Endothelial Vascular Function in Hypertensive Patients After Renin—Angiotensin System Blockad

It is unclear whether single and combined pharmacologic inhibition of the renin-angiotensin-aldosterone system have similar effects on endothelial function and blood pressure (BP). The authors evaluated 63 hypertensive patients divided into 4 groups (hydrochlorothiazide 25 mg/d; irbesartan [IRBE] 150 mg/d; quinapril [QUIN] 20 mg/d; or IRBE 150 mg/d + QUIN 20 mg/d) and 25 healthy normotensive subjects (normal) followed for 12 weeks. Endothelium-dependent dysfunction measured as flow-mediated dilation at Weeks 0 and 12 were: normal, 11.5%±2.4% vs 13.5%±2.0%; hydrochlorothiazide, 7.3%±2.0% vs 12.8%±3.1%; QUIN, 7.2%±2.8% vs 13.2%±2.1%; IRBE, 7.1%±2.8% vs 13.0%±2.9%; and IRBE + QUIN, 7.5%±1.9% vs 12.8%±3.0%. Nitroglycerin-mediated responses were: normal, 26.0%±1.9% vs 24.0%±2.5%; hydrochlorothiazide, 17.0%±2.2% vs 18.3%±2.6%; QUIN, 17.8%±3.2% vs 23.4%±3.0%; IRBE, 16.8%±3.6% vs 24.7%±2.0%; and IRBE + QUIN, 17.3%±3.0% vs 25.1%±2.5%. Antihypertensive therapy restored BP to normal and improved the endothelium-dependent and -independent dysfunction after renin-angiotensin-aldosterone system blockade. In a further finding, the combined effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade was not superior to the action of either of these treatments separately.     

Update on the Interaction of Rifampin and Warfarin

A 79-year-old man with a history of deep vein thrombosis and pulmonary embolism received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was diagnosed with osteomyelitis and underwent partial metatarsal resection of his right foot. After surgery, antibiotics were initiated including ertapenem sodium 1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24 hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampin. A 5- to 6-fold increase in warfarin dose was prescribed to reach therapeutic international normalized ratios (INRs), but even these increases were insufficient to maintain his INR in the therapeutic range. After rifampin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin-rifampin therapy is necessary, vigilant monitoring is imperative and significant increases in warfarin doses are likely.     

Prospective Open-Label Study of Botulinum Toxin Type A in Patients with Axillary Hyperhidrosis: Effects on Functional Impairment and Quality of Life

BACKGROUND: Patients with primary axillary hyperhidrosis experience substantial functional impairment and reduced health-related quality of life (HRQOL). Few studies have comprehensively evaluated the effects of botulinum toxin type A (BoNT-A) on these symptoms. OBJECTIVE: To prospectively assess the effects of BoNT-A on functional impairment associated with primary axillary hyperhidrosis. METHODS: Patients treated with BoNT-A 50 U per axilla at baseline were assessed 4 and 12 weeks later. Outcome measures included functional impairment as assessed by the Hyperhidrosis Disease Severity Scale and the Hyperhidrosis Impact Questionnaire and dermatology-specific HRQOL as assessed by the Dermatology Life Quality Index. RESULTS: At weeks 4 and 12 after BoNT-A treatment, 85% and 90% of patients achieved the a priori definition of treatment responder. Patients reported less occupational and emotional impairment, spent less time managing their hyperhidrosis, and had fewer difficulties in social situations. Adverse events were uncommon (5.5%), were mild, and did not require treatment. At study end, 53% of patients reported no dermatology-specific HRQOL impairment and 90% were satisfied with treatment. CONCLUSIONS: Significant, meaningful, rapid, and durable reductions in disease severity and functional impairment, as well as improvements in HRQOL, were seen following BoNT-A treatment. BoNT-A was safe and well tolerated, producing high levels of patient satisfaction.     

Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10⁻³M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.     

The Environmental Context of Patient Safety and Medical Errors

The environmental context of patient safety and medical errors was explored with specific interest in rural settings. Special attention was paid to unique features of rural: healthcare organizations and their environment that relate to the patient safety issue and medical errors (including the distribution of patients, types of adverse events associated with learning, information flows, triage and transfer decisions, and culture of safety). Relevant organizational theories and strategies fo medical error reduction and prevention in rural health care settings were identified. Financial and technical assistance are needed to support the systematic collection of data from rural hospitals and other entities and to enhance relevant patient safety practices for rural America.     

An engineered biopolymer prevents mucositis induced by 5-fluorouracil in hamsters

Oral mucositis is a common, treatment-limiting, and costly side effect of cancer treatments whose biological underpinnings remain poorly understood. In this study, mucositis induced in hamsters by 5-fluorouracil (5-FU) was observed after cheek-pouch scarifications, with and without administration of RGTA (RG1503), a polymer engineered to mimic the protective effects of heparan sulfate. RG1503 had no effects on 5-FU-induced decreases in body weight, blood cell counts, or cheek-pouch and jejunum epithelium proliferation rates, suggesting absence of interference with the cytotoxic effects of 5-FU. Extensive mucositis occurred in all of the untreated animals, and consisted of severe damage to cheek pouch tissues (epithelium, underlying connective tissue, and muscle bundles). Only half of the RG1503-treated animals had mucositis, over a mean area 70% smaller than in the untreated animals. Basement membranes were almost completely destroyed in the untreated group but was preserved in the RG1503 group. RG1503 blunted or abolished the following 5-FU-induced effects: increases in matrix metalloproteinase (MMP)-2, MMP-9, and plasmin, and decreases in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These data indicate that mucositis lesions are related to massive release of proteolytic enzymes and are improved by RG1503 treatment, this effect being ascribable in part to restoration of the MMP-TIMP balance. RG1503 given with cancer treatment might protect patients from mucositis.     

Three patients with hallucal polydactyly and WAGR syndrome, including discordant expression of Wilms tumor in MZ twins

The WAGR contiguous gene deletion syndrome is a combination of Wilms tumor, Aniridia, Genito-urinary abnormalities, and growth and mental retardation which is invariably associated with an 11p13 deletion. We report two monozygotic twins and a third, unrelated patient with WAGR syndrome and additional clinical features not usually associated with WAGR. Both twins had developmental delay, growth deficiency, severe ocular involvement (nystagmus, aniridia, cataracts), atrial septal defect and two uncommon findings: agenesis of the corpus callosum and duplication of the halluces. One twin developed Wilms tumors aged 19 months while her sister remained tumor free by the age of 6.5 years. The singleton patient showed typical WAGR syndrome and preaxial hallucal polydactyly. Molecular cytogenetic studies refined the identification of the extent of the deleted segments, which were not identical in the two families. The two deletions included the PAX6 and WT1 genes as previously reported in typical WAGR patients. The unusual anomalies described in this report, may represent the expression of low penetrant traits associated with haploinsufficency of one or more of the genes present in the deletion (PAX6 is expressed in CNS) or may indicate epistatic influences of modifier genes on the expression of gene(s) present in the WAGR region.     

Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus

There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.     

Reinfektionsversuche an Lymnaea stagnalis mit Isthmiophora melis (Trematoda,Echinostomatidae) durch Miracidienexposition nach vorausgegangener Redienimplantation

Zusammenfassung Die natürliche intramolluskäre Entwicklung des Darmegels Isthmiophora melis verläuft über zwei morphologisch distinkte Redienformen: Auf zwei Generationen makropharyngeater Redien (Mutterredien) folgen nur noch Generationen mikropharyngeater Redien (Tochterredien) sowie Cercarien. Die Bildung von Mutterredien unterbleibt in Schnecken, die nur durch Implantation von Tochterredien experimentell infiziert wurden. Werden Schnecken nacheinander beiden Infektionsmodi unterworfen, der Tochterredienimplantation und der Miracidienexposition, so läßt sich aus dem Vorhandensein oder Fehlen von Mutterredien ablesen, welche der Infektionen von Erfolg war.Mittels dieser Methode wurde geprüft, ob Isthmiophora-parasitierte Lymnaea-Individuen gegen homologen Miracidienbefall resistent sind. Sie erwiesen sich als nicht resistent gegen Reinfektion, und zwar auch dann, wenn sie bereits in die Phase des Cercarienausstoßes eingetreten waren.

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Experimental re-infection of Lymnaea stagnalis with Isthmiophora melis (trematoda, echinostomatidae) by exposition to miracidia after implantation of rediae

Summary The natural intramolluscular development of the intestinal fluke Isthmiophora melis takes place in two morphologically distinct forms of rediae: Two generations of macropharyngeate rediae (mother rediae) are followed only by generations of micropharyngeate rediae (daughter rediae) and cercariae. Mother rediae are not produced in snails infected by implantation of daughter rediae only. If snails are subjected to the implantation of daughter rediae and exposed to miracidiae successsively, the presence, or absence, of mother rediae indicates which of the infections has been successful.This method of investigation was used in order to ascertain whether Lymnaea individuals parasitized by Isthmiophora are resistant against invading miracidia of homologous species. They proved not resistant against re-infection, even if they had already entered the stage of shedding cercariae.

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