Action of some hypoglycaemic sulphonylureas on the oxygen consumption of isolated pancreatic islets of mice

Summary Cartesian divers were used to evaluate the effects in vitro of some hypoglycaemic Sulphonylureas on the oxygen consumption of isolated pancreatic islets. The islet specimens were obtained from obese-hyper-glycaemic mice, and consisted of over 90% B-cells. When incubated with Krebs-Ringer phosphate medium, the islet cells displayed an increased rate of respiration upon addition to the incubation medium of either tolbutamide (D860; 0.1 mg/ml) or glibenclamide (HB 419; 0.1 .g/ ml). The respiratory rate increased with the concentration of HB 419 in the range 0.001–0.1 g/ml, but did not exceed 120% of the respiration in pure phosphate medium. Whereas the physiological excretion product of D 860 did not affect the respiratory rate, the corresponding derivative of HB 419 was still effective in stimulating the oxygen uptake of the islets. When islets were incubated with glucose at a high concentration (3 mg/ml), the oxygen uptake was inhibited by addition of D 860, or its metabolite, or HB 419. The last drug slightly increased the respiration of islets incubated with glucose at a concentration of 1 mg/ml, and a marked stimulation was noted at a still lower glucose concentration, 0.5 mg/ml. Attempts to evaluate the effect of mannoheptulose on the respiratory response of the islets to hypoglycaemic Sulphonylureas produced inconclusive results. It is suggested that Sulphonylureas effect an increased rate of endogenous substrate oxidation in the B-cells of the pancreatic islets.This work was supported by the Swedish Medical Research Council (B68-12X-109-04) and the U.S.Public Health Service (Grant AM-05759-06). The skilful technical assistance of Miss Gunilla Lekselius and Miss Ing-Britt Brolen is greatfully acknowledged.     

The effect of sleeved arms on oscillometric blood pressure measurement

The authors measured the blood pressures of 36 subjects who had bare and sleeved arms to determine the effect of wearing sleeves on automatic oscillometric blood pressure measurements. They found no statistically significant effect of sleeves on the measurement of either systolic or diastolic blood pressure (p>0.15). However, based on confidence intervals of possible sleeve effects, the authors recommend repeating blood pressure measurements on bared arms when the sleeved-arm oscillometric measurements are at least 86 mm Hg diastolic or 135 mm Hg systolic. Presented in part at the annual meeting of the Society of General Internal Medicine, Seattle, Washington, May 1–3, 1991.     

Waiting room time in the assessment of an appointment system in primary care

Excessive time spent waiting in health care facilities is a nuisance to patients as well as to physicians who then have to see these dissatisfied patients. Most efforts to enhance surgery efficiency have been to optimize physician working hours and patient waiting time has been a minor concern, in particular in countries with a shortage of physicians. At the V?nn?s Primary Health Care Centre in northern Sweden, efforts were made to reduce waiting time by making changes in office routines and by introducing a new appointment system. All visits to physicians during two four-week periods (March 1977 and March 1979) were analyzed, with the changes being introduced in the interim. The total time spent waiting by patients, and the patient waiting time in relation to the time scheduled were reduced. A slight increase in physician idle time was also noted. The measures taken to reduce waiting time were effective and contributed to the fulfillment of a postulated aim.     

Life, illness and death--existential reflections of a Swedish sample of patients who have undergone curative treatment for breast or prostatic cancer.

The aim of this study is to describe cancer patients' existential reflections and how these reflections were met by the nursing staff. A qualitative method of data collection was used. Ten patients with breast- or prostate cancer who had completed curative treatment were interviewed. The results showed that the cancer diagnosis resulted in existential reflections in some of the patients. These reflections concerned the meaning of life, God/a higher power, health, work, relations and sexuality. Reflections on the cancer consisted in beliefs about the causes of cancer, treatment and cancer and sexuality. It could also be seen that loss of important life values, such as health and sexuality could lead to loss of meaning of life. Explicit reflections on sexuality were only made by two of the men in the study. The patients reported a need of existential support as well as obstacles for giving such support. Obstacles could be lack of time and lack of continuity, as well as lack of knowledge resulting in an inability to identify existential issues. Some of the patients had wanted existential support from nurses, while others received the support they needed from family and friends.     

A G-->A transition creates a branch point sequence and activation of a cryptic exon, resulting in the hereditary disorder neurofibromatosis 2

We describe a G-->A transition within intron 5 of the NF2 gene. This mutation creates a consensus splice branch point sequence. To our knowledge this is the first report of a mutation that creates a functional branch point sequence in a human hereditary disorder. The new branch point sequence is located 18 bp upstream of a consensus splice acceptor site. A consensus splice donor site is found 106 bp 3' of the acceptor site. Asa consequence the G-->A transition results in an alternatively spliced mRNA containing an additional exon 5a of 106 bp derived from intron sequences. We cloned the mutant cDNA and show that due to an in-frame stop codon the cDNA codes for a truncated NF2 protein. The mutation was observed in three affected members of an NF2 family. In a tumour of one of the family members both alternatively spliced and wild-type mRNA were found, although the wild-type allele of the gene is absent due to an interstitial deletion on chromosome 22. We also show that immunoprecipitations reveal the presence of full-length wild-type NF2 protein in the tumour lysate. These data support the hypothesis that some degree of normal splicing of the mutant precursor RNA is taking place. It is therefore likely that this residual activity of the mutant allele explains the relatively mild phenotype in the family. These data also indicate that complete inactivation of the gene is not required for tumour formation.      

Regulation of in vitro and in vivo T cell activation by CD43

Accessory molecule interactions can be critical in determining the outcome of a T cell's encounter with antigen. Cell adhesion proteins may augment T cell responses by facilitating TCR engagement of the antigen-MHC complex, while co-stimulatory molecules may deliver distinct signals that modulate T cell responsiveness. CD43 (leukosialin, sialophorin) has been suggested to influence cell activation by steric hindrance based upon the large size and glycosylation of the protein, as well as the relative abundance of the protein on the cell surface. In this paper we examine both in vitro and in vivo T cell-dependent responses in CD43-deficient mice. We demonstrate that T cells from CD43-deficient mice are hyper-responsive following both in vivo and in vitro activation, and that this is observed in response to not only TCR-CD3-mediated stimulation, but also following receptor-independent activation. This data suggests that mechanisms other than non-specific steric hindrance are important in the regulation of T cell activation by CD43.