Relation of growth hormone and myocardial collagen accumulation in experimental diabetes

A pathogenic role of growth hormone in the tissue complications of diabetes has been postulated. Because collagen has been found to accumulate in myocardial interstitium in diabetes, we have undertaken a study of the relationship of plasma growth hormone levels to collagen accumulation in a canine model of chronic diabetes. Sedentary normal animals and diabetic animals were compared respectively with physically conditioned animals in which the collagen increment associated with diabetes was minimized. Basal growth hormone levels as well as increments induced by hormone release after clonidine have been related to the myocardial alteration. Myocardial collagen concentration was increased to 2.94 +/- 0.11 micrograms/mg dry weight in the sedentary diabetic animals vs. 1.97 +/- 0.07 micrograms/mg dry weight in sedentary normals (P less than 0.01), but was normal in the exercised diabetic animals after 1 year. However, levels of growth hormone in the basal state were similar in all four groups. After provocative stimulation with clonidine in the normals there was a progressive rise of growth hormone levels that was similar in the sedentary and physically conditioned animals. The diabetic groups exhibited a rise of plasma growth hormone that was not significantly higher in the nonexercised animals. Moreover the peak levels of growth hormone after clonidine were comparable. The data suggest that collagen accumulation in diabetic myocardium does not appear to be dependent on increased plasma levels of growth hormone, but a role for enhanced sensitivity to hormonal action is not excluded.     

Obsessive-compulsive disorder, depression, and the dexamethasone suppression test

Five of 29 obsessive-compulsive disorder patients were dexamethasone suppression test (DST) nonsuppressors, all of whom met standard Hamilton Depression Rating scale criteria for at least mild depression. None of 24 nondepressed obsessive-compulsive disorder patients had an abnormal DST. The relationship of the DST to specificity of psychiatric diagnoses is discussed.     

Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.     

Progression and regression of cervical lesions: Review of smears from women followed without initial biopsy or treatment

Cervical smears were reviewed from patients in whom a cytological abnormality was followed, after an interval without interference, either by regression to `negative' or else by progression to invasive carcinoma. Twenty-eight cases were from a previously analysed series with positive smears and an interval of at least two years before investigation, resulting from refusal or failure to trace. Slides were also reviewed from 25 cases in which `positive' smears had regressed to negative without escaping from surveillance, and from 10 patients subsequently developing invasive carcinoma whose previous slides, taken several years earlier, showed abnormalities on review. None of these 63 patients had any biopsy or other surgical procedure to the cervix between the initial smear and the outcome.

Slides showing `superficial cell dyskaryosis' and/or well-differentiated `parabasal cell dyskaryosis' were found only among the groups with subsequent regression. Those showing dissociated poorly differentiated dyskaryotic parabasal cells regressed to negative in two cases and progressed to invasion in nine. This suggests that many examples of spontaneous regression correspond to mild dysplasias which are not precancerous, and overdiagnosis must often have resulted in unnecessary surgical procedures in the past.

`Regressing' and `progressing' groups both included cases in which the spatula had removed coherent pieces of undifferentiated epithelium. These are difficult to interpret cytologically. In nine of them (including four which regressed) the cytological picture was that of carcinoma in situ. The remainder (14 cases) were probably examples of reserve cell hyperplasia, and it is noteworthy that, of the 21 cases subsequently progressing to invasive carcinoma, five were preceded by appearances of this type. It is concluded that cell aggregates suggesting an unusual degree of reserve cell hyperplasia are a danger signal and require careful surveillance.

     

Soft tissue infection with Absidia corymbifera in a patient with idiopathic aplastic anemia

We describe a case of primary cutaneous mucormycosis (zygomycosis) in a patient with idiopathic aplastic anemia which responded to surgical debridement and therapy with liposomal amphotericin B. The tissue removed at surgery showed dense infiltration with fungal hyphae on histopathological examination. Primary cultures of tissue on solid media were negative, but Absidia corymbifera was isolated from unprocessed tissue placed in brain heart infusion broth.     

The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.