Gentamicin inhibition of Na+,K(+)-ATPase in rat kidney cells.

Na,K(+)-ATPase activity is decreased in homogenized renal tissue from GM-treated rats. This study examines whether the site of the active effect of GM on Na,K(+)-ATPase activity in the kidney can be localized to the proximal convoluted tubules (PCT) where the drug is taken up and where it will produce necrosis. In rats treated with gentamicin (50 micrograms.kg-1.day-1 i.m.) for 7 days, PCT Na,K(+)-ATPase activity was reduced as compared to vehicle-treated rats but returned to control levels 7 days after treatment withdrawal. In another nephron segment, the medullary thick ascending limb of Henle (mTAL), where GM induced lesions are uncommon, Na,K(+)-ATPase activity was the same in GM- and vehicle-treated rats treatment. To study the in vitro effect of GM, dissected PCT and mTAL segments from untreated rats were preincubated for 30 min with GM 10(-3) M, a dose similar to the tissue concentration in chronically treated rats. In tubule segments that were permeabilized to allow the drug to enter the cells, GM 10(-3) M significantly inhibited Na,K(+)-ATPase activity both in PCT and mTAL. In non-permeabilized mTAL segments GM did not inhibit Na,K(+)-ATPase activity. GM inhibition of Na,K(+)-ATPase activity in permeabilized PCT segments persisted after the tubules were rinsed in GM free medium. GM does not inhibit Na,K(+)-ATPase partly purified from the renal cortex. Conclusion. Gentamicin inhibits Na,K(+)-ATPase activity in renal tubule cells when it has access to the cytoplasm. Treatment with GM will therefore cause a selective inhibition of Na,K(+)-ATPase in the proximal tubule cells.     

Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease

Objective. An inappropriate immune response to normal bowel flora is implicated in the etiology of Crohn's disease. Tolerance to bowel flora develops in infancy, so factors disrupting normal patterns of bowel colonization may increase the risk of Crohn's disease. The aim of this study was to test the hypothesis that antibiotic therapy between birth and age 5 years may disrupt the pattern of bowel colonization and increase the risk of Crohn's disease. Material and methods. Some 1098 patients with Crohn's disease and 6550 controls matched by delivery unit, year of birth, sex, and born between 1973 and 1997 were identified through the Swedish population registers. Seven inpatient diagnoses between birth and age 5 years associated with antibiotic therapy were identified by prospectively recorded data. Results. Of the seven diagnoses, only pneumonia and otitis media were sufficiently common for use in the analyses. Pneumonia and otitis media were not independent of each other in their association with Crohn's disease and the more important association was with pneumonia. Pneumonia by age 5 years was statistically significantly associated with both pediatric- and adult Crohn's disease, with odds ratios (and 95% CI) of 2.74 (1.04–7.21) and 4.94 (1.83–13.23), respectively. Pneumonia after age 5 years was not statistically significantly associated with Crohn's disease. Conclusions. Pneumonia prior to age 5 years, but not later, was associated with subsequent Crohn's disease and this may represent either susceptibility or causation. The results are consistent with early exposures influencing immune function, such as through disruption of bowel colonization, and thus increasing the risk of Crohn's disease.     

Bacteroides fragilis, Streptococcus intermedius and group B streptococci in ascending infection of pregnancy. An animal experimental study

By means of bacteriological, histological and immunofluorescence methods, the ascending spread of endocervically inoculated bacteria was studied in 14 pregnant sheep. 8 ewes near term were exposed to group B streptococci, Bacteroides fragilis or Streptococcus intermedius for 2-4 days. 6 other animals in mid pregnancy were exposed to one of the bacteria mentioned for 30 days. Before inoculation, aerobic and anaerobic culture specimens from cervix and amniotic fluid were obtained. At delivery by caesarean section, in addition to culture specimens, membrane and placental tissues were collected. Bacterial detection by means of indirect immunofluorescence showed significant invasion of the membranes and the placentas by the microorganisms inoculated. In one case, inoculated with S. intermedius, the ascending infection could be shown to pass the intact membranes reaching the amniotic fluid. It is concluded that endocervical bacteria in the indigenous microflora might cause pregnancy complications by establishing ascending infection. Furthermore, as the bacteria tested have been implicated in premature rupture of the membranes, an aetiological role of ascending infection in this pregnancy complication is postulated.     

Concentrations of doxycycline in human seminal plasma.

Single oral doses of 200 mg doxycycline was given to 16 healthy test subjects. The concentrations of the drug were measured in blood plasma and seminal plasma and related to the zinc content. Measurable concentrations of doxycycline were obtained in seminal plasma one to two hours after drug intake. The maximum level was reached after 4 to 6 hours and measurable concentrations were recorded in both blood plasma and seminal plasma after 24 hours. This means that measurable concentrations were maintained during almost the entire dose interval. In split ejaculate experiments it was shown that doxycycline is excreted mainly through the prostate gland. The mean concentration ratio for "prostatic fluid" vs. blood plasma in healthy volunteers was about 0.6. Indirect evidence is presented that the concentrations in the fluids from the accessory genital glands are higher if patients with prostatitis are given daily doses of 100 mg doxycycline.     

Time-sharing strategies in driving after various cerebral lesions

Primary objective: To analyse time-sharing strategies in patients with cerebral lesions when they performed everyday in-car tasks in real-life highway driving. Research design: A case-control study. Methods and procedures: Thirteen male patients with brain damage and 11 healthy controls participated. The frequency and duration of glances at the in-car tasks, total time of eyes-off the road during tasks, speed and lateral displacement of the car were recorded. Main outcomes and results: Long glances away from the road and consequent large lateral displacements were characteristic for patients with anterior damage, while the patients with more posterior lesions used frequent short glances at the in-car task. Conclusion: Two different time-sharing strategies that appeared to be related to different aetiology were found in the patients, indicating different control of the driving task. It is proposed that standardized on-road dual tasks should be used for detecting problems in allocation of attention during driving.     

Comparison of the bioabsorbable and metal screw fixation after ACL reconstruction with a hamstring autograft in MRI and clinical outcome: a prospective randomized study

There has never been an MRI study of tunnel widening comparing bioabsorbable to metal screw fixation in autologous hamstring anterior cruciate ligament (ACL) reconstruction. We randomized 62 patients to hamstring ACL reconstruction with either a bioabsorbable (n = 31) or metal screw (n = 31) fixation. The evaluation methods were clinical examination, KT-1000 arthrometric measurement, the International Knee Documentation Committee and Lysholm scores, and MRI. There were no differences between the groups preoperatively. Fifty-five patients (89%) were available at a minimum of 2-year follow-up (range 24–36 months). There was tunnel widening in both groups, but the increase was significantly greater in the AP dimension of the femoral tunnel in the bioabsorbable screw group compared to metal group (P = 0.01). The tibial tunnels showed no intergroup difference. Ninety-four percent of the knees were normal or nearly normal according to the IKDC scores and the average Lysholm score was 91 with no intergroup difference. The follow-up AP tibial tunnel diameter was smaller with normal knee laxity compared to abnormal knee laxity. The graft failure rate in the bioabsorbable screw group was 23% (7/31 patients) and 6% (2/31 patients) in the metal screw group. The use of bioabsorbable screws resulted in more femoral tunnel widening, and more graft failures compared to metal screws. The tunnel widening in the tibia was associated with the knee laxity (P = 0.02).     

Aging and time-sharing in highway driving.

PURPOSE: Proper time-sharing--visual attention allocation--between the road view ahead and other targets is an essential requirement for safe driving, along with other visual and attentional performance. Earlier on-road research has shown that neurologic problems (Alzheimer disease, brain injury) impair time-sharing during in-car tasks. This study analyzed age effects on time-sharing performance. METHODS: Thirty participants in three age groups (mean age 22, 34, and 67 years) drove an instrumented car a trip of 350 km and performed an in-car visual search task with either a motor (keying) or vocal response. The frequency and duration of glances at the in-car targets, total time eyes off the road during task, speed, and lateral displacement of the car were recorded. The participants were also tested on a battery of cognitive tasks during the midway break. RESULTS: The elderly used a longer total time looking at the in-car display and they traveled a longer distance with eyes away from the road. The number of long (>2 sec) glances and the car's lateral displacement on the road were larger among the elderly than the young drivers. The difference between the older and younger participants was larger when a motor (keying) response was required. The age effects were mediated by cognitive performance (best by the Trail Making A test) rather than by vision parameters. CONCLUSION: Older drivers have difficulties in time-sharing in highway driving already at the age of 65 to 70 years.     

Ciprofloxacin concentrations and impact of the colon microflora in patients undergoing colorectal surgery.

Ciprofloxacin was given perorally in two doses of 750 mg each with a 12-h interval starting 24 h prior to surgery, 400 mg of ciprofloxacin was given intravenously at the induction of anesthesia, and 400 mg of ciprofloxacin was given 12 h later to 21 patients undergoing elective colorectal surgery. The maximum concentrations in serum (mean value +/- standard deviation, 11.1 +/- 7.8 mg/liter) during surgery were reached 30 min after ciprofloxacin was administered. The ciprofloxacin concentrations in the intestinal mucosa samples were 2.7 to 37.8 mg/kg of tissue weight, and the concentrations in the fecal samples were less than 0.1 to 858 mg/kg. The aerobic and anaerobic bacteria in the fecal flora were suppressed markedly during the prophylaxis period. No postoperative infections occurred.