We adoptively transferred donor-derived cytomegalovirus (CMV)-specific T-cell lines into 8 stem cell transplant recipients lacking CMV-specific T-cell proliferation. All patients, of whom one was infected by a CMV strain that was genotypically ganciclovir resistant, had received unsuccessful antiviral chemotherapy for more than 4 weeks. CMVspecific lines had been prepared by repetitive stimulation with CMV antigen, which increased the percentage of CMV-specific T cells and ablated alloreactivity completely even against patients mismatched for 1 to 3 HLA antigens. After transfer of 10 7 T cells/m 2 at a median of 120 days (range, 79-479 days) after transplantation, no side effects were noticed. Despite cessation of antiviral chemotherapy, the CMV load dropped significantly in all 7 evaluable patients, with a maximal reduction after a median of 20 days (range, 5-31 days). In 2 patients with high virus load, the antiviral effect was only transient. One of these patients received a second T-cell infusion, which cleared the virus completely. At a median of 11 days after transfer, CMV-specific T-cell proliferation was demonstrated in 6 patients, and an increase in CMV-specific CD4 ؉ T cells was demonstrated in 5 patients. In 6 patients, 1.12 to 41 CMV-specific CD8 ؉ T cells/L blood were detected at a median of 13 days after transfer, with an increase in all patients lacking CMV-specific CD8 ؉ T cells prior to transfer. Hence, anti-CMV cellular therapy was successful in 5 of 7 patients, whereas in 2 of 7 patients, who received an intensified immune suppression at the time of or after T-cell therapy, only transient reductions in virus load were obtained. (Blood. 2002;99: 3916-3922)
Genotyping and antibiotic susceptibility testing were used to analyze Pseudomonas aeruginosa and Burkholderia cepacia strains from sink drain from 14 pediatric patients with cystic fibrosis (CF) and from hospital personnel as part of a 4 week prospective study of strain transmission in a pediatric ward. A total of 87.5% of all washbasin drains were contaminated with P. aeruginosa [102 to 105 colony forming units (CFU)/ml sink fluid], whereas B. cepacia was found only once in a sink drain. From the eight CF patients already infected with P. aeruginosa upon entering the ward, we isolated six genotypes that were identical with strains found in sink drains of the ward. Four of the 16 members of the personnel had one positive P. aeruginosa hand culture. B. cepacia was never found in patients or on personnel hands. Hand washing in contaminated sinks (≥ 103 CFU/ml) led to positive P. aeruginosa or B. cepacia hand cultures. P. aeruginosa or B. cepacia embedded in sputum were transmissable by hand shaking for up to 180 min, whereas both pathogens suspended in physiological saline were transmissable to other hands only up to 30 min. Genotyping of P. aeruginosa revealed strain transmission from CF patients or the environment to other patients or the personnel, as well as one transmission from the environment to a CF patient. The ability of CF sputum to prolong survival of P. aeruginosa and B. cepacia may be important for strain transmission. The results suggest that improved hygienic measures are required to prevent routes of bacterial transmission via the hands and sink drains. Pediatr Pulmonol. 1996; 21:90–100. © 1996 Wiley‐Liss, Inc.
The presented data suggest that gastritis induced by H. pylori may be associated with recurrent abdominal pain and that in Switzerland infections with H. pylori primarily involve persons who are non-Swiss. A combined therapy results in eradication of the bacterium and in improvement of the clinical symptoms in a significant majority of the patients.
Hippocampus volumes have been shown to be decreased in patients with major depression, but volume measurements are inconsistent in patients with bipolar disorder. Both disorders are associated with deficits in hippocampus-mediated cognitive functions. However, the underlying pathophysiology is widely unknown. In this post-mortem study, we used design-based stereology on Nissl-stained serial sections to investigate the number of neurons, oligodendrocytes and astrocytes in substructures of the posterior hippocampus in eight patients with major depression, eight patients with bipolar disorder and ten control patients without a neuropsychiatric disorder. Compared to controls, patients with bipolar disorder had significantly more neurons in the cornu ammonis subfield 1 (CA1) and the subiculum, while the number of oligodendrocytes was higher only in CA1. In patients with major depression, the density of oligodendrocytes was higher in CA2/3, CA4 and the subiculum. The dose of antidepressants correlated with the density and number of oligodendrocytes in CA2/3, indicating that antidepressants may affect our results. Treatment with neuroleptics expressed in chlorpromazine equivalents and benzodiazepines expressed in diazepam equivalents correlated negatively with the number of oligodendrocytes in CA2/3 and CA4, respectively, suggesting that treatment with these drugs do not influence cell number. We did not detect alterations in either volumes of substructures or numbers of astrocytes. Increased cell numbers argue for a denser packing of neurons and oligodendrocytes as a result of a decreased neuropils. This neuropathological process may be based on neurodevelopmental disturbances and may contribute to altered microconnectivity and cognitive deficits in affective disorders.
Aims Current guidelines recommend opportunistic screening for atrial fibrillation (AF) but the prognosis of individuals is unclear. The aim of this investigation is to determine prevalence and 1-year outcome of individuals with screen-detected AF. Methods and results We performed a prospective, pharmacy-based single time point AF screening study in 7107 elderly citizens (≥65 years) using a hand-held, single-lead electrocardiogram (ECG) device. Prevalence of AF was assessed, and data on all-cause death and hospitalization for cardiovascular (CV) causes were collected over a median follow-up of 401 (372; 435) days. Mean age of participants was 74 ± 5.9 years, with 58% (N = 4130) of female sex. Automated heart rhythm analyses identified AF in 432 (6.1%) participants, with newly diagnosed AF in 3.6% of all subjects. During follow-up, 62 participants (0.9%) died and 390 (6.0%) were hospitalized for CV causes. Total mortality was 2.3% in participants with a screen-detected AF and 0.8% in subjects with a normal ECG [hazard ratio (HR) 2.94; 95% confidence interval (CI) 1.49–5.78; P = 0.002]; hospitalization for CV causes occurred in 10.6% and 5.5%, respectively (HR 2.08; 95% CI 1.52–2.84; P < 0.001). Compared with subjects without a history of AF at baseline and a normal ECG, participants with newly diagnosed or known AF had a significantly higher mortality risk with HRs of 2.64 (95% CI 1.05–6.66; P = 0.04) and 2.68 (95% CI 1.44–4.97; P = 0.002), respectively. After multivariable adjustment, screen-detected AF remained a significant predictor of death or hospitalization for CV causes. Conclusion Pharmacy-based, automated AF screening in elderly citizens identified subjects with unknown AF and an excess mortality risk over the next year.
Our pilot study suggests, that creatine supplementation should be further evaluated as a possible clinically beneficial adjuvant therapy for patients with CF to increase muscle strength, body-weight and well-being.
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