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Biomedical subjects

P Barnes

Publications and source records attributed to P Barnes.

At least 73 records · Page 4Linked to original sources

Polymorphism of sulfathiazole.

The polymorphism of sulfathiazole has been reexamined. The issue of the separate existence of two of the forms, forms III and IV, has now been definitively resolved: both forms exist. Single crystals were used to generate X-ray diffraction patterns, equivalent to those normally obtained from polycrystalline samples, using the ingenious Gandolfi camera. The patterns obtained were distinct and in agreement with the theoretical powder patterns calculated from the reported structures of the two forms, thus confirming the separate existence. Disagreement between the results of previous workers has been traced to two main causes: characterization techniques are not very discriminating for the two forms (III and IV), and the samples examined have invariably been mixtures of III and IV, since the two forms usually crystallize together. Furthermore, crystals of form III exhibit marked preferred orientation, which complicates powder X-ray diffraction (PXRD) analysis. The IR, Raman, and 13C NMR spectra, and PXRD patterns are reported for all four forms. These distinct fingerprints should now enable one to isolate pure samples and to study the properties and the relationships between these forms with full confidence.

Calorimetry, Differential Scanning↗

A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

Adult↗

Spina bifida occulta: early clinical and radiographic diagnosis.

Tethered cord syndrome (TCS) is produced by traction of the lumbosacral spinal cord. Clinically, patients with tethered cord syndrome present with various combinations of neurologic, orthopedic, and cutaneous abnormalities. These abnormalities are often subtle. Early diagnosis, and treatment when indicated, is essential to prevent progressive and frequently irreversible neurological deterioration. Early diagnosis is aided by a high degree of clinical suspicion. Plain spine films are useful in the preliminary evaluation of suspected dysraphism. When plain film abnormalities are present, magnetic resonance imaging (MRI) has been found to be the single most effective procedure for both initial diagnosis and pre-operative evaluation of patients with myelodysplasia.

Diagnosis, Differential↗

Ifosfamide, etoposide, and thoracic irradiation therapy in 163 patients with unresectable small cell lung cancer.

One hundred sixty-three patients with small cell lung cancer were treated with six courses, at 3-week intervals, of ifosfamide (5 g/m2) with mesna and etoposide. Thoracic radiotherapy was delivered to the limited stage (LS) patients. The complete response rate (CR, determined clinically and radiologically) was 76% for the 78 LS patients with a further 14% partial response (PR). The majority of the CRs were confirmed on a follow-up bronchoscopy. The CR rate was 27% for extensive stage (ES) patients with another 38% undergoing a partial response. The median survival for LS patients was 11 months, (16 months for CR confirmed by rebronchoscopy) and 8 months for ES patients. The 2-year actuarial survival for LS patients is 27%, follow-up ranges from 12 months to 30 months with a median of 22 months. Toxicity was not severe for the patient population, of whom only 20% had a good performance status before chemotherapy. Parental antibiotics were required on 4% of all 844 chemotherapy courses and 12% of courses were delayed due to side effects. The majority of responses occurred within the first two courses of chemotherapy and there was a corresponding improvement in the patients' symptoms and performance status. The regimen produced rapid tumor response with corresponding improvement in symptoms without marked toxicity and allowed further treatment development.

Adult↗

Calcitonin gene-related peptide (CGRP) is a potent non-endothelium-dependent inhibitor of coronary vasomotor tone.

1 Ring segments of bovine left circumflex coronary artery were pre-contracted with 5-hydroxytryptamine or phenylephrine and then exposed to increasing concentrations of calcitonin gene-related peptide (CGRP) and other drugs. 2 CGRP administration resulted in dose-dependent inhibition of induced tone. Maximal relaxation to CGRP was 89 +/- 5% and the concentration required to achieve 50% maximal relaxation (EC50) was 2.11 +/- 1.35 X 10(-9)M. 3 CGRP-induced relaxation was not affected by removal of endothelial cells nor was it significantly altered by incubation of coronary vessels with atropine, propranolol, phentolamine (all 10(-6)M) or indomethacin (10(-5)M). 4 From these data we conclude that CGRP is a potent inhibitor of coronary artery vasomotor tone which appears to act directly on vascular smooth muscle rather than through the release of a secondary mediator. These data support the possibility that CGRP may play a role in non-adrenergic, non-cholinergic regulation of coronary artery tone.

Animals↗

Serum bile acid concentrations during pregnancy and their relationship to obstetric cholestasis.

We have prospectively studied changes in serum postprandial cholylglycine (CG) concentration during 297 pregnancies. We found an increase in CG concentration from 0.3 mumol/L at 15 weeks' pregnancy to 0.6 mumol/L at 40 weeks' pregnancy. Although this increase was statistically significant (p less than 0.005), median concentrations of CG remained well within the normal range (0-1.5 mumol/L). However, 10% of the group showed markedly elevated serum CG concentrations at 30 weeks' pregnancy, and the CG level in this group continued to rise during the third trimester. Pruritus was significantly more common in the group with elevated CG concentrations (48%) than in the group with normal CG levels (20%) (p less than 0.005). Serum CG was a much more sensitive predictor of pruritus during pregnancy than other biochemical liver tests. Elevated CG levels were found more commonly in Mediterranean and Asian patients than patients of other ethnic origins (p less than 0.025). No statistically significant associations were found between elevated CG concentrations and maternal age, number of previous pregnancies, pruritus during previous pregnancies, contraceptive-induced cholestasis, and fetal maturity. We conclude that obstetric cholestasis is probably much more common than previously suspected and that consideration should be given to the measurement of serum bile acids in all pregnant individuals with unexplained pruritus.

Adolescent↗

Comparative sensitivity of serum cholylglycine concentration and bromsulphalein retention in patients with early and late alcoholic liver disease.

Measurement of serum bile acids has been claimed to be a sensitive and specific biochemical test of hepatic function. We have prospectively measured post-prandial serum glycocholate (cholylglycine) concentrations in 31 patients with alcoholic liver disease and compared these measurements with those of bromsulphalein (BSP) retention, prothrombin time, and serum albumin. In the patients with early (non-cirrhotic) alcoholic liver disease (N = 14) BSP retention was abnormal significantly more frequently than was serum cholylglycine concentration (100% vs 29%, p less than 0.001). In contrast, amongst patients with late (cirrhotic) alcoholic liver disease, BSP retention and serum cholylglycine were abnormal with equal frequency (94%). In both groups of patients BSP retention and serum cholylglycine were abnormal significantly more often than were prothrombin time and serum albumin concentrations. We conclude that moderately severe hepatocellular dysfunction is required before serum cholylglycine can become a reliable biochemical indicator of liver disease.

Adult↗

Antibiotic therapy for treatment in relapse of intestinal Crohn's disease. A prospective randomized study.

We have undertaken a prospective randomized trial of one month's antimicrobial therapy for patients with symptomatic relapse of Crohn's disease. Criteria for entry included two major symptoms: fever, abdominal pain, diarrhea, weight loss, abdominal mass or complications (excluding perianal disease); and two hematologic abnormalities: hemoglobin, ESR, albumin, C reactive protein, iron, or total iron binding capacity. Patients were monitored for the aforementioned clinical and hematologic (hemoglobin, albumin, CRP) parameters over six weeks and for changes in fecal flora. Randomization was to four groups: metronidazole alone (M), cotrimoxazole alone (C), metronidazole and cotrimoxazole (C plus M), or double placebo (P). Seventy-two patients entered the study (18 = M, 16 = C, 21 = C plus M, 17 = P). After two weeks, improvement was reported as follows: M = 67 percent, C = 17 percent, C plus M = 71 percent, P = 35 percent. In the metronidazole group, two patients required surgery and one had troublesome side effects. In the cotrimoxazole group, two had side effects. In the combined group (C plus M), four had troublesome side effects and two of the placebo group (P) required operation. By four weeks, there was no difference in response among the groups: (M = 44 percent, C = 62 percent, C plus M = 57 percent, P = 41 percent). Antimicrobials had no effect on fecal flora or hematologic parameters. These results indicate that antimicrobials have little therapeutic potential for relapse of intestinal Crohn's disease.

Adult↗