Non-linkage of the islet amyloid polypeptide gene with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Type 2 (non-insulin-dependent) diabetes is associated with the deposition of islet amyloid. The major formative peptide, islet amyloid polypeptide, has recently been characterised and an abnormality of the structure or expression of this gene is a possible candidate for the inherited component of Type 2 diabetes. A restriction fragment length polymorphism of the gene has been identified with Pvu II. To study the relationship between the islet amyloid polypeptide gene and Type 2 diabetes, two distinct genetic approaches have been undertaken. Firstly, non-linkage has been demonstrated in four pedigrees, with four normoglycaemic first degree relatives having an allele associated with diabetes in other family members, and one affected relative not having the putatively associated allele. The LOD score taking age-related penetrance into account was –1.68, making linkage unlikely (p=0.02). Secondly, in a population-based restriction fragment length polymorphism survey, no linkage disequilibrium of the alleles was found between a population of unrelated Caucasian subjects with Type 2 diabetes and a normal population. A mutation in or near the islet amyloid polypeptide gene is thus unlikely to be a common cause of Type 2 diabetes.     

Early mobilisation after percutaneous cardiac catheterisation using collagen plug (VasoSeal) haemostasis.

OBJECTIVE--To assess the efficacy and safety of a haemostatic bovine collagen plug (VasoSeal) in reducing patient immobilisation after cardiac catheterisation from a percutaneous femoral arterial approach. DESIGN--A non-randomised, prospective analysis of a new biodegradable haemostatic agent on an intention to treat basis. SETTING--The catheterisation suite of a regional cardiothoracic unit. PATIENTS--A series of 63 patients having various diagnostic investigations and therapeutic interventions agreed to participate in this study. INTERVENTIONS--Cardiac catheterisation was performed from a percutaneous femoral artery approach. Patients taking aspirin and those who required formal anticoagulation were not excluded. Patients were measured for the appropriate sized collagen delivery system at the beginning of the procedure. At the end of the procedure two bovine collagen plugs were applied to the surface of the femoral artery through the channel created by the application device. MAIN OUTCOME MEASURES--Incidence of successful delivery, insertion time, immediate outcome, inpatient complications, success of mobilisation of the patient at one and two hours after the procedure, and whether these variables relate to individual patient characteristics. RESULTS--Successful placement of the device was achieved in 57 of 63 consecutive patients (90.5%). The mean (SD) insertion time was 86 (24) seconds. Six (9.5%) patients did not receive the haemostat because of femoral artery perforation by the tissue dilator (n = 3), inability to compress the femoral artery proximal to the site of delivery (n = 1), pre-existing haematoma (n = 1), or patient withdrawal from the study (n = 1). Uncomplicated mobilisation within two hours of investigation was possible in 54 of 57 (94.7%) patients receiving this device. A sizeable haematoma (> 5 x 5 cm) prevented early mobilisation in the remaining three patients. Mobilisation was uncomplicated in 32 of 34 (94.1%) patients mobilised at two hours and 22 of 23 (95.6%) at one hour (NS). One patient who was mobilised early without complication later developed evidence of claudication in the treated leg. Femoral arteriography showed a smooth intraluminal filling defect attached to the wall of the femoral artery at the puncture site. This obstruction, presumed to be a collagen plug, was treated successfully with angioplasty. Sheath size, arterial pressure, the use of aspirin, heparin or warfarin, and body mass index did not influence patient outcome. The pattern of complications did not relate to a learning curve experience. CONCLUSIONS--The bovine collagen haemostat is a relatively safe and effective device that allows far earlier patient mobilisation than conventional haemostasis after diagnostic and therapeutic interventions from a percutaneous femoral artery approach. These results have important implications for patients undergoing investigation in mobile x ray units or in hospital based day case units.     

Factors influencing calcitriol metabolism in renal failure

Metabolic clearance rate (MCR) and production rate (PR) of calcitriol is decreased in experimental renal failure. In this experiment, we studied uremia and secondary hyperparathyroidism as possible causes of the abnormal calcitriol metabolism. Normal rats were made uremic by infusing phosphorus-free urine for 24 hours. Both the MCR (0.22 +/- 0.01 ml/min/kg, N = 6 P less than 0.001) and the PR (16.6 +/- 1.97 ng/kg/day, P less than 0.01) of calcitriol were significantly suppressed in normal rats following urine infusion when compared to saline infused rats (MCR, 0.30 +/- 0.01; PR, 32.9 +/- 4.1, N = 6). Different levels of protein intake by rats with renal failure produced by subtotal nephrectomy also alter the PR but not the MCR of calcitriol. Thus, the synthesis of calcitriol was significantly lower in rats with renal failure fed a high protein (50% protein) diet (17.6 +/- 0.7 ng/kg/day, N = 8, P less than 0.001) than in rats with renal failure fed a normal protein (20% protein) diet (22.2 +/- 1.4, N = 7). Thyroparathyroidectomy (TPTX) did not alter the MCR of calcitriol in renal failure, even though parathyroid hormone, which may suppress the degradation enzyme, could be elevated in this model of renal failure. The MCR of TPTXed rats with renal failure (0.15 +/- 0.01 ml/min/kg, N = 7) remained lower than that of the TPTXed control rats (0.19 +/- 0.01, N = 7, P less than 0.001), and chronic infusion of PTH to TPTXed rats with renal failure did not change the MCR of calcitriol (0.15 +/- 0.01, vs. control, 0.24 +/- 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

T lymphocyte subsets and antilymphocyte antibodies in lupus nephritis

T lymphocyte subsets were determined in 12 patients with untreated systemic lupus erythematosus (SLE) and in 14 healthy controls. Six out of 8 (75%) patients with lupus nephritis had reduction in the percentage of T helper cells and low helper: suppressor cell ratios compared with controls. None of the 4 patients without nephritis had low ratios. Cold-reactive anti-lymphocyte antibodies cytotoxic to both the helper and the suppressor cells were detected in 7 of the 8 patients who had nephritis. Low T helper: suppressor cell ratio in SLE seems to correlate with the presence of active nephritis.     

Chronic lithium treatment increases the phosphorylation of a 64-kDa protein in rat brains

Despite the wide clinical use of lithium in the treatment of manic depressive illness there is no adequate explanation for its mechanism of action. In the light of lithium's suggestive effects on the second messenger system in the brain, we studied the effects of chronic dietary lithium treatment (achieving blood levels in the therapeutic range) on protein phosphorylation in different areas of rat brain. An increase in the phosphorylation of a 64-kDa membrane-associated protein was evident in the lithium-treated rats compared to controls. This increase was observed only under basal phosphorylating conditions and was abolished when the phosphorylation was performed in the presence of Ca²⁺ or Ca²⁺ and calmodulin. The possibility that this 64-kDa protein affected by lithium is the beta-subunit of the calmodulin-dependent protein kinase or a different protein which co-migrates with it is discussed.     

Muscle strength in healthy white and Asian subjects: the relationship of quadriceps maximum voluntary contraction to age, sex, body build and vitamin D

1. The maximum voluntary isometric contraction (MVC) of the dominant quadriceps muscle was measured in 136 healthy White and 172 healthy Hindu Asian subjects resident in London, using a specially designed chair equipped with a force measuring load cell. 2. Males were stronger than females, and for both sexes MVC declined with age. From age 20 to 60 the annual decline in MVC ranged from 0.56% in White males to 1.5% in female Asians. 3. White subjects were stronger than Asian subjects even after correcting for the effect of age, height, weight and sex in a multi-factorial analysis. 4. Only in males did MVC correlate with height and weight. Asian women were more obese than any other group, and showed an increase in body mass index with age. 5. Twenty-two per cent of Asian subjects had marked vitamin D deficiency (plasma 25-hydroxycholecalciferol less than 10 nmol/1). There was no correlation between MVC, and plasma 25-hydroxycholecalciferol.     

Restorative treatment need assessment by dentally and nondentally trained subjects

A study was carried out which compared how two groups of people, one with clinical dental experience and one without, assessed restorative dental treatment need. Using a visual analogue scale, a group of final year dental students ( n = 50) and nonclinical university students ( n = 50) assessed the extent to which they considered common dental imperfections, viz. spacing of the upper anterior teeth and discolouration of upper anterior teeth, warranted restorative correction. The group of dental students judged the necessity for treatment of discolouration to be more urgent than correction of spacing. The nondental group did not differentiate between the degrees of need. Data were non‐normal in distribution but the use of appropriate statistical tests showed the differences in mean assessments to be significant.