The pharmacokinetic diversity of two von Willebrand factor (VWF)/ factor VIII (FVIII) concentrates in subjects with congenital von Willebrand disease. Results from a prospective, randomised crossover study

The pharmacokinetic (PK) profiles of von Willebrand factor (VWF) /factor VIII (FVIII) concentrates are important for treatment efficacy and safety of von Willebrand disease (VWD) patients. This prospective, head-to-head, randomised crossover study compared the PK profile of a new, high purity, human plasma-derived (pd)VWF/FVIII concentrate, Wilate, with the PK profile of an intermediate purity (pd)VWF/FVIII concentrate, Humate-P, in VWD patients. Subjects with inherited VWD were randomised to a single intravenous dose (40 IU/kg VWF ristocetin cofactor activity [VWF:RCo]) of Wilate or Humate-P in Period 1, and switched to the other study drug in Period 2. Each period was preceded by a washout time of ≥ 7 days. Coagulation factor parameters were analysed at multiple time-points. Of 22 randomised subjects, 20 had evaluable PK profiles, which indicated comparability for VWF antigen and VWF:RCo between Wilate and Humate-P. The reported VWF:RCo average and terminal t1/2 of 10.4 and 15.8 hours (h), respectively, for Wilate and 9.3 h and 12.8 h for Humate-P, were not statistically different. Also, the mean VWF:RCo in vivo recoveries (Wilate 1.89, Humate-P 1.99 IU/dl per IU/kg) were similar between the two replacement therapies. Wilate showed parallel decay curves for VWF:RCo and FVIII clotting activity (FVIII:C) over time, while FVIII:C of Humate-P displayed a plateau between 0 and 12-24 h. This study demonstrated bioequivalent PK properties for VWF between Wilate and Humate-P. The PK profile of Wilate, combined with the 1:1 VWF/FVIII ratio, theoretically should facilitate dosing and laboratory monitoring of VWF replacement to prevent bleeding in individuals with VWD.     

Management of zygomatic complex fracture in armed forces

Introduction: The Armed Forces personnel are exposed to various kinds of injuries due to the nature of their duties. Increase in motorized population without taking protective measures and rise in violence has contributed towards maxillofacial injuries. The aim of this study was to determine the incidence, aetiology and management of injuries resulting in fracture of the Zygomatic complex in Armed Forces personnel and their families.     

Surgical considerations for ‘intrinsic＇ brainstem gliomas： proposal of a modification in classification

BACKGROUND： Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE： To evaluate the clinical, radiological and surgical outcome of 40 focal ＂intrinsic＂ brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS： A total of 40 focal ‘intrinsie’ （＂expanding variety＂） tumors have been operated over a period of 8.5-years （January 1998-June 2007）. Our criteria included patients with （1） well-defined gadolinium enhancing tumor, （2） relatively long duration of symptoms （〉 six months） and （3） good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS： The ＂intrinsic＂ brainstem tumors were classified into three types： Expanding, diffuse infiltrative and pure ventral varieties.     

Der in vitro-Effekt der Hyperthermie auf den Einbau von Nucleinsäurevorläufern in Tumoren und normale Gewebe

Zusammenfassung Die Inkorporation von Präkursoren der Nucleinsäuresynthese wie ³H-Thymidin und ³H-Uridin in Zellen schnell proliferierender Gewebe kann in vitro durch Erhöhung der Temperatur im Inkubationsansatz auf 39,0° C und 41,0° C gehemmt werden. Tumorgewebe, embryonale Gewebe und regenerierende Leber verhalten sich dabei gleichartig. Die Hemmwirkung ist bei allen diesen Geweben proportional sowohl zum Ausmaß als auch zur Dauer der Temperaturerhöhung. Unsere Befunde sprechen außerdem für eine individuelle Wärmesensibilität der untersuchten Tumoren und der anderen rasch proliferierenden Gewebe. Die gleichzeitige Anwendung von Wärme und Bleomycin führt weder beim Jensen Sarkom noch beim Tumor GW-39 zu einem Additionseffekt. Dagegen zeigen Hydroxyharnstoff und Wärme gleichzeitig angewendet eine additive Hemmwirkung auf den ³H-Thymidineinbau in den Tumor GW-39.Da entsprechende Temperatureinflüsse bei ruhenden Geweben nicht nachzuweisen sind, scheint es sich bei der beobachteten Temperaturempfindlichkeit um eine Besonderheit proliferierender Zellsysteme zu handeln. Es ist daher zu klären, ob sie nur unter den Bedingungen des in vitro-Versuches zum Ausdruck kommt oder, ob sie als Indiz einer allgemeinen Thermosensibilität der Nucleinsäurebiosynthese bei schnell proliferierenden Zellverbänden angesehen werden muß.

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In vitro effect of hyperthermia on the incorporation rate of nucleic acid precursors in tumours and normal tissues

Summary The incorporation of precursors of the nucleic acid synthesis, such as ³H-thymidine and ³H-uridine, in cells of rapidly proliferating tissues can be inhibited in vitro by increasing the temperature in the early stages of incubation from 37–39° C and to 41° C. Tumour tissues, embryo tissues and regenerating liver react to this in the same way. The degree of inhibition in all these tissues is proportionate to both the extent and the duration of the increase in temperature. Our findings also speak for an individual sensitivity to heat among the tumours tested and among other rapidly proliferating tissues. The simultaneous application of heat and Bleomycin leads to no additive effect either with Jensen's sarcoma or with tumour GW-39. On the other hand, hydroxyurea and heat applied simultaneously show an additive inhibitory effect on the incorporation of ³H-thymidine in tumour GW-39.As no corresponding influences of temperature are to be proved with non-proliferating tissues, the observed sensitivity to temperature appears to be a peculiarity of proliferating cell systems. The question must therefore be clarified as to whether this sensitivity is expressed only under the conditions of the in vitro experiment or whether it is to be regarded as evidence of a general sensitivity to heat in the nucleic acid biosynthesis of rapidly proliferating groups of cells.

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Mit Unterstützung der Deutschen Forschungsgesellschaft.     

Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals     

Experimental allergic encephalomyelitis: Modulation by intraventricular injection of myelin basic protein

Antigen-induced suppression and therapy of experimental allergic encephalomyelitis in Lewis rats was studied using guinea pig myelin basic protein administered either intravenously or intraventricularly. A small intraventricular dose of basic protein was effective when given shortly before the onset of clinical signs (suppression) as well as when given after the disease (therapy). In contrast, the same amount of basic protein administered intravenously was effective only in the therapy of disease.