Disuse osteoporosis. A case report.
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Biomedical subjects
Publications and source records attributed to R Wright.
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A five-year study of all newly diagnosed cases of chronic active hepatitis (CAH) from a defined population of 404,000, in which the internationally accepted diagnostic criteria were applied, is reported. A putative aetiological agent was identified in all but 14 (23%) of 61 cases. Alcohol (26%) and hepatitis B (20%) were the commonest aetiological factors. The incidence of CAH was 3 per 100,000 per year. Patients were often elderly, mean age 56, with a third aged over 65. A third were symptom-free at diagnosis, and the disease was biochemically or histologically severe in only a few. 9 of 61 (15%) fulfilled the criteria for treatment used in the Mayo Clinic trials. Even after exclusion of those with CAH unresponsive to corticosteroids (i.e., where hepatitis B, drugs, alcohol are involved in the aetiology) and widening of the criteria, only 7 of the remaining 31 (23%) are likely to benefit from corticosteroids. The variety of aetiological agents, spectrum of clinical features, and range of disease severity are very different in an unselected group from those reported from specialised referral centres.
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The widely held belief that 2-naphthylamine is not carcinogenic for the rat has been re-examined. Twenty female Wistar rats were dosed by gastric intubation weekly for 57 weeks with 2-naphthylamine, 300 mg/kg body wt, in arachis oil and 20 controls were given arachis oil alone. Animals which became moribund were killed during the course of the experiment and the remainder after 100 weeks. A 2-naphthylamine-treated animal died at 21 weeks; all others survived 57 weeks or longer. The urinary tracts of all but two 2-naphthylamine-treated animals, which were found dead and cannibalized, were examined histologically.No neoplastic disease of the urinary tract was present in control animals. In 10 of the 2-naphthylamine-treated rats there was neither neoplasia nor hyperplasia of the urothelium, but 4 of the 18 examined histologically had large, macroscopically visible bladder cancers; one of these also had bilateral transitional cell tumours of the kidney calyces and multiple tumours in both ureters. Another animal had bilateral urothelial cancers in the ureters. The histology and ultrastructure of these urothelial cancers were comparable to those of rat transitional-cell carcinomas experimentally induced with other chemical carcinogens.These results, considered in the context both of early and more recently published biochemical studies of 2-naphthylamine metabolism in the rat, support the possibility that production of the active carcinogenic metabolite in this species may be influenced by a pH-dependent, non-enzymic mechanism in the urine, which could account for individual, strain- and diet-related variations in response in the rat.
Experiments were conducted to determine the dose response of rat bladder urothelium to a range of different single and fractionated intravesicular doses of the carcinogen, N-methyl-N-nitrosourea (MNU). A dose-related response of bladder-tumour incidence to single graded doses of MNU was found, and a threshold does suitable for use of multistage carcinogenesis experiments was derived from these data. For any given total dose of MNU, the tumour incidence was greater if the MNU had been administered in several small fractions than if it had been administered in fewer larger ones. Extending the interval between doses did not reduce the tumour incidence. It is argued that these results support the multistage theory of carcinogenesis. The histopathology and cell-surface alterations which characterize the development of MNU-induced bladder cancer are described and the contribution of hyperplasia and calculi are discussed.
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The hormonal and metabolic response to 50 g oral glucose has been studied in fifteen patients with hepatic cirrhosis and seven control subjects. Fasting blood glucose concentration was similar in both groups but cirrhotics showed higher glucose levels throughout the glucose tolerance test. Fasting serum insulin concentration was raised in the patient group (0.12 +/- 0.02 vs 0.07 +/- 0.01 nmol/l, p less than 0.05 and hyperinsulinaemia persisted after oral glucose. Blood lactate and pyruvate concentrations were elevated in cirrhotic patients, both fasting and post-glucose, while mean blood lactate correlated with mean serum insulin concentrations (rs 0.55, p less than). Plasma glucagon concentrations although highly variable, did not differ significantly in control and cirrhotic subjects before or after oral glucose. Fasting blood glycerol was increased in the patient group (O.11 +/- 0.01 vs 0.06 +/- 0.01 mmol/l, p less than 0.05) but fasting blood ketone body levels were normal and both glycerol and ketone body concentrations fell normally after glucose. Basal serum cortisol levels were similar in patient and control groups but the expected fall in cortisol concentration found in the control group over the test period was absent in cirrhotics. The hormonal and metabolic abnormalities did not correlate with severity of disease assessed by liver function test and abnormalities were not related to the presence or absence of portal-systemic shunting.
Family life satisfaction can be seen and analyzed within a cost/reward exchange framework. Within this context satisfaction of the primary caregiver with living in a multigenerational household was examined for 99 Midwestern families. Important predictors of satisfaction were identified using path analysis. These predictors consisted of characteristics of the older person (in particular, indicators of dependency status, characteristics of the primary caregiver, and the situational problems of daily life).
A prospective, randomized study was performed in 100 consecutive patients undergoing coronary artery bypass surgery to assess the efficacy of the early reinstitution of propranolol in reducing the incidence of postoperative supraventricular tachyarrhythmias (SVT). Patients were randomized to receive propranolol 10 mg every 6 hours enterally starting the morning after surgery (Group I, 50 patients) or to serve as controls (Group II, 50 patients). No patient was excluded because of poor ventricular function, need for urgent revascularization, or transient necessity for ionotropic support. Both groups had a comparable incidence of risk factors, previous infarction, unstable angina, and abnormal ventricular function. The extent of coronary disease, preoperative propranolol dose, and number of grafts performed were also similar. SVT occurred in 3/50 (6%) patients in Group I compared with 14/50 (28%) in Group II (p less than 0.01). There were no preoperative or intraoperative discriminators to predict the occurrence of SVT. In addition, perioperative infarction and the need for mechanical or pharmacologic circulatory support did not predispose to SVT. The data indicate that early administration of propranolol should be given to all patients after myocardial revascularization to decrease the incidence of these postoperative rhythm disturbances.
To investigate the possibility that a "spillover effect" of substances from the portal vein into the systemic circulation accounts for the abnormal monocyte function in patients with liver disease, we have incubated human peripheral blood monocytes with paired specimens of portal and systemic serum from humans and rabbits. Monocytes incubated with portal serum released more of a lysosomal enzyme, N-acetyl-B-glucosaminidase, than those incubated with systemic serum (p less than 0.05). In order to delineate the factors responsible for this increased activity, the content of immune complexes, immunoglobulins and endotoxin in the paired specimens of portal and systemic serum was measured. Endotoxin was found in none of 16 human specimens of portal blood and five of the 16 rabbit specimens. Modestly increased levels of immune complexes, particularly of the IgG class, were found in the portal serum compared to the systemic serum (p less than 0.01). Corresponding studies on immunoglobulins showed a higher concentration of IgA in portal serum (p less than 0.05), but no difference in other classes of immunoglobulins or complement levels. There was good correlation between the enzyme production by monocytes and the concentration of immune complexes, particularly IgA (r = 0.687, p less than 0.001), but there was no relationship to the presence or absence of endotoxin. This evidence suggests that portal serum contains substances, particularly immune complexes, which under normal circumstances are sequestered by the liver. These are capable of "activating" monocytes in vitro and may play a role in the pathogenesis of certain types of liver disease.
Glycerol clearance was studied by a primed dose-constant infusion technique in 14 patients with alcoholic liver disease and six normal control subjects. Fasting blood glycerol concentrations were raised in the alcoholic subjects (0.09 +/- 0.01 vs 0.06 +/- 0.01 mumol/l, p less than 0.05) and glycerol clearance was impaired (24.5 +/- 1.9 vs 37.5 +/- 3.2 ml/kg/min, p less than 0.005). Endogenous production rate of glycerol and distribution space at steady state were similar in alcoholic and control subjects. The metabolic clearance rate of glycerol correlated negatively with basal glycerol concentrations. Thus tissue uptake of glycerol is impaired in liver disease. As glycerol is metabolised primarily in the liver by conversion to glucose, these data suggest a defect of gluconeogenesis in alcoholic liver disease.
Monocyte function has been studied in a total of 51 patients with biopsy-proven cirrhosis and 35 controls. There was significantly reduced monocyte spreading (p less than 0.05), chemotaxis (p less than 0.02), bacterial phagocytosis (p less than 0.05) and bacterial killing (p less than 0.02) in the cirrhotics compared to the controls. Monocytes from patients with cirrhosis produced significantly less of the lysosomal enzymes N-acetyl beta-glucosaminidase and beta-glucuronidase than those obtained from the controls (p less than 0.02). There was no significant difference in the number of monocytes obtained, the number of macrophage precursors, and the nitro-blue tetrazoline (NBT) reduction between the cirrhotic and the controls. The reduced function appeared to be mainly due to a circulating inhibitory factor and could be corrected by incubation of the cirrhotic cells in serum from control subjects. The response of monocytes from patients with cirrhosis did not differ from the controls in their response to added endotoxin or latex particles suggesting that they are capable of a normal response in the absence of the inhibitory factor. Paired specimens of portal and systemic serum were collected from patients with no evidence of liver disease undergoing vascular surgery. When added to normal human monocytes the portal serum caused a significant reduction in bacterial killing (p less than 0.02) and chemotaxis (p less than 0.05) compared to results obtained in the paired systemic serum. Mixing experiments suggests the presence of an active inhibitor in the portal serum. The results suggest that monocyte function is reduced in cirrhosis apparently due to a serum inhibitor which may have originated from the portal vein. The abnormalities may account in part for the increased susceptibility of these patients to infection.
Six hundred and thirty-two blood samples from 879 consecutive admissions to one resettlement camp for Indochinese refugees in Great Britain were screened for markers of hepatitis B (HB) virus infection. The overall prevalence of HB surface antigen (HBsAg) was 15%, being 16% in those aged 40 years or less, and falling to 8% in those older than 40 (P less than 0.05). No significant difference in prevalence was found between males and females. HBe antigen was detected in 56% of those with HBsAg and was demonstrable in 55-76% of those under 30 years of age. HBe antibody was found in 21% of HBsAg-positive refugees. In those under 40 years old, HB core (HBc) antibody was commoner in males (P less than 0.01). HBc antibody prevalence increased significantly with age in females (P less than 0.01) but not in males. There was no definite evidence that vertical transmission of hepatitis B was present in the group studied.
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To determine the prevalence of alpha 1-antitrypsin deficiency in patients with cirrhosis or chronic active hepatitis, we performed a five-year prospective study of liver-biopsy specimens from 1055 adults. Thirty-four patients whose specimens contained hepatocyte inclusions characteristic of the deficiency were phenotyped, and 25 had phenotype MZ (2.4 per cent). The distribution of patients with this phenotype among the 185 patients with cirrhosis diagnosed histologically was three of 84 patients with alcoholic cirrhosis (3.5 per cent), seven of 34 with non-B chronic active hepatitis (20.5 per cent), six of 28 with cryptogenic cirrhosis (21 per cent), and one of 39 with other kinds of cirrhosis (2.6 per cent). The increased prevalence of MZ in patients with cryptogenic cirrhosis and with chronic active hepatitis is highly significant (P < 0.001). Because serum levels of alpha 1-antitrypsin may be unreliable for identification of the subgroup of patients with chronic active hepatitis or cryptogenic cirrhosis, analysis of serum for the MZ phenotype and meticulous examination of biopsy specimens may be necessary.