Laboratory tests of renal function

The kidneys are vital organs in the management of fluid balance, waste product removal, electrolyte homeostasis, acid–base balance and endocrine function. Waste products removed by the kidney are urea, uric acid and creatinine; other foreign products with similar physiochemical properties are also excreted. Urea and uric acid are by products of protein metabolism and creatinine is generated by the metabolism of creatine compounds from muscle. The kidney regulates fluid and electrolyte balance through controlling the composition and volume of urine. In the proximal convoluted tubule and the loop of Henle, 90% of sodium, potassium, calcium and magnesium are reabsorbed. Acid–base balance is achieved by regulating the excretion of hydrogen ions and bicarbonate buffering. The kidney also has a number of endocrine functions including the production of renin and erythropoietin as well as hydroxylation of vitamin D. The kidneys receive 25% of cardiac output, generating 170–200 litres of ultrafiltrate per day. Urine output is approximately 1.5 litres per day, which is concentrated ultrafiltrate through selective reabsorption of solutes and water. In this article we will discuss tests frequently used to assess renal function.     

Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipients

Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17–2.89) after the first (median OD 3.41, IQR 2.54–3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39–3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 10⁶ CD4+ T cells; IQR: 46–180) to the first (median 128 per 10⁶ CD4+ T cells; IQR: 82–353; p = .023) and after the second dose (median 361 per 10⁶ CD4+ T cells; IQR: 146–848; p < .0001). Tenderness (83.0%; 95%CI: 69.2–92.4%) and redness (31.9%; 95%CI: 19.1–47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population.     

Family Belongingness Attenuates Entrapment and Buffers Its Association with Suicidal Ideation in a Sample of Dutch Sexual Minority Emerging Adults

Sexual minority emerging adults are more likely to engage in suicidal ideation than their heterosexual counterparts. Experiences of homophobic violence are associated with suicidal ideation. Yet, the specific mechanisms linking homophobic violence to suicidal ideation remain unclear. Entrapment and social belongingness were tested to determine their relevance for understanding the link between homophobic violence and suicidal ideation. A sample of sexual minority Dutch emerging adults (N?=?675; ages 18–29, M?=?21.93 years, SD?=?3.20) were recruited through online platforms and flyers. Homophobic violence was expected to be positively associated with suicidal ideation and entrapment. The association between homophobic violence and suicidal ideation was expected to be indirectly linked through entrapment. We explored whether various sources of social belongingness moderated the path between entrapment and suicidal ideation and whether those sources of social belongingness moderated the indirect effect of homophobic violence on suicidal ideation through entrapment. Results showed that homophobic violence and entrapment were positively associated with suicidal ideation and that family belongingness was negatively associated with suicidal ideation. Homophobic violence and suicidal ideation were not indirectly linked through entrapment. The interaction effect between entrapment and family belongingness was significant, suggesting that, on average, the effect of entrapment on suicidal ideation decreased when family belongingness was high. These results suggest that family belongingness may reduce the association between entrapment and suicidal ideation while adjusting for homophonic violence. Reducing entrapment and improving family belongingness may be useful targets for programs aimed at preventing suicidal ideation among sexual minority emerging adults.

     

Characterization of ompA genotypes by sequence analysis of DNA from all detected cases of Chlamydia trachomatis infections during 1 year of contact tracing in a Swedish County

In this study we aimed to characterize the ompA gene by sequencing DNA from all detected cases of Chlamydia trachomatis infection in a Swedish county during 2001, in order to improve the efficiency of contact tracing. Approximately 990 bp of the ompA gene was amplified, and sequence analysis was achieved in 678 (94%) of 725 C. trachomatis-positive cases in this unselected population. The most prevalent genotype was serotype E (39%), followed by F (21%), G (11%), D (9%), K (9%), J (7%), H (2%), B (1%), and Ia (1%). Serotype E was found in five genotype variants, with the reference sequence comprising 96% of all E cases. Serotype D was the most variable, and of seven sequence variants, three were identified as recombinants with serotype E. Altogether 29 genetic variants were detected, and mutations and recombination events are discussed. Clinical manifestations were not associated with genotypes. Sequence variation was linked to sexual networks identified by contact tracing and improved epidemiological knowledge but was of limited benefit.     

Enhancement of in vivo antitumor activity of classical anticancer agents by combination with the new, glutathione-interacting DNA minor groove-binder, brostallicin.

PURPOSE: Brostallicin (PNU-166196) is a alpha-bromoacrylic DNA minor groove binder, currently in clinical evaluation. This drug has the peculiarity of showing enhanced antitumor activity in cells with high glutathione S-transferase (GST)/glutathione content. The purpose of the study was to study multiple combinations of brostallicin with classical anticancer agents. EXPERIMENTAL DESIGN: The cis-dichloro-diammine-platinum (cDDP)/brostallicin combination was tested in the human colon carcinoma (HCT-116) model transplanted in nude mice. Two treatment schedules were tested: cDDP followed by brostallicin 48 h after or brostallicin followed by cDDP. These two schemes were selected from the observation that tumor cells in vitro show an increased activity of GST 48 h after cDDP treatment. The HCT-116 model was used also to test the irinotecan (cPT-11)/brostallicin combination. The effect of brostallicin in combination with doxorubicin (DX) was studied in the i.v. injected murine L1210 leukemia. Three administration schedules were tested. The antitumor activity of brostallicin and Taxotere was tested on the A549 lung cancer xenografts. RESULTS: In line with the increased GST activity observed after treatment with cDDP, the cDDP/brostallicin interaction was sequence-dependent, leading to a more than additive antitumor effect, without additional toxicity, only when cDDP was given before brostallicin. The antitumor effect of CPT-11 was enhanced significantly by brostallicin cotreatment. A more than additive antitumor effect, without additional toxicity, was observed when DX/brostallicin were sequentially administered in L1210-bearing mice. Finally, additivity was observed when brostallicin/Taxotere simultaneous combination was tested. CONCLUSIONS: Although the precise molecular mechanism of interaction between brostallicin and the other tested cytotoxics has not yet been identified, a clear therapeutic gain is observed in preclinical models when brostallicin is combined with anticancer agents such as cDDP, DX, CPT-11, and Taxotere. These results indicate the potential therapeutic value of brostallicin in cancer combination treatment therapy.     

Patient Capacity in Mental Health Care: Legal Overview

The discriminatory effects of categorizing psychiatric patients into competent and incompetent, have urged lawyers, philosophers and health care professionals to seek a functional approach to capacity assessment. Dutch and English law have produced some guidelines concerning this issue. So far, most legal systems under investigation have concentrated on alternatives for informed consent by the patient in case of mental incapacity, notably substitute decision-making, intervention of a judge and advance directives. It is hard to judge the way in which the law may further adapt to a more functional assessment of capacity, because the nature of law shows that legal reforms usually take place only when new methods have been accepted by the field. This is not yet the case today.     

Malignant laryngotracheal obstruction: a way to treat serial stenoses of the upper airways

BACKGROUND: Six patients known to have inoperable esophageal carcinoma presented with stridor due to both malignant tracheal stenosis (n = 6) and bilateral vocal cord paralysis. Two patients also had respiratory-digestive fistula. METHODS: Patency was restored by endotracheal stenting plus unilateral cordectomy. Four patients had immediate relief. Two patients required enlargement of the cord incision. One of them declined reoperation and underwent tracheotomy. RESULTS: Stent function was uneventful. There was no dislodgement or mucous impaction. Fistula seal was complete. There was no aspiration through the new-shaped glottic orifice. Peak expiratory flow increased from 24.4% +/- 9.7% predicted normal before to 40.5% +/- 13.7% after the procedure, whereas the dyspnea score decreased from 74.2 +/- 12.7 to 24.2 +/- 14.0. CONCLUSIONS: Restoration of airway continuity in serial laryngotracheal stenoses using a combined approach is a feasible technique in end-stage cancer patients. It effectively relieves respiratory distress and ensures voice preservation. In addition, it may avoid the risks of tracheotomy.