Hair loss with minoxidil withdrawal.
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Alopecia↗
Biomedical subjects
M George
Publications and source records attributed to M George.
Developmental regulation of insulin in the mammalian central nervous system.
We delineated the ontogeny of rabbit brain insulin concentrations to define the regulatory role of development on this hormone in the central nervous system. Employing a sensitive ELISA, we observed higher concentrations in the late gestation fetal brain (approximately 80-90 ng/g) and early neonatal brain (approximately 195 ng/g) in comparison to the adult (approximately 32 ng/g; P less than 0.01). Further, we characterized this hormone to determine the identity of insulin (or an insulin-like substance) in brain. Employing porcine/bovine or rabbit insulin as standards, we observed that brain insulin mimicked authentic insulin in its migration on SDS-polyacrylamide and native gel electrophoresis, immunogenicity on Western blot analysis, and its elution profile on immunoaffinity column chromatographic, and high performance liquid chromatographic separation. We then examined the developmental effects on circulating and cerebrospinal fluid (CSF) radioimmunoassayable insulin levels. No statistically significant differences (ANOVA) existed through development in either the serum or CSF insulin levels. Employing multiple regression analysis, no correlation was evident between brain and either serum or CSF insulin concentration. A search for insulin mRNA by Northern blot analysis yielded minute amounts of atypical large sized transcripts. We conclude that the insulin peptide in the central nervous system closely resembles (or is identical to) circulating insulin in many properties and that there is a developmental increase in brain insulin concentrations, the maximal peak occuring in the late gestation fetus and early neonate. Insulin concentrations in brain demonstrate no conventional relationship to either the serum or CSF insulin levels, suggesting an additional source of peptide, which contributes beyond that which is available via the circulation. The amounts of insulin present within the central nervous system are minute (difficult to detect) but in the range (10-100 ng) where the hormone can interact with either insulin or insulin-like growth factor I (IGF-I) receptors that are abundantly present on developing brain cells, thereby executing the biological function of the hormone.
Aging↗
The LCR-like alpha-globin positive regulatory element functions as an enhancer in transiently transfected cells during erythroid differentiation.
A positive regulatory element (PRE) similar to the locus control region (LCR) of the human beta-globin gene cluster has recently been identified 40 kb upstream of the human zeta-globin mRNA cap site (Higgs D.R. W.G. Wood, A.P. Jarman, J. Sharpe, J. Lida, I.M. Pretorius, and H. Ayyub. 1990). We investigated the influence of the alpha PRE on human alpha-globin promoter activity in transiently transfected cells. The introduction of the alpha PRE into alpha-globin promoter/CAT expression constructs increased alpha-globin promoter activity by 15-30 fold in a human erythroid cell line (Putko) as well as in mouse erythroleukemia cells (MELCs) induced with hexamethylene bisacetamide (HMBA). When these constructs were introduced into uninduced MELCs or HeLa cells, only a 2-3 fold increase in alpha-globin promoter activity was observed. Deletion of 600 bp of alpha-globin 5' flanking sequences containing six putative SP1-binding sites had no significant effect on levels of alpha-globin promoter enhancement by the alpha PRE. We further demonstrated that the alpha PRE and HS2 of the beta-LCR could similarly enhance transcriptional activity of the SV40 early promoter in HMBA induced MELCs. Finally, we showed that alpha-globin promoter activity in the presence of the alpha PRE increased with continued HMBA exposure and was coincident with transcriptional activation of endogenous globin genes.
Acetamides↗
Preliminary evidence for methamphetamine-induced behavioral and ocular effects in rat offspring following exposure during early organogenesis.
Gravid Sprague-Dawley CD (VAF) rats received 50 mg/kg (d,l)-methamphetamine (MA) HCl (expressed as free base, N = 15) or distilled water (N = 6) by SC injection x 2/day in a 3 ml/kg volume on embryonic (E) days 7-12. Control rats were pair-fed to MA-exposed dams on days E7-18. No control dams failed to deliver; however, of 15 MA-exposed dams 4 did not deliver (2 died and 2 had completely resorbed litters). One additional MA litter had all the offspring die shortly after birth. There was no difference between groups on offspring postnatal (P) body weight. The offspring exposed prenatally to MA had significantly lower olfactory orientation scores (P9, 11, 13) to their home cage scent. In a test of early activity (P10, 12, 14) the MA-exposed progeny were marginally less active than controls. MA-exposed offspring exhibited hyperreactivity and marginally shortened response latency on a test of acoustic startle (P27). Motor activity showed no differential response in MA treated or control offspring to MA (P63) or fluoxetine challenge (P70). However, the MA offspring were more active than controls with respect to central and side activity during the second week of testing. No group differences were found for performance in a straight swimming channel or on the number of errors committed or latency to escape in a complex (Cincinnati) water maze (P84). Prenatal exposure to MA also induced eye defects (i.e., anophthalmia, microphthalmia and folded retina) in 16.7% of the progeny. However, MA did not effect hippocampal or neostriatal monoamine levels when measured on P28.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
[Vascular effects of urapidil administrated during extracorporeal circulation].
Urapidil exerts a combined central sympathetic and peripheral alpha-1 adrenergic receptor inhibition. Urapidil induces arterial vasodilation but its effects on venous capacitance are more difficult to assess. During cardiopulmonary bypass with constant perfusion index (2.4 l.min-1 x m-2) total peripheral resistance varies similarly as to arterial pressure and, as the apparatus venous reservoir is filled continuously by simple gravity from the right atrium, a decrease in venous blood reservoir level reflects an increased venous capacitance. Twenty-six patients undergoing cardiac surgery were anaesthetized with fentanyl and midazolam and randomly assigned to one of two groups. During normothermic cardiopulmonary bypass, group 1 was administered i.v. urapidil 12.5 mg and group 2 a placebo. In group 1, arterial pressure decreased by 33 +/- 14% (mean +/- SD) at the second minute while total peripheral resistance decreased from 1,384 +/- 255 to 927 +/- 193 dyn.s.cm-5. Then this two parameters regained group 2 values after the eighth minute. Reservoir blood level was lower in group 1 than in group 2 from the second to the eight minute (p < 0.05) with maximum effect at 7 minutes. It is concluded that urapidil exerts arterial and venous dilation. Its arterial effects seem greater during normothermic cardiopulmonary bypass than in normal conditions and its maximum venous effects seem to occur after its maximum arterial effects. The short duration of action may be due to the small dose administered.
Aged↗
Diabetes mellitus in The Gambia, west Africa.
A register of diabetic patients attending the Royal Victoria Hospital, Banjul, The Gambia, was kept and data on hospital admissions recorded over a 1-year period. Two hundred and sixty-nine patients (110 men, 159 women) were registered of whom 66 (25%) were receiving insulin. Seventy-five patients (28%: 40 men, 35 women) were newly diagnosed. There were significant differences in age (p less than 0.001) and obesity (p less than 0.001) between men and women and between patients with different types of diabetes. There were 95 hospital admissions (5.2%) related to diabetes, as were a fifth of medical out-patient attendances. Ketoacidosis was the major cause of death while foot infections were more common (p less than 0.01) in women. Diabetes imposed a heavy burden on the health services of The Gambia, a small developing country in West Africa; more than 3.6% of the annual health budget was spent on the treatment of diabetic patients.
Adult↗
GP's attitudes towards drug users.
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Attitude of Health Personnel↗
Helicobacter pylori. Its role in the pathogenesis of peptic ulcer disease in a new animal model.
The association and causative role of Helicobacter pylori infection of the stomach with gastric ulcer, duodenal ulcer, non-ulcer dyspepsia, and gastritis has remained controversial. The authors studied the effects of daily intragastric administration of H. pylori suspension in saline (10(8) CFU/ml) and bacteria-free filtrates of saline H. pylori suspensions in 85 Sprague-Dawley rats (weight, 150 to 200 g) with normal mucosa and with surgically produced experimental gastric ulcers. Group I rats (n = 30) with pre-existent experimental gastric ulcers received H. pylori suspension (ATCC 43504, 10(8) CFU/ml); Group II rats (n = 20) with experimental gastric ulcers received bacteria-free H. pylori filtrates; Group III rats with ulcers (n = 20) received saline alone; and Group IV control rats (n = 15) without ulcers received intact H. pylori organisms in suspension (ATCC 43504, 10(8) CFU/ml). At death, ulcer surface areas were measured with a dissecting microscope. Full-thickness sections were obtained for quantitative and qualitative histologic parameters, including the area of remaining mucosal necrosis; characteristics and cellular composition of restored mucosal architectures; and presence or absence of inflammation including counts of neutrophils and lymphocytes. H. pylori organisms were identified within the surface mucus and crypts using routine, special, and immunohistochemical stains. Our results indicate that the continued presence of either intact H. pylori organisms or bacteria-free H. pylori filtrates in the stomachs of rats with pre-existent gastric ulcers resulted in delayed healing of the ulcers and persistence of chronic active inflammation. Daily administration of suspensions of H. pylori organisms to sham-operated rats with intact gastric mucosa, however, resulted in no ulceration or inflammation despite identification of surface H. pylori organisms at death. The authors conclude that H. pylori alone causes little or no effect on an intact gastric mucosa in the rat, that either intact organisms or bacteria-free filtrates cause similar prolongation and delayed healing of pre-existing ulcers with active chronic inflammation, and that the presence of predisposing factors leading to disruption of gastric mucosal integrity may be required for the H. pylori enhancement of inflammation and tissue damage in the stomach.
Animals↗
Peripartum cardiac failure in The Gambia.
Twenty-seven patients with peripartum cardiac failure were seen at the Royal Victoria Hospital, Banjul over a 2-year period while one further patient presented 6 months after delivery with a cerebral embolus secondary to a dilated cardiomyopathy. Five (18%, P less than 0.001) patients had twin pregnancies. Seventeen (63%) patients attended for follow-up, of whom eight had evidence of continuing cardiac dysfunction and required treatment with diuretics; two patients were known to have died. In five asymptomatic patients the electrocardiogram had reverted to normal and three patients had further pregnancies without relapse. The bipolar distribution of onset of symptoms in relation to pregnancy was suggestive of two different pathological processes. There was no evidence that cultural habits played any significant part in the aetiology of peripartum cardiac failure in The Gambia.
Adolescent↗
Haemodynamic and biological effects of intravenous milrinone in patients with a low cardiac output syndrome following cardiac surgery: multicentre study.
The haemodynamic and biological effects of intravenous milrinone were studied in 24 adult patients with a low cardiac output syndrome following cardiac surgery. The patients received a milrinone bolus of 50 micrograms kg-1 over 10 min followed by a 0.375-0.750 micrograms kg-1 min-1 infusion over 48 h. After the first hour of treatment, an increase in cardiac index, systolic index and left ventricular stroke work index, and a decrease in right and left loading pressures, pulmonary artery pressure, systemic vascular resistance and pulmonary vascular resistance were observed while heart rate and systemic arterial pressure were not modified. These haemodynamic effects were maintained over the 48 h of treatment and persisted 3 h after discontinuation of treatment. Milrinone, which possesses inotropic and vasodilatory effects, increased cardiac performance and corrected the low cardiac output in all patients.
Adult↗
The use of cerebral activation procedures with single photon emission tomography.
Single photon emission tomography allows the imaging of dynamic brain functioning. The use of cerebral activating procedures within the scan protocol enables investigation of the mechanisms involved in specific brain functions in health and disease. Activation studies involve the comparison of at least two data sets describing brain activity generated in conditions that differ for the specific function in question. When designing an activation study, decisions regarding methodology include: the nature of the activation regime, the tracer-ligand utilized, the SPET instrument and the manner of subsequent data analysis. These issues are discussed in this review, both theoretically and with reference to published studies. Means of activating particular cerebral structures and functions are reviewed, as are the limitations of the techniques with respect to temporal and spatial resolution and the potentially confounding nature of preconceived ideas regarding the mechanisms of brain function.
Brain↗
Helicobacter pylori affects the quality of experimental gastric ulcer healing in a new animal model.
Helicobacter pylori has been implicated in the genesis of human gastritis, dyspepsia, and peptic ulcers. However, its influence in the quality of experimental gastric ulcer healing has not been previously investigated. Standardized gastric fundic ulcers were produced in 50 male Sprague-Dawley rats (150-200 g) by a 4 mm in diameter focal, serosal application of 100% acetic acid. Thirty rats were administered 2 ml H. pylori suspension (urease producing, ATCC 43504) in normal saline (10(8) CFU/ml) 2x/day for 7 days. Twenty rats (controls) received 2 ml normal saline 2x/day for 7 days. Gastric ulcer surface area was measured under a dissecting microscope and mucosal specimens were obtained for qualitative and quantitative histology. No gross or microscopic duodenal abnormalities were identified at sacrifice. Ninety percent of control rats showed grossly and microscopically entirely healed ulcers. The remaining 10% showed partially reepithelialized ulcers (area, 0.78 to 1.77 mm2; mean, 1.27 +/- 0.7 mm2). The grossly "healed" mucosa demonstrated marked dilatation of gastric glands lined with mature surface epithelial cells. Parietal cells were scanty (5-10% of all cells). One hundred percent of the H. pylori-exposed rats showed persistence of chronic active ulcers (area, 1.76 to 19.63 mm2; mean, 8.95 +/- 6.15 mm2). The ulcer beds were infiltrated by acute and chronic inflammatory cells, abundant fibroblasts, and capillary networks. The raised ulcer borders were characterized by dilated glands lined by mature surface epithelial cells. Various special stains demonstrated the presence of H. pylori in the surface mucus and within the crypts.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetates↗
[Hemodynamic effects of amrinone in low cardiac output after mitral valve replacement].
The efficacy of amrinone was assessed in the treatment of low cardiac output states occurring within 24 h after mitral valve replacement in an open prospective trial. It included 7 women and 5 men, aged 58 +/- 10 years. Four patients had also had simultaneous aortic valve replacement. Patients entered in the study if their cardiac index (CI) remained less than 2.2 l.min-1.m-2 after pulmonary wedged pressure (Ppw) had been increased to at least 15 mmHg, the patient having a temperature greater than 36 degrees C. Amrinone was given so as to increase Cl by at least 30% and to decrease Ppw by at least 30%. Patients were given a mean of 1.5 mg.kg-1 amrinone during the first hour, followed by a constant rate infusion of 9 +/- 3 micrograms.kg-1.min-1 over at least 24 h. The usual haemodynamic parameters were measured and calculated before giving amrinone, and after 1, 3, 6, 24, and 48 h. After 1 h of treatment, systolic arterial pressure, cardiac index, systolic index and left ventricular stroke work increased by 22, 42, 23, and 47% respectively, whilst Ppw decreased by 27% (p less than 0.01). Heart rate rose and systemic vascular resistance decreased but not significantly. Right atrial pressure, right ventricular stroke work, pulmonary artery pressure and pulmonary vascular resistance did not change. These effects were all maintained throughout the 48 h infusion. Amrinone had to be replaced by another agent (a beta-agonist) in 3 cases because of arrhythmia, lack of efficacy or thrombocytopaenia. In this setting, amrinone increased left ventricular performance with little effect on the right ventricle.
Adult↗
A phase I trial of 14-day continuous intravenous infusion mitoxantrone.
Based on clinical evidence that prolonged exposure to anti-neoplastic agents may ameliorate dose-limiting toxicity while facilitating anti-tumor activity, we conducted a phase I trial of 14-day continuous intravenous infusion mitoxantrone. Study objectives were to: (1) determine the maximally tolerated dose for phase II trials; (2) determine the incidence and severity of side effects; and (3) study the pharmacokinetics of continuous infusion mitoxantrone. Sixteen patients with drug-resistant advanced cancers were entered into the trial. Three or more patients were treated at each dose level (1.0, 1.25, and 1.5 mg/m2/day) for a total of 33 courses (mean 2.1 courses/patient, range, 1-4). Courses were repeated every 4 weeks. The maximally tolerated dose (MTD) was found to be 1.5 mg/m2/day. At this dose four of six patients had grade III or IV leukopenia (mean WBC nadir 1900/microliters, range, 800-3600/microliters). Other toxicities were grade I or II stomatitis (two patients), grade I diarrhea (one patient), and grade I nausea (one patient). Renal and hepatic toxicity were not observed. No alopecia or infectious complications occurred. Pharmacokinetic studies were performed using high-performance liquid chromatography (HPLC). Steady-state plasma levels at the 1.5 mg/m2/day dose were reached by 48 h, with a mean steady-state plasma concentration of 3.2 +/- 0.7 ng/ml, mean total body clearance of 340 +/- 79 ml/min/m2, and mean area under the plasma disappearance curve (AUC) of 955 +/- 185 micrograms h/l. No responses were observed, although no patients with mitoxantrone-sensitive tumors were treated.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Continuous venovenous hemodialysis after cardiac surgery.
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Acute Kidney Injury↗
5 q-syndrome and monoclonal gammopathy with alpha 1 antitrypsin deficiency.
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Aged↗
[Study of high doses of carboplatin as a first choice in the therapy of advanced ovarian cancers].
Thirty female patients with ovarian cancer of poor prognosis were included in a chemotherapy trial using high dose IV carboplatin--800 mg/m2 every 5 weeks. The subjects had three to six cycles prior to second laparotomy. Twenty-eight patients were assessable. There was no neurological, auditory or renal toxicity. Limiting toxicity was haematological, the mean neutrophil count was less than 650 mm3 and the mean platelet count less than 30,000/mm3. No death occurred from toxicity. The clinical response rate was 67%, and the surgical response rate 53.5%, with 15% complete histological responses. Survival at 18 months is 36%. A trial concerning 36 patients treated with an association of carboplatin at the same dose combined with cyclophosphamide has just been completed and the results are being analyzed.
Adenocarcinoma↗
Rural community mental health consumer satisfaction and psychiatric symptoms.
This study examined the impact of therapy on psychiatric symptoms and consumer satisfaction in a rural community mental health center. Utilizing the Brief Symptom Inventory (BSI) and an evaluation of service questionnaire (EOS), designed by the authors, results indicated positive outcomes for both measures (88 subjects). Small but significant correlations were obtained for the BSI and EOS (r's .29 to .59). Implications for future research and treatment are discussed focusing on time of intervention and symptom quality.
Adaptation, Psychological↗