Abnormal renal vasodilation to an amino acid infusion in congestive heart failure: normalization by enalapril

In congestive heart failure (CHF), the neurohormonal mechanisms that cause renal vasoconstriction, particularly those depending on the renin-angiotensin system, could interfere with renal vasodilating mechanisms. To elucidate this issue, we studied the kidney response to an amino acid infusion (known to cause renal vasodilation in healthy individuals) in eight patients with CHF. We found that the amino acid infusion (0.7 mL/kg/h of a 10% solution) elicited no renal hemodynamic response, in marked contrast to healthy subjects. We next hypothesized that the renin-angiotensin system (known to be activated in heart failure) has a role in the lack of response to the amino acid infusion. To test this hypothesis, we repeated the study after two 5-mg doses of enalapril, an inhibitor of the angiotensin-converting enzyme, administered 12 hours apart. After enalapril treatment, the amino acid infusion caused a 45% increase in mean renal blood flow (RBF) from 383 +/- 55 to 557 +/- 51 mL/min at the fifth hour (P < 0.05). This normalization of the renal response to the amino acid infusion occurred without changes in cardiac output or in systemic vascular resistance. Hence, the renal fraction of the cardiac output increased during the amino acid infusion. The recovery of the renal vascular response was not accompanied by an increase in glomerular filtration rate (GFR; filtration fraction decreased), suggesting a predominant efferent arteriole dilatation. Our study shows that, in heart failure, the kidney loses its ability to increase RBF in response to an amino acid load. This lack of renal vascular response can be restored by inhibiting the renin-angiotensin system and is unrelated to changes in systemic hemodynamics.     

Toll-like receptor 9 in systemic sclerosis patients: relation to modified Rodnan skin score,disease severity,and functional status

Clinical Rheumatology - The objective of this study is to assess toll-like receptor-9 (TLR9) expression in CD3-positive T lymphocytes and CD19-positive B lymphocytes in systemic sclerosis (SSc)...     

The Prevalence of Cryptosporidium spp. in Children,Taiz District,Yemen

Background

This is the first work done on cryptosporidiosis among the children in Taiz, Yemen.

Methods

A number of 712 samples were collected from children of different ages (ranging from 1 month to 12 years) from Dec 2006 to Aug 2007. The collected samples were examined by Sheather''s sugar floatation and Modified Ziehl- Neelsen stain as well as ELISA methods. The test results were statistically analyzed by SPSS software.

Results

The overall positive percentage was 43.7%. The higher incidence (36.2%) was occurred in males while the lowest incidence (32.7%) was observed in females (r=0.876; P=0.001). The correlation between infected cases and the type of drinking water was r =0.121. Among the cases examined by ELISA (92 cases), 26.1% were infected. The correlation between seropositivity and gender was r=0.652 (P=0.031).

Conclusion

Cryptosporidium spp. is a significant pathogen among children at Taiz. Fresh water supplies, education, eating habits and domestic animals are considered the main sources for transmission of cryptosporidiosis.     

Naevus comedonicus of the scalp

We report the case of a 3-year-old boy with naevus comedonicus, characterized by confluent clusters of dilated follicular orifices plugged with keratinous material that resemble open comedones, located on the scalp.     

The Impact of Trans-thoracic Ultrasound on Cardiac Injuries

Objective:

To determine the impact of trans-thoracic ultrasound (TTUS) in patients with chest trauma and potential cardiac injuries and to determine the outcome of patients with cardiac injury detected on TTUS.

Method:

Data were obtained from the Trauma Registry for all patients presenting alive to the University Hospital of the West Indies during the 10-year period commencing January 1, 2001 and who were subjected to a TTUS or emergency thoracotomy for cardiac injuries, or had cardiac injuries at postmortem. In addition to demographics, variables analysed included mechanism and site of injury and outcome.

Results:

Of 405 patients being subjected to a TTUS during the period, 12 (3%) had cardiac injuries. During the same period, 63 patients in the Trauma Registry had proven cardiac injuries. Transthoracic ultrasound was thus conducted on 19% of all patients with cardiac injuries. Three patients had positive TTUS but no cardiac injuries. Of the patients with injuries, the mean age was 30.4 years, 92.1% were male and 65% were as a result of stab wounds, while 22% were as a result of gunshot wounds. The right ventricle was the most common site of injury, accounting for 41% of cases, while the left ventricle, both ventricles and other sites accounted for 27%, 17% and 14%, respectively. Ninety per cent of the group was subjected to emergency thoracotomy; mortality of the entire group was 48%, including one patient who had TTUS.

Conclusions:

This review demonstrates that cardiac injuries remain lethal, diagnosis is largely clinical and TTUS may be over-utilized, having little impact on clinical outcome of patients presenting with this injury.     

Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas

The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight ‘anomalous’ cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first ‘anomalous’ non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.