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The clinical use of estrogens and progestogens for menopausal women is reviewed, discussing the indications, results of studies on effectiveness of various agents o each target organ, contraindications, risk-benefit ratio, and types of drug preparations available and used in European countries. The indications for menopausal hormone replacement are primarily to prevent myocardial infarction and osteoporosis, and also to treat early menopause, urogenital atrophy, and severe skin, mucous membrane and psychic disorders. Mechanisms of action of estrogens and progestins, and anticipated results are detailed for each of the indications. Contraindications typical of oral contraceptives usually do not apply for hormone replacement. For example, only severe acute liver disease, current thromboembolism, endometrial cancer other than I, and breast cancer within 3-5 years of primary treatment are contraindications. Neither cervical, ovarian or vulvar cancer, diabetes, varicose veins, hypertension, nor history of liver disease or thromboembolism are contraindications: in some cases progestins or transdermal estrogens are recommended. Estrogen side effects suggest overdosage. Progesterone or its derivatives rather than oral contraceptive progestins are prescribed. There is a clear benefit, comparing cost of medication to that of treating consequences of estrogen deficiency. The preparations currently used in Europe include oral micronized estradiol, conjugated estrogens, transdermal patches, local vaginal estrogens, and injectable estradiol esters for those who cannot tolerate oral or transdermal agents. Preparations should contain progesterone unless the woman has had a hysterectomy. Combinations designed to avoid withdrawal bleeding are available.
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PMID:Clinical use of oestrogens and progestogens. 221 69

The relation between various aspects of medical history, selected indicator foods and the risk of pancreatic cancer was analyzed in a hospital-based case-control study conducted in Northern Italy on 247 patients with cancer of the pancreas, and 1,089 controls in hospitals for acute, nonneoplastic or digestive conditions. There was a significant association with history of pancreatitis (relative risk, RR 3.2, 95% confidence interval = 1.3-7.9), which was however reduced when the condition was first diagnosed at least 5 years previously. The point estimates were slightly, but not significantly, above unity for diabetes (RR = 1.5), gastrectomy (RR = 1.1) and cholelithiasis (RR = 1.3), and no association was found with liver disease or drug allergy. In relation to diet, there was some tendency for the risk to decrease with more frequent fruit consumption, but the results were largely inconsistent in relation to various indicators of meat, animal protein or fat intake. Although no important associations were found in this study with various aspects of medical history or diet indicators and pancreatic cancer risk, on account of the size of the dataset and the statistical power, this study contributes usefully to the debate on a common cancer whose causes are still largely undefined.
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PMID:Medical history, diet and pancreatic cancer. 224 64

Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients are still significant. Cardiovascular disease accounts for much of the mortality in long-term survivors; screening before the transplant procedure and adequate control of hypertension should help improve patient survival. Many of the gastrointestinal complications are due to overimmunosuppression and sepsis. Adequate management must include withdrawal of all immunosuppressive medications in order to save the patient's life. Liver disease is usually of viral origin; patients with chronic active hepatitis or cirrhosis should remain on dialysis. Chronic rejection is the major cause of graft loss in long-term survivors; it is unresponsive to antirejection treatment and its progression may be mediated by nonimmunologic mechanisms. Correctable problems such as renal artery stenosis and ureteral obstruction should be ruled out before a late deterioration in graft function is disregarded as chronic rejection. Post-transplant diabetes, osteonecrosis, cataracts, and nephrotoxicity are directly related to the various immunosuppressive drugs currently used. The lowest dose compatible with graft acceptance should help reduce the incidence of these nonfatal but significant complications. Recurrence of disease is a common histologic finding in many transplant recipients but, except for a few diseases such as HUS, FSGS, and oxalosis, it usually does not lead to graft failure. Successful transplantation restores fertility in many uremic patients. Adequate counseling on contraception is imperative in order to avoid unwanted pregnancies and to delay parenthood for at least 1 year. Current immunosuppressive agents are not teratogenic, no dose adjustments are necessary, and an ill-advised decrease in medication may precipitate a rejection episode. Premature delivery is the major problem in these patients and can be avoided by maintaining adequate graft function and controlling hypertension and infections. It is evident from this review that most of the long-term morbidity and mortality seen in renal allograft recipients are due to overimmunosuppression with sepsis or to side effects of the individual drugs, steroids being a common denominator in almost all cases. New immunosuppressive protocols must aim not only to improve patient and graft survival but also to avoid the many complications that limit the full rehabilitation of these patients.
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PMID:Problems in the long-term renal allograft recipient. 226 90

A newly recognized disease in dogs, ulcerative dermatosis associated with diabetes mellitus (diabetic dermatopathy), was diagnosed in 2 dogs with pancreatic endocrine tumors that had immunohistologic evidence of glucagon production. Dogs developed diabetes mellitus in the later stages of the illness, months after the skin disease was first observed. Liver disease was identified and characterized by high serum alkaline phosphatase and alanine transaminase activities. Clinically, erythema and crusting involved the footpads, the face, perioral and genital skin, and ventrum. Histologically, skin lesions were intercellular and intracellular edema and necrosis of the upper half of the epidermis and diffuse parakeratosis. Clinically and histologically, skin lesions closely resembled necrolytic migratory erythema of people, a skin disease that usually is associated with a glucagon-secreting pancreatic endocrine tumor and diabetes mellitus (glucagonoma syndrome): The morphologically descriptive term, superficial necrolytic dermatitis, was preferred over the previously proposed names hepatocutaneous syndrome and diabetic dermatopathy, which each connote only a single feature of the disease.
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PMID:Glucagon-producing pancreatic endocrine tumors in two dogs with superficial necrolytic dermatitis. 227 59

Forty-two patients with nonalcoholic steatohepatitis were followed for a median of 4.5 yr (range = 1.5 to 21.5 yr). Except for two patients with lipodystrophy, all were obese; 35 of 42 were women, 26 of 32 were hyperlipidemic and 15 were hyperglycemic. Upper abdominal pain was the most common reason for presentation. Initial liver biopsy specimens showed the presence of macrovesicular fatty infiltration, lobular (acinar) inflammation, apoptosis, Mallory bodies (in four cases) and fibrosis (in 18 cases). Cirrhosis was present at initial diagnosis in one subject and in another two subjects liver biopsy showed marked fibrosis with disturbed architecture. Serial liver biopsy specimens revealed minimal or no apparent progression of the disorder in most of the patients, in keeping with their benign clinical course. However, one patient showed progression from fibrosis to cirrhosis during the 5-yr observation period, and in the patients with extensive fibrosis the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation. The patient with cirrhosis later died of hepatocellular carcinoma. The severity or type of hepatic change did not correlate with the degree of obesity, hyperlipidemia or hyperglycemia. However, in individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis. We conclude that nonalcoholic steatohepatitis is a cause of hepatic inflammation histologically resembling that of alcohol-induced liver disease but usually slowly progressive and of low-grade severity. However, the disorder may ultimately result in cirrhosis. Nonalcoholic steatohepatitis should be distinguished from alcoholic steatohepatitis and recognized as a further cause of "cryptogenic cirrhosis."
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PMID:The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. 1503 Sep 72

In a prospective study involving eleven general practices, dry-chemical laboratory methods were compared with wet-chemical methods in the establishment of the diagnosis. The study included 658 patients in whom defined liver disease, lipid metabolic disturbances, diabetes mellitus or hyperuricemia were clinically suspected. In the "dry chemistry" group, between 12 and 29% fewer basic examinations (ESR, Hb, erythrocytes, leukocytes) were performed than in the "wet chemistry" group. In addition the number of analyses per patient in the so-called search program and among the subsequently requested laboratory analyses were also lower by about 21% in the "dry chemistry" group. This indicates that through the use of "dry chemistry", laboratory examinations can be used with greater selectivity. A further advantage of "dry chemistry" is the appreciably shorter time required to establish and report the diagnosis.
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PMID:[The evaluation of dry chemical laboratory methods. Their value within the framework of step-by-step diagnosis in general medicine]. 234 Nov 3

A 28-year-old man with poorly controlled juvenile-onset diabetes mellitus presented with jaundice and type 5 hyperlipoproteinemia. A liver biopsy showed fatty liver hepatitis (steatonecrosis). This case represents one end in a spectrum of lipid disorders and liver disease in diabetes mellitus. With increasing insulin deficiency, liver steatosis and the more common type 4 hyperlipoproteinemia pattern may progress to fatty liver hepatitis and type 5 hyperlipoproteinemia.
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PMID:Fatty liver hepatitis and type 5 hyperlipoproteinemia in juvenile diabetes mellitus. Case report and review of the literature. 240 34

Hypoglycemia is an underappreciated and potentially fatal complication of insulin and sulfonylurea treatment of diabetes mellitus in the elderly. After several years of diabetes, patients typically lose glucagon and epinephrine responses to hypoglycemia, resulting in loss of adrenergic warning symptoms, as well as prolongation of hypoglycemic episodes. Also of pertinence to the elderly, renal disease, liver disease, congestive heart failure, hypothyroidism, hypoadrenalism, medications, and inadequate monitoring may also contribute to hypoglycemia. The benefits of tight control can be observed only if it is applied to appropriately selected patients.
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PMID:Hypoglycemia: still a risk in the elderly. 240 23

Hepatocytes and bile duct epithelium express several types of cytokeratins, the characteristic intermediate-filament proteins of epithelial cells. The cytokeratin antigen expression was studied in normal and diseased livers, intrahepatic cholangiocarcinomas, and hepatocellular carcinomas by immunohistochemical methods using a panel of polyclonal and monoclonal antibodies to cytokeratins. Ten percent formaldehyde solution-fixed, paraffin-embedded sections obtained from ten patients without liver disease, 18 patients without liver disease, 18 patients with different stages of primary biliary cirrhosis, 14 patients with alcoholic hepatitis, ten patients with fatty liver hepatitis secondary to diabetes mellitus or morbid obesity, five patients with hepatocellular carcinomas, and five patients with cholangiocarcinomas were examined. The results suggested that hepatocytes and bile duct epithelium retain their distinct cytokeratin profiles in liver disease, including malignant transformation. Therefore, demonstration of cytokeratins in the liver is useful in establishing the cellular origin of neoplasms and understanding the pathogenesis of liver diseases.
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PMID:Expression of cytokeratins in normal and diseased livers and in primary liver carcinomas. 246 75

Recent longitudinal studies have improved the knowledge of the natural history of chronic pancreatitis. This disease is mainly induced by alcohol abuse. Mean age at onset of the disease is 40 years. First symptoms are generally pain, often related to acute pancreatitis. Over the first five years of course, complications as pseudocysts or common bile duct stenoses can occur, often necessitating surgical treatment. In the late course, the disease becomes less symptomatic but the risk of diabetes mellitus increases. Occurrence of pancreatic calcifications is observed with time in the majority of patients. Chronic pancreatitis is associated with overmortality but the causes of death are mainly extrapancreatic (alcoholic liver disease and cancers). Abnormalities of pancreatic secretion induced by alcohol abuse play an important role in the pathophysiology of the disease: it is possible that the decrease of concentration of the "pancreatic stone protein" promotes formation of calcifications. Direct toxicity of alcohol is another possible factor.
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PMID:[The natural history and physiopathology of chronic pancreatitis]. 248 15


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