyarthritis, or this may develop later.

High Throughput Inlets and Microfabricated Fluidic Systems

Rapid technological developments in nanotechnology (reviewed in Reference 159) have led to the exploration of microfluidic devices both for sample preparation and as sample introduction devices for mass spectrometric analyses. There is an increasing need for large-scale, high-throughput analysis of exceedingly small sample quantities in several research areas,160 most notably in proteomics (Section 6.1.1). Despite the huge differences in physical dimensions, microdevices can be conveniently interfaced with ESI sources because of similar flow rate requirements (reviewed in References 160,161). Sample preparation protocols, such as cleanup by dialysis,157 enzymatic digestion,162 preconcentration,141 and separation of proteins and their digested products by electro-kinetic or chromatographic approaches have been accomplished on single microchips.35,39,163,164 In most cases, microfabricated and chip-based interfaces for CE-MS have used ESI for ionization.165,166 A 100-element...

Contraindications Precautions And Interactions

These drugs are used with caution in patients with tachycardia, cardiac arrhythmias, hypertension, hypotension, those with a tendency toward urinary retention, those with decreased liver or kidney function, and those with obstructive disease of the urinary system or gastrointestinal tract. The anticholinergic drugs are given with caution to the older adult.

Steps Of Process Development For Largescale Protein Crystallization

In this stage of identifying the operating window,'' 5-50 mg ml protein solution can be used at as low as 500 ml volume. Of course, these values may vary depending on the solubility and availability of the target protein. When the quantity of the protein sample is the limiting factor, several screening methods have been proposed. Dialysis button was used by which protein could be easily reused by dialysis against a buffer to remove precipitant. Carter et al. (1988) used this in an incomplete factorial approach. Jancarik and Kim (1991) described the use of a sparse set of conditions, which was later developed commercially. The idea was to provide a broad sampling by random combination of conditions initially and then improve on them later.

Biotinylation of the Oxidized Antibody

Desalt the biotinylated antibody by dialysis or gel filtration. Note that after hydrazide-based biotinylations, many researchers feel that it is necessary to stabilize the linkages between the hydrazides and aldehydes by treating the conjugate with sodium cyanoborohydride.

Diffusionweighted MR Imaging

Diffusion-weighted imaging is feasible for assessment of vascular related renal dysfunction. Larger B factors are necessary to eliminate the confounding influences of glomerular filtration, tubular reabsorption, tubular secretion and urine flow on the apparent diffusion coefficient (ADC) 46 . The cortex of ischemic kidneys shows lower ADC values than that of the contralateral ones because significantly reduced blood flow may have more physiological impact on cortex than medulla. In acute or chronic renal failure caused by other factors, both cortex and medulla show reduced ADC values 47 .

The Kidneys Normally Maintain K Balance

The major cause of K+ imbalances is abnormal renal K+ excretion. The kidneys may excrete too little K+ if the dietary intake of K+ continues, hyperkalemia can result. For example, in Addison's disease, a low plasma aldosterone level leads to deficient K+ excretion. Inadequate renal K+ excretion also occurs with acute renal failure the hyperkalemia caused by inade-

Our Experience with the MET

A number of reports have described the benefits of the MET (10-13). Data was collected at Austin Hospital before and after introduction of the MET to assess its impact on cardiac arrests, serious adverse events, and hospital mortality. Studied over 2 comparative 4-month periods, for surgical patients the introduction of an ICU-based MET was associated with a 65 reduction in hospital cardiac arrests and 26 reduction in hospital mortality (14) (Figure 15.3). A number of serious adverse events were studied in a cohort of patients undergoing major surgery during these same periods. The MET was associated with a statistically significant reduction in the frequency of severe sepsis, respiratory failure requiring ventilation, stroke, emergency ICU admission, and acute renal failure requiring renal replacement therapy, and also in the number of postoperative deaths (15) (Figure 15.4). Substantial cost savings, far exceeding the cost of implementing the MET, were estimated based on reduced...

Assessment of Diastolic Function

Diastolic dysfunction is the hallmark of diabetic cardiomyopathy and echocardi-ography is invariably the most commonly employed test at the present time to reliably assess diastolic functional abnormalities. Left ventricular diastolic filling abnormalities in patients with diabetes do not correlate with the duration of diabetes nor with the presence of other complications such as retinopathy, nephropathy, or peripheral neuropathy. In diabetic cardiomyopathy, the initial abnormality of diastolic filling is characterized by a slowed or impaired myocardial relaxation as is the case for most other cardiac diseases. It should be noted that there is a gradual impairment of myocardial relaxation with normal aging, but in pathological states it is more pronounced than what is usually expected for the patient's age. With continued progression of the disease, LV compliance is reduced and elevation in left atrial pressure results in a restrictive LV filling pattern, which initially may be...

Clinical Focus Box 251

Renal tubular acidosis (RTA) is a group of kidney disorders characterized by chronic metabolic acidosis, a normal plasma anion gap, and the absence of renal failure. The kidneys show inadequate H+ secretion by the distal nephron, excessive excretion of HCO3 , or reduced excretion of NH4+.

What is the goal of blood pressure management

The ultimate goal of antihypertensive therapy is to delay, prevent, or reverse blood pressure-related end-organ vascular damage. To achieve this most effectively, blood pressure should be reduced to target levels specified in the current guidelines. The current (seventh) report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (JNC7) recommends a goal of < 140 90 mmHg in the general population (16). However, a substantial proportion of patients with metabolic syndrome have diabetes or chronic kidney disease JNC7 and the American Diabetes Association recommend a goal of < 130 80 mmHg for such individuals (16,17). Thus, the physician is challenged to be bold enough to adopt an intensive blood pressure management strategy to achieve and maintain goal blood pressure and protect the patient against future morbidity and mortality.

Clinical presentation

Important predisposing factors of an acute gouty attack include diuretic use, recent surgery, alcohol abuse, chronic renal disease, rapid weight reduction, and infection. A positive family history of gout is helpful in supporting a diagnosis of primary gout. In patients taking cyclosporine, an especially rapidly progressing form of gout can develop, often with tophi.

Patients Unsuitable For Strict Control

The DCCT demonstrated that any reduction in glycated haemoglobin is associated with a reduced risk of microvascular complications over time, and the benefits are greater with higher glycated haemoglobin concentrations (The Diabetes Control and Complications Trial Research Group, 1996b). A cross-sectional study which suggested that the risk reduction for nephropathy is near-maximal at a glycated haemoglobin of 8 (Krolewski et al., 1995) cannot be extrapolated to other microvascular complications, because in the DCCT no glycaemic threshold (estimated by glycated haemoglobin) for the development of retinopathy was demonstrated in a patient group whose average HbA1c was 7 . The long-term follow-up of the DCCT cohort has confirmed that intensive therapy benefits macrovascular as well as microvascular risk and that its effects are sustained (Writing team for the Diabetes Control and Complications Trial Epidemiology of Diabetes Interventions and Complications Research Group, 2002). Thus,...

Other Potential Causes of Androgen Deficiency

Men with pre-existing testicular dysfunction (including renal failure) may be more susceptible to further impairment of steroidogenesis caused by medications or illnesses. HMG-CoA reductase inhibitors inhibit cholesterol synthesis and may, therefore, impair steroidogenesis, particularly because adverse events consistent with androgen deficiency (gynecomastia and impotence) have been reported. A prospective, open-label study of 25 nephrotic, hyperlipidemic men with moderate chronic renal failure treated for 12 mo with lovastatin (40 mg d) showed no change in baseline and GnRH-stimulated LH, FSH, and testosterone levels (38). A more discerning test of testicular steroidogenesis, such as testosterone response to submaximal hCG stimulation, was not reported. Adrenal steroidogenesis (plasma cortisol before and after adrenocor-ticotropic hormone ACTH stimulation) was comparable with age-matched healthy controls at entry and remained unchanged by lovastatin treatment. Not surprisingly,...

Analgesic drugs used postoperatively

The pharmacology of opioid drugs and their side-effects are covered on page 37. In the UK, morphine is most commonly used to control severe postoperative pain on surgical units, and dia-morphine (heroin) on medical wards, for example coronary care units, mainly for historical reasons. There are few pharmacological differences between these two drugs. Morphine can be given by several routes (Table 3.4). One of the principal metabolites, morphine-6-glucuronide (M6G), has potent opioid effects and may accumulate and cause toxicity in patients with renal failure, particularly the elderly. Fentanyl and oxycodone have less active metabolites than morphine and so may be more suitable for these patients.

Pathogenesis and Clinical Features

Yellow fever is a hemorrhagic fever with a difference the liver is the major target, with virus replicating in Kupffer cells and massive necrosis of hepato-cytes leading to a decrease in the rate of formation of prothrombin as well as to jaundice. Although most cases are mild, presenting with fever, chills, headache, backache, myalgia, and vomiting, a minority progress (sometimes after a brief remission) to severe jaundice, massive gastrointestinal hemorrhages (hematemesis and rnelena), hypotension, dehydration, proteinuria, and oliguria signaling kidney failure. Mortality from this severe form of the disease is of the order of 20-50 .

Goodpastures Syndrome

Of the type IV collagen matrix within the basement membrane (Kalluri et al., 1995). When both the lung and kidney are disease targets, the autoantigen is part of thea3(IV)NCl collagen chain. The epitope resides in the C-terminus and consists of a discontinuous association of the last 36 amino acid residues. Over 85 of patients with lung and kidney disease form antibodies directed toward the a3(IV)NCl collagen chain. The kidney is the sole target organ in the remaining 15 of patients with Goodpasture's. These subjects produce antibodies directed toward theal(IV)NCl ora4(IV)NCl collagen chains (Hudson et al., 1993 Kalluri etal., 1995). This collagen form is antigenically and structurally distinct from thea3(IV)NCl chain.

Roberta D Laredo RD CDE

Diabetes nieilitus is a chronic disease resulting Iront absolute or relative insulin deficiency that occurs in both children and adults. Approximately one of every 600 children in the United States has diabetes, making it one of the most common chronic childhood illnesses. Diabetes occurs when insulin, normally produced by the beta cells of the pancreas, is cither absent, insufficient, or not used properly by the target tissues. Glucose builds up in the blood stream when insulin is unavailable to allow it to enter the cells. Long-term elevated blood glucose levels can lead to the chronic complications of diabetes, including retinopathy, nephropathy, neuropathy, and macrovas-cular disease.

Biochemical examination

Proteinuria may be due to increased leakage from the glomeruli, or may be due to tubular dysfunction. Even in health there is some filtration of proteins through the glomeruli, but most is reabsorbed and catabolised by the renal tubules. Proteinuria greater than 2 g per day suggests glomerular disease. Major renal disease may be present without significant proteinuria. This is common in polycystic kidney disease, renal scarring and obstructive uropathy. The proteinuria test strip is impregnated with tetrabromophcnol blue, and false-positive and false-negative results may occur (Table 5.36). The test is relatively insensitive to Bence Jones proteins (immunoglobulin light chains, often found in the urine in myeloma), which should be sought by a specific laboratory test. (microalbuminuria) occur in the early stages of diabetic nephropathy.

Acute and Chronic Complications

The chronic complications of diabetes are microvascular disease (neuropathy, nephropathy, retinopathy), macro-vascular disease (ischemic heart disease, cerebrovascular disease, peripheral vascular disease), and poor growth and development. Many of the chronic complications can be prevented or delayed with optimal blood glucose control, management of dyslipidemia and hypertension, proper weight management, and smoking cessation.

Hepaciviruses Hepatitis C and G

The incidence of HCV in Europe is about 0.3 , with a decreasing tendency in the younger segment of the population. About 50 of acute hepatitis cases are HCV infections. Transmission is by blood and blood products. High-risk persons include dialysis patients, healthcare staff, and needle-sharing drug consumers. Perinatal transmission is possible, but sexual contact does not appear to be a risk factor. The transmission route is not apparent in many cases, giving rise to the expression community-acquired infection. Feasible protective measures are the same as in hep

Diseases of the genitourinary system N00N99

N99.0 Postprocedural renal failure N99.1 Postprocedural urethral stricture Postcatheterization urethral stricture N99.2 Postoperative adhesions of vagina N99.3 Prolapse of vaginal vault after hysterectomy N99.4 Postprocedural pelvic peritoneal adhesions N99.5 Malfunction of external stoma of urinary tract N99.8 Other postprocedural disorders of genitourinary system

Gerontologie Alert

Angina is a common problem in older adults. When an older adult requires an antianginal drug, the dosage may be reduced to compensate for impaired renal function or heart disease. Older patients are at increased risk for postural hypotension. Blood pressure and ability to ambulate should be monitored closely.

Microbial iron acquisition

The ability of malleobactin to mobilize iron from LF and TF was examined in an equilibrium dialysis assay in the absence of bacteria (Yang et al., 1993). Malleobactin was capable of removing iron from both LF and TF at pH values of 7.4, 6.0, and 5.0. However, the levels of iron mobilization were greater for TF than for LF at all the pH values used in the assay. Bordetella bronchiseptica uses a hydroxamate siderophore for removal of iron from LF and TF rather than relying upon a receptor for these host iron-binding proteins (Foster & Dyer, 1993).

Display 422 Importance of the Systolic Blood Pressure

In most individuals, the systolic pressure increases sharply with age, whereas the diastolic pressure increases until about age 55 years and then declines. Older individuals with an elevated systolic pressure have a condition known as isolated systolic hypertension (ISH). When the systolic pressure is high, blood vessels become less flexible and stiffen, leading to cardiovascular disease and kidney damage. Research indicates that treating ISH saves lives and reduces illness. The treatment is the same for ISH as for other forms of hypertension.

Bile Acid Sequestrants

The bile acid sequestrants are contraindicated in patients with known hypersensitivity to the drugs. Bile acid sequestrants are also contraindicated in those with complete biliary obstruction. These drugs are used cautiously in patients with a history of liver or kidney disease. Bile acid sequestrants are used cautiously during pregnancy (Pregnancy Category C) and lactation (decreased absorption of vitamins may affect the infant).

Pancreas transplantation

Pancreas transplantation is used to prevent the sequelae of diabetes, which include damage to the kidneys (nephropathy), nerves (neuropathy) and retinas (retinopathy). Since the purpose of the procedure is to provide biologically responsive insulin-producing tissue, it may be performed with a whole organ, a segmental graft or dispersed islets of Langerhans. Recipients and donor organs are typed for both blood group and human leukocyte antigens and recipients undergo cross-matching.

Box 212 Biochemistry In Medicine

Aspirin (now a generic name) is one of a number of nonsteroidal antiinflammatory drugs (NSAIDs) others include ibuprofen and naproxen (see Fig. 21-15), all now sold over the counter. Unfortunately, aspirin reduces but does not eliminate the side effects of salicylates. In some patients, aspirin itself can produce stomach bleeding, kidney failure, and, in extreme cases, death. New NSAIDs with the beneficial effects of aspirin but without its side effects would be medically valuable.

Gaining Knowledge Through Experimentation

Squid have giant neurons they are so large that physiologists were able to insert electrodes inside them to discover the electrical events that produce nervous impulses and thus information transfer. Beyond this, the neurons are so large that it is possible to remove their contents and substitute artificial solutions to see how this alters neural impulse production. This is how it was discovered that the ions sodium and potassium are responsible for neural impulses. This research started in the 1920's, and developing technology has shown that mammalian neural function operates essentially the same way as squid neural function. Another example of such use of comparative physiology has led to the understanding of kidney function. In the early twentieth century, it was observed that kidney tubules in amphibians such as frogs and salamanders are large enough to allow samples of nephric tubular fluid to be removed and analyzed. Such studies led to the...

Management of Diabetes in Patients with Heart Failure

Poorly controlled diabetes should be managed aggressively in any patient with CHF because the attendant metabolic stress can certainly have adverse effects on myocardial function. Stringent control of blood glucose reduces the incidence of several complications of diabetes, specifically retinopathy, neuropathy, and nephropathy, but no data are available pertaining to the long-term effects of stringent control on diabetic cardiomyopathy or CHF in general in patients with diabetes. To the extent that diabetic cardiomyopathy is caused by hyperglycemia per se (e.g., matrix glycosylation) or the intracellular metabolic effects of reduced glucose transport (e.g., free radical damage to membranes), normalization of carbohydrate metabolism makes intuitive sense. Moreover, stringent control has been shown to modestly reduce event rates after an index myocardial infarction. On the other hand, prolonged hyperinsulinemia may be atherogenic and pro-thrombotic in type II diabetic patients. Thus, it...

Frequency Of Hypoglycaemia In Type 2 Diabetes

The frequency of hypoglycaemia relates to the individual pharmacokinetic properties of each sulphonylurea (Table 11.3), with the long-acting agents such as chlorpropamide, glibenclamide and long-acting glipizide being associated with the greatest risk (Stahl and Berger, 1999 Del Prato et al., 2002 Rendell 2004). Glibenclamide is associated with a greater risk of severe hypoglycaemia than gliclazide (Tessier et al., 1994) because active metabolites prolong its hypoglycaemic effects for 24 hours (Jonsson et al., 2001 Rendell 2004). Glibenclamide also attentuates the glucagon response to hypoglycaemia in non-diabetic volunteers (ter Braak et al., 2002) and in people with type 2 diabetes (Landstedt-Hallin et al., 1999 Banarer et al., 2002). Several drugs may potentiate the hypoglycaemic effects of sulphonylureas (Table 11.4). Risk factors for severe hypoglycaemia associated with sulphonylurea therapy include age, a past history of cardiovascular disease or stroke, renal failure, reduced...

Nursing Diagnoses Checklist

The drug is given three times weekly IV or SC, or if the patient is receiving dialysis, the drug is administered into the venous access line. The drug is mixed gently during preparation for administration. Shaking may denature the glycoprotein. The vial is used for only one dose any remaining or unused portion is discarded.

Critical Thinking Exercises

Garcia, age 54 years, has chronic renal failure. He undergoes dialysis three times a week. The physician orders epoetin alfa to be administered. Discuss the preadministration and ongoing assessments for Mr. Garcia. During a discussion with you, Mr. Garcia asks why he is receiving this drug. Discuss how you would answer Mr. Garcia's question.

Hemorrhagic Fever with Renal Syndrome

During the Korean war of 1950-1952, thousands of United Nations troops developed a disease marked by fever, hemorrhagic manifestations, and acute renal failure with shock the case-fatality rate was 5-10 . The etiologic agent of this disease remained a mystery until 1978 when a virus, named Hantaan virus, was isolated in Korea from the field rodent Apodemus agrarius and identified as a unique bunyavirus. Since then, several related viruses have been found in other parts of the world in association with other rodents. These viruses comprise the genus Hantavirus. Five hantaviruses, Hantaan, Puumala, Belgrade, Seoul, and Muerto Canyon viruses, are associated with human diseases with different epidemiologic patterns, varying clinical manifestations, and a variety of local names (see Table 33-2).

Training and education of wardbased medical and nursing staff

Recognition of patients at risk of becoming critically ill is a key point and often the limiting step in initiating appropriate management. Even when this is achieved, there is no substitute for experience when it comes to the management of critical illness, and the importance of referring such patients to senior colleagues at an early stage cannot be emphasized enough. All too often, misinterpretation of the clinical picture may lead either to a lack of action or to treatment being commenced which is inappropriate. A common example is the elderly postoperative patient who is breathless, hy-potensive, oliguric and has crackles on auscultation of the chest. Acute heart failure is diagnosed and a large dose of an intravenous diuretic is given. The correct diagnosis is often pneumonia, sepsis and pre-renal failure, secondary to hypovolaemia and hypotension. Although the intravenous diuretic may initially result in a slight increase in urine output, ultimately it will exacerbate the...

Thiazides and Related Diuretics

The thiazide diuretics are used cautiously in patients with liver or kidney disease, lupus erythe-matosus (may exacerbate or activate the disease), or diabetes. Additive hypotensive effects occur when the thiazides are given with alcohol, other antihypertensive drugs, or nitrates.

Organ Transplantation

Late in the summer of 1954, Richard Herrick was referred by his doctor to the Peter Bent Brigham Hospital in Boston, Massachusetts. Richard was 24 years old and had been suffering for some time from high blood pressure and puffiness around the face and eyes. His doctor suspected a kidney problem, and the Brigham is where you went if you were worried about your kidneys. The medical staff at the Brigham ran a battery of tests that initially might have indicated any number of problems. But they noticed that in addition to high blood pressure, Richard had more protein than normal in his urine, as well as traces of blood. Together with other findings, this confirmed the diagnosis of a kidney dysfunction. Richard was transfused with several units of blood, which improved his condition considerably, and he was sent home. Only time would tell how serious the problem with his kidneys was. Five months later, Richard Herrick was back, and this time it was clear he was in trouble. His blood...

Other Medical Conditions

Other areas of telemonitoring applications include the use of videophone technology for supervising therapy in patients with tuberculosis 8 or home monitoring of pulmonary function in patients after lung transplantation 53 . A computerized system for monitoring of dialysis remote sites and for follow-up of chronic patients was implemented with smart phones in G.Bosco Hospital in Torino, Italy 9 . The TELEDIAL system was designed for patients undergoing chronic ambulatory peritoneal dialysis at home. The data that may be transmitted by the patients include information about course of dialysis, symptom appearance, accidents or consumption of drugs unrelated to the main therapy scope. The physician taking care of the patients performing ambulatory peritoneal dialysis may change the mode of the therapy remotely.

Crude Estimates Of Mortality From Hypoglycaemia

If deaths caused by renal failure or coronary heart disease in people with diabetes continue to decline as diabetes care improves, then the relative proportion of deaths caused by hypoglycaemia may increase. This is particularly likely if intensive insulin therapy continues to be adopted more widely in an attempt to prevent or reduce microvascular disease (The DCCT Research Group 1991 The Diabetes Control and Complications Trial Research Group 1993).

Other Dietary Treatment Programmes

VLCDs should not be used in patients with unstable metabolic conditions (such as renal or hepatic insufficiency), in patients with eating disorders, infections, or other acute catabolic conditions such as renal failure, severe liver disease etc. When VLCDs were introduced, several medical precautions were taken and patients kept under strict medical supervision. Later experience has demonstrated that after an initial metabolic screening, laboratory tests and safety control can be kept to a minimum.

Clinical Transplantation

Alexis Carrel reported the first systematic study of transplantation in 1908 he interchanged both kidneys in a series of nine cats. Some of those receiving kidneys from other cats maintained urinary output for up to 25 days. Although all the cats eventually died, the experiment established that a transplanted organ could carry out its normal function in the recipient. The first human kidney transplant, attempted in 1935 by a Russian surgeon, failed because there was a mismatch of blood types between donor and recipient. This incompatibility caused almost immediate rejection of the kidney, and the patient died without establishing renal function. The rapid immune response experienced here, termed hyperacute rejection, is mediated by antibodies and will be described in this chapter. The first successful human kidney transplant, which was between identical twins, was accomplished in Boston in 1954. Today, kidney, pancreas, heart, lung, liver, bone-marrow, and cornea transplantations are...

High Versus Low Protein Hypocaloric Diets

Patients selected, consumed or returned could be adequately assessed. Weight loss after 6 months was 5.1 kg in the low protein group vs. 8.9 kg in the high protein group (P < 0.001). No negative side effects with the high protein diet were observed in particular, kidney function remained unaffected. The authors conclude that replacement of some dietary carbohydrates by protein in the ad libitum fat-reduced diet improved weight loss without any adverse effects. These effects could be explained by satiating signals of the protein or the increased diet-induced thermogenesis of the high protein diet. It has been suggested that the inhibition of energy intake caused by the high protein diet may be due to other mechanisms than energy density, such as release of cholecystokinin (46), insulin glucagon effects (47) in the liver or a direct effect in the central nervous system of certain amino acids (48).

Vibrio alginolyticus

V. algininolyticus has been implicated as a causative agent of infection in various extraintestinal sites. The most common presentations of these infections are cellulitis, otitis media, otitis externa, and conjunctivitis, and bacteremia in immunocompromised hosts. Pien et al. (49) reviewed eight cases in which the pathogen was isolated from infections in the toe, shin, foot, scalp, and ear. It was the only bacterium isolated from four of the infections and was considered to be the most probable causative agent. It has been isolated from wound infections of patients who have had recent exposure to seawater (50-59). The patients had conditions such as wound infections in the leg, cellulitis of the leg and leg ulcer, ulcerated lesions, necrotizing fasciitis, superficial septicemic lesions, and open head injury. In a study in Western Australia, it was isolated from 20 of the 36 samples of infected superficial wounds that had come in contact with seawater (60). The pathogen has been...

What may be the Mechanisms

Very schematically, iron in excess can result in an increased risk and worse outcome of infections for the three following reasons. First, it is clear that the growth of most microorganisms is inhibited by iron restriction and enhanced by the presence of iron in the growth medium (Weinberg, 1978). Second, some important iron-withholding strategies of the host may become ineffective in the presence of an excessive amount of iron. To cite just one example, the iron restriction afforded by physiologic iron saturation of transferrin (only 30 ) is abrogated when transferrin is nearly fully iron saturated and even more in the presence of NTBI (see Chapter 5) in the serum. Third, iron in excess grossly impairs the immune system and phagocyte functions in particular. Let us consider macrophages and neutrophils. Iron-loaded macrophages monocytes exhibit a decreased responsiveness to g-interferon and a decreased production of both TNF-a and NO (Weiss etal., 1994, 1995). They also have a limited...

Monoclonal Antibodies Can Suppress Graft Rejection Responses

The CD3 receptor and the high-affinity IL-2 receptor are targets present on all activated T cells molecules present on particular T-cell subpopulations may also be targeted for im-munosuppressive therapy. For example, a monoclonal antibody to CD4 has been shown to prolong graft survival. In one study, monkeys were given a single large dose of anti-CD4 just before they received a kidney transplant. Graft survival in the treated animals was markedly increased over that in untreated control animals. Interestingly, the anti-CD4 did not reduce the CD4+ T-cell count, but instead appeared to induce the T cells to enter an immunosuppressed state. This is an example of a nondepleting antibody.

The Most Commonly Transplanted Organ Is the Kidney

As mentioned above, the most commonly transplanted organ is the kidney in 2000, there were 13,258 kidney transplants performed in the United States. Major factors contributing to this number are the numerous clinical indications for kidney transplantation. Many common diseases, such as diabetes and various types of nephritis, result in kidney failure that can be alleviated by transplantation. With respect to availability, kidneys can be obtained not only from cadavers but also from living relatives or volunteers, because it is possible to donate a kidney and live a normal life with the remaining kidney. In 1999,4457 of the 12,483 kidneys transplanted in the U.S. came from living donors. Surgical procedures for transplantation are straightforward technically, the kidney is simpler to reimplant than the liver or heart. Because many kidney transplants have been done, patient-care procedures have been worked out in detail. Matching of blood and histocompatibility groups is advantageous in...

Thiazolidinediones

The thiazolidinediones are contraindicated in patients with a hypersensitivity to the drug or any component of the drug and severe heart failure. These drugs are Pregnancy Category C drugs and should not be used during pregnancy unless the potential benefit of therapy outweighs the potential risk to the fetus. The thiazolidinediones are used cautiously in patients with edema, cardiovascular disease, and liver or kidney disease. These drugs may alter the effects of oral contraceptives.

Pancreas Transplantation Offers a Cure for Diabetes Mellitus

One of the more common diseases in the United States is diabetes mellitus. This disease is caused by malfunction of insulin-producing islet cells in the pancreas. Transplantation of a pancreas could provide the appropriately regulated levels of insulin necessary to make the diabetic individual normal. Recently, one-year success rates for pancreas transplantation of about 55 have been reported. Transplantation of the complete pancreas is not necessary to restore the function needed to produce insulin in a controlled fashion transplantation of the islet cells alone could restore function. Kidney failure is a frequent complication of advanced diabetes occurring in about 30 of diabetics, therefore kidney and pancreas transplants are indicated. In 2000, there were 420 pancreas transplants and 904 simultaneous kidney pancreas transplants. A group at the University of Wisconsin reports that they have overcome surgical and medical barriers to the dual transplant and have achieved survival...

Protein Macromolecules

Although serum albumin is a relatively pure fraction, it is still contaminated with fatty acids and other small molecules (213). The latter includes an embryotrophic factor, which stimulates cleavage and growth in rabbit morulae and blastocysts. This factor has been determined to be citrate (214). Not only are there significant differences between sources of serum albumin (215,216), but also between batches from the same source (215,217). Furthermore, some HSA preparations contain the preservative sodium caprylate, which binds to the hydrophobic domains of the proteins and therefore cannot be removed by dialysis (Pool TB. Personal communication, 1998). The effects of such a preservative on embryo development have yet to be determined. Therefore when using serum albumin or any albumin preparation, it is essential for each batch to be screened for its ability to adequately support embryo development in the mouse prior to

Salt and Drug Induced Renal Injuries

Chronic renal failure in humans can lead to end-stage renal disease, which eventually requires kidney transplant or dialysis. A high-salt diet can also cause extensive renal damage in Dahl-SS rats. Therefore, this is an excellent animal model for studying salt-induced renal damage in humans. A previous study showed that long-term infusion of purified rat tissue kallikrein via minipump attenuated glomerular sclerosis without affecting blood pressure in Dahl-SS rats on a high-salt diet (78,79). The protective effect of kallikrein protein infusion was blocked by icatibant, indicating that the tissue kallikrein via kinin B2 receptor could exert a direct effect in protection against salt-induced renal lesions, independent of blood pressure reduction. Consistent with this finding, we showed that adenovirus-mediated kallikrein gene delivery enhanced renal function in Dahl-SS, 2K1C, and 5 6 nephrectomy hypertensive rats as evidenced by increases in renal blood flow, urine flow, glomerular...

Table 352 Special Aspects of Nutritional Assessment in Renal Disease

Current renal replacement modality (conservative, dialysis, Peritoneal dialysis is the more common dialysis treatment for children with ESRD. and renal transplantation is more common in younger children than in older children and adults. Transplantation is highly encouraged for all suitable children, eventually providing them a more normal lifestyle.

Manganese Chemistry and Biochemistry

1 Erythropoietin is the protein growth factor secreted by the kidney which stimulates the production of red blood cells, and is used in the treatment of anaemia arising from kidney disease. Erythropoietin, now available as a recombinant human protein for routine clinical use, is the latest in a series of 'illegal substances' whose utilization by professional athletes has caused scandal and shame in events as different as the Tour de France and the Olympic games. The rationale for its use is that by increasing the red cell mass, it makes more oxygen available to muscle during prolonged physical effort - a kind of short cut to achieving the kinds of performances that may underly the dominance of long distance running events by Ethiopean and Kenyan athletes.

Stress Induced Changes in Caveolin1 Expression

Apoptotic agents, including simvastatin, camptothecin, or glucose deprivation 125 . In this case, caveolin-1 was found to co-localize with phosphatidylserine on the cell surface of the apoptotic cells, thus serving as an indicator of macrophage apoptosis. Other stress signals that were reported to increase caveolin-1 protein levels included exposure to various cytostatic drugs in lung cancer cells 45,126,127 . The acute up-regulation of caveolin-1 expression by chemother-apeutic drugs may be related to the constitutively elevated caveolin-1 levels observed in MDR human cancer cell lines 44,45,128,129 and the correlation of caveolin-1 expression with expression of the MDR1 gene in leukemic bone marrow leukocytes 130 . Another stress condition reported to induce caveolin-1 protein levels in endothelial cells at G0 G1 cell-cycle phase is hypergravity stress 131 . In the latter case, the up-regulation of caveolin-1 was associated with the redistribution of caveolin-1 to an intracellular...

Affected Organs And Cell Types In Polyomavirusassociated Disease And Persistent Virus Infection

Urogenital Diseases Associated with BKV and Asymptomatic Infection. BKV is a urotheliotropic virus, which was originally detected in the urine of a patient with ureteral stenosis after renal transplantation (RT) (Gardner et al., 1971). Nevertheless, studies from recent years suggest that interstitial tubular nephritis is the most frequent BKV-associated disease after RT (Mathur et al., 1997 Pappo et al., 1996 Purighalla et al., 1995). Clinical features may mimic graft rejection or drug toxicity (Binet et al., 1999 Randhawa et al., 1999), but histopathologic examination almost always shows interstitial infiltrates of plasma cells and lymphocytes, interstitial fibrosis, tubular atrophy, and large intranuclear inclusions in tubular epithelial cells. Cells of the transitional bladder epithelium were identified as target cells for BKV infection (Gerber et al., 1980). Virus isolation, DNA detection by polymerase chain reaction (PCR), electronmicroscopy, immunohistologic staining of BKV...

Renal hemodynamics and vascular functions

Gene-targeting strategies in mice provide novel approaches in the study of the physiological responses corresponding to gene-dosage in vivo (208,209). Gene-targeted mice carrying gene disruption or gene duplication have provided strong support for the physiological roles of natriuretic peptides and their receptor systems in kidney function (15,16,198,210-216). The studies with Npr1 (coding for NPRA) gene-disrupted mice demonstrated that at birth, the absence of NPRA allows greater renin and ANG II levels and increased renin mRNA expression compared with the wild-type mice (198). However, at 3-16 wk of age, both circulating and kidney renin and ANG II levels were decreased dramatically in Npr1 homozygous null mutant mice as compared with wildtype control mice. This decrease in renin activity in adult null mutant mice is implicated because of progressive elevation in arterial pressure leading to inhibition of renin synthesis and release from the kidney juxtaglomerular cells. It has been...

Furuncles and carbuncles

Furuncles (ie, boils) are single hair follicle-associated inflammatory nodules extending into the dermis and the subcutaneous tissue, usually affecting moist, hairy, friction-prone areas of the body, such as the face, axillae, neck, and buttocks. Firm and tender, these nodular erythematous lesions may spontaneously drain purulent material. Fever and other constitutional symptoms rarely are present. The most common causative microorganism is S aureus, but the microbiology of furuncles depends on the location of the lesions. Risk factors for developing this condition include obesity, diabetes mellitus, atopic dermatitis, parenteral drug use, chronic kidney disease, impaired neutrophil function, use of corticosteroids, close exposure to

Is Lazer Treatment For Crps Type 1 Dangerous

Bier Block Technique

The mechanism of action of nonsteroidal antiinflammatory drugs (NSAIDs) is the inhibition of cyclooxygenase. This leads to a reduction in the production of pain mediators and a reduction in inflammation. NSAIDs may be helpful in the early stages of CRPS type 1 however, the potential for gastrointestinal complications and renal failure must be considered if continued use is to be recommended.

Allopurinol Xyloprim Lopurin

Refractory recurrent gouty arthritis, tophaceous gout, nephrolithiasis, urate nephropathy. Metabolism Maculopapular rash is the most common side effect and occurs in 3 of patients. Immune complex dermatitis and hepatitis, occasionally with vasculitis and nephritis, can occur pruritus is an important warning symptom. Side effects of allopurinol are increased in the presence of marked renal failure (creatinine clearance < 20 mL min). To prevent uric acid nephropathy during the treatment of neoplastic disease, a daily dose of 600 to 800 mg may be required, with the maintenance of large volumes of an alkaline urine.

Tacrolimus and Sirolimus

Malonyl Coa Methylmalonyl Coa Groups

Tacrolimus (FK-506) (Figure 3.69) is a macrolide immunosuppressant isolated from cultures of Streptomyces tsukubaensis. It is used in liver and kidney transplant surgery. Despite the significant structural differences between tacrolimus and the cyclic peptide cyclosporin A (ciclosporin see page 429), these two agents have a similar mode of action. They both inhibit T-cell activation in the immunosuppressive mechanism by binding first to a receptor protein giving a complex, which then inhibits a phosphatase enzyme called calcineurin. The resultant aberrant phosphorylation reactions prevent appropriate gene transcription and subsequent T-cell activation. Structural similarities between the region C-17 to C-22 and fragments of the cyclosporin A peptide chain have been postulated to account for this binding. Tacrolimus is

Materials And Methods

In the study, 58 patients who underwent orthotopic liver transplantation (8 males and 8 females, mean age 36 years, range 8 to 57 years), kidney transplantation (14 males and 4 females, mean age 44 years, range 25 to 61 years), and heart transplantation (21 males and 3 females, mean age 46 years, range 10 to 61 years) were monitored during operation and followed up to 7 days after a successful transplantation. Control groups of healthy subjects were also included in the study for whole-blood CL activity (n 23) and plasma total antioxidative capacity (n 14) measurements.

New Peptide Analogue for Treating Lupus Patients The Potential of Peptide P140

By testing a series of overlapping peptides, we identified an epitope present in residues 131-151 of the spliceosomal U1-70K small nuclear ribonucleoprotein (snRNP), recognized very early by IgG antibodies and CD4+ LN T cells from both H-2k MRL lpr and H-2d z BW lupus-prone mice (Monneaux et al. 2000, 2001). Fibroblasts transfected with MHC class II molecules were used to demonstrate that peptides 131-151 readily binds I-Ak, I-Ek, I-Ad and I-Ed murine MHC molecules (Monneaux et al. 2000, 2001). We further showed that an analogue of this sequence phosphory-lated on Ser140 (named peptide P140) was strongly recognized by LN and peripheral CD4+ T cells and by IgG antibodies from MRL lpr mice (Monneaux, 2003, 2004). This analogue and the cognate peptides 131-151 were used in therapeutic trials in lupus-prone mice to investigate their ability to restore tolerance. Young MRL lpr mice were given the peptides i.v. in saline (4 X 100 xg), and we found that P140 peptide, but not the...

Nucleotides Are Poor Sources Of Energy

Structure Azaserine

Treatment of Gout Allopurinol (see Fig. 22-47), an inhibitor of xanthine oxidase, is used to treat chronic gout. Explain the biochemical basis for this treatment. Patients treated with allopurinol sometimes develop xanthine stones in the kidneys, although the incidence of kidney damage is much lower than in untreated gout. Explain this observation in the light of the following solubilities in urine uric acid, 0.15 g L xanthine, 0.05 g L and hypox-anthine, 1.4 g L.

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