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Biomedical subjects

P Baker

Publications and source records attributed to P Baker.

At least 73 records · Page 4Linked to original sources
PubMed1998

Fetal development of Leydig cell activity in the mouse is independent of pituitary gonadotroph function.

During fetal development the testes secrete anti-Mullerian hormone and testosterone to induce formation of the male phenotype. Adult Leydig cells secrete testosterone under the control of LH, but the role of the fetal pituitary in regulating fetal Leydig cell function is unclear. To study the early relationship between pituitary and Leydig cell function, we have examined the development of fetal pituitary LH levels and Leydig cell function in normal mice and in hypogonadal (hpg) mice that lack GnRH and, thus, circulating gonadotropins. In normal and hpg mice, pituitary LH content was barely detectable until embryonic day 17 (E17), when levels began to increase significantly in both groups. Pituitary levels of LH in hpg mice were, however, only about 10% of normal at all ages. Full-length LH receptor transcripts were first detectable in fetal testes on E16 in both normal and hpg mice. In normal mice, levels of testicular messenger RNA (mRNA) encoding cytochrome P450 side-chain cleavage and 17alpha-hydroxylase increased from E13 to reach a peak around birth. In hpg mice, levels of mRNA encoding these enzymes were normal until around birth, at which time there was a significant decline. Levels of testicular mRNA encoding 3beta-hydroxysteroid dehydrogenase type I were similar in normal and hpg mice and showed little change during development. Intratesticular testosterone reached a peak on E18 in normal animals before declining again after birth. In hpg mice, intratesticular testosterone levels were normal throughout fetal development and on the day of birth, but were barely detectable by postnatal day 5. Results show 1) that fetal Leydig cell function in the mouse is normal in the absence of endogenous circulating gonadotropins; 2) that Leydig cells become dependent on gonadotropins shortly after birth; and 3) that pituitary LH synthesis can start in the absence of GnRH but is dependent on LH for a normal level of synthesis and secretion.

Animals↗
PubMed1998

Hoarding and treatment response in 38 nondepressed subjects with obsessive-compulsive disorder.

OBJECTIVE: The authors studied factors associated with short-term treatment response in 38 nondepressed subjects with DSM-III-R obsessive-compulsive disorder (OCD). METHOD: The subjects completed 12 weeks of treatment with paroxetine (N = 20), placebo (N = 8), or cognitive-behavioral therapy (N = 10). Clinician and self-rated measures were gathered at baseline, during treatment, and after treatment. RESULTS: Seventeen (45%) subjects had "much" or "very much" improvement and achieved at least a 40% decrease in their total Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. Responders had lower obsessive-compulsive scores on the Symptom Checklist 90-Revised, had a lower checking score on the Maudsley Obsessive-Compulsive Inventory, were less likely to have had prior drug therapy, and in general suffered more obsessive-compulsive symptoms. They were significantly less likely to have hoarding obsessions and corresponding compulsions. The latter finding was confirmed using multiple regression analysis. CONCLUSION: Hoarding is an important symptom that predicts poor treatment response in patients with OCD.

Age Factors↗
PubMed1997

Laboratory evaluation in the diagnosis of Lyme disease.

PURPOSE: To provide a qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease and to use the resultant data to formulate guidelines for clinical diagnosis. DATA SOURCES: A MEDLINE search of English-language articles or articles with English-language abstracts published from 1982 to 1996. DATA EXTRACTION: Sensitivity, specificity, and likelihood ratios were calculated, and a random-effects model was used to combine the proportions from the eligible studies. Prespecified criteria were used to determine which studies were eligible for analysis. DATA SYNTHESIS: Laboratory testing in general is not clinically useful if the pretest probability of Lyme disease is less than 0.20 or greater than 0.80. When the pretest probability is 0.20 to 0.80, sequential testing with enzyme-linked immunosorbent assay and Western blot is the most accurate method for ruling in or ruling out the possibility of Lyme disease. CONCLUSIONS: Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease.

Bacteriological Techniques↗
PubMed1997

The effect of delayed analysis or freeze-thawing on the measurement of natural anticoagulants, resistance to activated protein C and markers of activation of the haemostatic system.

We provide a centralised thrombophilia screening service with sample transfer by courier or first class mail, a practice common to many centres. Sample quality is of prime importance, thus we have assessed the effect of delayed sample handling upon the haemostatic variables within our thrombophilia profile. This comprises screening for familial natural anticoagulant deficiency and APC resistance (1-4), and acquired lupus anticoagulant (5,6). The effect upon hypercoagulable markers were also assessed to facilitate evaluation of these in prospective clinical studies (7).

Anticoagulants↗
PubMed1997

Crystallization and preliminary X-ray studies of nitrogenase component 1 (the MoFe protein) from Klebsiella pneumoniae.

Two crystal forms of component 1 (the MoFe protein) of nitrogenase from Klebsiella pneumoniae have been isolated and characterized. The triclinic form has cell dimensions a = 76.0, b = 109.6, c = 144.6 A, alpha = 80.3, beta = 74.9 and gamma = 69.6 degrees, diffracts to around 3.0 A and has two molecules in the asymmetric unit. The monoclinic form belongs to space group P2(1) with a = 76.6, b = 127.8, c = 109.1 A and beta = 104.6 degrees (frozen at 100 K), diffracts to 1.5 A and has one molecule in the asymmetric unit. At this resolution the outstanding questions concerning the structure and the operation of the enzyme, in particular the linkage between the Fe(4)S(4) units in the P clusters, the true geometry of the apparently trigonal Fe atoms in the FeMoco and the reduction site itself, should be answerable.

Journal Article↗
PubMed1997

Progress report. A randomized multicenter European study comparing adjuvant radiotherapy, 6-mo chemotherapy, and combination therapy vs no-adjuvant treatment in resectable pancreatic cancer (ESPAC-1).

CONCLUSION: The ESPAC-1 trial is the largest study of its kind in pancreatic cancer and should definitively address the question of the role of conventional methods of adjuvant treatment in pancreatic cancer. BACKGROUND: At the joint International Association of Pancreatology and the European Pancreatic Club meeting in Mannheim, Germany (June 12-15, 1996) a satellite meeting of the European Study Group for Pancreatic Cancer (ESPAC) met to discuss the progress of the ESPAC-1 trial. METHODS: A randomized multicenter study to address which, if any, of the following adjuvant treatments are of benefit in patients with resectable pancreatic cancer: radiotherapy (40 Gy with 5-FU as a sensitizing agent), 6 mo of chemotherapy (5-FU and folinic acid), or a combination of these treatments. RESULTS: From February 1994 to June 1996 (the time of the Mannheim meeting) 221 patients so far have been recruited into the three treatment arms and one control arm.

Adenocarcinoma↗
PubMed1997

Renal artery dissection causing renal infarction in otherwise healthy men.

Arterial dissection is usually associated with pathological states such as malignant hypertension, severe atherosclerosis, severe trauma, Marfan syndrome, or Ehlers-Danlos syndrome. However, we report three cases in which renal artery dissection occurred in otherwise healthy, normotensive men. In two cases, the onset of symptoms of renal artery dissection was coincident with an unusual degree of physical activity. In the third case, the symptoms occurred while the patient was sitting but during a stressful business meeting. In each case, the patient experienced severe unilateral flank pain. Urolithiasis was suspected, but intravenous pyelography showed only ipsilateral impaired renal cortical perfusion, and the urinalyses showed no hematuria. The diagnosis of renal artery dissection was established by arteriography in two cases and by nephrectomy in one case. The latter case showed fibromuscular dysplasia by arteriography performed after the nephrectomy. The other two cases showed no evidence of fibromuscular dysplasia. We conclude that spontaneous renal artery dissection can occur in otherwise healthy individuals. Our experience and the reports of others indicate that this condition occurs mainly in men, conservative (nonsurgical) management is generally indicated, and the long-term prognosis is generally excellent. In some patients, an unusual degree of physical exertion might be the cause of renal artery dissection.

Adult↗
PubMed1997

Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3'-untranslated region of the prothrombin gene.

The odds ratio for the FII 20210G/A mutation in 504 patients with venous thromboembolism compared to controls was 2.0 (95% CI 1.0-4.0) and, for factor V Leiden, 5.8 (95% CI 3.3-10.3). 3/504 patients were heterozygous for both mutations. None of the patients had combined natural anticoagulant deficiency and the FII 20210G/A mutation. We conclude that the FII 20210G/A mutation is present in 2.6% of the population and the relative risk of venous thromboembolism in carriers is 2.0.

Factor V↗
PubMed1997

Infection control and contaminated waste disposal practices in Southern Sydney Area Health Service Dental Clinics.

The sterilization and contaminated waste disposal practices in all 14 dental clinics operated by the Southern Sydney Area Health Service were surveyed. All of the clinics used autoclaves for sterilization. All hand instruments, handpieces and triplex syringes were autoclaved between patients. Chemical disinfection solutions were used in 12 of the 14 dental clinics, mainly for surface decontamination. Five dental clinics had separate storage areas for contaminated waste which compiled with contaminated waste separation and disposal guidelines. The practice of recapping needles with fingers and some inadequate washing facilities are areas that require particular attention.

Catchment Area, Health↗
PubMed1997

Analysis of actinomycete communities by specific amplification of genes encoding 16S rRNA and gel-electrophoretic separation in denaturing gradients.

A group-specific primer, F243 (positions 226 to 243, Escherichia coli numbering), was developed by comparison of sequences of genes encoding 16S rRNA (16S rDNA) for the detection of actinomycetes in the environment with PCR and temperature or denaturing gradient gel electrophoresis (TGGE or DGGE, respectively). The specificity of the forward primer in combination with different reverse ones was tested with genomic DNA from a variety of bacterial strains. Most actinomycetes investigated could be separated by TGGE and DGGE, with both techniques giving similar results. Two strategies were employed to study natural microbial communities. First, we used the selective amplification of actinomycete sequences (E. coli positions 226 to 528) for direct analysis of the products in denaturing gradients. Second, a nested PCR providing actinomycete-specific fragments (E. coli positions 226 to 1401) was used which served as template for a PCR when conserved primers were used. The products (E. coli positions 968 to 1401) of this indirect approach were then separated by use of gradient gels. Both approaches allowed detection of actinomycete communities in soil. The second strategy allowed the estimation of the relative abundance of actinomycetes within the bacterial community. Mixtures of PCR-derived 16S rDNA fragments were used as model communities consisting of five actinomycetes and five other bacterial species. Actinomycete products were obtained over a 100-fold dilution range of the actinomycete DNA in the model community by specific PCR; detection of the diluted actinomycete DNA was not possible when conserved primers were used. The methods tested for detection were applied to monitor actinomycete community changes in potato rhizosphere and to investigate actinomycete diversity in different soils.

Actinomycetales↗
PubMed1997

Interaction between cyclosporin A and nonsteroidal antiinflammatory drugs.

OBJECTIVE: Although cyclosporin A (CyA) has been shown in a series of controlled trials to be of benefit to patients with rheumatoid arthritis (RA), the majority of patients continue to require nonsteroidal antiinflammatory drugs (NSAID) for relief of joint pain and stiffness. Our aim was to determine whether there is a clinically important difference in calculated creatinine clearance when CyA is given concurrently with NSAID with high cyclooxygenase activity (indomethacin and ketoprofen) compared with sulindac, which has been claimed to have fewer renal effects than other NSAID, and compared with a simple analgesic, paracetamol. METHODS: Patients with RA started 2.5 mg/kg CyA/day and dosage was increased cautiously to 5 mg/kg/day or less if the serum creatinine rose by > or = 30% above baseline. The mean stabilized dose was 171.43 +/- 48.94 mg/day. Once CyA dose was stabilized, patients were allocated in random order to possible sequences of 4 week periods of acetaminophen, indomethacin, ketoprofen, and sulindac. Monitoring of cyclosporine levels, nephrotoxicity, and hepatoxicity, and adjustment of doses were by an "unblinded" clinician not in direct contact with study patients. All other assessments were made by a "blinded" clinician. Patients were instructed to take the identical appearing gelatin capsules qid. The multiple crossover design was analyzed using analysis of variance procedures for repeated measures. RESULTS: 35 patients were enrolled, of whom 32 patients completed the acetaminophen and at least one course of NSAID. The calculated creatinine clearance was increased by 2.79 ml/min (3.5%) on average for acetaminophen versus all 3 NSAID (6% for indomethacin, 2.3% for ketoprofen, 2.6% for sulindac). The study had adequate power to detect a true difference of more than 10% in mean creatinine clearance for each major comparison. CONCLUSION: NSAID studied did not produce a clinically important difference in the calculated creatinine clearance in these patients-the difference with acetaminophen was modest and not of clinical significance. There is no evidence that any of the 3 NSAID studied have an advantage or disadvantage. It seems reasonable to allow patients to continue an NSAID of their or their clinician's choice.

Acetaminophen↗
PubMed1996

Temperature dependence of the exchange of monovalent anions in human red blood cells.

The temperature dependence of anion exchange across the red cell membrane was studied between 5 degrees C and 55 degrees C by measuring the rate of shrinkage of cells when transferred from a medium of pH 7.6 to one of pH 9.3 (as measured at 22 degrees C). The rates of shrinkage varied with the anion studied, the order being F-> Cl-> Br-> I-> SCN- but were faster in the presence of trace amounts of carbon dioxide than in its absence. NO3- was as fast as Cl- when carbon dioxide was present but comparable with I- when it was removed. Arrhenius plots of the rates were linear for all anions over the temperature range studied and gave the following apparent activation energies in kJ mol-1; F-, 67.7; NO3-, 68.4; Cl-, 70.2; Br-, 79.6; SCN-, 87.4 and I-, 95.1 in the presence of carbon dioxide. Inhibition of carbonic anhydrase with 5 microns ethoxzolamide and the removal of the carbon dioxide by degassing raised the activation energies to; F-, 124.8; NO3-, 129.0; Cl-, 141.5: Br-, 159.4; SCN-, 150.0 and I-, 185.6 kJ. mol-1. With the exception of F-, the apparent activation energies of the anions were linearly related to their thermochemical (dehydrated) radii in both cases. The relationship between the ionic radii and the energy of transfer suggests that anion exchange involves transfer through a hydrophobic pathway and that additional energy is required to overcome restrictions experienced in passing through the pathway. It is proposed that this, rather than a conformational change in the protein determines the activation energy of the process.

Anions↗
PubMed1996

Both reductive forms of 17 beta-hydroxysteroid dehydrogenase (types 1 and 3) are expressed during development in the mouse testis.

Androstenedione is reduced to form testosterone by 17-beta-hydroxysteroid dehydrogenase (17 beta HSD) and two different reductive isoforms of the enzyme have been identified (types 1 and 3). In this study, levels of mRNA encoding both reductive isoforms have been measured during fetal and post-natal development in the mouse. In fetal and neonatal testes mRNA encoding both type 1 and type 3 isoforms was present at relatively high levels reaching a peak at postnatal day 5. Thereafter, mRNA levels of both 17 beta HSD isoforms fell to low levels until day 30 when there was a marked increase in the levels of the type 3 isoform. The presence of the type 1 17 beta HSD enzyme in fetal testes may explain the virilization of the mesonephric (Wolffian) duct which occurs in pseudohermaphrodite individuals lacking the type 3 isoform.

17-Hydroxysteroid Dehydrogenases↗