Age-related changes in adenylyl cyclase activity in rat aorta membranes.

Blood vessels from aged animals and humans have impaired relaxation and cAMP production to beta-adrenergic stimulation. Direct activators of adenylyl cyclase (AC) such as forskolin are not affected. We hypothesized that analogous findings would occur in membrane preparations. Aortic media membrane preparations from Fischer 344 rats of four age groups (6 weeks to 24 months) were studied. Basal AC activity increased significantly with age. Forskolin-stimulated activity compared to basal tended to be greater in the 6-week and 6-month preparations compared to the 12- and 24-month preparations. AC activity was assessed in the presence of the G protein activators (GTP, GppNHp, NaF). There was no age-related decrease in responsiveness. The receptor agonists isoproterenol (beta-adrenergic), and PGE-1 (prostaglandin), were studied. There was no significant age-related change in responsiveness over basal activity to either of these agonists. There was a slight, but significant increase in the isoproterenol responsiveness over GTP responsiveness in the 6-week-old animals which also approached significance in the 6-month-old animals, but was not seen in the 12- and 24-month-old animals. These data suggest that using a membrane system to assess age-related changes in beta-adrenergic responsiveness in vascular smooth muscle does not retain the robust differences seen in whole vessels.

Effect of implanted insulin pumps on fluorescein transcapillary escape time in type 1 diabetes mellitus.

OBJECTIVE: To determine whether significant increases in fluorescein transcapillary escape time (FTET) would occur after treatment of patients with type 1 diabetes with insulin delivered intraperitoneally by a surgically implanted pump. METHODS: Nine patients with type 1 diabetes who were otherwise healthy and had received surgically implanted insulin pumps on a study protocol were recruited to have three measurements of FTET and glycosylated hemoglobin during an 18-month period. Serum fluorescein-albumin binding was measured at the time of the final test. Control FTETs were measured in 46 patients with type 1 diabetes who did not have insulin pumps and in 15 adults without diabetes. RESULTS: In the implanted insulin pump group, 50% of the FTETs were below normal, but no significant longitudinal change in FTETs was noted in eight of the nine study patients. The mean FTETs in the implanted insulin pump group were significantly higher than those of the control patients with diabetes but without insulin pumps (mean, 88 versus 62 seconds; P<0.05) but significantly lower than those of the control subjects without diabetes (88 versus 163 seconds; P<0.001). Four of the nine patients with implanted insulin pumps had normal FTETs on all three studies. This subgroup had used insulin pumps (external + implanted) for significantly longer periods (6.2 versus 2.6 years; P<0.05) than the other five patients. These differences within the implanted pump group did not correlate with differences in glycosylated hemoglobin values or fluorescein-albumin binding; however, the glycosylated hemoglobin levels before insulin pump implantation were significantly lower than those of the other five patients. Three patients with onset of type 1 diabetes before age 10 years had the lowest FTETs. CONCLUSION: Implanted insulin pumps did not alter FTETs between 6 months and 32 months after pump implantation. Total time on insulin pumps (external and implanted) is associated with normal FTET, and onset of diabetes before age 10 years is associated with abnormal FTET.

Health service reform: the perceptions of medical specialists in Australia (New South Wales), the United Kingdom and New Zealand.

OBJECTIVE: To examine the effect of recent healthcare service changes (including significant resource constraint and a greater role for the non-medical manager) in the United Kingdom, Australia and New Zealand on medical specialists' perceptions of their healthcare organisation goals and service delivery, and their enthusiasm for their work. DESIGN: Postal questionnaire survey, answered anonymously. PARTICIPANTS AND SETTING: Medical specialists employed either part- or full-time in two United Kingdom National Health Service Trusts (one acute, one mental health/community service), an Australian Area Health Service and a New Zealand Crown Health Enterprise in 1995. MAIN OUTCOME MEASURES: Participants' rating of their knowledge of employers' organisational goals, ability to influence management, perceptions of changes in resources and service availability since 1990 and changes in enthusiasm for their work over the past four years. RESULTS: 369 of 521 eligible specialists responded (71%); by country-United Kingdom, 123/186 (66%); New Zealand, 123/160 (77%); Australia, 123/175 (70%). New Zealand specialists were less aware of their employers' organisational goals and had less congruence between these and their own personal goals than United Kingdom or Australian specialists (P < 0.05). Interest in influencing central management was similar in the three countries, but Australian specialists felt management was less likely to follow their advice compared with United Kingdom specialists (P < 0.05). New Zealand specialists perceived that waiting times for non-urgent patients were currently longer than in 1990 compared to United Kingdom specialists (P = 0.02). In all three countries, inpatient beds were perceived to be less available than in 1990, but less so in New Zealand. The ease of replacing equipment was better in New Zealand than in Australia and the United Kingdom (P = 0.00001). More than 50% of participants in all three countries (183/361; 50.7%) reported that their enthusiasm for their work had decreased in the past four years. CONCLUSION: The effects of health service reforms seem to have reduced enthusiasm for work among medical specialists in Australia, the United Kingdom and New Zealand.

Plasma fluorescein binding and transcapillary fluorescein escape rate in renal failure associated with diabetes.

Microvascular damage, often resulting in renal failure, is a common complication of diabetes. Transcapillary fluorescein escape rate (TCFER) as monitored by intravital microscopy has been used as an indicator of the extent of capillary damage in diabetes and to assess improvement in microvascular function after combined kidney-pancreas transplant. However, fluorescein anion binds to plasma albumin, and albumin-ligand binding may be altered in the presence of renal disease. The purpose of this study was to compare fluorescein binding by plasma from diabetics with renal failure with plasma from healthy nondiabetics. Fluorescein binding by plasma from seven type I diabetics awaiting kidney-pancreas transplant and seven healthy adults of similar age and sex was studied using ultrafiltration and dialysis. There was no significant difference in the apparent albumin binding of fluorescein at physiologically relevant fluorescein concentrations, even though the TCFER was significantly increased in the diabetics as compared with the controls. Hippurate, a ligand that accumulates in renal failure, did alter fluorescein binding in a defatted albumin solution but not sufficiently to account for the differences in TCFERs. These data indicate that impaired albumin binding of fluorescein does not contribute significantly to the TCFER in diabetics with renal failure.

Sources of stress and satisfaction in crown health enterprise senior medical staff.

AIM: To report the sources of stress and satisfaction in the specialist workforce of three crown health enterprises (CHEs). METHOD: Ninety eight specialists in Northland Health, Waitemata Health and Southern Health completed a questionnaire rating 39 factors for causing stress and satisfaction in their daily work. RESULTS: The commonest sources of stress for specialists were keeping up to date, carrying a heavy clinical workload and time pressure generally. There were significant differences between specialty groups as well as regional differences. Specialists in two CHEs found dealing with management a major stressor. This finding is a major difference from previous overseas studies. CONCLUSIONS: Doing the job properly, having a job that seems worthwhile, having control of one's professional life and a job that is interesting provide the greatest sources of work satisfaction for medical specialists.

Antibiotic protocol for appendicectomy--costs and benefits of single dose therapy.

AIMS: To examine possible savings from the introduction of an antibiotic protocol for one surgical procedure and to define antibiotic charting techniques. METHODS: An antibiotic policy for patients undergoing an appendicectomy was instituted in the surgical unit at North Shore Hospital to examine possible savings and to define antibiotic charting techniques. Depending on the macroscopic findings at surgery a third generation cephalosporin was used either as a single dose intraoperatively or for multiple doses postoperatively. RESULTS: The case notes of a control group of 55 patients were reviewed. This showed an average antibiotic cost per appendicectomy of $69.00 ($52.00) for nongangrenous nonperforated appendices (NGNPA). During the study period 57 patients underwent appendicectomy at an average antibiotic cost of $51.00 ($32.00 for NGNPA). This represented a 26% saving per patient during the study period and a 39% saving for those with NGNPA: CONCLUSIONS: The findings advocate the use of frequently updated guidelines for antibiotic use in surgical procedures. It reaffirms that medical staff must chart precisely as poor charting represents significant waste of expenditure in hospitals.

Effect of low-level and intermittent minocycline therapy on the growth of Mycobacterium leprae in mice.

We evaluated the minimal concentrations of minocycline in the diet and in serum required to inhibit the growth of seven Mycobacterium leprae isolates in mice. Minocycline concentrations of 0.01 and 0.04% in the diet, which resulted in levels in serum of less than or equal to 0.17 and 0.51 microgram/ml, respectively, were consistently and completely inhibitory. Even 0.004% dietary minocycline (levels in serum, less than or equal to 0.08 microgram/ml) partially inhibited five of these strains, while 0.001% minocycline was consistently inactive. For five of these isolates, minocycline at a concentration of 0.04% in the diet given 3 days (Monday, Wednesday, Friday) and 1 day weekly completely inhibited the growth of M. leprae, and minocycline given even 1 day monthly was partially inhibitory for three of these five M. leprae isolates.

Prescription drug therapy in the podiatric outpatient population: interactions and precautions.

A survey of 2,000 outpatients at the clinic of the Dr. William M. Scholl College of Podiatric Medicine was conducted analyzing both medications reported by the patients at the time of treatment and drugs by the attending podiatrist. The major groups of medications already used by the patients included diuretics, vitamins and minerals, nonsteroidal antiinflammatory drugs, cardiovascular medications, insulin and oral hypoglycemics, estrogen and thyroid hormone replacement, and antibiotics. Patients with asthma, ulcers, epilepsy, affective disorders and Parkinsonism represented significant subgroups. The major drugs used by podiatrists in the outpatient clinic included analgesics and antiinflammatory agents, local anesthetics, antibiotics, sedative-hypnotics, and a variety of topical agents. These two sources of medication serve as the basis for a review of drug interactions in the podiatric outpatient population. In addition, precautions for the use of drugs commonly administered by podiatrists are reviewed.

Comparison of the pyrimidine nucleoside phosphorylase activity in human tumors and normal tissues.

The novel fluoropyrimidine, 5'-deoxy-5-fluorouridine (5'-dFUDR) has strong tumor-inhibiting effect without severe cytotoxic effects on the normal cells. This pro-drug is metabolized by the enzyme pyrimidine nucleoside phosphorylase (PN'ase) to the active form 5-fluorouracil. Comparative determinations of pyrimidine nucleoside phosphorylase activity in tissue extracts revealed a significantly higher activity in the human gastrointestinal cancer tissues (6.84 +/- 0.70 nmol/mg protein) than in normal tissues from the same organ (2.37 +/- 0.21 nmol/min/mg protein).

Age and sex differences in right colon cancer.

In a prospective study of 402 colorectal cancer patients, 133 patients (46 men and 87 women) presented with right colon cancer. There was no significant difference between men and women in right colon cancer incidence. Common presenting features were abdominal pain, weight loss, and anemia. Ninety-one patients underwent resection with curative intent. There were significantly fewer Dukes' A tumors in the right colon cancer series (P less than 0.05). Significantly more women in the right colon cancer group were over 70 years old (P less than 0.05). The findings of peritoneal metastases and poorly differentiated lesions at initial surgery also were associated significantly with women who had right colon cancer (P less than 0.05). This study confirms previous reports of more advanced tumors in the right colon. The need for age, sex, and subsite differences to be taken into account when assessing treatment outcomes or survival is emphasized.

Colorectal cancer in Auckland 1981-1982: patients with liver metastases.

In a population-based study of 402 cases of colorectal cancer in Auckland, 72 patients (18%) demonstrated liver metastases either at presentation or at initial surgery. The findings of pre-operative weight loss, hepatomegaly and elevated alkaline phosphatase were significantly associated with heptic metastases. Individually these factors were insensitive indicators of the presence of liver metastases. Two or more of these risk factors were demonstrated by 54% of the patients with liver secondaries compared to 19% in the series without liver metastases. Continuing surveillance of the latter group of patients will show whether they are also at risk of developing liver secondaries. The median survival for the 69 patients who were diagnosed before death was 6.0 months. When the primary lesion was resected and the patient survived the post-operative period the median survival was 11.0 months.

DNA-damaging activity in ethanol-soluble fractions of feces from New Zealand groups at varying risks of colorectal cancer.

Using repair-proficient and repair-deficient strains of E. coli, we investigated the application of a liquid incubation assay to measure the DNA-damaging activity of ethanol-soluble fecal extracts. This method appears to be suitable for the study of a wide range of sample types. It was used to measure the DNA-modifying activity of ethanol-soluble fecal extracts from a group of European colorectal cancer patients. Data were compared with those from Europeans of similar age and sex distribution who did not have bowel cancer. We also studied groups of Maoris, Samoans, and European Seventh-Day Adventists who followed an ovo-lacto vegetarian diet. There are significant levels of DNA-modifying materials in the feces of many Europeans on a mixed diet, regardless of whether or not they have cancer. The number of positive samples was less in the Polynesian groups, and there were no samples that could be unequivocally scored as positive in the Seventh-Day Adventist groups. We conclude that diet can significantly reduce the level of ethanol-soluble mutagens, at least in New Zealand Europeans. The data may provide an explanation for the reduced incidence of bowel cancer in Seventh-Day Adventist groups.