Treatment of osteoporosis with calcitonin, with and without growth hormone

A 24 month randomized parallel study of the treatment of postmenopausal osteoporosis with calcitonin alone v calcitonin alternating with growth hormone (combined treatment) was conducted. Each group received 1000 mg daily of oral calcium supplements. The rate of change in total body calcium for the combined and calcitonin groups was + 1.68%/yr and + 1.33/yr, respectively (P less than .05). However, the difference in the two groups was not statistically significant. Further, the total body calcium level did not increase after 12 to 18 months of treatment. There was significant difference in the rates of change of bone mineral content (BMC) of the radius for the two groups, with a loss of BMC in the combined treatment group (F = 4.80, P less than .05). Calcitonin treatment is effective in producing an increment in bone mass. The addition of growth hormone to this regimen appears to have a deleterious effect on cortical bone mass.     

Efficiency of carcinogenesis with and without a mutator mutation

Carcinogenesis involves the acquisition of multiple genetic changes altering various cellular phenotypes. These changes occur within the fixed time period of a human lifespan, and mechanisms that accelerate this process are more likely to result in clinical cancers. Mutator mutations decrease genome stability and, hence, accelerate the accumulation of random mutations, including those in oncogenes and tumor suppressor genes. However, if the mutator mutation is not in itself oncogenic, acquiring that mutation would add an extra, potentially time-consuming step in carcinogenesis. We present a deterministic mathematical model that allows quantitative prediction of the efficiency of carcinogenesis with and without a mutator mutation occurring at any time point in the process. By focusing on the ratio of probabilities of pathways with and without mutator mutations within cell lineages, we can define the frequency or importance of mutator mutations in populations independently of absolute rates and circumvent the question of whether mutator mutations are "necessary" for cancers to evolve within a human lifetime. We analyze key parameters that predict the relative contribution of mutator mutants in carcinogenesis. Mechanisms of carcinogenesis involving mutator mutations are more likely if they occur early. Involvement of mutator mutations in carcinogenesis is favored by an increased initial mutation rate, by greater fold-increase in mutation rate due to the mutator mutation, by increased required steps in carcinogenesis, and by increased number of cell generations to the development of cancer.     

Carcinogenicity study of trichloroethylene,with and without epoxide stabilizer,in mice

Summary Previous analytical studies of industrial samples of trichloroethylene (TRI) have revealed the presence of mutageneic and carcinogenic epoxides which, it was proposed, might be responsible for the carcinogenicity of such samples, as demonstrated with mice in other laboratories. To test this hypothesis, Swiss mice (ICR/HA) of both sexes, bred and kept in SPF conditions, were dosed daily with TRI in corn oil by gavage (males: 2.4 g/kg, females: 1.8 g/kg) with or without the addition of epichlorohydrin (EPC, 0.8%, w/w), 1,2-epoxybutane (BO, 0,8%), or EPC+BO (0.25%+0,25%) for 18 months. The ensuing observation period terminated at 106 weeks (from start of experiment). Gross and microscopic examination of all organs revealed a statistically significant increase in the incidence of forestomach papillomas and carcinomas after EPC-, BO-, and (EPC+BO)-stabilized samples of TRI, but not after pure, amine base-stabilized TRI. This type of tumor is believed to be induced by the direct alkylating epoxides epichlorohydrin and epoxybutane, whose industrial use in stabilizing chlorinated aliphatic hydrocarbons should be discontinued. No other significant increase in tumor incidences was found. Again, this study does not support the suggestion that trichloroethylene itself is carcinogenic under realistic exposure conditions.     

Mortality,disability, and nursing home use for persons with and without hip fracture: a population-based study

OBJECTIVES: To compare persons with and without hip fracture for subsequent mortality and change in disability and nursing home (NH) use. DESIGN: Population-based historical cohort study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: All residents who experienced a first hip fracture between January 1, 1989, and December 31, 1993, and, for each case, a resident of the same sex and similar age who had not experienced a hip fracture and was seen by a local care provider. MEASUREMENTS: Data on disability (Rankin score), comorbidity (Charlson Index), and NH residency before baseline (fracture date for cases and registration date for controls) were obtained by review of complete community-based medical records. The records were then reviewed from baseline through December 31, 1994, for Rankin disability at 1 month and 1 year, all NH admissions and discharges, and date of death for those who died. RESULTS: There were 312 cases and 312 controls (81% female, mean age +/- standard deviation = 81 +/- 12 years). Before baseline, cases had higher comorbidity (45% vs 30% had Charlson Index >/= 1, P <.001) and disability (mean Rankin score = 2.5 +/- 1.1 vs 2.2 +/- 1.1, P <.001) and were more likely to be in a NH (28% vs 18%, P <.001) than controls. One year after baseline, estimated mortality was 20% (95% confidence interval (CI) = 16-24) for cases vs 11% (95% CI = 8-15) for controls, 51% of cases versus 16% of controls had a level of disability one or more units worse than before baseline (P <.001), and the cumulative incidence of first NH admission was 64% (95% CI = 58-71) for cases versus 7% (95% CI = 4-11) for controls. The risk of NH admission for cases relative to controls diminished over time, but remained elevated 5 years after the event (risk ratio = 20.0 at 3 months and 2.1 at 5 years), but, in persons admitted to a nursing home, cases were two times more likely than controls to be discharged alive within a year (P <.001). CONCLUSIONS: Hip fracture is an important contributor to disability and NH use, but the potential savings from hip fracture prophylaxis may be overestimated by studies that fail to consider differential risk, mortality, and long-term follow-up.     

Antianginal efficiency of nifedipine with and without a beta-blocker, studied with exercise test. A double-blind, randomized subacute study.

Twenty-one patients, mean age 60.3 years, with stable angina pectoris earlier treated with beta-blockers, were investigated with standardized exercise tests to evaluate the action of nifedipine alone and in combination with a beta-blocker. The first exercise test was performed 3 weeks after treatment with the patient's usual beta-blocker. Following this, the patients were tested twice after a double-blind cross-over 3-week trial with nifedipine and placebo. The patients were subsequently treated for 3 weeks with nifedipine 10 mg 3 times daily or placebo and then performed an exercise test. During the 4th period of 3 weeks the patients took a combination of nifedipine, 10 mg 3 times daily, and their usual beta-blocker and then performed the final exercise test. Nifedipine alone raised the heart rate by 5 beats/min at rest and diminished the systolic blood pressure at rest by 17 mm Hg. During exercise at comparable load the heart rate did not change significantly, but the systolic blood pressure decreased with 22 mm Hg. The exercise tolerance expressed as total work increased on a average by 20%, range-14 - + 194%. Nifedipine in combination with a beta-blocker gave a further decrease in the systolic blood pressure, totally 37 mm Hg at comparable load. The exercise tolerance increased more, totally by an average of 41%. There was a significant correlation between basal values for systolic blood pressure registered during the placebo period at rest and the percentage change in total work. The atrioventricular conduction time did not change significantly compared to placebo during treatment with nifedipine or the combination nifedipine + beta-blocker. No serious side-effects were observed during the study.     

Are the results of electrophysiological study different in patients with a pre-excitation syndrome, with and without syncope?

AIMS: Syncope in Wolff-Parkinson-White (WPW) syndrome may reveal an arrhythmic event or is not WPW syndrome related. The aim of the study is to evaluate the results of electrophysiological study in WPW syndrome according to the presence or not of syncope and the possible causes of syncope. METHODS AND RESULTS: Among 518 consecutive patients with diagnosis of WPW syndrome, 71 patients, mean age 34.5 +/- 17, presented syncope. Transoesophageal electrophysiological study in control state and after isoproterenol infusion was performed in the out-patient clinic. Atrioventricular re-entrant tachycardia (AVRT) was more frequently induced than in asymptomatic patients (n = 38, 53.5%, P < 0.01), less frequently than in those with tachycardia; atrial fibrillation (AF) and/or antidromic tachycardia (ATD) was induced in 28 patients (39%) more frequently (P < 0.05) than in asymptomatic patients or those with tachycardia. The incidence of high-risk form [rapid conduction over accessory pathway (AP) and AF or ATD induction] was higher in syncope group (n = 18, 25%, P < 0.001) than in asymptomatic subjects (8%) or those with tachycardias (7.5%). Maximal rate conducted over AP was similar in patients with and without syncope, and higher in patients with spontaneous AF, but without syncope. Results were not age-related. CONCLUSION: Tachycardia inducibility was higher in patients with syncope than in the asymptomatic group. The incidence of malignant WPW syndrome was higher in patients with syncope than in asymptomatic or symptomatic population, but the maximal rate conducted over AP was not higher and another mechanism could be also implicated in the mechanism of syncope.     

Bacterial Infection in Cirrhosis, with and without Hepatocellular Carcinoma

Objective: The extent and type of bacterial infection occurring with liver cirrhosis has remained unknown. Further, while hepatocellular carcinoma (HCC) is known to occur mainly in patients with liver cirrhosis, no report has yet investigated the incidence of bacterial infection in HCC. The purpose of the present study was to establish the prevalence of bacterial infection in patients with HCC. Methods : We have retrospectively investigated all 1140 patients with hepatic cirrhosis and/or HCC for any incidence of bacterial infection. Results : The incidence of bacterial infection was found to be 15.4%. in 740 patients with HCC. This was approximately equal to the incidence of bacterial infection in 400 patients with cirrhosis without HCC, which was found to be 15.3%. When the severity of cirrhosis was graded according to Child-Pugh classification, the incidences of bacterial infection in Child-Pugh class A. class B, and class C were 3.3%, 11.1%, and 31.2%, respectively, in cirrhosis, and 2.3%, 9.1%, and 25.6% in HCC The incidence of bacterial infection increased with the severitv of cirrhosis and severe bacterial infections occurred in Child-Pugh class B and C patients. Conclusion : The data suggest that the susceptibility of HCC patients to bacterial infection is mainly related to the underlying cirrhosis and not to the HCC.     

Role of endothelial function and inflammation in patients with cardiovascular risk factors, with and without a history of myocardial infarction

BACKGROUND: Endothelial dysfunction and inflammation, in particular their lack of improvement after risk reduction, might better reflect advanced atherosclerosis than just the presence of risk factors. The aim of this study was to compare endothelial function and inflammatory parameters in high-risk patients who had no history of myocardial infarction and in patients in a stable phase after myocardial infarction. METHODS: We compared endothelial function of the brachial artery, measured using high-resolution ultrasound, in 45 patients with hyperlipidaemia (Group 1), and in 45 patients in a stable period after myocardial infarction (Group 2). Forty-five healthy individuals served as a control group (Group 3). RESULTS: Compared to patients with treated hyperlipidaemia, patients after myocardial infarction had lower values of total and LDL cholesterol (p = 0.015; 0.005) and homocysteine (p < 0.005), but marginally higher IL-6 levels (p = 0.1). Other measurements were comparable. However, flow-mediated dilation of the brachial artery was significantly diminished in patients after myocardial infarction (10.6 +/- 3.0; 5.9 +/- 4.0; 14.0 +/- 1.9% for Groups 1-3; ANOVA p = 0.0001; respectively). CONCLUSIONS: We found that patients with previous myocardial infarction have substantially lower endothelial function and increased some inflammatory parameters than patients with a similar level of atherosclerotic risk profile but without clinically evident coronary artery disease.     

Small intestinal transit, absorption, and permeability in patients with AIDS with and without diarrhoea

BACKGROUND: Diarrhoea in AIDS is associated with anorexia and weight loss. The importance of gastrointestinal transit in such symptoms has not been addressed. AIMS: To assess jejunal to caecal transit times in subjects with AIDS related diarrhoea and weight loss and correlate these with measures of absorptive capacity and intestinal permeability. METHODS: Jejunal to caecal transit times were assessed in 20 seronegative controls and 60 HIV seropositive subjects from serum analysis of 3-O-methyl-D-glucose and sulphapyridine after ingestion of the monosaccharide and sulphasalazine in aqueous solution. The method also allows an estimation of gastric emptying times for liquids. Intestinal absorptive capacity and permeability were assessed by a combined test using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose. RESULTS: Gastric emptying was significantly delayed in all groups of patients with AIDS. Mean jejunal to caecal transit times were not significantly different between controls (246 (62) minutes) and patients without diarrhoea (AIDS, well: 278 (103) minutes; AIDS, wasting: 236 (68) minutes), cytomegalovirus colitis (289 (83) minutes), pathogen negative diarrhoea (192 (100) minutes), or microsporidiosis (190 (113) minutes), although 30% of patients had values below the control range. Patients with cryptosporidiosis differed significantly from controls (135 (35) minutes, p<0.0001), seven of 10 having rapid transit times. Absorptive capacity was reduced and intestinal permeability significantly increased in AIDS, but did not correlate significantly with transit times. CONCLUSION: Small bowel transit is accelerated in many patients with AIDS, particularily in protozoal diarrhoea, but is not the sole explanation for malabsorption of monosaccharides.     

Residents with AIDS: a comparison of facilities with experience and those without

there were a great number of concerns. The primary concern was could we care for this patient adequately. The fears of the staff, the fears of contracting the disease, the fear that we could lose staff because we had AIDS patients in our facility. The very real fear that other patients would leave the facility because we had an AIDS patient, financial concerns because these, very frankly, are costly folks to care for and the reimbursement is usually Medicaid which does not cover the cost. Those were the major problems. (Headley, 1993) As with most LTC, care for people with AIDS is largely provided through personal networks of family and friends. Yet, as with other chronic needs, there are people for whom informal caregiving network are not available, are not well enough developed to provide adequately, of become overwhelmed at the magnitude and duration of care that is sometimes required. These people must turn to the formal LTC system for the services that supplement of supplant informal efforts.     

Hormonal, global, and regional haemodynamic responses to a vascular antagonist of vasopressin in patients with congestive heart failure with and without hyponatraemia

The pathophysiological role of an increase in circulating vasopressin in sustaining global and regional vasoconstriction in patients with congestive heart failure has not been established, particularly in patients with hyponatraemia. To assess this further, 20 patients with congestive heart failure refractory to digoxin and diuretics were studied before and 60 minutes after the intravenous injection (5 micrograms/kg) of the vascular antagonist of vasopressin [1(beta-mercapto-beta,beta-cyclopentamethylene-propionic acid), 2-(0-methyl) tyrosine] arginine vasopressin. Ten patients were hyponatraemic (plasma sodium less than 135 mmol/l) and 10 were normonatraemic. In both groups of patients the vascular vasopressin antagonist did not alter systemic or pulmonary artery pressures, right atrial pressure, pulmonary capillary wedge pressure, cardiac index, or vascular resistances. Furthermore, there was no change in skin and hepatic blood flow in either group after the injection of the vascular antagonist. Only one patient in the hyponatraemic group showed considerable haemodynamic improvement. He had severe congestive heart failure and a high concentration of plasma vasopressin (51 pmol/l). Plasma renin activity, vasopressin, or catecholamine concentrations were not significantly changed in response to the administration of the vasopressin antagonist in either the hyponatraemic or the normonatraemic groups. Patients with hyponatraemia, however, had higher baseline plasma catecholamine concentrations, heart rate, pulmonary pressure and resistance, and lower hepatic blood flow than patients without hyponatraemia. Plasma vasopressin and plasma renin activity were slightly, though not significantly, higher in the hyponatraemic group. Thus the role of vasopressin in sustaining regional or global vasoconstriction seems limited in patients with congestive heart failure whether or not concomitant hyponatraemia is present. Vasopressin significantly increases the vascular tone only in rare patients with severe congestive heart failure and considerably increased vasopressin concentrations. Patients with hyponatraemia do, however, have raised baseline catecholamine concentrations, heart rate, pulmonary arterial pressure and resistance, and decreased hepatic blood flow.