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Biomedical subjects

A Kimball

Publications and source records attributed to A Kimball.

13 recordsLinked to original sources

Invasive serotype a Haemophilus influenzae infections with a virulence genotype resembling Haemophilus influenzae type b: emerging pathogen in the vaccine era?

OBJECTIVE: Haemophilus influenzae type b causes severe disease in nonimmune infants and young children; other serotypes are uncommon pathogens and thought to have low virulence. Some have hypothesized that with the virtual elimination of H influenzae type b, other serotypes might acquire virulence traits and emerge as important pathogens of children. We describe the clinical, epidemiologic, and molecular biologic features of 5 cases of severe disease attributable to Haemophilus influenzae type a. METHODS: After observing 4 cases of invasive disease caused by H influenzae type a, we reviewed microbiology records at 3 reference laboratories that perform all serotyping in Utah and surveillance databases. Strains of H influenzae type a and control strains were examined by Southern blotting with the use of the cap probe pUO38 and by pulsed-field gel electrophoresis. The putative virulence mutation, the IS1016-bexA deletion, was detected by polymerase chain reaction amplification and sequencing. RESULTS: During a 10-month period, we observed 5 children with severe invasive disease caused by H influenzae type a. No isolates of H influenzae type a had been submitted to the reference laboratories between 1992 and 1998. The median age of patients was 12 months (range: 6-48 months). Four of 5 had meningitis and bacteremia; 1 had purpura fulminans. Three isolates, representing 1 of 2 pulsed-field gel electrophoresis patterns, contained the IS1016-bexA deletion and were associated with particularly severe disease. CONCLUSIONS: We describe an unusual cluster of severe disease caused by H influenzae type a that resembles the clinical and epidemiologic features of H influenzae type b disease. Our data support the hypothesis that the IS1016-bexA deletion may identify more virulent strains of H influenzae. Haemophilus influenzae, epidemiology, virulence, serotyping, pathogenicity.

Base Sequence↗

The effect of regular exercise on women receiving danazol for treatment of endometriosis.

OBJECTIVE: To determine the effects of regular exercise on women receiving danazol for the treatment of endometriosis. METHODS: Thirty-nine patients were randomized to a danazol-only or a danazol/exercise regimen in a prospective clinical trial carried out at tertiary care institutions. Patients in the danazol/exercise group were instructed to exercise four times per week, for 40 min per session, at an intensity of 20 metabolic units. Side effect profiles, pelvic symptoms, aerobic fitness, strength and hormone levels were compared for all subjects. The number of side effects of danazol was analyzed by the method of generalized estimating equations. RESULTS: The number of side effects reported during a 4-week period was 1.09-2.17 times greater for the danazol-only than for the danazol/exercise group. All patients had improvement of symptoms during treatment. The danazol/exercise group had significantly lower testosterone levels during treatment. The time to recurrence of endometriosis was not different between groups. CONCLUSIONS: Exercise during danazol therapy reduces the number of androgenic side effects. Relief of pain and time to recurrence are unaffected.

Adult↗

Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C]flumazenil.

Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration (Bmax) and equilibrium dissociation constant (Kd) from high and low specific activity (SA) [11C]flumazenil ([11C] Ro 15-1788) positron emission tomography studies of five normal volunteers. The high and low SA data were simultaneously fit to linear and nonlinear three-compartment models, respectively. An additional inhibition study (pretreatment with 0.15 mg/kg of flumazenil) was performed on one of the volunteers, which resulted in an average gray matter K1/k2 estimate of 0.68 +/- 0.08 ml/ml (linear three-compartment model, nine brain regions). The free fraction of flumazenil in plasma (f1) was determined for each study (high SA f1: 0.50 +/- 0.03; low SA f1: 0.48 +/- 0.05). The free fraction in brain (f2) was calculated using the inhibition K1/k2 ratio and each volunteer's mean f1 value (f2 across volunteers = 0.72 +/- 0.03 ml/ml). Three methods (Methods I-III) were examined. Method I determined five kinetic parameters simultaneously [K1, k2, k3 (= konf2Bmax), k4, and konf2/SA] with no priori constraints. An average kon value of 0.030 +/- 0.003 nM-1 min-1 was estimated for receptor-rich regions using Method I. In Methods II and III, the konf2/SA parameter was specifically constrained using the Method I value of kon and the volunteer's values of f2 and low SA (Ci/mumol). Four parameters were determined simultaneously using Method II. In Method III, K1/k2 was fixed to the inhibition value and only three parameters were estimated. Method I provided the most variable results and convergence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems. However, the K1/k2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K1/k2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability. The average Bmax values obtained using Method III were 100 +/- 25 nM in the occipital cortex, 64 +/- 18 nM in the cerebellum, and 38 +/- 5.5 nM in the thalamus; the average Kd was 8.9 +/- 1.0 nM (five brain regions).

Adult↗

Superovulation with or without intrauterine insemination for the treatment of infertility.

Patients undergoing human menopausal gonadotropin (hMG) superovulation were reviewed retrospectively to determine whether fecundity was greater for intrauterine insemination (IUI) than timed intercourse. Forty patients with unexplained infertility, American Fertility Society I or II endometriosis, luteal phase defect and/or cervical factor were treated with hMG alone or hMG plus IUI. Twenty-eight underwent 52 cycles of hMG/IUI, and 19 underwent 31 cycles of hMG. The probability of pregnancy after four cycles was significantly better in the hMG/IUI group (.90) than the hMG group (.37, P = .049). There was a 54.5% multiple pregnancy rate, and one patient was admitted to the hospital for hyperstimulation. When traditional therapy fails, hMG/IUI significantly increases the pregnancy rates as compared to hMG with timed intercourse in a "good prognosis" group of patients.

Baltimore↗

Construction and analysis of parallel and antiparallel Holliday junctions.

The Holliday junction is a four-stranded DNA intermediate that arises during recombination reactions. We have designed and constructed a set of Holliday junction analogs that model each of the ideal conformations available to a 2-fold symmetric four-arm junction. The strategy used is to connect two arms of a junction molecule with a short tether of thymidines. These DNA molecules share a common core sequence but have different arms that are connected so that each molecule is constrained in either an antiparallel or a parallel structure. For tethered antiparallel molecules the identity of the crossover strands is determined by which arms are connected. Different arm connections gave molecules representing each of the two antiparallel crossover isomers. Two parallel molecules that differ in the length and position of the tether exhibit opposite biases in their choice of crossover strands. Thus, a physical constraint applied at a distance from the branch point can determine the conformation of a junction.

Base Sequence↗

The efficacy of presacral neurectomy for the relief of midline dysmenorrhea.

The present study was undertaken to evaluate prospectively the efficacy of presacral neurectomy for the treatment of midline dysmenorrhea. All patients had moderate to severe dysmenorrhea and stage III-IV endometriosis. Of the patients undergoing presacral neurectomy (N = 17), only two had a recurrence of pain. The remainder of the patients undergoing presacral neurectomy remain pain-free at 42 months of follow-up. Of the patients undergoing resection of endometriosis but not presacral neurectomy (N = 9), none received relief of midline pain. Relief of lateral pain, back pain, and dyspareunia was variable in both groups. Our findings corroborate previous retrospective studies showing that presacral neurectomy is highly effective in the treatment of dysmenorrhea. We speculate that the most common reasons for failure of presacral neurectomy are inappropriate selection of patients and incomplete resection of the presacral nerve plexus.

Adult↗

Branch vein occlusion. Retinal neovascularization outside the involved segment.

Three hundred sixty-six cases of branch vein occlusion entered within the multicenter Branch Vein Occlusion Randomized Clinical Trial have been reviewed. Four cases that developed retinal neovascularization outside of the retinal area involved with the occlusion have been documented by photography and fluorescein angiography.

Aged↗

Fetal acceleration determinations and perinatal outcome.

The importance of a laboratory test, especially when used as a screening procedure, is its ability to accurately provide information which can be used in the clinical management of patients. The fetal acceleration determination (FAD) has been utilized by many clinical obstetric services to assess the fetus at risk and to avoid the cumbersome and expensive oxytocin challenge test (OCT). In an effort to determine the usefulness of this modality in assessing the high-risk obstetric patient, a retrospective study of FADs was performed on 264 patients. All the tests were performed within one week of delivery. Fetal outcome was measured by Apgar scores, fetal morbidity and mortality and length of nursery stay. Chi square row by column contingency analysis was performed, and Bayes theorem was applied to our data to predict FAD specificity. The probability of false-positive and false-negative tests was high, and no correlation with outcome was observed. Analysis of these data indicates that the FAD is of limited value in identifying the fetus at risk.

Apgar Score↗

Composition of biliary lipids and kinetics of bile acids after cholecystectomy in man.

Postcholecystectomy biliary lipid composition and bile acid kinetics were studied in 24 women and 4 men. Hepatic bile was collected periodically for as long as 4 months without interrupting the enterohepatic circulation and without infecting the biliary system. In 23 patients with cholesterol gallstones, fasting biliary cholesterol made up 10.2% of total lipids in the steady state; in 5 patients with bilirubinate stones, saturation of fasting hepatic bile with cholesterol was lower (8.7% of total lipids). The percentage of deoxycholic acid after cholecystectomy was not higher than that of seven healthy, noncholecystectomized controls. Postcholecystectomy studies of diurnal variation of biliary lipids (7 patients) showed that postprandial hepatic bile had a significantly lower cholesterol saturation than fasting bile. Pool sizes of cholic and chenodeoxycholic acids were low (average 0.4 g/70 kg, each); total synthesis for both bile acids was normal (average 460 mg/day/70 kg), but fractional turnover rates of the two primary bile acids increased after cholecystectomy, probably due to more frequent recycling of the small bile acid pool.

Adolescent↗