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Biomedical subjects

S G Smith

Publications and source records attributed to S G Smith.

At least 55 records · Page 3Linked to original sources

An investigation of the pharmacokinetics of topical terbinafine (Lamisil) 1% cream.

Twenty human volunteers were entered into a study to investigate the pharmacokinetics of terbinafine 1% cream. Subjects were randomized to receive terbinafine 1% cream applied to the back on 1 day, or on 3, 5 or 7 consecutive days. Up to five sequential skin surface biopsies were taken at a site on the upper back at various time-points both during treatment, and following cessation of treatment. Terbinafine levels in these biopsies were analysed using HPLC. The study showed that increasing the number of applications from one to seven did not significantly increase the peak concentration (Cmax) in the stratum corneum. It did, however, increase the total amount of terbinafine found in the stratum corneum, resulting in terbinafine being detected for longer periods after cessation of therapy. Treatment for 7 days resulted in terbinafine still being detectable 7 days after cessation of therapy, when the terbinafine concentration was significantly higher than the known cidal concentrations for the common causative organisms of superficial dermatomycoses. This study indicates a significant potential for short-duration treatment with terbinafine (Lamisil) 1% cream in superficial dermatomycoses.

Administration, Topical↗

The stimulatory and inhibitory effects of dopamine on prolactin secretion involve different G-proteins.

The reverse hemolytic plaque assay (RHPA) was used in this study to further characterize the mechanism whereby low concentrations of dopamine (DA) stimulate PRL secretion in vitro. Female Sprague-Dawley rats were used as a source of anterior pituitary cells for the RHPA. Pituitary cells were infused into Cunningham chambers along with a suspension of protein-A-coated ovine red blood cells. Excess cells were rinsed from the chambers leaving a monolayer of cells attached to the glass. The cells were then incubated with solutions containing PRL antiserum (1:40) and various concentrations of DA. After 4 h, a solution containing guinea pig complement (1:60) was infused into the chambers. Thirty minutes later, the cells were fixed and plaques (zones of hemolysis) surrounding PRL-producing cells (lactotrophs) were measured and used as an index of the amount of PRL secreted. Control cells that received no DA had a mean plaque area of 8,000 microns 2 and two distinct subpopulations of plaque sizes. This biphasic population of cells consisted of a small and a large plaque producing population. The mean plaque area surrounding lactotrophs was significantly (P less than 0.05) decreased if 1 microM or 10 microM DA was present (4,500 microns 2 and 3,500 microns 2, respectively). These cells which received inhibitory concentrations of DA demonstrated a monophasic distribution of plaque-forming cells. On the other hand, mean plaque area was significantly (P less than 0.05) increased if 0.1 nM or 1 nM DA was presented to the cells (15,000 microns 2 and 14,500 microns 2, respectively). These cells receiving stimulatory doses of DA exhibited a multiphasic distribution of plaque-forming cells. The possibility that the two physiological opposing actions of DA on PRL secretion might be mediated by different GTP binding proteins was also examined using cholera toxin (CTX) and pertussis toxin (PTX). Anterior pituitary cells were pretreated with either CTX (50 micrograms/ml) or PTX (5 micrograms/ml) for 1 h before initiation of the RHPA. In the RHPA, cells received no DA, a stimulatory dose of DA (0.1 nM), or a inhibitory dose of DA (10 microM). The effects of toxin pretreatment on mean plaque area of DA-treated cells was determined. PTX pretreatment significantly attenuated the inhibitory effects of DA while having no effect on the stimulatory effects of DA on PRL secretion. CTX significantly (P less than 0.05) potentiated the stimulatory effects of DA on PRL secretion and had no effect on inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

An interesting case presentation: peripartum meningococcal meningitis.

Meningococcal disease during pregnancy is extremely rare. A single reported case occurred more than 20 years ago in England. We present the case of a young woman who just hours after delivery of her baby developed fulminant meningococcal meningitis with its classic findings. Our experience illustrates the importance of early diagnosis and appropriate therapy of meningococcal disease in the gravid as well as in the nongravid population.

Adult↗

Peripheral anterior synechiae formation with anterior chamber intraocular lenses.

In a cross-sectional study, 88 eyes with anterior chamber intraocular lenses (AC-IOLs) were evaluated by goniophotography by one masked observer for the presence of peripheral anterior synechiae (PAS) and by another masked observer for the length of the AC-IOL. Sixty-eight of the 88 lenses had PAS which were strongly correlated with the lens being oversized (P less than .001). However, differences in haptic style or lens rigidity were not associated with the presence of PAS.

Anterior Chamber↗

2% hydroxypropyl methylcellulose as a viscous surgical adjunct. A multicenter prospective randomized trial.

A multicenter prospective trial was conducted comparing preoperative and postoperative endothelial cell counts in patients who had extracapsular cataract extraction with posterior chamber lens implantation or phacoemulsification and posterior chamber lens implantation. One hundred sixty six eyes received 2% hydroxypropyl methylcellulose (Occucoat) and 56 eyes received sodium hyaluronate (Healon). The average cell loss in the Occucoat group was 12.1%; in the Healon group it was 10% (P = NS). There was no significant difference between the two groups in intraocular pressure at 24 hours. In this study Occucoat was as effective in protecting the corneal endothelium as Healon.

Aged↗

Nucleus-splitting phacoemulsification technique.

A technique for phacoemulsification that can be used with or without capsulorhexis and that allows surgery to be performed at the 12 o'clock position is described. Following central sculpting, the nucleus is tipped superiorly to the level of the iris plane with a second instrument and the phacoemulsification tip. The hard nucleus is split from the soft nucleus, leaving two bowl-shaped pieces. The nucleus is rotated and the hard nucleus is removed with a phacoemulsification tip while the softer nucleus or epinucleus is ignored. Once the hard nucleus has been removed, the epinucleus follows easily into the phacoemulsification tip. The technique is advantageous for beginning phacoemulsification surgeons and offers an alternative for very hard nuclei with small pupils.

Cataract Extraction↗

Pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-deoxy-2',3'-didehydrothymidine in rats.

Concentrations of 3'-fluoro-3'-deoxythymidine (FDT) and 3'-deoxy-2',3'-didehydrothymidine (D4T) in plasma declined in a biexponential fashion. Total clearance of D4T (1.75 +/- 0.22 liters/h/kg; mean +/- standard deviation) was significantly greater than that of FDT (1.19 +/- 0.19 liters/h/kg) owing to greater renal and nonrenal clearances of the former. Steady-state volumes of distribution of FDT (1.20 +/- 0.12 liters/kg) and D4T (1.07 +/- 0.15 liters/kg) were similar.

Animals↗

Endoscopic palliation of tracheobronchial malignancies.

The prognosis for tracheobronchial tumours remains poor. Most patients can be offered only palliation. When the main symptom is breathlessness or refractory haemoptysis from a large airway tumour endoscopic treatment may be very effective. Over the last decade most attention has focused on the neodymium YAG laser. This often produces dramatic effects but has some important limitations. In the last few years better techniques for stenting and intrabronchial radiotherapy (brachytherapy) have also been developed. This article discusses the range of techniques now available and aims to help clinicians decide which patients may benefit from referral to centres providing these techniques.

Brachytherapy↗

Purification and characterization of the reduced-nicotinamide-dependent 2,2'-dithiodiethanesulfonate reductase from Methanobacterium thermoautotrophicum delta H.

A novel reduced nicotinamide-dependent disulfide reductase, the 2,2'-dithiodiethanesulfonate [(S-CoM)2] reductase (CoMDSR) of Methanobacterium thermoautotrophicum was purified 405-fold to electrophoretic homogeneity. Both NADPH and NADH functioned as electron donors, although rates with NADPH were three times higher. Reduced factor F420, the deazaflavin electron carrier characteristic of methanogenic bacteria, was not a substrate for the enzyme. The enzyme was most active with (S-CoM)2 but could also reduce L-cystine at 23% the (S-CoM)2 rate. Results of sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that the enzyme was monomeric with an Mr of about 64,000; spectral analysis showed that it was a flavoprotein with an estimated composition of one molecule of flavin per polypeptide. Maximal activity occurred at 64 degrees C, and the pH optimum was 8.5. The apparent Km for both NADPH and (S-CoM)2 was 80 microM. The enzyme was completely inactivated by oxygen in crude cell extracts but was oxygen stable in the homogeneous state. The low activity of the CoMDSR in cell extracts as well as its relatively low rate of reducing CoM-S-S-HTP (the heterodisulfide of the two thiol cofactors involved in the last step of methanogenesis) make it unlikely that it plays a role in the methylreductase system. It may be involved in the redox balance of the cell, such as the NADPH-dependent bis-gamma-glutamylcystine reductase with which it shows physical similarity in another archaebacterium, Halobacterium halobium (A. R. Sundquist and R. C. Fahey, J. Bacteriol. 170:3459-3467, 1988). The CoMDSR might also be involved in regenerating the coenzyme M trapped as its homodisulfide, a nonutilizable form of the cofactor.

Chromatography, Affinity↗

Enalapril: benefit-to-risk ratio in hypertensive patients.

Enalapril is an effective agent in the treatment of mild to severe hypertension. It is equally effective in elderly and young adult patients but appears to be more effective in white than in black hypertensive patients. Following treatment with enalapril, an assessment of maximum exercise performance found a decrease in total peripheral resistance without significant changes in cardiac output, heart rate, or stroke volume compared with pretreatment values. In addition, there have been reports of reversal of left ventricular hypertrophy in enalapril-treated hypertensive patients. Enalapril is also effective and well tolerated in hypertensive patients with renal impairment of varying etiology. The most common adverse experiences reported in controlled clinical trials were headache (5.2%), dizziness (4.3%), and fatigue (3.0%). In high-risk hypertensive patients, no enalapril-treated neutropenia, proteinuria, dysgeusia, or ageusia were reported. It may be concluded that the benefit-to-risk ratio of enalapril is among the best of the antihypertensive therapies currently available.

Angiotensin-Converting Enzyme Inhibitors↗

Reproductive impairment in a fish inhabiting a contaminated coastal environment off Southern California.

White croaker (Genyonemus lineatus), collected from a highly contaminated site in San Pedro Bay and from a reference site 80 km away (Dana Point), were induced to spawn in the laboratory. Forty-one per cent of San Pedro Bay females and 54% of Dana Point females spawned. Examination of the ovaries of non-spwaning females revealed that spawning was imminent in the remainder of Dana Point fish but only in 16% of the San Pedro Bay fish. The remainder of the San Pedro Bay fish (43%) contained only immature, yolky oocytes. No croakers containing more than 3.8 ppm ovarian total DDT could be induced to spawn whereas 36% of a contemporaneous San Pedro Bay sample had ovarian total DDT residues in excess of 4 ppm. This suggests that the inability to induce spawning in white croaker may be associated with an ovarian total DDT threshold of about 4 ppm. These data, coupled with observed decreases in fecundity (32%), fertility (14%), and early oocyte loss (30%) relative to reference fish, could partially explain the population declines observed for many southern California fishes since the 1940s.

Journal Article↗

Intraocular lens removal for chronic cystoid macular edema.

Intraocular lenses were removed from ten eyes with chronic cystoid macular edema demonstrated by fluorescein angiography. No corneal transplantation was done at the time of intraocular lens removal. Five eyes achieved a visual acuity of 20/50 or better. Exchange for a posterior chamber intraocular lens did not appear to have an adverse affect compared to simple intraocular lens removal.

Anterior Chamber↗

Effects of mutations on enzyme activity and immunoreactivity of the S1 subunit of pertussis toxin.

By introducing a series of six different substitutions at and around position 9, we investigated the structural requirements of the amino-terminal region of the S1 subunit of pertussis toxin for both enzyme activity and immunoreactivity. All mutant S1 analogs with a substitution at this location exhibited severely decreased ADP-ribosyltransferase activity (range, 400- to 2,500-fold). In contrast, alteration of arginine 58 had considerably less effect. The reactivity of the mutant molecules with monoclonal antibody 1B7 varied with the nature of the substitution. These findings indicate an absolute requirement for the presence of an arginine residue at position 9 for the maintenance of efficient ADP-ribosyltransferase activity and illustrate the specific participation of vicinal residues in the formation of the protective epitope.

Adenosine Diphosphate Ribose↗

Efficacy and safety of indomethacin versus ritodrine in the management of preterm labor: a randomized study.

One hundred six patients in preterm labor with intact amniotic membranes and gestational age less than or equal to 32 weeks were randomized to receive either ritodrine hydrochloride or a 48-hour course of indomethacin for tocolysis. The relative efficacy, maternal and neonatal safety, and costs were evaluated to determine which may be the more appropriate first-line pharmacologic agent used to manage preterm labor. Fifty-four patients and 52 patients were randomized to receive ritodrine hydrochloride or indomethacin, respectively. Ritodrine hydrochloride and indomethacin were equally effective in inhibiting uterine contractions and delaying delivery. Delivery was delayed for at least 48 hours in 83 and 94%, and for at least 7 days in 70 and 75% of patients receiving ritodrine or indomethacin, respectively. Tocolysis with indomethacin was associated with no maternal side effects, whereas tocolysis with ritodrine hydrochloride was associated with a 24% incidence of serious cardiovascular and metabolic adverse effects prompting discontinuation of the drug. There were no differences in outcome between the infants exposed to indomethacin versus ritodrine hydrochloride when delivered either remote from therapy or during therapy, except for a statistically higher serum glucose in the infants exposed to ritodrine hydrochloride when delivered during tocolytic therapy. There were no cases of premature closure of the ductus arteriosus or pulmonary hypertension. Tocolysis with indomethacin was 17 times less costly than tocolysis with ritodrine hydrochloride. For gestations less than or equal to 32 weeks complicated by preterm labor, indomethacin may be an appropriate alternative as a first-line tocolytic agent.

Adult↗

Efficacy and safety of lisinopril in older patients with essential hypertension.

Angiotensin-converting enzyme inhibitor therapy has been thought to be more effective in hypertensive patients with normal or elevated levels of renin in the plasma. However, several studies have challenged this concept by demonstrating the efficacy of angiotensin-converting enzyme inhibitors (captopril and enalapril) in older patients, among whom a low level of renin activity in the plasma is common, and in other patients with low-renin essential hypertension. Lisinopril, a new long-acting angiotensin-converting enzyme inhibitor, also has been shown to be an effective antihypertensive agent in older patients. This report examines data from 97 older and 710 younger hypertensive patients enrolled in four multicenter trials of eight to 12 weeks' duration. In these trials, the dose of lisinopril was titrated until a diastolic pressure of less than 90 mm Hg was reached, or to a maximal dose of 80 mg per day. In general, the antihypertensive effect achieved in older patients with lisinopril was equal to or greater than that achieved in younger patients. The drug was generally well tolerated. Lisinopril can be expected to be used frequently in older patients.

Adolescent↗