Die Wirkung von Erythromycin in Kombination mit anderen Antibiotica auf Escherichia Coli

Journal of Molecular Medicine - An vier verschiedenen Escherichia Colistämmen, die alle mehr oder weniger starke Erythromycin-Resistenz aufwiesen, wurde der Einfluß von Erythromycin in...     

Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans

Pancreatic tissue obtained by hemipancreatectomy from healthy living related donors has been transplanted into recipients with Type I diabetes mellitus. To determine the metabolic consequences of this procedure for the donors, we carried out oral glucose-tolerance testing and 24-hour monitoring of serum glucose levels and urinary C-peptide excretion as a measure of insulin secretion in 28 donors, both before and one year after hemipancreatectomy. The mean fasting serum glucose level was significantly higher one year after the procedure (mean +/- SD, 5.4 +/- 0.9 vs. 4.9 +/- 0.5 mmol per liter; P less than 0.003), as was the serum glucose value two hours after the administration of glucose (8.7 +/- 2.9 vs. 6.5 +/- 1.0 mmol per liter; P less than 0.001). The fasting serum insulin level was significantly lower one year after hemipancreatectomy (33.0 +/- 21.6 vs. 38.4 +/- 21.6 pmol per liter; P less than 0.05), as was the area under the insulin curves during the oral glucose-tolerance test (52,554 +/- 22,320 vs. 76,230 +/- 33,354 pmol per liter per minute; P less than 0.04). The mean 24-hour serum glucose-profile value was higher at one year, and the 24-hour urinary C-peptide excretion was lower in the 17 donors who underwent these studies. Seven of the 28 donors had abnormal glucose tolerance one year after hemipancreatectomy; however, insulin secretion in these 7 donors was indistinguishable from that in the 21 donors who had normal glucose tolerance. All 28 donors had fasting serum glucose concentrations lower than 7.8 mmol per liter, and their mean 24-hour plasma glucose levels remained within the normal range. We conclude that in healthy donors hemipancreatectomy results in a deterioration of insulin secretion and glucose tolerance, as measured one year later. Further study is required to ascertain whether the development of clinical diabetes mellitus is a risk inherent in hemipancreatectomy.     

Acute hypervolemia does not improve arterial oxygenation in maximally exercising thoroughbred horses

Recently, it was reported that acute hypervolemia improves arterial oxygen tension in human athletes known to experience exercise-induced arterial hypoxemia. Since exercise-induced arterial hypoxemia is routinely observed in racehorses and is known to limit performance, we examined whether pre-exercise induction of acute hypervolemia would similarly benefit arterial oxygenation in maximally exercising thoroughbred horses. Two sets of experiments, namely, placebo [intravenous (IV) physiological saline] and acute hypervolemia (IV 7.2% NaCl, causing an 18.2% expansion of plasma volume) studies were carried out in random order on 13 healthy, exercise-trained thoroughbred horses, 7 days apart. An incremental exercise protocol leading to 120 s of galloping at 14 m s^–1 on a 3.5% uphill incline was used. Galloping at this workload elicited maximal heart rate and induced pulmonary hemorrhage in all horses in both treatments. In the placebo study, arterial oxygen tension decreased to 76.1 (2) mmHg (P<0.0001) at 30 s of maximal exertion, but further significant changes did not occur as exercise duration increased to 120 s [arterial oxygen tension 72.4 (2) mmHg]. A significant arterial hypoxemia also developed in galloping horses in the acute hypervolemia study [arterial oxygen tension at 30 and 120 s was 76.7 (1.7) and 71.9 (1.6) mmHg, respectively], but significant differences between treatments could not be demonstrated. In both treatments, a similar desaturation of arterial hemoglobin was also observed at 30 s of maximal exercise, which intensified with increasing exercise duration as hyperthermia, acidosis and hypercapnia intensified. Thus, acute expansion of plasma volume did not benefit arterial oxygenation in maximally exercising thoroughbred horses.     

Charcot on Parkinson's disease

Charcot saluted Parkinson for his early observations, but condemned his use of the term "paralysis agitans." He emphasized that patients were neither dramatically weak nor were they necessarily plagued with tremor. Charcot suggested the name "Parkinson's disease," although he could not resist the comment in his amphitheater lecture series at the Salpêtrière that French physicians (unnamed) had probably described the disorder before 1817. Tremor, rigidity, postural instability, and bradykinesia were all recognized by Charcot. He classified the disorder as a "névrose," meaning a neurologic disorder without a known pathologic lesion, and found little benefit from therapies available at the time, including belladonna and ergot products.     

Complete genomic screen in Parkinson disease: evidence for multiple genes.

CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.     

Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.     

The effects of surface roughness and polymethylmethacrylate precoating on the radiographic and clinical results of the Iowa hip prosthesis. A study of patients less than fifty years old

BACKGROUND: The purpose of the present study was to compare the results associated with two different surface finishes (bead-blasted and grit-blasted) for Iowa femoral components used in total hip arthroplasties performed between January 1979 and June 1991 in patients who were less than fifty years old. METHODS: Between January 1979 and December 1985, thirty-six primary total hip replacements were performed in twenty-five patients with insertion of a bead-blasted Iowa femoral component (average surface roughness, 0.8 micrometer) with cement and insertion of a titanium-backed acetabular component (thirty-five hips) or non-metal-backed acetabular component (one hip) with cement. Between January 1986 and June 1991, forty-five primary total hip replacements were performed in thirty-seven patients with use of a precoated grit-blasted Iowa femoral component (average surface roughness, 2.1 micrometers) and a Harris-Galante-I porous ingrowth acetabular component (forty-one hips) or an Osteonics component (four hips). The only change in the design of the femoral component (other than the surface finish) between the two consecutive series was the addition of polymethylmethacrylate precoating to the proximal third of all forty-five grit-blasted stems and modularity of the femoral head of the last eight grit-blasted stems. RESULTS: No hip was lost to follow-up. The duration of radiographic follow-up of the hips treated with the bead-blasted component averaged 11.3 years (range, ten to sixteen years) postoperatively, whereas that of the hips treated with the precoated grit-blasted component averaged 8.2 years (range, five to eleven years). Two (6 percent) of the bead-blasted femoral components were revised because of aseptic loosening compared with eight (18 percent) of the precoated grit-blasted components. Four bead-blasted components (11 percent) were either radiographically loose or were revised because of loosening compared with eleven precoated grit-blasted components (24 percent). Kaplan-Meier survivorship curves evaluated with log-rank analysis revealed that the bead-blasted Iowa femoral components were revised because of aseptic loosening (p = 0.0184) and were radiographically loose (p = 0.0068) less often than the precoated grit-blasted Iowa femoral components. CONCLUSIONS: The findings of the present study have led the senior ones of us to resume using femoral components with a polished surface and fixed with cement.     

Switching dopamine agonists in advanced Parkinson's disease: is rapid titration preferable to slow?

BACKGROUND: New dopamine agonists are available, but no study has examined safe and effective ways to switch from one agonist to another. OBJECTIVE: To compare rapid- versus slow-titration schedules for starting a new dopamine agonist in patients already on chronic agonist therapy for Parkinson's disease. METHODS: Sixteen patients on stable carbidopa/levodopa and a dopamine agonist (bromocriptine or pergolide) switched to pramipexole using a conversion calculation of 1:1 for pergolide dose and 10:1 for bromocriptine dose. Patients were randomized to two titration schedules-either slow titration, following the package insert and taking up to 8 weeks to reach their equivalent dosage (8 patients), or rapid titration, receiving the full converted dose the day after stopping the former agonist (8 patients) with subsequent weekly dose adjustments. Using a blinded observer, the primary outcome variable was the time required to a Unified Parkinson's Disease Rating Scale (UPDRS) motor score superior to baseline without increased adverse effects. RESULTS: Both groups showed equivalent and statistically significant improvement after switching to the new agonist. The mean time to reach a UPDRS score that was superior to baseline without increased adverse effects was significantly shorter in the rapid-titration group (mean 2.1 weeks versus 5.3 weeks). Furthermore, with slow titration two patients experienced enhanced parkinsonian serious adverse effects requiring hospitalization (two falls with fractures). CONCLUSION: The switchover from one agonist to another can be safely and successfully accomplished with a rapid titration based on an equivalency dose calculation.