Biomedical subjects

M Franklin

Publications and source records attributed to M Franklin.

At least 55 records · Page 3Linked to original sources

PubMed1998

Drug-associated facial dyskinesias--a study of 238 patients.

UNLABELLED: The purpose of this study was to determine whether antidepressant, antimania, antipsychotic, antihistamine, or antiparkinsonian drugs are associated with eyelid and facial dyskinesias; whether discontinuing such drugs results in improvement in the facial dyskinesias; and whether response to botulinum toxin treatment is influenced by such medications. METHODS: A retrospective review was performed on a population of 238 patients with presumed benign essential blepharospasm and Meige syndrome. Types of drugs taken before the development of disease and clinical response to botulinum toxin injections were studied. RESULTS: Fourteen of 238 patients (5.9%) with facial dyskinesias had been prescribed a variety of antidepressants, antimania medications, antipsychotics, antihistamines, antiparkinsonian drugs, or a combination of these substances before their condition developed. The onset of blepharospasm varied from 2 months to 35 years after administration of the drug. Three of seven patients who discontinued the presumed responsible drug had improvement in their facial dyskinesias. Of the 11 patients who did not improve when their drugs were stopped or whose medication could not be stopped, all but one patient had a good response to treatment with botulinum toxin A. CONCLUSIONS: Drug-induced blepharospasm should be considered in all patients who present with facial dyskinesias, and such patients should undergo withdrawal of the medication when possible. When withdrawal of medication is not possible or does not result in improvement in the facial dyskinesia, treatment with botulinum toxin injections should be initiated. The possible role in the production of facial dyskinesias of antidepressants that block reuptake of serotonin requires further evaluation.

Adult↗

PubMed1997

Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease.

BACKGROUND: Localized Lyme disease, manifested by erythema migrans, is usually treated with oral doxycycline or amoxicillin. Whether acute disseminated Borrelia burgdorferi infection should be treated differently from localized infection is unknown. METHODS: We conducted a prospective, open-label, randomized, multicenter study comparing parenteral ceftriaxone (2 g once daily for 14 days) with oral doxycycline (100 mg twice daily for 21 days) in patients with acute disseminated B. burgdorferi infection but without meningitis. The erythema migrans skin lesion was required for study entry, and disseminated disease had to be indicated by either multiple erythema migrans lesions or objective evidence of organ involvement. RESULTS: Of 140 patients enrolled, 133 had multiple erythema migrans lesions. Both treatments were highly effective. Rates of clinical cure at the last evaluation were similar among the patients treated with ceftriaxone (85 percent) and those treated with doxycycline (88 percent); treatment was considered to have failed in only one patient in each group. Among patients whose infections were cured, 18 of 67 patients in the ceftriaxone group (27 percent) reported one or more residual symptoms at the last follow-up visit, as did 10 of 71 patients in the doxycycline group (14 percent, P > or = 0.05). Mild arthralgia was the most common persistent symptom. Both regimens were well tolerated; only four patients (6 percent) in each group withdrew because of adverse events. CONCLUSIONS: In patients with acute disseminated Lyme disease but without meningitis, oral doxycycline and parenterally administered ceftriaxone were equally effective in preventing the late manifestations of disease.

Acute Disease↗

PubMed1997

Insights into thymic purine metabolism and adenosine deaminase deficiency revealed by transgenic mice overexpressing ecto-5'-nucleotidase (CD73).

The adenosine producing enzyme ecto-5'-nucleotidase (5'-NT) is not normally expressed during thymocyte development until the medullary stage. To determine whether earlier expression would lead to adenosine accumulation and/or be deleterious for thymocyte maturation, thymic purine metabolism, and T cell differentiation were studied in lckNT transgenic mice overexpressing 5'-NT in cortical thymocytes under the control of the lck proximal promoter. In spite of a 100-fold elevation in thymic 5'-NT activity, transgenic adenosine levels were unchanged and T cell immunity was normal. Inosine, the product of adenosine deamination, was elevated more than twofold, however, indicating that adenosine deaminase (ADA) can prevent the accumulation of adenosine, even with a dramatic increase in 5'-NT activity, and demonstrating the availability of 5'-NT substrates in the thymus for the first time. Thymic adenosine concentrations of mice treated with the ADA inhibitor 2'-deoxycoformycin (dCF) were elevated over 30-fold, suggesting that high ADA activity, rather than an absence of 5'-NT, is mainly responsible for low thymic adenosine levels. The adenosine concentrations in dCF-treated mice are sufficient to cause adenosine receptor-mediated thymocyte apoptosis in vitro, suggesting that adenosine accumulation could play a role in ADA-deficient severe combined immunodeficiency.

5'-Nucleotidase↗

PubMed1997

Comet assay in human biomonitoring studies: reliability, validation, and applications.

The comet assay (single-cell gel electrophoresis), which measures DNA strand breaks at the level of single cells, is very easily applied to human lymphocytes, and therefore lends itself to human biomonitoring studies. For the examination of DNA base oxidation (a specific marker of oxidative damage), the assay is modified by including a stage at which the DNA is incubated with a suitable lesion-specific endonuclease. Here we report on the reliability and reproducibility of this approach, from the level of comparing results from duplicate gels prepared from the same sample of cells, up to an assessment of the natural intra- and interindividual variability in lymphocyte DNA damage measured in groups of normal, healthy human volunteers. We applied the assay in investigations of human disease and occupational exposure of factory workers.

Analysis of Variance↗

PubMed1997

Complications of gold weight eyelid implants for treatment of fifth and seventh nerve paralysis.

Complications occurred in six patients after gold weights were implanted into the upper eyelid tissues for fifth and seventh nerve palsies. These complications included implant infection without extrusion (in one patient); entropion with trichiasis and presumed inflammatory reaction to the gold weight material (in one patient); upper eyelid distortion and poor eyelid contour with corneal ulceration and scarring (in one patient); significant residual lagophthalmos with exposure keratitis (in one patient); and blepharoptosis obscuring the pupillary access (in two patients). Resolution of the complications required 1. implant removal in four of six patients without reinsertion of a second weight, 2. recession of the retractors of the upper eyelids with medial and lateral canthoplasty (in four patients), and 3. permanent tarsorrhaphy (in one patient). The authors conclude that complications may be minimized by careful preoperative determination of the optimum implant size, weight, and placement within the eyelid as well as meticulous attention to the surgical technique of implantation. The use of other eyelid protective procedures is often necessary to augment corneal protection especially in patients with combined fifth and seventh cranial nerve palsies. Endogenous implant infection without extrusion of the gold weight may be distinguished from presumed inflammation due to gold allergy by clinical response to antibiotics in the former and requirements of steroids or removal of the implant in the latter.

Adult↗

PubMed1997

Activation of MAP kinase in vivo follows balloon overstretch injury of porcine coronary and carotid arteries.

Vascular restenosis involves contraction, proliferation, and remodeling of the arterial wall in response to overstretch injury. Mitogen-activated protein kinases (MAPKs) are implicated in both contraction and proliferation of vascular smooth muscle (VSM), and studies of porcine carotid arterial muscle strips have shown that mechanical stretch leads to the activation of the extracellular signal-regulated kinase (ERK) family of MAPKs in vivo. We, therefore, analyzed the acute effect of mechanical overstretch injury on ERK-MAPK (herein referred to simply as MAPK) activity in porcine coronary and carotid arteries in vivo. Balloon angioplasty catheters were inflated to 6 atm three times over 5 minutes at a balloon-artery ratio of 1.2:1 in either porcine coronary or carotid arteries. The arteries were snap-frozen after angioplasty, and MAPK activity was measured. Angioplasty of the left anterior descending (LAD, n = 5), left circumflex (LCx, n = 5), and carotid (n = 5) arteries effected an increase in MAPK activity compared with the activity in uninstrumented right coronary arteries (RCAs) or carotid arteries from the same animals used for controls. Balloon angioplasty of carotid arteries led to an increase in MAPK activity that was 7.7-fold over the activity in control arteries and comparable to the activity in stretched carotid arterial muscle strips in vivo. The increase in coronary artery kinase activity on angioplasty was variable from animal to animal. The increase in MAPK activity over that in control arteries ranged from 4.5- to 31.7-fold (mean +/- SEM, 10.7 +/- 5.3) in the LAD and 1.8- to 31.3-fold (mean +/- SEM, 9.7 +/- 5.7) in the LCx. There were no apparent inherent differences in the levels of MAPK activity in the three different types of coronary arteries (RCA, LAD, and LCx) without instrumentation. MAPK activation occurs rapidly during angioplasty, suggesting that this kinase may play an early role in initiating the injury response in both porcine coronary and carotid arteries. MAPKs may be key enzymes targeted to treat or prevent restenosis.

Angioplasty, Balloon↗

PubMed1997

Absorption of amino acids from the intestine and their net flux across the mesenteric- and portal-drained viscera of lambs.

Experiments were conducted to compare the rates of apparent absorption (disappearance) of individual essential amino acids (EAA) from the small intestine with their net fluxes across the mesenteric- (MDV) and portal- (PDV) drained viscera in sheep given a pelleted alfalfa diet at two levels of intake. Disappearances of individual EAA across the region of the small intestine drained by the mesenteric arcade (jejunum to ileum) were similar to those across the whole of the small intestine (duodenum to ileum). The net MDV flux of each EAA was similar to its rate of disappearance, but, with the exception of threonine on the low intake level, the net PDV flux was lower (P < .05). Increasing the intake of alfalfa from 800 to 1,200 g/d increased the rate of disappearance of individual EAA between the duodenum and ileum by .56 (range .43 to .65) and between the jejunum and ileum by .51 (range .45 to .60). The MDV and PDV blood flows increased by .35 and .39, respectively, and, with the exception of valine, net fluxes of individual EAA increased by .39 (range .20 to .50) across the MDV and by .44 (range .21 to .71) across the PDV. When net fluxes across the MDV and PDV were measured simultaneously, the ratio of PDV: MDV flux for each EAA was less than (P < .05) unity (mean .61, range .55 to .69), even though all MDV blood enters the PDV, contributing approximately .45 of the total portal flow. This observation suggests that, in regions of the tract not drained by the MDV, extraction of arterial blood EAA for tissue and secretory protein synthesis must exceed the release of protein degradation products into the venous drainage. The results are discussed in terms of endogenous protein secretions into the lumen of the tract anterior to the small intestine.

Amino Acids, Essential↗

PubMed1996

Determination of sumatriptan succinate in human plasma by high-performance liquid chromatography with coulometric detection and utilization of solid-phase extraction.

Sumatriptan succinate (the analyte) and naloxone (the internal standard) were extracted from plasma with a solid-phase extraction technique. Chromatography and detection were performed by isocratic reversed-phase high-performance liquid chromatography with coulometric end-point detection. The standard curve was linear over the range 0-100 ng/ml of sumatriptan succinate in plasma. The reproducibility (as defined by the coefficient of variation, C.V.) over the range of the standard curve was 4.9-7.3%. The recovery averaged 83%. The sensitivity was 0.25 ng of sumatriptan on column (allowing a concentration of 0.5 ng/ml to be determined from a 1-ml plasma sample volume). Plasma profiles of the analyte following subcutaneous (s.c.) administration in eight normal male volunteers, are presented.

Chromatography, High Pressure Liquid↗

PubMed1996

Determination of naloxone in human plasma by high-performance liquid chromatography with coulometric detection.

Naloxone, the analyte and the internal standard, sumatriptan, are extracted from plasma using solid-phase extraction columns. Chromatography and detection are performed using isocratic reversed-phase high-performance liquid chromatography (HPLC) with coulometric end-point detection. The standard curve was linear over the range 0-50 ng/ml of naloxone in plasma. The reproducibility, the coefficient of variation (C.V.) of the method over the range of the standard curve was 6.2-11.2%. The recovery averaged 90.4 +/- 8.9%. A plasma profile following i.v. administration of naloxone in one normal healthy volunteer is presented.

Analysis of Variance↗

PubMed1996

The effects of clozapine and haloperidol on serotonin-1A, -2A and -2C receptor gene expression and serotonin metabolism in the rat forebrain.

The therapeutic and side-effect profiles of clozapine differ from those of typical antipsychotic drugs such as haloperidol. Effects on the serotonin system, especially serotonin-2 receptors, may contribute to clozapine's atypicality. We injected rats for 14 days with clozapine (25 mg/kg/day) or haloperidol (2 mg/kg/day), and measured three aspects of the serotonin system in forebrain regions: abundance of serotonin-2A, -2C and -1A receptor messenger RNAs by in situ hybridization histochemistry; serotonin-2A and -1A binding sites using receptor autoradiography, and levels of serotonin and 5-hydroxyindoleacetic acid with high-performance liquid chromatography. Clozapine administration decreased serotonin-2A receptor messenger RNA and the density of [3H]ketanserin binding in cingulate and frontal cortex, but not in piriform cortex. Serotonin-1A receptor expression and serotonin-2C receptor messenger RNA were unchanged in all areas. The treatment markedly decreased serotonin and 5-hydroxyindoleacetic acid concentrations in striatum with similar trends in cortex and hippocampus. Haloperidol administration did not affect the expression of the three serotonin receptors, but was associated with a modest reduction of striatal and hippocampal 5-hydroxyindoleacetic acid. The selective reduction of serotonin-2A receptors confirms earlier findings and supports the view that this receptor may have relevance for the actions of clozapine. The fact that the encoding messenger RNA is decreased shows that the the effect is mediated at the level of gene expression. In contrast, the unchanged serotonin-2C receptor messenger RNA level indicates that the reported loss of serotonin-2C receptors after clozapine treatment is due to translational or post-translational events. The relationship between the reduction in serotonin-2A receptor expression and the altered serotonin metabolism remains unclear.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Simultaneous quantitation of buspirone and its major metabolite 1-(2-pyrimidinyl)piperazine in human plasma by high-performance liquid chromatography with coulometric detection.

Buspirone is a member of the azapirone group of anxiolytic drugs and has one major metabolite, 1-(2-pyrimidinyl)piperazine (1-PP). The analyte, its metabolite and the internal standard were extracted from plasma utilizing solid-phase extraction columns. Chromatography was performed using isocratic reversed-phase high-performance liquid chromatography with coulometric end-point detection. The calibration graph was linear over the range 0-50 ng ml-1 of plasma. The lower limits of quantitation for buspirone and 1-PP were 0.5 and 2 ng ml-1, respectively, when 1 ml of plasma was extracted. The intra-assay relative standard deviations (RSD) over the range of the calibration graph varied from 4 to 12.5% for buspirone and 1-PP. The inter-assay RSD was 6.9% for 1-PP and 9.6% for buspirone. The recovery averaged 96% for buspirone and 66% for 1-PP. Plasma profiles of buspirone and 1-PP following oral dosing are presented.

Adult↗

PubMed1996

Mechanisms of gastric and esophageal perforations during laparoscopic Nissen fundoplication.

OBJECTIVE: The purpose of this study was to determine possible mechanisms of 17 gastric and esophageal perforations that occurred during laparoscopic Nissen fundoplication. METHODS: Specific details of each perforation relating to mechanism of injury, surgeon experience, diagnosis, treatment, and outcome were obtained. For each perforation, an attempt was made to accurately determine the mechanism of perforation. RESULTS: Three mechanisms accounted for the 17 perforations, the majority of which occurred within the first ten laparoscopic Nissen fundoplications performed by the surgeon. Ten perforations resulted from injuries related to improper retroesophageal dissection, five occurred during passage of the bougie dilator or nasogastric tube, and two occurred after surgery secondary to suture pullthrough. Six patients received a delayed diagnosis, which adversely affected outcome. Most of the perforations were successfully managed by primary closure and wrap to include the repair. Morbidity was significantly increased for perforations recognized late. One death, attributed to sepsis, occurred in association with a delay in diagnosis. CONCLUSIONS: Gastric and esophageal perforations are serious complications of the new laparoscopic method of Nissen fundoplication. The mechanisms of these complications are specifically related to limitations of the laparoscopic technique. Prevention of these potentially lethal complications requires a full understanding of the detailed anatomy of the gastroesophageal region and awareness of the recognized mechanisms of perforation.

Adult↗

PubMed1996

Nebulised antipseudomonal antibiotic therapy in cystic fibrosis: a meta-analysis of benefits and risks.

BACKGROUND: To establish the benefits and risks of nebulised antipseudomonal therapy in cystic fibrosis the results of relevant randomised controlled trials were combined. METHODS: The therapeutic end points compared were (a) number of pulmonary exacerbations requiring treatment with systemic antibiotics, (b) measurable alteration in respiratory tract pseudomonal load, (c) alteration in lung function on spirometric assessment, (d) development of resistance in respiratory tract Pseudomonas strains to the nebulised antipseudomonal used in each randomised controlled trial, and (e) renal and auditory impairment. RESULTS: Five studies were suitable for meta-analysis, eight others could not be included because of inadequate outcome description or the lack of appropriate randomisation. Meta-analysis shows benefit for nebulised antipseudomonal antibiotic therapy with no demonstrable adverse effect other than a possible increase in in vitro antibiotic resistance of Pseudomonas aeruginosa of the respiratory tract. CONCLUSIONS: Although inferences drawn from individual randomised controlled trials concerning the benefits and risks of this form of therapy are conflicting, pooled effect size establishes benefit with nebulised antipseudomonal antibiotic therapy and emphasises its relevance to the integration of information in other areas of controversy relating to the treatment of this disease.

Administration, Inhalation↗

PubMed1996

Cardiomyocyte DNA synthesis and binucleation during murine development.

Cardiomyocyte DNA synthesis and binucleation indexes were determined during murine development. Cardiomyocyte DNA synthesis occurred in two temporally distinct phases. The first phase occurred during fetal life and was associated exclusively with cardiomyocyte proliferation. The second phase occurred during early neonatal life and was associated with binucleation. Collectively, these results suggest that cardiomyocyte reduplication ceases during late fetal life. Northern and Western blot analyses identified several candidate genes that were differentially expressed during the reduplicative and binucleation phases of cardiomyocyte growth.

Animals↗

PubMed1996

Standardization of clinical decision making for the conduct of credible clinical research in complicated medical environments.

The likelihood that past experience will produce correct guides to current practice depends on the signal-to-noise ratio for the clinical problem of interest. If the signal-to-noise ratio is high, the decision will be sound and patient benefit likely to occur. If the signal-to-noise ratio is low, as is commonly the case with difficult clinical decisions, then personal experience and the best intentions will not assure sound clinical decisions. When the probability of benefit cannot be quantified, clinicians in complex settings are in danger of being misled by data and experience. Quantifiable probabilities established by group experiment or observation will be necessary for clinical decisions that can be expected to confer benefit on the patient. Explicit methods are necessary for interventions that can be replicated in experiments or in practice. Computerized protocols force the articulation of explicit clinical care methods and standardize clinical decision making. We have developed explicit, rule-based protocols, implemented them in our hospital, exported them to other hospitals, and successfully achieved a rigorous experimental environment in the clinical ICU. Exportation of such explicit methods may narrow the gap between efficacy (university hospital) and effectiveness (community hospital) research results.

Clinical Trials as Topic↗

PubMed1995

Dieting decreases plasma tryptophan and increases the prolactin response to d-fenfluramine in women but not men.

We studied the effect of 3 weeks of moderate calorie restriction on 5-HT-mediated prolactin (PRL) release in healthy volunteers using the 5-HT-releasing agent d-fenfluramine. In women, dieting significantly lowered plasma total and free tryptophan (TRP) and increased the PRL response to d-fenfluramine. None of these measures were altered in men who dieted. These findings add to the data indicating that dieting alters brain 5-HT function in women, perhaps as a consequence of reducing the availability of plasma TRP.

Adult↗

PubMed1995

Laparoscopic-assisted colectomy learning curve.

PURPOSE: The purpose of this paper is to establish the number of cases necessary to master laparoscopic removal of the left or right colon. METHODS: Data were obtained by chart review and by individually completed questionnaires. RESULTS: A total of 144 laparoscopic-assisted or intracorporeal right or left hemicolectomies were completed by four surgeons at separate institutions. Questionnaires were completed by each surgeon for each sequential hemicolectomy, and data concerning the type of surgery and total operating time were recorded. Times were plotted to diagram individual learning curves for each surgeon, and data grouping methods were used to determine the curve for each surgeon as well as for the combined data base. Learning was said to have been completed when the surgeon's operative time reached a low point and subsequently did not vary by more than 30 minutes. A total of 78 right colectomies and 66 left colectomies were completed by the group. Respectively, each surgeon appeared to learn the procedure after 16, 21, 11, and 6 cases. When the entire database was analyzed as a whole, it was shown that between 11 and 15 completed colectomies were needed for learning, after which operative times remained relatively stable. CONCLUSIONS: This analysis, using total operative time as an indication of learning, shows that approximately 11 to 15 completed laparoscopic colectomies are needed to comfortably learn this procedure.

Colectomy↗

PubMed1995

Micronutrient status of the besieged residents of Sarajevo: May 1993.

OBJECTIVE: To assess micronutrient status indices in blood and plasma of subjects subjected to siege conditions. DESIGN: Whole blood and serum samples were taken from subjects, sampled from 30 clusters in four Municipal Areas of Sarajevo. The blood samples were flown, under appropriate refrigeration, to the UK for analysis. SETTING: The study was conducted in besieged Sarajevo and laboratory analyses were carried out at Department of Clinical Chemistry, Aberdeen Royal Infirmary and at Rowett Research Institute, Aberdeen, Scotland. SUBJECTS: 202 subjects, aged from 1 to 82 years were included in the sample. INTERVENTIONS: Serum folate, ferritin, transferrin, retinol, retinol-binding protein, beta-carotene, alpha-tocopherol, 25-hydroxycholecalciferol, C-reactive protein, haemoglobin and mean corpuscular volume of blood were determined. Micronutrient status was assessed by comparison with a range of values derived from multinational data sets from both pathologically malnourished and normal subjects. RESULTS: Haemoglobin, ferritin, folate, retinol and 25-hydroxycholecalciferol levels were lower in the Sarajevan sample than in normal reference populations. Serum alpha-tocopherol was low in children and adolescents while a low beta-carotene level probably reflected the scarcity of green vegetables. No consistent evidence of protein/energy deficits were detected. CONCLUSIONS: Data for retinol binding protein and transferrin, when considered in association with BMI and Z-score data, provided no significant evidence of protein-energy undernutrition. However, the prevailing food aid rations failed to maintain adequate reserves of several micronutrients, particularly iron, folate and vitamin D. The significance of low values for serum retinol and beta-carotene and of low serum alpha-tocopherol in children must be investigated further.

Adolescent↗