Effect of BMI and fat mass on HIV disease progression in HIV-infected, antiretroviral treatment-naïve adults in Botswana.

An obesity paradox has been proposed in many conditions including HIV. Studies conducted to investigate obesity and its effect on HIV disease progression have been inconclusive and are lacking for African settings. This study investigated the relationship between overweight/obesity (BMI≥25 kg/m2) and HIV disease progression in HIV+ asymptomatic adults not on antiretroviral treatment (ART) in Botswana over 18 months. A cohort study in asymptomatic, ART-naïve, HIV+ adults included 217 participants, 139 with BMI of 18·0-24·9 kg/m2 and seventy-eight participants with BMI≥25 kg/m2. The primary outcome was time to event (≥25 % decrease in cluster of differentiation 4 (CD4) cell count) during 18 months of follow-up; secondary outcomes were time to event of CD4 cell count<250 cells/µl and AIDS-defining conditions. Proportional survival hazard models were used to compare hazard ratios (HR) on time to events of HIV disease progression over 18 months. Higher baseline BMI was associated with significantly lower risk of an AIDS-defining condition during the follow-up (HR 0·218; 95 % CI 0·068, 0·701; P=0·011). Higher fat mass at baseline was also significantly associated with decreased risk of AIDS-defining conditions during the follow-up (HR 0·855; 95 % CI 0·741, 0·987; P=0·033) and the combined outcome of having CD4 cell count≤250/µl and AIDS-defining conditions, whichever occurred earlier (HR 0·918; 95 % CI 0·847, 0·994; P=0·036). All models were adjusted for covariates. Higher BMI and fat mass among the HIV-infected, ART-naïve participants were associated with slower disease progression. Mechanistic research is needed to evaluate the association between BMI, fat mass and HIV disease progression.

Interactions of poly (anhydride) nanoparticles with macrophages in light of their vaccine adjuvant properties.

Understanding how nanoparticles are formed and how those processes ultimately determine the nanoparticles' properties and their impact on their capture by immune cells is key in vaccination studies. Accordingly, we wanted to evaluate how the previously described poly (anhydride)-based nanoparticles of the copolymer of methyl vinyl ether and maleic anhydride (NP) interact with macrophages, and how this process depends on the physicochemical properties derived from the method of preparation. First, we studied the influence of the desolvation and drying processes used to obtain the nanoparticles. NP prepared by the desolvation of the polymers in acetone with a mixture of ethanol and water yielded higher mean diameters than those obtained in the presence of water (250nm vs. 180nm). In addition, nanoparticles dried by lyophilization presented higher negative zeta potentials than those dried by spray-drying (-47mV vs. -35mV). Second, the influence of the NP formulation on the phagocytosis by J774 murine macrophage-like cell line was investigated. The data indicated that NPs prepared in the presence of water were at least three-times more efficiently internalized by cells than NPs prepared with the mixture of ethanol and water. Besides, lyophilized nanoparticles appeared to be more efficiently taken up by J744 cells than those dried by spray-drying. To further understand the specific mechanisms involved in the cellular internalization of NPs, different pharmacological inhibitors were used to interfere with specific uptake pathways. Results suggest that the NP formulations, particularly, nanoparticles prepared by the addition of ethanol:water, are internalized by the clathrin-mediated endocytosis, rather than caveolae-mediated mechanisms, supporting their previously described vaccine adjuvant properties.

Conceptional considerations for a German influenza pandemic preparedness plan.

A pandemic appearance of influenza A virus must be expected at any time. The limitations of health preserving and life-saving resources, which will inevitably be reached in the event of a pandemic, will be accompanied by ethical and possibly social conflicts, which can be lessened or resolved only through precautionary planning, clearly specified competencies and transparent decisions within a social consensus. In case of a shortage of vaccines and virostatic agents, decisions will have to be made with regard to the segment of the population that absolutely must be vaccinated. It is currently estimated that a (monovalent) vaccine developed for a new pandemic strain would only suffice for the single vaccination of approximately half of the German population after a year; only 10-14 million vaccine dosages would be available to provide basic immunization and single boosters to personnel required to maintain basic medical care and essential infrastructure after half a year. In the event of local influenza outbreaks, antiviral chemotherapeutic agents could be used to close the gap until a vaccine can become effective. Even if suitable influenza vaccines and virostatic agents are not sufficiently available at the start of a pandemic, it is still possible to at least prevent an outbreak of two of the most feared secondary infections that accompany influenza: pneumococcal pneumonia or meningitis and illnesses resulting from Haemophilus influenzae. Agreement still needs to be reached with manufacturers for guaranteeing the necessary vaccine production or ensuring that they have a sufficient stock to meet the minimum demand for antiviral agents and agents for symptomatic treatment.

[Studies on the importance of tick-borne encephalitis in Rhineland-Pfalz]. / Untersuchungen zur Bedeutung der Frühsommer-Meningoenzephalitis in Rheinland-Pfalz.

Within the scope of a prospective clinical study during 2001 in Rhineland-Palatinate specimen from sera and cerebrospinal fluids of 163 patients with suspected meningitis were controlled in an enzyme immunoassay concerning a TBE infection. Questionable results were checked via a neutralisation test. In no case such an infection was confirmed. No virus specific nucleic acids could be detected in 998 nymphs and adults of Ixodes ricinus in an additional investigation in 2000. Therefore Rhineland-Palatinate has to be considered as a region with low virus prevalence. A general recommendation for vaccination is not necessary.

[Influence of information campaigns on the vaccination immunity among the population of a small town area - seroepidemiological results of the 'Wittlich Vaccination Study']. / Einfluss von Informationsmassnahmen auf die Impfimmunität der Bevölkerung einer kleinstädtischen Region - Seroepidemiologische Ergebnisse der "Impfstudie Wittlich" -

In the course of the three-phase 'Wittlich Vaccination Study' the population immunity against tetanus, diphtheria and poliomyelitis was controlled in all age groups of the regional population. Antibody measuring was done in specific validated enzyme immunoassays and neutralisation tests. After performing several campaigns for training and informing medical staff and the population about vaccinations the effect of these campaigns was checked in an additional control of the population immunity. The part of not or only partially protected participants decreased for tetanus from 36.7 % to 2.8 % and for diphtheria from 61 % to 51 %. The gap in population immunity was reduced for polio virus type 1 from 6.7 % to 3.1 %, for polio virus type 2 from 6.2 % to 2.5 % and for polio virus type 3 from 13.2 % to 3.6 %. The study design can be transferred to regions with comparable structure of their population.

Influenza pandemic: preparedness planning in Germany.

The following conceptual framework formed the basis for a common decision made by the health ministers of Germany's 16 federal states to set up an influenza pandemic preparedness plan. The worst case scenario was used, on the basis of the data from the pandemic of 'Spanish flu', in 1918-20. The priority groups for vaccination were assessed, as well as the potentially available antiviral treatments. National policies could be highly improved by a common European view.

Feasibility of an ultrasound service on district health care level in Botswana.

OBJECTIVE: To assess the clinical benefit and financial feasibility of an ultrasound service in a district hospital in Botswana. METHOD: An ultrasound service was established in the study hospital. Clinical and ultrasound-aided diagnoses were compared in patients who met eligibility criteria laid down in an indication list. RESULTS: We enrolled 2309 patients over 18 months. The most frequent indications for ultrasound were pregnancy-related diagnoses followed by gynaecological and hepato-biliary disorders. Ultrasound assistance improved case management in 696 cases (30%) and led to an immediate change in management in 151 patients. Ultrasound diagnosis was used as gold standard to assess the accuracy of the clinical diagnosis of incomplete abortion (sensitivity 24%; positive predictive value, PPV 66%), pelvic mass (sensitivity 53%; PPV 69%), ectopic pregnancy (sensitivity 75%; PPV 28%), and gall bladder stones (sensitivity 30%; PPV 32%). CONCLUSIONS: Ultrasound improved case management for a wide diversity of clinical problems encountered on district health care level. The service proved to be affordable for the Botswana health care system.

[Skelefon framework concept for defence against risks in unusual epidemics: steps by public health offices]. / Rahmenkonzept zur Gefahrenabwehr bei aussergewöhnlichen Seuchengeschehen - Massnahmen des Gesundheitsamtes -

Necessary anti-epidemic measures have to be promulgated or taken immediately in case of a suspected case of pneumonic plague or a viral haemorrhagic fever which can be transmitted from human to human. A live threatening highly contagious infectious disease may occur at any place in Germany. Therefore each health office should have the relevant information on the available infrastructure in Germany concerning treatment and competence centres, diagnostic laboratories, dispatch of samples and patient transportation. They should also be able to give qualified recommendations to physicians and hospitals concerning the necessary measures in such a case. Contacts at risk have to be notified. Based on a risk assessment and the special living conditions of the contact person they should decide if and which further measures have to be initiated, especially in the case of post-exposure prophylaxis, separation and prohibition of work. In general, imported cases of dangerous infectious diseases quickly find the interest of the media, including all the implications resulting from this. A well-organized cooperation with the media and public relations helps to avoid unnecessary irritations and panic.

Elevated tumor necrosis factor-alpha activation of human immunodeficiency virus type 1 subtype C in Southern Africa is associated with an NF-kappaB enhancer gain-of-function.

The human immunodeficiency virus type 1 (HIV-1) epidemic within southern Africa is predominantly associated with the HIV-1C subtype. Functional analysis of the enhancer region within the long terminal repeat (LTR) indicates that HIV-1C isolates have >/=3 NF-kappaB binding sites, unlike other subtypes, which have only 1 or 2 sites. A correlation was shown between NF-kappaB enhancer configuration and responsiveness to the proinflammatory cytokine tumor necrosis factor (TNF)-alpha within the context of naturally occurring subtype LTRs, subtype-specific NF-kappaB enhancer regions cloned upstream of an isogenic HXB2 core promoter or a heterologous SV40 minimal promoter, and full-genome subtype clones. In all cases, TNF-alpha activation was correlated with the subtype configuration of the NF-kappaB enhancer. Whether the naturally occurring gain-of-function in the NF-kappaB enhancer of HIV-1C observed in this study can provide a selective advantage for the virus in vivo remains to be determined and warrants further study.

Validity and reliability of measurements obtained with an "activity monitor" in people with and without a transtibial amputation.

BACKGROUND AND PURPOSE: In this study, the validity and reliability of measurements obtained with an "Activity Monitor" (AM) were examined. The instrument is designed to monitor ambulatory activity by use of accelerometer signals, and it detects several activities associated with mobility (standing, sitting, lying, transitions, movement-related activities). SUBJECTS: Four men with a transtibial amputation and 4 men without a transtibial amputation participated. METHODS: The subjects performed normal daily activities, during which accelerations were measured and videotape recording were made (reference method). Validity was assessed by calculating agreement scores between the AM output and the videotape recordings and by comparing the number of transitions and the duration of activities determined by both methods. RESULTS: The overall agreement between the AM output and the videotape recordings was 90%. Other agreement scores, in addition to the determination of the number of transitions and the duration of activities, were generally within a range of error of 0% to 10%. CONCLUSION AND DISCUSSION: The reliability and validity of the AM measurements appeared to be good, which supports its potential use in rehabilitation and physical therapy. [Bussmann HBJ, Reuvekamp PJ, Veltink PH, et al. Validity and reliability of measurements obtained with an "Activity Monitor" in people with and without a transtibial amputation.

A novel tool to quantify physical activities: ambulatory accelerometry in psychopharmacology.

Accelerometry by means of body-mounted piezoresistive sensors was evaluated as a new method to quantify physical activities (body posture and physical and locomotor activity) in relation to the sedative and cardiovascular effects of benzodiazepines, in an ambulatory study. In a double-blind, randomized, crossover study, 12 healthy men received either an oral dose of 2 mg lorazepam, 0.5 mg alprazolam, 1 mg alprazolam, or a placebo on 4 different days. By means of a portable digital recorder, each day 4 hours of continuous measurements of accelerometer signals and heart rate were performed in a living room in the hospital. Changes in subjective sleepiness were assessed at the beginning, halfway, and at the end of the recording period. A separate validation study of the ambulatory environment was performed in three subjects, in which computer classification of activities based on accelerometry was compared with visual evaluation of simultaneously recorded videotapes. In our validation study, comparison of the computer classification with visual analysis based on videotapes revealed an overall agreement for spontaneous and standardized activities of 88% and 96%, respectively. In our pharmacological study, the subjects spent more time in the lying position (p < 0.01) and less time in the sitting position (p < 0.01) after benzodiazepine administration; the effects were strongest for lorazepam. Motility during static activities was reduced (p < 0.025), with motility after lorazepam administration being lowest. Both lorazepam and alprazolam (0.5 and 1 mg) increased subjective sleepiness (p < 0.01). On average , lorazepam induced an overall increase in mean heart rate of about 6%, whereas alprazolam reduced mean heart rate by 2% versus placebo (p < 0.01); the effects were not dependent on posture. The validation study showed that accelerometry forms a reliable method to quantify aspects of normal daily activities. Our pharmacological study revealed that quantification of body postures, physical activity, and motility by means of ambulatory accelerometry proves to be an objective and promising tool to evaluate the psychological and cardiovascular effects of (psycho) pharmaca in relation to the postural and mobility activities of normal daily life.

Detection of static and dynamic activities using uniaxial accelerometers.

Rehabilitation treatment may be improved by objective analysis of activities of daily living. For this reason, the feasibility of distinguishing several static and dynamic activities (standing, sitting, lying, walking, ascending stairs, descending stairs, cycling) using a small set of two or three uniaxial accelerometers signals can be measured with a portable data acquisition system, which potentially makes it possible to perform online detection of static and dynamic activities in the home environment. However, the procedures described in this paper have yet to be evaluated in the home environment. Experiments were conducted on ten healthy subjects, with accelerometers mounted on several positions and orientations on the body, performing static and dynamic activities according to a fixed protocol. Specifically, accelerometers on the sternum and thigh were evaluated. These accelerometers were oriented in the sagittal plane, perpendicular to the long axis of the segment (tangential), or along this axis (radial). First, discrimination between the static or dynamic character of activities was investigated. This appeared to be feasible using an rms-detector applied on the signal of one sensor tangentially mounted on the thigh. Second, the distinction between static activities was investigated. Standing, sitting, lying supine, on a side and prone could be distinguished by observing the static signals of two accelerometers, one mounted tangentially on the thigh, and the second mounted radially on the sternum. Third, the distinction between the cyclical dynamic activities walking, stair ascent, stair descent and cycling was investigated. The discriminating potentials of several features of the accelerometer signals were assessed: the mean value, the standard deviation, the cycle time and the morphology. Signal morphology was expressed by the maximal cross-correlation coefficients with template signals for the different dynamic activities. The mean signal values and signal morphology of accelerometers mounted tangentially on the thigh and the sternum appeared to contribute to the discrimination of dynamic activities with varying detection performances. The standard deviation of the signal and the cycle time were primarily related to the speed of the dynamic activities, and did not contribute to the discrimination of the activities. Therefore, discrimination of dynamic activities on the basis of the combined evaluation of the mean signal value and signal morphology is proposed.

[Variability of clinical symptoms in neuronal intestinal dysplasia]. / Variabilität klinischer Symptome bei neuronaler intestinaler Dysplasie.

Neuronal intestinal dysplasia is defined as a structural disorder of the innervation of the gut which clinically resembles Hirschsprung's disease. Between 1977 and 1988 12 patients were diagnosed by enzyme histochemistry. In 3 of these patients Hirschsprung's disease was associated. Constipation was the main symptom in 6 patients with neuronal intestinal disease and in all three patients with associated Hirschsprung's disease. The other patients firstly presented with an enterocolitis, a congenital atresia of the jejunum and a chronic enteritis with malabsorption. The wide clinical variability and the lack of a clear therapeutic management valid for all patients is conspicuous.

[Is myositis in chronic polyarthritis using d-penicillamine drug-induced?]. / Myositis bei chronischer Polyarthritis unter d-Penicillamin, medikamentös induziert?

Myositis was diagnosed twenty months after starting treatment with d-penicillamine in a patient suffering from uncomplicated rheumatoid arthritis for nearly three years. The diagnosis was established by electromyographic investigation and by biopsy. In this patient d-penicillamine had been intermittently increased to a dose over 1 g per day and then reduced because of mild proteinuria. The appearance of myositis during d-penicillamine therapy, its immediate regression on discontinuing the drug, and the absence of signs of vasculitis or other extraarticular manifestations in this patient suggest that this complication may be drug-induced. The clinical course is compared with isolated cases reported in the literature. The significance of this rare side effect is discussed.

Investigations of the sensory blockade effect of perineurally injected ethanol on the tail nerve of the mouse.

The effect of an alcohol block on the conduction of sensory stimuli in the tail nerve of the mouse was investigated using the perineural injection of solutions of ethanol (35, 40 and 45%). One hundred and fifty white mice of either sex were given 2 X 0.03 ml of the relevant alcohol solution into both sides of the tail. Before and after the injections repeated sensory conduction measurements were made using the rat tail method. Using 35% ethanol a temporary block of pain conduction could be achieved in both sexes. By increasing the concentration to 40 or 45%, a prolongation of the blocking effect and an increase in the accompanying increase of the pain threshold was observed in some animals. On the other hand, in some animals, temporary motor paralysis occurred following 35% ethanol, and this effect became more frequent and severe using 40 and 45% ethanol. A further increase in the alcohol concentration was not possible because of the occurrence of anatomical changes in the tails of the experimental animals.