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Biomedical subjects

T Grünewald

Publications and source records attributed to T Grünewald.

At least 19 recordsLinked to original sources

[Management of bioterroristic attacks with dangerous infectious agents].

The ongoing discussion on threats by terrorist attacks leads to a realignment of tasks and responsibilities within the health care system. Especially the public health services are developing from exercising mainly an advisory function to becoming an integral part in disaster response to devastating biological scenarios. Recent risk assessment recommends authoritative integration of public health officials into disaster response planning and to define their role inside the command and control structures of disaster management. Interdisciplinary networks of public health services, medical treatment centres, emergency medical services, reference laboratories and hospital hygiene services have appeared to be successful in the management of life-threatening, contagious diseases and unexpected bioterrorist incidents as well. In March 2003 the "StAKoB" was established as a permanent working group of the centres for prepared ness and treatment. Major objectives of the working group are ex change of information, mutual support in cases of emergency and standardisation in staff training.

Biological Warfare↗

Effectiveness of twice-weekly pyrimethamine-sulfadoxine as primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in patients with advanced HIV infection.

The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus. All patients had a CD4+ T-lymphocyte count of less than 100 cells/microl at study entry. Efficacy in this single-arm open-label prospective study was analyzed on an as-treated basis. No patient received highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. PCP developed in four patients, one of whom had been noncompliant. No PCP episode occurred in the first year. Probabilities of freedom from PCP were 0.97 (95%CI, 0.92-1) after 24 months and 0.93 (95%CI, 0.84-1) after 36 months. Of 74 (69.8%) patients positive for anti-toxoplasma IgG antibodies, one noncompliant patient developed toxoplasmic encephalitis after 24 months. Allergic reactions were observed in 18 (17%) patients and resulted in permanent discontinuation in 7 (6.6%) patients. One (0.9%) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction (Stevens-Johnson syndrome). The median survival of study participants was 29 months, with relentless progression of AIDS accounting for most deaths. The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance. Efficacy and safety compare favorably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens.

AIDS-Related Opportunistic Infections↗

Novel mitochondrial DNA mutations in Parkinson's disease.

Despite the recent discovery of several chromosomal gene mutations in familial Parkinson's disease (PD) the genetic background for idiopathic PD remains to be elusive. Since the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) action on dopaminergic neuronal cells and the specific decrease of mitochondrial complex I activity in substantia nigra of PD patients mitochondrial biochemistry and genetics emerged to become Pandora's box in the pathogenesis of PD. One approach was to establish the potential role of defective mitochondrial DNA (mtDNA). As complex I genes are the most vulnerable part of mtDNA we analyzed the mitochondrial MTND1 and MTND2 genes of 10 substantia nigra and 85 platelet samples from PD patients. We were uneventful to detect heteroplasmic base changes even applying techniques able to visualize mutations with low percentage of heteroplasmy but here we report novel homoplasmic base changes. These results add further evidence that there are no inherited disease specific mtDNA mutations, hence individual homoplasmic mutations or very low grade heteroplasmic mutations in the vicinity of mitochondrial metabolism and oxidative stress may contribute to selective neuronal vulnerability in PD.

Base Sequence↗

[Nosocomial epidemiology and transmission of Clostridium difficile infection].

BACKGROUND: Clostridium difficile is of growing importance as a hospital-acquired pathogen. Pseudomembraneous colitis is the main clinical disease. Transmission and epidemiological features are not yet fully understood. PATIENTS AND METHODS: Stool samples from 1164 individuals (571 women and 593 men) attending were examined for the presence of C. difficile. Follow-up examinations and molecular typing methods were used for the detection nosocomial transmissions. Additionally, hospital-borne environmental samples as well as staff samples were tested. RESULTS: Incidence of C. difficile infection was 8.4%. Nearly all patients (92.9%) had antibiotics given. Using molecular typing nosocomial transmission was evident. Though, environmental samples in general had a low positivity, toilet chairs were contaminated in 15.4% and may be a potential source of transmission. Staff was positive in only one case. CONCLUSIONS: Prevention of infections with C. difficile becomes to be a major threat for the clinical and hygienic management.

Adolescent↗

Twice-weekly pyrimethamine-sulfadoxine effectively prevents Pneumocystis carinii pneumonia relapse and toxoplasmic encephalitis in patients with AIDS.

OBJECTIVE: To evaluate the safety and efficacy of a fixed 25mg pyrimethamine--500mg sulfadoxine combination plus 15mg folinic acid given twice weekly for the prevention of relapses of Pneumocystis carinii pneumonia (PCP) and primary episodes of toxoplasmic encephalitis. METHODS: Ninety-five HIV-infected patients with successfully treated PCP and without history of toxoplasmic encephalitis were enrolled between January 1990 and October 1995 in a single-arm open-label prospective study. No patient was receiving highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. Efficacy was analysed on an "as-treated" basis. RESULTS: Five patients (5.3%) suffered a PCP relapse while on study medication, three of whom had been non-compliant. No relapse occurred in the first year. Probabilities of freedom from relapse were 0.96 after 24 months and 0.90 after 36 months. Of 69 patients positive for anti-toxoplasma IgG antibodies, one (1.5%) developed cerebral lesions compatible with toxoplasmic encephalitis after 50 months. Cutaneous allergic reactions were observed in 16 patients (16.8%) resulting in permanent discontinuation in six patients (6.3%). Two patients (2.1%) developed serious adverse reactions (Stevens-Johnson syndrome), both of whom had continued prophylaxis despite progressive hypersensitivity reactions. CONCLUSIONS: The prophylactic regimen used is effective in preventing PCP relapses and toxoplasmic encephalitis. The regimen appears to be safe. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance of the regimen. Efficacy and safety compare favourably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients unable to tolerate approved regimens.

AIDS-Related Opportunistic Infections↗

[Tuberculous coxitis. Case report and surgical treatment].

The possibility of a specific origin of joint infection should be considered in finding the diagnosis. This is demonstrated in a case of tuberculosis of the hip treated in the Dept. of Trauma Surgery in collaboration with the Medical Dept. of the Klinikum Minden. Microbiological and imaging examinations are essential to plan and perform a combined therapy of hip arthroplasty and concommitant medical antituberculous therapy. In accordance to a literature review, this procedure proved successful for both eliminating the local infection and the functional outcome of the operation.

Aged↗

[Primary palliative treatment of malignant gastric outlet obstruction with a self-expanding metal stent].

BACKGROUND AND OBJECTIVE: A high operative mortality, diffuse local tumor growth and abnormal wound healing are significant risk factors in the palliative surgical treatment of gastric outlet obstruction caused by a malignant tumor. This study was undertaken to evaluate the use of self-expanding metal stents as an alternative. PATIENTS AND METHODS: Over a period of 33 months, nine previously unoperated patients (three women, six men; mean age 71.4 [66-76] years) with gastric outlet obstruction by a malignant tumor underwent endoscopic implantation of an uncoated self-expanding nitinol Ultraflex stent. The stent's length was 7 and 10 cm, respectively, the length of the carrier catheter was 92 cm. The stent was implanted after balloon dilatation of the stenosis and marking the distal tumor margin with lipiodol injected over a guide-wire under fluoroscopic control. RESULTS: The implantation was successful in only two of the first five patients, but after modifying the method of stent release in three of the four subsequent patients. All patients reported an improved quality of life. One patient died after 10 days of the underlying malignancy. There were no complications associated with the implantation. CONCLUSIONS: Insertion of a self-expanding metal stent can provide palliation in patients with inoperable gastric outlet stenosis due to malignant tumour. The number of successful implantations can probably be increased by optimizing some of the devices used, for example by lengthening the carrier catheter.

Aged↗

Anti-phospholipid antibodies and CD5+ B cells in HIV infection.

This cross-sectional study evaluates the correlation between anti-phospholipid antibodies and CD5+ B cells in 110 patients infected with HIV-1. There were 89.1% of the patients who had IgG antibodies against cardiolipin and phosphatidylserine. The prevalence of IgM and IgA antibodies was < 22%. AIDS was associated with lower frequencies of IgM antibodies against cardiolipin (P = 0.05) and IgG-antibodies against cardiolipin and phosphatidylserine (P = 0.011). Drug users had higher IgM antibodies against phospholipids than patients from other risk groups (P = 0.02). A history of thromboembolic events was not accompanied by higher levels of anti-phospholipid antibodies (P > 0.2). No correlation between anti-phospholipid antibodies and CD5+ B cells was detected. Percentage part of CD5+ B lymphocytes was elevated in all patients and absolute CD4+ T lymphocyte counts and HIV p24 antigen were inversely correlated. In advanced disease a significant reduction of anti-phospholipid antibodies was contrasted with persistent elevation of CD5+ B lymphocytes. These observations may reflect immunological dysfunction involving apoptosis and endothelial damage rather than polyclonal B cell hyperstimulation. A possible explanation would be that in HIV infection an increased rate of spontaneous apoptosis in peripheral blood lymphocytes is accompanied by functional and structural changes of mitochondria. Therefore, structurally altered mitochondrial phospholipids could serve as antigen to induce specific humoral immune responses.

Adolescent↗

Thoracic computed tomography of patients infected with the human immunodeficiency virus: relevance for the course of disease.

To determine the diagnostic accuracy and prognostic implications of thoracic computed tomography (CT) in patients with human immunodeficiency virus infection (HIV), CT scans of 154 HIV-infected patients (mean age, 41 years; range 23-65 years; 18 female) with suspicion of pulmonary disease were retrospectively reviewed for signs of disease by two investigators blinded to clinical data other than positive HIV serology. Abnormal CT features were correlated with CD4-T lymphocyte count, histologic or microbiologic diagnosis, and survival. Computed tomography detected features of pulmonary disease in 133 patients. A recent chest film was available in 96 patients, and it was normal in 16. In 17 of 99 patients (17%) with histologic or microbiologic correlation, pathologic CT features could be demonstrated, though histologic and microbiological studies were unrevealing. Median survival was 649 days. Confluent pulmonary infiltrates and bilateral masses on CT indicated advanced disease with a median survival of 115 days (n = 11, p = 0.0005) and 174 days (n = 15, p < 0.0001), respectively. The authors concluded that thoracic CT detects pulmonary lesions in an appreciable portion of HIV-infected patients in whom chest radiographs, microbiologic methods, or histology failed to establish a diagnosis, and that CT findings allow for an estimation of patient survival in acquired immunodeficiency syndrome.

Adult↗

A single dose of ceftriaxone administered 30 minutes before percutaneous endoscopic gastrostomy significantly reduces local and systemic infective complications.

OBJECTIVE: The aim of this study was to determine the efficacy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG). METHODS: An open prospective, randomised, multicenter study was conducted in 141 patients; 72 received ceftriaxone 1 g i.v. 30 min preintervention, and 69 received no study medication. A standardized protocol was followed for PEG preparation, insertion, and aftercare; all patients received a 15-Fr gastrostomy tube. Follow-up of local and systemic infection and clinical course was continued to postintervention day 10. An aggregate erythema and exudation score >3 or the presence of pus was taken as indicative of peristomal infection. The pharmacoeconomics of antibiotic use were also examined. RESULTS: In no-prophylaxis patients, wound infection rates were 25% on day 4 and 26.4% on day 10, versus 10.1% (p = 0.03) and 14.5% (p = 0.10), respectively, in prophylaxis patients. Results were disproportionally better in tumor patients: systemic infection rates were 16.7% versus 5.8% in no-prophylaxis versus prophylaxis patients (p = 0.045), and overall infection rates 38.9% versus 17.4%, respectively (p = 0.046). Pneumonia was more frequent in patients with underlying neurological disease. Antibiotic costs were the same in both groups (p = 0.792). CONCLUSIONS: Single dose ceftriaxone 1 g is an effective prophylaxis against local and systemic infection after PEG.

Aged↗

Bioenergetics in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder with relentless course and prototypical clinical symptoms. In 1993 HD was associated with an expanded CAG triplet repeat stretch on chromosome 4 in the coding region of its target protein, huntington. The length of the resulting polyglutamine++ extensions correlates with lower age of onset and a higher density of ubiquitin-positive neuronal intranuclear inclusions. Recently it has been proposed that mutant huntington induces progressive neuronal cell death by an apoptotic mechanism. There is strong evidence that disturbances in cellular energy homeostasis and oxidative damage contribute to neurodegeneration. This review will summarize and discuss the current concepts that point towards an involvement of free radical-induced oxidative stress, glutamate excitotoxicity and mitochondrial respiratory chain defects in pathogenesis of HD.

Animals↗