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Biomedical subjects

G Gilbert

Publications and source records attributed to G Gilbert.

At least 19 recordsLinked to original sources

Navigation and analysis of the energy landscape of small proteins using the activation-relaxation technique.

The resolution of the protein folding problem has been tied to the development of a detailed understanding of the configurational energy or of the free energy landscape associated with these molecules. Using the activation-relaxation technique and a simplified energy model, we present here a detailed analysis of the energy landscape of 16-residue peptide that folds into a beta-hairpin. Our results support the concept of an energy landscape with an effective topology consistent with a scale-free network.

Biophysics↗

Superovulation and embryo recovery from peripubertal Holstein heifers.

The use of peripubertal donors in embryo transfer (ET) programs presents significant opportunity to accelerate genetic gain in domestic livestock by reducing the generation interval. These studies were designed to evaluate feasibility of superovulation and embryo recovery in peripubertal heifers (starting at 7.8 months of age), and to determine whether subsequent reproductive and lactational performance of donor heifers were impaired. Study 1 utilized 10 pairs of contemporary full-sibling heifers in which one heifer in each pair was assigned to receive a superovulation regimen and her full-sibling contemporary received placebo. Treated heifers were artificially inseminated at estrus and embryos were flushed transcervically 4-6 days later. Based on recovery of oocytes and/or embryos, 9 of 10 heifers responded to the hormonal regimen and 12 total embryos were recovered. Seven embryos (58%) were transferred into recipients resulting in five pregnancies. Control and treated heifers remained in the herd and were bred at a natural estrus by AI at 15 months of age. Lactation records, i.e., 305 days mature equivalent (305 d ME) were obtained, and all animals were evaluated for udder conformation traits between 32 and 38 months of age. Reproductive traits (age at first calving and days to conception) and lactational traits of heifers subjected to embryo transfer and their non-treated full-siblings did not differ (P > 0.05). Study 2 was conducted to establish the commercial feasibility of hormonally programming peripubertal heifers ranging in age from 7.8 to 9.9; 10 to 11.9; 12 to 13.9 and >/= 14 months. In total, 3982 embryos were recovered from 520 heifers, with 2419 (60.7%) of those categorized as viable (transferable). The number of ova/embryos obtained per flush (5.6 +/- 1.0) and the number of transferable embryos (2.8 +/- 0.5) was reduced (P < 0.05) in heifers of age 7.8-9.9 months compared to all other age groups. There was no difference (P > 0.05) in the number of ova/embryos recovered (7.8 +/- 0.3), or the number of transferable embryos (4.8 +/- 0.2), among heifers that were >/=10 months of age. The number of unfertilized ova did not differ by age, however, more degenerate embryos tended to be recovered from heifers <10 months of age compared to heifers >/=14 months of age. These data indicate that transferable embryos can be safely recovered from heifers beginning at 10 months of age without compromising subsequent reproductive or lactational performance of the donor.

Aging↗

Outbreak of extended spectrum beta lactamase producing Klebsiella pneumoniae in a neonatal unit.

An outbreak of extended spectrum beta lactamase producing Klebsiella pneumoniae (ESBLKp) in a neonatal unit was controlled using simple measures. Normally, the control of such infections can be time consuming and expensive. Seven cases of septicaemia resulted in two deaths. ESBLKp isolates were subtyped by pulsed field gel electrophoresis, and four of the five isolates typed were identical. Control of the outbreak was achieved by altered empiric antibiotic treatment for late onset sepsis and prevention of cross infection by strict attention to hand washing. Widespread colonisation of babies in the unit was presumed, so initial surveillance cultures were not performed. No further episodes of sepsis occurred.

Amikacin↗

Oropharyngeal candidiasis in immunocompromised children: a randomized, multicenter study of orally administered fluconazole suspension versus nystatin. The Multicenter Fluconazole Study Group.

OBJECTIVE: To compare the efficacy, safety, and tolerance of fluconazole suspension versus nystatin in the treatment of oropharyngeal thrush in immunocompromised children. DESIGN: Multicenter, randomized, observer-masked trial. SETTING: Thirty-two centers participated, including hospitals and ambulatory care clinics. PATIENTS: We enrolled 182 immunocompromised infants and children, ages 5 months to 14 years, with signs of oral thrush and presence of yeasts on potassium hydroxide- or gram-stained preparations. Subjects were randomly assigned to receive a single daily dose of fluconazole suspension, 2 to 3 mg/kg per day, or nystatin, 400,000 units four times daily for 14 days; 159 patients, who had culture confirmation of thrush and received at least 7 days of study drug, were evaluated for efficacy; all patients were evaluated for safety. RESULTS: Clinical cure was demonstrated in 91% of the subjects in the fluconazole group and 51% of the subjects in the nystatin group (p < 0.001), and eradication of the organism cultured at entry occurred in 76% and 11% (p < 0.001), respectively. Gastrointestinal conditions developed in six patients who received fluconazole and in three who received nystatin; two fluconazole recipients were subsequently withdrawn from the study. Laboratory abnormalities occurred with equal frequency in both groups. Clinical relapse rates were similar in both groups at 2 weeks (18% and 24% for fluconazole and nystatin, respectively) and 1 month (28% and 27%, respectively) after the completion of study drug. CONCLUSIONS: Fluconazole suspension is more effective than nystatin in the treatment of thrush in immunocompromised children. Both regimens were well tolerated.

Administration, Oral↗

The MicroScan WalkAway diagnostic microbiology system--an evaluation.

The MicroScan WalkAway is an automated bacterial identification and susceptibility testing system that has only recently been marketed in Australasia. We evaluated the performance of the instrument using MicroScan Rapid fluorescent panels to determine the identity and antibiotic susceptibilities of 100 Gram negative and 100 Gram positive organisms representing both common clinical isolates and selected organisms of interest. MicroScan results were compared with those obtained by conventional biochemical identification, and antibiotic susceptibility testing using agar dilution following the National Committee on Clinical Laboratory Standards guidelines. MicroScan and reference identifications were in agreement for 93% of Gram negative organisms. MicroScan results were available within 2 hrs. Additional tests were required to confirm the identity of 9 isolates but on only 2 occasions would a definitive identification been delayed beyond 24 hrs. Very major or major discrepancies were seen in 2% and minor discrepancies in 8% of Gram negative susceptibility tests. Susceptibility results were available within 7 hrs but could not be obtained for 13 slow growing organisms. With Gram positive organisms MicroScan agreed with the reference identification of 87% of isolates cultured on horse and 90% of those cultured on sheep blood agar. Discrepancies that occurred in the identification of some streptococci made us question the suitability of MicroScan as the sole means of identifying these organisms. All identifications were available within 24 hrs and the requirement for additional tests was minimal. Susceptibility results closely matched those obtained by agar dilution with < 1% major and 7% and 9% minor discrepancies occurring with sheep and horse blood respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriological Techniques↗

[Significance of a screening questionnaire for diagnosis of sleep apnea].

More and more patients present with nocturnal respiratory disorders, especially with sleep apnoea (SA). This makes it mandatory to develop methods for preselecting the patients. A symptom assessment questionnaire was developed according to the Marburg stepwise concept on sleep apnoea diagnostics. Every patient completes this questionnaire as a matter of routine before he is given an appointment for an examination. The procedure to be followed depends on the evaluation of this questionnaire. Questions asked: Weight, height, use of soporifics and sleeping pills, hypertension, snoring, involuntary falling asleep, respiratory standstills, tendency to fall asleep during car driving and accidents in which the tendency to fall asleep was also involved. Three categories result from the evaluation: presence of sleep apnoea improbable (negative), more accurate details of symptoms mandatory (checking required) sleep apnoea probable (positive), patient is given an appointment date. This method was tested on 124 patients (108 male, 16 female, average age 50 yrs., average body-mass index 29.1, average apnoea index (AI) 12.8) who completed the questionnaire and were examined as outpatients, independent of the evaluation of the questionnaire, using the MESAM-IV system (nocturnal long-term recording of respiratory noises, heart rate, oxygen saturation and posture sensor). Measurements according to MESAM-IV system yielded in 69 patients (55.6%) and AI < 6 (apnoea-negative). 12 patients (9.7%) had AI 6-10 (checking required), and 43 AI < 10 (positive). Basing on evaluation of the questionnaire, 42 of 43 apnoea-positive patients had been correctly classified (98%).(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Differential↗

A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group.

BACKGROUND AND METHODS: In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase. RESULTS: Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry. Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53). Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage. There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1). Survival and toxicity were similar in the two maintenance-treatment groups. CONCLUSIONS: In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis. Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection.

Acquired Immunodeficiency Syndrome↗

Peptic ulcer disease. How to treat it now.

Options for treatment of peptic ulcer disease are becoming more diverse. Most new agents are effective yet offer no real advantage over more traditional therapy. However, omeprazole (Prilosec) may be of benefit owing to its potent inhibition of acid secretion, but it is not yet approved for this purpose. Whether treatment of Helicobacter pylori infection will prove beneficial is not yet known, but the answer should be forthcoming. Finally, as with any disease process, alleviation of risk factors is always important. Appropriate counseling regarding use of nonsteroidal anti-inflammatory drugs and cigarette smoking is a necessity.

Anti-Ulcer Agents↗

Familial hidradenitis suppurativa: evidence in favour of single gene transmission.

The three English families in this report have a total of 21 members (16 females and five males) suffering from chronic hidradenitis suppurativa. In family A the condition is associated with acne conglobata and there is vertical transmission of the disorder through three generations. In the others there is no associated cystic acne, but all those affected had a history of acne vulgaris with comedone formation, and the condition has been confirmed in two generations. It is likely that a male in an earlier generation in family B suffered from the disease and affected sibs in family C were born to different fathers. The familial aggregation and number of affected subjects suggests a single gene disorder and the pattern of transmission is consistent with autosomal dominant inheritance. Males and females are affected in successive generations and there is the anticipated variation in clinical severity in those suffering from the condition.

Adolescent↗

Medicine in Zambia.

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Delivery of Health Care↗

Epidemic of hospital-acquired infection due to methicillin-resistant Staphylococcus aureus in major Victorian hospitals.

During 1979, the Victorian Health Commission received reports of a rising proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from an increasing number of institutions. At least 31 metropolitan hospitals were involved, and six of these reported MRSA totaling between 20% and 40% of all Staph. aureus isolates. Since that time, the problem has continued. In some university teaching hospitals, strains of MRSA now cause from 200 to 300 new cases of hospital-acquired infection each year. Sepsis occurs mainly in patients who underwent surgery, premature neonates and in the immunocompromised or debilitated patients. The organism involved is multiresistant. Recent isolates show increasing resistance, particularly against gentamicin, chloramphenicol and, more lately, fusidic acid and rifampicin. Only vancomycin can be relied upon for empirical treatment. There is concern that increasing use of vancomycin will select vancomycin-resistant strains of MRSA, so that, in the near future, there may no longer be any effective antibiotic therapy against hospital staphylococci.

Australia↗

Exercise capacity, residual abnormalities and activity habits following total correction for tetralogy of Fallot.

The maximal oxygen consumption (VO2 max) of 68 patients, at a mean of 5.6 years after total correction for tetralogy of Fallot, was lower than that of normal subjects (36.3 +/- 7.5 and 43.1 +/- 9.0 ml/kg-min). At the time of treadmill evaluation only the female patients were less active in daily life than the normals. Patients having had an elevated right ventricle to pulmonary artery resting systolic pressure gradient, evaluated at a mean of 2.2 years after surgery, had lower VO2 max than those with lesser residual gradients (34.7 +/- 7.2 and 38 +/- 7.3 ml/kg-min). No significant differences in VO2 max were found between patients with none or slight versus moderate to severe pulmonary regurgitation as well as between patients with and without a residual left-to-right ventricular shunt.

Activities of Daily Living↗