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What then are the lessons to be learned about prevention and treatment of hemochromatosis? Early diagnosis is essential. The best indicator would be testing of serum iron and total saturation followed by a serum ferritin if elevated. Once these indices are abnormally high, MRI and or a liver biopsy should confirm the stage of the iron over-loaded state. If indeed the patient is not iron-overloaded (normal liver biopsy in the face of high saturation and ferritin level) phlebotomies should be performed until these indices are normal and then maintained at a normal level. This should entail four to six phlebotomies a year. Family members should also be screened and managed in a like manner. HLA typing may be a partially helpful screening device. The abnormal gene is closely linked on chromosome 6 with HLA histocompatibility loci. Now, by means of HLA typing, we can identify heterozygote carriers and homozygous (abnormal) among first degree relatives of patients with hemochromatosis. Unfortunately, HLA typing can only be used within a given family and cannot be used to screen the general population. It is estimated that 70% of hemochromatoics have the antigen HLA-A3; however, so does 28% of the (well) general population. Patients with unexplained cirrhosis, arthritis, liver disease, diabetes, impotency, cardiomyopathy and neurological symptoms should be screened in a like manner. Routine health practice profile chemistries must include a serum iron and iron saturation, and if high followed by a serum ferritin. Once diagnosed, therapy must be maintained with phlebotomy for the life time of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemochromatosis: diagnosis and treatment. 179 61

Enoximone, a new phosphodiesterase-inhibitor with positive inotropic and vasodilating activities is available for intravenous use in patients with severe heart failure. A review of the current knowledge regarding the adverse effects of this substance reveals that they are characterized by cardiovascular, central nervous, and gastrointestinal side effects. Adverse effects occurred in 20% of patients and were mostly due to the pharmacological properties of enoximone. Cardiovascular side effects (10%) were the most frequent; ventricular and supraventricular arrhythmias were most common. Two to three percent of the patients experienced hypotension due to the vasodilator activity of enoximone. Headache, insomnia, and anxiety were the most frequent adverse effects on the central nervous system. Three percent of the patients treated experienced vomiting, nausea, abdominal pain, and diarrhea. An increase of liver enzymes and serum glucose could be observed, mostly in patients with previous liver disease or diabetes. Pharmacokinetic drug interactions are not known; possible pharmacodynamic interactions result from the pharmacological properties of the drugs. Intravenous therapy with enoximone causes a few serious side effects that can only be controlled by careful observation of the patients treated.
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PMID:[Tolerance of enoximone in patients with heart failure]. 183 4

When prescribing a contraceptive method, physicians must consider factors such as cultural background, age, phase of the family life cycle, and the presence of any specific illnesses. Most diversified are the contraceptive needs of newly married couples, some of whom will want to delay childbearing. In cases of 2nd marriages where no additional children are desired, high efficacy contraception or sexual sterilization may be indicated. For those who wish to space births, condoms and the IUD are popular choices. Given a trend toward postponed childbearing, women in their 30s need counseling on the effects of age and parity on fertility. Healthy nonsmokers can continue to use low-dose combined oral contraceptives (OCs) into their 40s, while smokers should use the progestogen-only OC. Contraceptive services also need to be attuned to religious views on issues such as marriage and abortion. Requests for female physicians should be respected, and women from cultures that grant them low status may require participation from their husbands in the consultation. Finally, combined OCs can be tolerated by women with well-controlled diabetes mellitus, epilepsy, and sickle-cell disease, but should not be prescribed to women with liver disease.
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PMID:Contrasting contraceptive needs. 184 11

Little information has been reported on the metabolic characteristics of the totally pancreatectomized patient or the efficacy of medical management after radical pancreatic surgery. The prospective evaluation of 49 such patients, with 31% followed for 48 or more months, forms the basis of this report. The major immediate postoperative challenge is control of diarrhea and weight stabilization. Chronically patients have an increased daily caloric requirement (mean +/- SE, 56 +/- 1 kcal/kg), not wholly explained by moderate steatorrhea (fecal fat excretion, 16% +/- 2% of unrestricted fat intake). Despite persistent malabsorption, deficiencies in fat-soluble vitamin, magnesium, and trace element serum levels can be prevented in most patients. Pancreatogenic diabetes is characterized by (1) absence of the major glucoregulatory hormones insulin and glucagon, (2) instability, and (3) frequent hypoglycemia, with the latter parameters improving with rigorous home glucose monitoring. No patient has developed clinically overt diabetic micro- or macrovascular disease. Performance status in long-term survivors has been reasonable. However adverse chronic sequelae of the operation occur and include an unusual frequency of liver disease, characterized by accelerated fatty infiltration, and osteopenia, with an 18% reduction in radial bone mineral content noted in pancreatectomized patients studied more than 5 years after surgery.
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PMID:Metabolic consequences of (regional) total pancreatectomy. 186 20

In the period 1981-1988, 333 cases of bacteriologically confirmed Vibrio illness were reported in Florida adult residents. A total of 197 patients (59.2%) had consumed raw oysters the week prior to becoming ill, and among those 197, 38 (19.3%) had a liver disease, 13 (6.6%) had past gastric surgery, and 15 (7.6%) were diabetic. To calculate a population-based incidence rate, the authors obtained prevalence estimates of annual raw oyster consumption, liver disease, previous gastric surgery, and diabetes through a random telephone survey of Florida adult residents and applied them to the January 1985 Florida population. The estimated age-standardized annual incidence of Vibrio illness per million was 95.4 for raw oyster eaters with liver disease, 9.2 for raw oyster eaters without liver disease, and 2.2 for non-raw oyster eaters. Those with prior gastric surgery had a moderately increased risk of Vibrio illness. The annual incidence for Vibrio septicemia was 82.8 for raw oyster eaters with liver disease, 2.0 for raw oyster eaters without liver disease, and 0.4 for non-raw oyster eaters. While estimates on which these data are based are subject to a number of potential biases, this is the first study to provide estimates of the risk of Vibrio illness in raw oyster eaters, and it supports the recommendation that raw oyster consumption should be avoided by persons with liver disease.
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PMID:The risk of Vibrio illness in the Florida raw oyster eating population, 1981-1988. 187 87

Heart transplantation (HTx) has now become an accepted treatment modality for end-stage heart disease. The limited supply of suitable donor organs imposes constraints upon the decision of who should be selected for transplantation. Usually patients are candidates for HTx, who remain NYHA functional class III or IV despite maximal medical therapy. Further criteria are low left ventricular ejection fraction (less than 20%) with heart rhythm disturbances class IIIA-V (LOWN), which are associated with poor prognosis. Additionally, the suffering of the patient and also the course of heart failure are essential for judging the urgency of HTx. Contraindications are absolute in patients with untreated infections, fixed pulmonary vascular resistance (PVR) above 8 WOOD-degrees, severe irreversible kidney and liver disease, active ventricular or duodenal ulcers and acute, psychiatric illness. HTx is relatively contraindicated in patients with diabetes mellitus, age over 60 years, PVR above 6 WOOD-degrees and an unstable psychosocial situation. To prevent rejection of the transplant heart, live-long immunosuppressive therapy is needed. Most immunosuppressive regimes consist of Cyclosporine A and Azathioprine (double drug therapy) or in combination (tripple drug therapy) with Prednisolone. For monitoring of this therapy, control of hole blood cyclosporine A level and white blood count is needed. Rejection episodes can be suspected if there is a greater than 20 mmHg decrease of systolic blood pressure, elevated body temperature, malaise, tachycardia or heart rhythm disturbance. The diagnosis of cardiac rejection can be established by endomyocardial biopsy. Measurement of the voltage of either the surface or intramyocardial ECG, echocardiography with special consideration to early left ventricular filling time as well as immunological methods are additionally used tools. Graft sclerosis as the main risk factor of the late transplant period remains an unsolved problem.
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PMID:[Therapy of terminal heart failure using heart transplantation]. 192 Dec 33

Noncommunicable diseases--cardiovascular and cerebrovascular disease, pulmonary diseases, liver disease, cancer, diabetes, osteoporosis and trauma--constitute the major cause of death in developed countries and are predictably emerging as significant threats to health in countries at intermediate stages of the epidemiological transition. Based on the philosophy that diseases with common risk factors (inadequate prevention/control services, smoking, fat/salt diet, alcohol use, etc.) require common preventive strategies, the INTERHEALTH demonstration projects are designed to build regional capacities and to exchange social and medical technologies for broad-gauged noncommunicable disease prevention and control. Projects are at various stages of planning and implementation in all WHO regions: Africa (Mauritius, United Republic of Tanzania); the Americas (Chile, Cuba, United States); Eastern Mediterranean (Cyprus); Europe (Finland, Malta, USSR); South-East Asia (Sri Lanka, Thailand); the Western Pacific (Australia, China, Fiji, Japan). This article presents selected data which illustrate the long-term mortality trends and present noncommunicable disease risk-factor levels in participating countries at different stages of the epidemiological transition. The shift towards noncommunicable diseases as a cause of death is readily apparent and combinations of risk factors are present in each of the populations studied in the baseline phase of this research and demonstration programme. The use of data to estimate the noncommunicable disease-related mortality burden from different lifestyles and risk factors is illustrated and findings from the most advanced demonstration studies are briefly outlined.
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PMID:Demonstration projects for the integrated prevention and control of noncommunicable diseases (INTERHEALTH programme): epidemiological background and rationale. INTERHEALTH Sterring Committee. 192 92

Fifty-nine cases of mucormycosis in dialysis patients have been reported to the registry (25 new cases and 34 previously reported cases). The presenting forms of mucormycosis included disseminated in 44%, rhinocerebral in 31%, and other forms in 25%. The diagnosis was made during life in only 39%, while the diagnosis was discovered at autopsy in 61% of the cases. The fungus, cultured in only 36%, was always Rhizopus. The infection was fatal in 86% of cases. No known risk factors for fungal infections, eg, diabetes mellitus, liver disease, splenectomy, neutropenia, steroid therapy, or other immunosuppressive therapy, were present in 70% of patients, but 78% of patients were being treated with deferoxamine. The role played by this drug and more particularly by its iron chelate, feroxamine, in the pathogenesis of mucormycosis in these patients is underscored. Because of this risk, deferoxamine therapy in dialysis patients should be limited to severe aluminum toxicity, the deferoxamine should be given at the lowest possible dose, and dialytic methods to augment the removal of feroxamine should be studied.
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PMID:Deferoxamine therapy and mucormycosis in dialysis patients: report of an international registry. 196 50

Hemochromatosis was recognized as an iron-storage disease for 50 years before it was proposed to treat it by removing hemoglobin. Davis and Arrowsmith are credited with the first report that demonstrated its value. Larger series have provided statistically valid evidence of improved quality of life and increased longevity. The earlier the disease is discovered, the less risk of morbidity and mortality. Screening tests (serum iron, total iron-binding capacity, serum ferritin) are recommended for all blood relatives of index cases of this hereditary disease and for all clinics where complications of hemochromatosis may be treated: liver disorder however mild, diabetes mellitus, heart disease, arthropathies, sterility, impotence, premature menopause, and abnormal pigmentation of the skin.
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PMID:A history of phlebotomy therapy for hemochromatosis. 199 28

Cytochrome P450IIE1 (IIE1) is a microsomal xenobiotic-activating enzyme that is inducible not only by various chemical agents but also by fasting and diabetes. Using a rat model that mimics human obesity, we have found that hepatic IIE1 levels are also increased by this common clinical disorder. Liver microsomes from rats made obese by feeding with an energy-dense diet displayed elevated aggregate P450 content (+28%) and enhanced catalytic activities associated with IIE1, including low-Km N-nitrosodimethylamine demethylation (+66%), aniline hydroxylation (+52%), p-nitrophenol hydroxylation (+170%), and acetaminophen-cysteine conjugate formation (+28%). In contrast, obesity had no significant effect on cytochrome b5 content, P450 reductase activity, benzphetamine demethylation, or erythromycin demethylation, with the latter two reactions being linked with rat IIC11 and IIIA1, respectively. The enhancement of IIE1-dependent drug-metabolizing activities noted in liver microsomes from obese rats was paralleled by a similar increase (111%) in hepatic IIE1 protein content in these animals, as assessed on immunoblots developed with anti-hamster IIE1 IgG. Anti-IIE1-inhibitable rates of microsomal p-nitrophenol metabolism, a reaction highly correlated with IIE1 content (r = 0.88, p less than 0.01), were over 3-fold higher in obese rats than in nonobese controls, providing additional evidence for the obesity-related increase of hepatic IIE1. The induction of IIE1 by the pathophysiological condition of obesity may provide a biochemical basis for the increased incidence of occult liver disease and certain cancers noted in obese individuals.
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PMID:Induction of cytochrome P450IIE1 in the obese overfed rat. 200 76


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