Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene

Isolated growth hormone (GH) deficiency (IGHD) is a rare cause of short stature. The same mutation of the gene encoding the growth hormone-releasing hormone receptor (GHRHR) has been identified as the basis for IGHD in three families from the Indian subcontinent. The prevalence and heterogeneity of defects in the GHRHR gene are not known. Twenty-two dwarf members of a large, extended kindred containing at least 105 affected members with autosomal recessive short stature underwent extensive endocrine evaluation, which confirmed markedly reduced or undetectable serum concentrations of GH that did not increase in response to different stimuli. DNA sequences of the 13 exons and intron-exon boundaries of the GHRHR gene were determined in an index patient. A novel homozygous 5' splice site mutation (G-->A at position +1) in IVS1 was found. Thirty of the affected subjects tested were homozygous for this mutation, and 64 clinically unaffected patients were either heterozygous for the mutation (n = 41, including 9 obligate carriers) or homozygous for the wild-type sequence (n = 23). We describe a novel mutation in the GHRHR gene as cause of dwarfism in the largest kindred with familial IGHD described to date.     

Small-intestinal mucosa in pseudoobstruction syndromes

The purpose of this investigation was to determine the frequency and severity of small intestinal mucosal damage in pseudoobstruction syndromes. One hundred eighty-nine interpretable biopsies from 12 patients were blindly reviewed by two investigatiors. The underlying disorders were scleroderma in 7 and idiopathic intestinal pseudoobstruction in 5. All 12 had small-intestinal dilatation on small-bowel series. Eight of the 12 patients had biopsies characterized by moderate, to severe mucosal damage; 3 of these had some biopsies which were flat. The damage did not correlate with: (1) types and numbers of organisms recovered from small intestinal aspirates; (2) duration of illness; (3) degree of dilatation of the proximal small bowel; (4) concentrations of deconjugated bile salts in small intestinal fluid; or (5) amount of fat absorbed in fat-balance studies. We conclude that mucosal damage is common in pseudoobstruction syndromes. The pathogenesis of the damage and its relationship to intraluminal bacteria remain undefined.     

Effect of 2'-deoxycoformycin on erythroid, granulocytic, and T- lymphocyte colony growth

The finding of elevated intracellular levels of adenosine deaminase (ADA) in some patients with acute lymphoblastic leukemia has led to attempts to control this disease with the adenosine deaminase inhibitor 2'-deoxycoformycin (dCF). Because of clinical reports indicating its relative freedom from myelotoxicity, we have tested the effects of this drug on erythroid, granulocytic, and T-lymphocyte colony formation by normal marrow and peripheral blood cells. While clinically the drug has been found to be active at serum concentrations of approximately 10 microM, we have tested it at concentrations up to and including 1 mM. It was found that both erythroid and granulocytic colony growth was completely unaffected by 1 mM dCF, a concentration at least 2 magnitudes higher than that necessary to totally ablate intracellular ADA levels. T-lymphocyte colony growth was unaffected by 100 microM dCF, but at 1 mM some inhibition was observed. These findings therefore indicate that dCF, while able to cause leukemic cell lysis in vivo, has no inhibitory effect on the proliferative capacity of normal hematopoietic cells.     

Ventricular remodeling in growing rats with experimental diabetes: The impact of swimming training

Diabetic cardiomyopathy is associated with cardiac muscle remodeling, resulting in myocardial dysfunction, whereas exercise training (ET) is a useful nonpharmacological strategy for the therapy of cardiac diseases. This study tested the effects of low-intensity swimming-training on the structural remodeling of the left ventricle (LV) in growing rats with unmanaged experimental diabetes. Thirty-day-old male Wistar rats were divided into four groups (n = 5/group): sedentary-control (SC), exercised-control (EC), sedentary-diabetic (SD), and exercised-diabetic (ED). Swimming-training rats exercised 5 days/week, 90 min/day, with a load of 5% BW during 8 weeks. Sections of LV were stained with Periodic acid-Schiff, Sirius Red, and Gomori's reticulin. Seven days and 8 weeks after streptozotocin (STZ) induction (60 mg kg⁻¹ BW), blood glucose (BG) in the diabetic groups (SD = 581.40 ± 40.48; ED = 558.00 ± 48.89) was greater (p < 0.05) than in their controls (SC = 88.80 ± 21.70; EC = 85.60 ± 11.55). Swimming-training reduced BG by 23 mg/dL in the diabetics (p > 0.05). The LV of diabetic rats had increased interstitial collagen and reticular fibers on the extracellular matrix and presented glycogen accumulation. More importantly, all these adverse tissue changes induced by STZ were attenuated by ET. Together, these findings support the idea of a beneficial role of exercise in the LV remodeling in rats with unmanaged type-1 diabetes mellitus.     

Self-reported symptoms in healthy young adults to predict potential coronavirus disease 2019

ObjectiveTo assess the utility of self-reported symptoms in identifying positive coronavirus disease 2019 (COVID-19) cases among predominantly healthy young adults in a military setting.MethodsA questionnaire regarding COVID-19 symptoms and exposure history was administered to all individuals contacting the Israeli Defence Forces Corona call-centre, before PCR testing. Surveyed symptoms included cough, fever, sore throat, rhinorrhoea, loss of taste or smell, chest pain and gastrointestinal symptoms. Factors were compared between positive and negative cases based on confirmatory test results, and positive likelihood ratios (LR) were calculated. Results were stratified by sex, body mass index, previous medical history and dates of questioning, and a multivariable analysis for association with positive test was conducted.ResultsOf 24 362 respondents, 59.1% were men with a median age of 20.5 years (interquartile range 19.6–22.4 years). Significant positive LRs were associated with loss of taste or smell (LR 3.38, 95% CI 3.01–3.79), suspected exposure (LR 1.33, 95% CI 1.28–1.39) and fever (LR 1.26, 95% CI 1.17–1.36). Those factors were also associated with positive PCR result in a multivariable analysis (OR 3.51, 95% CI 3.04–4.06; OR 1.86, 95% CI 1.65–2.09; and OR 1.34, 95% CI 1.19–1.51, respectively). Reports of loss of taste or smell increased gradually over time and were significantly more frequent during the late period of the study (63/5231, 1.21%; 156/7941, 1.96%; and 1505/11 190, 13.45%: p < 0.001).ConclusionLoss of taste or smell, report of a suspicious exposure and fever (>37.5°C) were consistently associated with positive LRs for a positive SARS-CoV-2 PCR test result, in a population of predominantly young and healthy adults.     

A useful panel for the diagnosis of Hirschsprung disease in rectal biopsies: calretinin immunostaining and acetylcholinesterase histochesmistry

The pathological evaluation of rectal biopsies for the diagnosis of Hirschsprung disease has been a challenging issue. We analyzed prospectively the usefulness of calretinin immunostaining and acetylcholinesterase (AChE) histochesmistry in rectal biopsies for the diagnosis of Hirschsprung disease. Frozen tissue samples from 43 patients were used for AChE histochemistry and paraffin-embedded sections for calretinin immunohistochemistry and conventional histology (hematoxylin and eosin [H&E]). Activity for AChE, was demonstrated in 13 of 43 cases, and the absence of immunoreactivity for calretinin was observed in 14 of 43 cases. Conventional histology (H&E) did not reveal ganglion cells in 24 of 43 cases. The results on calretinin were in good agreement with AChE according to the κ index (0.946; P < .001) and presented significantly higher specificity (96.7 × 63.3; P < .002) and accuracy (97.6 × 74.4; P < .003) when compared with conventional histology (H&E). The final diagnosis of Hirschsprung disease was confirmed in 13 of 43 patients who were submitted to surgical treatment. The results of the present study indicate that calretinin can be a good tool in ruling out the diagnosis of Hirschsprung disease, by showing positive staining in ganglion cells and intrinsic nerve fibers, whereas AChE is useful in confirming the diagnosis of Hirschsprung disease, by revealing activity of this enzyme in hypertrophied nerve fibers. The association between calretinin and AChE can be a useful panel for the histopathologic evaluation of rectal biopsies for the diagnosis of Hirschsprung disease.     

Laser therapy for recurrent aphthous stomatitis: an overview

Clinical Oral Investigations - To evaluate therapeutic effects of laser therapy on patients with recurrent aphthous stomatitis assessing evidences from previously published systematic reviews. An...     

Myocardial revascularization. The evolution of 100 cases

The postoperative course of 100 pts. that underwent aorto-coronary bypass surgery was studied at the Instituto Nacional de Cardiología "Ignacio Chávez": 84 were men and 16 women between 37 and 74 years. 56 had previous history of myocardial infarction, while in 16 of them occurred within 30 days of the surgical procedure. 88 had symptomatic angina and 8 were in cardiac failure. The coronariography showed trivascular lesions in 73% and 8 pts. had stenosis of the left main coronary artery. Two pts. had 5 coronary grafts, 4 had 17, 3 had 37, two 35 and one 9 pts. All anterior descending coronary arteries were grafted. 61 of them and the 8 main left damaged were grafted with internal mammary artery Afert surgery; 15 pts had AMI, 4 profuse bleeding, one cardiac failure and shock. CPK enzyme levels of 500 were found in the majority of the pts with AMI with 81.2 positive predictive value and negative of 97.6. Three pts died, two at the OR with cardiac failure one of them had ventricular rupture, and the last at the ICU also with cardiac failure. We emphasize that CPK values of 500 UI or more in the postoperative course may be diagnostic of AMI.