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Biomedical subjects

H Fletcher

Publications and source records attributed to H Fletcher.

At least 55 records · Page 3Linked to original sources
PubMed1999

Synthesis and SAR of adatanserin: novel adamantyl aryl- and heteroarylpiperazines with dual serotonin 5-HT(1A) and 5-HT(2) activity as potential anxiolytic and antidepressant agents.

Several novel functionalized adamantyl aryl- and heteroarylpiperazine derivatives were prepared and examined in various receptor binding and behavioral tests to determine their serotonin receptor activities. Many compounds demonstrated modest to high affinity for 5-HT(1A) receptors, with compounds 9, 13, 23, 33, 34, and 43 being the most potent at this site. Compound 1, 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl adamantyl-1-carboxylate, demonstrated relatively high affinity for 5-HT(1A) receptors (K(i) = 8 nM) and acceptable selectivity versus D(2) receptors (K(i) = 708 mM); however, it lacked in vivo activity in serotonergic behavioral models. In contrast, compounds 9 (WY-50,324, SEB-324, adatanserin), adamantyl-1-carboxylic acid 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamide, and 13, adamantyl-1-carboxylic acid 2-[4-(2-methoxyphenyl)-1-piperazinyl]ethylamide, demonstrated high affinity for 5-HT(1A) binding sites (K(i) = 1 nM for both) and moderate affinity for 5-HT(2) receptors (K(i) = 73 and 75 nM, respectively). Both compounds also demonstrated partial 5-HT(1A) agonist activity in vivo in rat serotonin syndrome and 5-HT(2) antagonist activity in quipazine- and DOI-induced head shake paradigms. The selective 5-HT(1A) partial agonist and 5-HT(2) antagonist activity of 9 was accompanied by significant anxiolytic activity in an animal conflict model. On the basis of this profile, compound 9 entered development as a combined anxiolytic and antidepressant agent.

Animals↗
PubMed1999

An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia.

Placental blood flow is decreased in pre-eclampsia and is worsened by decreasing blood pressure. Hydralazine, which causes vasodilatation, does not affect placental bed vessels. Calcium channel blockers (like isradipine) are vasodilators that do affect placental bed vessels and should improve blood flow even while decreasing blood pressure. The aim of the study was to determine if isradipine (parenteral and oral) was better than parenteral hydralazine and oral methyl dopa in severe pre-eclampsia in achieving better control of blood pressure. The study was a prospective randomised trial performed at The University Hospital of the West Indies. The sample consisted of 39 women with severe pre-eclampsia. Variables examined consisted of blood pressure before and after treatment, the increment in gestational age at delivery related to treatment, fetal Apgar score and birth weight. There were no significant differences in any of these variables between the two groups. Isradipine was as effective as hydralazine in reducing maternal blood pressure and in prolonging pregnancy.

Clinical Trial↗
PubMed1999

Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults.

UNLABELLED: A variety of methods have been used to quantify aspects of recovery after anesthesia. Most are narrowly focused, are not patient-rated, and have not been validated. We therefore set out to develop a patient-rated quality of recovery score. We constructed a 61-item questionnaire that asked individuals (patients and relatives, medical and nursing staff; total n = 136) to rate various postoperative items describing features a patient may experience postoperatively. The most highly ranked items were included in a final nine-point index score, which we called the "QoR Score." We then studied two cohorts of surgical patients (n = 449). There was good convergent validity between the QoR Score and the visual analog scale score (rho = 0.55, P < 0.0001). Discriminant construct validity was supported by comparing resultant QoR Scores in patients undergoing day-stay, minor, and major surgery (P = 0.008), as well as a negative correlation with duration of hospital stay (rho = -0.20, P < 0.0001), and, using multivariate regression, demonstrating a significant negative relationship between QoR Score and female gender (P = 0.048) and older age (P = 0.041). There was also good interrater agreement (rho = 0.55, P < 0.0001), test-retest reliability (median rho = 0.61, P < 0.0001), and internal consistency (alpha = 0.57 and 0.90, P < 0.0001). There was a significant difference between the groups of patients recovering from major and minor surgery (P < 0.001). This study demonstrates that the QoR Score has good validity, reliability, and clinical acceptability in patients undergoing many types of surgery. IMPLICATIONS: We set out to develop a patient-rated quality of recovery score (QoR) that could be used both as a measure of outcome in perioperative trials and for clinical audit. We first surveyed patients and staff to identify important aspects of recovery, then developed a nine-point QoR Score. This was then compared with other measures of postoperative outcome. We found that the QoR Score is a useful measure of recovery after anesthesia and surgery.

Adolescent↗
PubMed1999

Lupus anticoagulant in Jamaican primiparae and the clinical significance in asymptomatic patients.

Sera from one thousand pregnant primiparous women from the antenatal clinic of the University Hospital of the West Indies (UHWI) were screened for lupus anticoagulant. Twenty-three women (2.3%) were seropositive. A review was performed after delivery and eight hundred and sixty-eight (87%) of the case notes were found: 20/23 (87%) of those with positive tests and 848/977 (87%) of those with negative tests. The outcome variables examined were pre-eclampsia, postpartum haemorrhage, type of delivery, birth weight of the baby, foetal outcome, foetal distress, still birth, neonatal death, Apgar score at birth and need for admission to the special care nursery. No differences were found between the two groups for any of these variables.

Female↗
PubMed1999

Massive ascites secondary to severe endometriosis.

Massive ascites is an unusual association with endometriosis. This case report is of such a condition in an Afro-Jamaican woman. The diagnosis was made at laparotomy and conservative treatment was adopted allowing for retention of reproductive function. Postoperative therapy was Goserelin, a Gonadotropin Releasing Hormone (GnRH) agonist, for six months. This relieved all of her symptoms. However, long term follow-up is needed, as recurrence is possible.

Adult↗
PubMed1996

A randomized comparison of vasopressin and tourniquet as hemostatic agents during myomectomy.

OBJECTIVE: To assess the comparative efficacy of perivascular vasopressin and tourniquet in minimizing bleeding and its sequelae at myomectomy. METHODS: Between March 1994 and February 1995, 52 women with symptomatic uterine leiomyomas scheduled for myomectomy were entered into a randomized trial comparing vasopressin (26 patients) and tourniquet (26 patients) for hemostasis. Myomectomy was performed after either the perivascular injection of 20 U of vasopressin diluted to 20 mL with normal saline or with the use of a Foley catheter tourniquet around both uterine vessels. The efficacy of each method was measured by comparing differences in pre- and postoperative hemoglobin levels, intraoperative blood pressure, measured blood loss, need for blood transfusion, evidence of postoperative febrile morbidity, complications, and length of hospital stay. RESULTS: Vasopressin resulted in less blood loss (mean 287.3 mL [standard deviation (SD) 195] versus 512.7 mL [SD 400] for tourniquet [P = .036]). Six of 26 patients in the tourniquet group lost more than 1000 mL of blood, whereas all of the vasopressin subjects lost less than this amount (P = .023). However, there were no significant differences between the two groups in the fall in the hemoglobin level, number of blood transfusions given, intraoperative blood pressure, highest postoperative pulse and temperature, or other complications. CONCLUSION: Vasopressin prevents blood loss better than using the tourniquet during myomectomy.

Adult↗
PubMed1994

Intramyometrial vasopressin as a haemostatic agent during myomectomy.

OBJECTIVE: To assess the efficacy of intramyometrial vasopressin for minimising bleeding and its sequelae at myomectomy. DESIGN: A randomised placebo controlled trial. SETTING: University Hospital of the West Indies, Kingston, Jamaica. SUBJECTS: Twenty women with symptomatic uterine fibroids scheduled for myomectomy who satisfied entry criteria: 10 randomised to the vasopressin group and 10 to the control group. INTERVENTION: Myomectomy was performed after the intramyometrial injection of either 20 units vasopressin diluted to 20 ml in normal saline or placebo (20 ml normal saline). MAIN OUTCOME MEASURES: The efficacy of vasopressin was measured by comparing pre- and post-operative haemoglobin levels and haematocrit, changes in intra-operative pulse and blood pressure, measured blood loss, need for blood transfusion and post-operative febrile morbidity in the treatment and control groups. RESULTS: The use of vasopressin resulted in median blood loss of 225 ml (range 150-400 ml) compared with 675 ml (range 500-800 ml) in the placebo group (P < 0.001). The vasopressin group had a correspondingly lower fall in haemoglobin level (median 1.7 g/dl vs 5.3 g/dl, P < 0.001) and haematocrit (median 5% vs 13%, P < 0.001) compared with the controls. Fifty percent of the placebo group had blood transfusions compared with none in the vasopressin group (P = 0.03). There were no significant differences between the groups in intra-operative pulse and blood pressure or post-operative white blood cell counts or temperature. CONCLUSION: The results indicate that vasopressin is effective in preventing blood loss and reducing the need for blood transfusion during myomectomy.

Adult↗
PubMed1994

Intravaginal misoprostol versus dinoprostone as cervical ripening and labor-inducing agents.

OBJECTIVE: To compare dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for ripening the cervix and inducing labor at term. METHODS: Sixty-three women were randomized to receive 100 micrograms misoprostol or 3 mg dinoprostone, both as intravaginal tablets. RESULTS: There was no statistical difference between the groups for pre-induction status. The mean Bishop scores before drug insertion were almost identical. Twelve hours after insertion, the mean change in the Bishop score was significantly higher in those receiving misoprostol (5.0 versus 3.3) (P = .008). However, there were no significant differences in induction-to-delivery interval, spontaneous labor rates, type of delivery, fetal outcome, or maternal complications. CONCLUSION: Misoprostol is as effective as dinoprostone for inducing labor at term.

Administration, Intravaginal↗
PubMed1992

Radical vulvectomy--a 21-year review.

The factors surrounding patients subjected to radical vulvectomy were examined. Most patients were over the age of 40 years. The standard butterfly incision was used in all but 2 cases. The histology in all cases was invasive squamous cell carcinoma. The main complications were primary haemorrhage, urinary tract infection and wound dehiscence. The mean hospital stay was 50 days and the mortality rate was 4 per cent.

Adult↗
PubMed1990

2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and antidepressant activity.

A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined for the ability to inhibit both rat brain imipramine receptor binding and the synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter uptake inhibition was highest for a subset of 2-phenyl-2-(1-hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or methoxy substituent at the 3- and/or 4-positions. Potential antidepressant activity in this subset was assayed in three rodent models--the antagonism of reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release, and the ability to reduce noradrenergic responsiveness in the rat pineal gland. An acute effect seen in the rat pineal gland with several analogues, including 1-[1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2-(dimethylamino)-1)-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a possible correlate of a rapid onset of antidepressant activity. Compound 4 (venlafaxine) is presently undergoing clinical evaluation.

Adrenocorticotropic Hormone↗
PubMed1990

Penile prostheses in the management of impotence in sickle cell disease.

Priapism lasting more than 24 h in adults with homozygous sickle cell disease usually results in impotence. The dense fibrosis of the corpora cavernosa which destroys the normal vascular erectile system of the penis also complicates insertion of penile prostheses. Our experience in 5 patients is reviewed. Sharp dissection and dilatation were necessary to form a tunnel for the prosthesis, which was more easily excavated anteriorly and posteriorly through a dorsal incision than for the length of the corpora through a traditional perineal-scrotal incision. Damage to the tunica was common and subsequent migration of the prosthesis necessitated an additional 11 procedures under general anaesthesia. Despite these technical difficulties, the procedure allowed satisfactory intercourse. The average interval between onset of impotence and implantation was 4 years. Early implantation before the dense fibrosis develops might give more satisfactory results.

Adult↗
PubMed1989

Emergence of isolates resistant to ampicillin.

Clinical isolates of Streptococcus faecium demonstrating ampicillin resistance were recovered from eight pediatric patients. Sites of isolation included blood, surgical wound, bile drainage, urine, burns, and peritoneal fluid. Seven patients had prolonged hospitalization, and all had been treated with broad-spectrum antibiotics prior to isolation of the resistant enterococcus. One isolate was from an ill, bacteremic patient; the others were in mixed culture and were not considered causes of disease. The isolates were not epidemiologically related. Minimal inhibitory concentrations for various antibiotics included ampicillin (16 to 32 mg/L), penicillin (128 mg/L), gentamicin (16 mg/L), and vancomycin (2 mg/L). Three isolates demonstrated high-level resistance (greater than 2000 mg/L) to streptomycin; none did so to gentamicin. In vitro synergy testing performed on seven available isolates for ampicillin and gentamicin demonstrated no synergy to this combination. None produced beta-lactamase. Combined antibiogram and plasmid data showed at least five distinct patterns. These strains present a new clinical problem in their high level of resistance to ampicillin and to the combination of ampicillin and gentamicin.

Ampicillin Resistance↗