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Biomedical subjects

M Franklin

Publications and source records attributed to M Franklin.

At least 37 records · Page 2Linked to original sources

Communication breakdown in the outpatient referral process.

OBJECTIVE: To evaluate primary care and specialist physicians' satisfaction with interphysician communication and to identify the major problems in the current referral process. DESIGN: Surveys were mailed to providers to determine satisfaction with the referral process; then patient-specific surveys were e-mailed to this group to obtain real-time referral information. SETTING: Academic tertiary care medical center. PARTICIPANTS: Attending-level primary care physicians (PCPs) and specialists. MEASUREMENTS AND MAIN RESULTS: The response rate for mail surveys for PCPs was 57% and for specialists was 51%. In the mail survey, 63% of PCPs and 35% of specialists were dissatisfied with the current referral process. Respondents felt that major problems with the current referral system were lack of timeliness of information and inadequate referral letter content. Information considered important by recipient groups was often not included in letters that were sent. The response rate for the referral specific e-mail surveys was 56% for PCPs and 53% for specialists. In this e-mail survey, 68% of specialists reported that they received no information from the PCP prior to specific referral visits, and 38% of these said that this information would have been helpful. In addition, four weeks after specific referral visits, 25% of PCPs had still not received any information from specialists. CONCLUSIONS: Substantial problems were present in the referral process. The major issues were physician dissatisfaction, lack of timeliness, and inadequate content of interphysician communication. Information obtained from the general survey and referral-specific survey was congruent. Efforts to improve the referral system could improve both physician satisfaction and quality of patient care.

Ambulatory Care↗

Acute effects of LI 160 (extract of Hypericum perforatum, St John's wort) and two of its constituents on neuroendocrine responses in the rat.

Extracts of Hypericum perforatum (St John's wort), such as LI 160, which are effective antidepressants have several active constituents. Their mode of action in depression, however, is unclear. In the present investigation, we assessed the effect of equivalent doses of LI 160 and two of its components, hypericin and hyperforin on serotonin (5-HT) and dopamine (DA)-mediated neuroendocrine responses in the rat. LI 160, hypericin and hyperforin significantly and equivalently increased plasma corticosterone. This effect was blocked by ketanserin but not WAY-100635, suggesting mediation via 5-HT2 receptors. LI 160 also lowered plasma prolactin and prevented the increase in plasma prolactin following haloperidol administration. Hyperforin had a similar but somewhat less pronounced effect. We conclude that LI 160, hypericin and hyperforin all increase 5-HT-mediated corticosterone release while LI 160 enhances DA-mediated inhibition of prolactin release. Hyperforin may contribute to the facilitatory effect of LI 160 on DA function, but hypericin does not.

Animals↗

Measurement of hyperforin a constituent of St. John's wort in plasma by high-performance liquid chromatography.

Hyperforin is a constituent of Hypericum perforatum extracts (St. John's wort, H. perforatum), which have antidepressant action. Hyperforin was extracted from plasma utilising a solid-phase extraction procedure. Chromatography was performed by isocratic reversed-phase high-performance liquid chromatography with UV end-point detection. The calibration curve was linear over the range 0.15-3 microg per ml of plasma. The sensitivity for hyperforin was 4.5 ng on-column. Mean inter- and intra-assay relative standard deviations over the range of the standard curve were less than 5%. The absolute recovery for hyperforin averaged 97.8%.

Animals↗

Simultaneous determination of catecholamines in rat brain tissue by high-performance liquid chromatography.

A novel and highly sensitive method has been developed for the determination of catecholamines [noradrenaline (NA), dopamine (DA), serotonin (5-HT) and their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA)] in brain tissue. The method uses isocratic reversed-phase HPLC with amperometric end-point detection. The calibration curve was linear over the range 10-150 pg on-column. The assay limits of detection for NA, DA, 5-HT, 5-HIAA and HVA were 3.8, 3.8, 6.8, 5 and 7.5 pg on-column, respectively. The mean inter- and intra-assay relative standard deviations (RSDs) over the range of the standard curve were less than 5%. The absolute recoveries averaged 99.1%, 99.5%, 97.7%, 99.5% and 98.8% for NA, DA, 5-HT, 5-HIAA and HVA, respectively.

Animals↗

Neuroendocrine evidence for dopaminergic actions of hypericum extract (LI 160) in healthy volunteers.

BACKGROUND: We studied the effect of a single dose of a formulation of a methanolic extract of Hypericum perforatum (HP), also known as St. John's wort, on plasma concentrations of growth hormone (GH), prolactin (PRL), and cortisol (CORT) in 12 healthy male volunteers. METHODS: Subjects received 9 tablets of the finished product Jarsin 300 and placebo in a double-blind, balanced-order, cross-over design. RESULTS: Following HP relative to placebo, there was a significant increase in plasma GH and a significant decrease in plasma PRL. Plasma CORT levels were unchanged. CONCLUSIONS: Taken together with data from animal experimental studies, the findings suggest that this dose of HP may increase some aspects of brain dopamine function in humans.

Adult↗

Technology assessment of multileaf collimation: a North American users survey.

PURPOSE: The American Association of Physicists in Medicine (AAPM) initiated an Assessment of Technology Subcommittee (ATS) to help the radiotherapy community evaluate emerging technologies. The ATS decided to first address multileaf collimation (MLC) by means of a North American users survey. The survey attempted to address issues such as MLC utility, efficacy, cost-effectiveness, and customer satisfaction. METHODS AND MATERIALS: The survey was designed with 38 questions, with cross-tabulation set up to decipher a particular clinic's perception of MLC. The surveys were coded according to MLC types, which were narrowed to four: Elekta, Siemens, Varian 52-leaf, and Varian 80-leaf. A 40% return rate was desired. RESULTS: A 44% (108 of 250) return was achieved. On an MLC machine, 76.5% of photon patients are being treated with MLC. The main reasons for not using MLC were stair stepping, field size limitation, and physician objection. The most common sites in which MLC is being used are lung, pelvis, and prostate. The least used sites are head & neck and mantle fields. Of the facilities, 31% claimed an increase in number of patients being treated since MLC was installed, and 44% claimed an increase in the number of fields. Though the staffing for block cutting has decreased, therapist staffing has not. However, 91% of the facilities claimed a decreased workload for the therapists, despite the increase in daily treated patients and fields. Of the facilities that justified MLC purchase for more daily patients, 63% are actually treating more patients. Only 26% of the facilities that justified an MLC purchase for intensity-modulated radiotherapy (IMRT) are currently using it for that purpose. The satisfaction rating (1 = low to 5 = high) for department groups averaged 4.0. Therapists ranked MLC as 4.6. CONCLUSIONS: Our survey shows that most users have successfully introduced MLC into the clinic as a block replacement. Most have found MLC to be cost-effective and efficient. The use of MLC for IMRT has progressed slower, but users anticipate escalated use.

Consumer Behavior↗

Determination of hypericin in plasma by high-performance liquid chromatography.

Hypericin, a polycyclic dianthroquinone, is one of the characteristic ingredients of Hypericum perforatum extracts (St. John's wort, HP), which has antidepressant effects. Hypericin and the internal standard (I.S.), dansylamide, were extracted from plasma utilizing solid-phase extraction (SPE). Chromatography was performed using isocratic reversed-phase high-performance liquid chromatography (HPLC) with fluorescence end-point detection. The calibration curve was linear over the range 5-100 ng per ml of plasma. The sensitivity for hypericin was 75 pg on column. Mean inter- and intra-assay coefficients of variation (C.V.s) over the range of the standard curve were less than 10%. The absolute recovery for hypericin averaged 72.6%.

Anthracenes↗

Long-term enhancement of botulinum toxin injections by upper-eyelid surgery in 14 patients with facial dyskinesias.

OBJECTIVES: To determine the effects of upper-eyelid surgery (limited myectomy, blepharoplasty, and levator aponeurotic advancement) on patients who demonstrated a suboptimal response or residual heaviness of the upper eyelids after botulinum toxin eyelid injections for facial dyskinesia. DESIGN: Retrospective study. SUBJECTS: Charts of 358 patients with a diagnosis of benign essential blepharospasm, Meige syndrome (with eyelid involvement), and hemifacial spasm were reviewed. METHODS: Data were retrospectively analyzed and included subjective and objective responses about botulinum toxin injections (number and duration of effect of injections before and after eyelid surgery). RESULTS: Of 358 patients with facial dyskinesias, 14 (3.91%) underwent upper-eyelid limited myectomy with or without upper-lid blepharoplasty (n = 5), upper-lid blepharoplasty alone (n = 6), or levator advancement with or without blepharoplasty (n = 3). Mean subjective improvement was 68.75% after limited myectomy combined with blepharoplasty and 58.33% after levator and/or blepharoplasty surgery. Average duration of effect of injections increased from 122.1 days in the patients prior to undergoing eyelid surgery to 210.5 days after surgery. CONCLUSIONS: Upper-eyelid surgery, including limited myectomy, enhanced the effect of the botulinum toxin in this small group of patients. Patients with a suboptimal response to injections in terms or moderate to marked dermatochalasis with subjective heaviness of the eyelids, upper-eyelid blepharoplasty, and/or limited myectomy should be considered.

Aged↗

A computer-based outpatient clinical referral system.

The process of generating a clinical referral for a patient, and the resulting transfer of information from the primary care physician to the specialist and back again, are key components in the struggle to deliver less costly and more effective clinical care. We have created a computer-based, outpatient clinical referral application that facilitates: (1) identifying an appropriate specialist; (2) collecting the clinical, demographic, and financial data required to generate a referral; and (3) transferring the information between the specialist and the primary care physician (PCP). This article describes the development of the application itself and several of the knowledge bases that were created to facilitate this process. Preliminary results indicate that the new computer-based referral process is faster to use than conventional methods.

Ambulatory Care↗

Systematic review of antistaphylococcal antibiotic therapy in cystic fibrosis.

BACKGROUND: The respiratory tract in patients with cystic fibrosis is frequently colonised with Staphylococcus aureus. There is great diversity of clinical practice in this area of cystic fibrosis. A systematic review was conducted to study the evidence relating antistaphylococcal therapy to clinical outcome in patients with cystic fibrosis. METHODS: A search strategy already evaluated for the study of the epidemiology of cystic fibrosis clinical trials was used. This yielded 3188 references from which 13 clinical trials of antistaphylococcal therapy were identified. RESULTS: Substantial heterogeneity was observed between trials. In the 13 clinical trials a total of 19 antibiotics were used to assess a wide variety of outcome measures (11 clinical, six laboratory). Both intermittent and continuous treatment strategies were used. Sputum clearance of S aureus was more frequently achieved than any other beneficial outcome. A beneficial effect on pulmonary function was rarely measured or observed. Although five randomised clinical trials were identified, the extent of heterogeneity precluded the use of meta-analysis for further synthesis of information. CONCLUSIONS: Antistaphylococcal treatment achieves sputum clearance of S aureus in patients with cystic fibrosis. Prophylactic antistaphylococcal treatment in young children with cystic fibrosis is likely to be of clinical benefit. It remains to be determined whether the use of "prophylactic" versus "intermittent" antistaphylococcal therapy in cystic fibrosis is associated with improved lung function and/or chest radiographic scores, an increase in bacterial resistance, or earlier acquisition of Pseudomonas aeruginosa. A large randomised clinical trial lasting approximately two years is urgently required to address this problem.

Anti-Bacterial Agents↗

Effect of a long-term low tryptophan diet on the prolactin responses to the 5-HT1A and 5-HT2C agonists, 8-OH-DPAT and mCPP in the male rat.

The study was undertaken to assess the long term effects of tryptophan (TRP) depletion through diet on the prolactin (PRL) responses to the serotonin (5-hydroxytryptophan, 5-HT) agonists m-chlorophenyl-piperazine (mCPP) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the male rat. The low TRP diet caused significant reductions in both plasma total TRP and brain cortical 5-HT content together with a significant increase in the PRL responses to mCPP. In contrast the PRL responses to 8-OH-DPAT in animals on the low TRP diet for 1 week and 6 weeks were similar to control rats. However, a small but significant increase in PRL was observed at 2 min after dosing in the 1-week group. At the same time the 3H-8-OH-DPAT binding parameters, Kd and Bmax, were similar in both control and TRP depleted animals. The results confirm that long-term TRP depletion causes a deficiency of brain TRP and a subsequent reduction of brain 5-HT. This is associated with an enhanced PRL response to mCPP probably resulting from a functional up-regulation of post-synaptic 5-HT2C receptors. The small or transient changes brought about by long-term TRP depletion on post-synaptic 5-HT1A receptors, suggests that these receptors may be less susceptible to 5-HT depleting effects than the 5-HT2C subtype.

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

Prolonged opioid antagonism with naloxone in chronic renal failure.

Respiratory depression secondary to morphine intoxication occurred in an elderly patient with chronic renal failure (CRF). It was reversed with a continuous infusion of naloxone. Approximately 11 hours after the infusion was discontinued, the patient relapsed into respiratory depression consistent with opioid intoxication. He was rechallenged with a naloxone infusion with resolution of the opioid effects. This case suggests prolonged antagonism of opioid effects inconsistent with naloxone's reported pharmacologic effects. Serum naloxone concentrations measured after the end of the infusion suggest that the drug's pharmacokinetics were significantly altered. Further research is necessary to characterize pharmacokinetic changes that occur in CRF. In the absence of this information, similar patients should be closely monitored for relapse of respiratory depression after naloxone is discontinued.

Aged↗

Simultaneous measurement of venlafaxine and its major metabolite, oxydesmethylvenlafaxine, in human plasma by high-performance liquid chromatography with coulometric detection and utilisation of solid-phase extraction.

Venlafaxine, oxydesmethylvenlafaxine and an internal standard (paroxetine) were extracted from plasma by a solid-phase extraction technique. Chromatography was performed using isocratic reversed-phase high-performance liquid chromatography (HPLC) with coulometric endpoint detection. The standard curves were linear over the range 0-200 ng/ml for both venlafaxine and oxydesmethylvenlafaxine in plasma. The mean inter- and intra-assay coefficients of variation over the range of the standard curves were less than 10%. The absolute recovery averaged 74% for venlafaxine and 67% for oxydesmethylvenlafaxine. The sensitivity was 0.5 ng for both the analytes. Plasma profiles of the analytes following oral administration of venlafaxine, are presented.

Administration, Oral↗

Effect of antidepressant drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the rat.

This study examined the effect of repeated treatment with the antidepressant drugs, fluoxetine, desipramine and tranylcypromine, on dopamine receptor expression (mRNA and binding site density) in sub-regions of the nucleus accumbens and striatum of the rat. The effect of these treatments on extracellular levels of dopamine in the nucleus accumbens was also measured. Experiments using in situ hybridisation showed that the antidepressants caused a region-specific increase in D2 mRNA, this effect being most prominent in the nucleus accumbens shell. In contrast, none of the treatments increased D1 mRNA in any of the regions examined. Measurement of D2-like binding by receptor autoradiography, using the ligand [3H]YM-09151-2, revealed that both fluoxetine and desipramine increased D2-like binding in the nucleus accumbens shell; fluoxetine had a similar effect in the nucleus accumbens core. Tranylcypromine, however, had no effect on D2-like binding in the nucleus accumbens but decreased binding in the striatum. In micro-dialysis experiments, our data showed that levels of extracellular dopamine in the nucleus accumbens were not altered in rats treated with either fluoxetine or desipramine, but increased by tranylcypromine. From our findings, we propose that the antidepressant drugs tested enhance dopamine function in the nucleus accumbens through either increased expression of post-synaptic D2 receptors (fluoxetine and desipramine) or increased dopamine release (tranylcypromine).

Animals↗

Evaluation of natural killer cell expansion and activation in vivo with daily subcutaneous low-dose interleukin-2 plus periodic intermediate-dose pulsing.

Natural killer (NK) cells may be expanded in vivo with a prolonged course of daily subcutaneous interleukin-2 (IL-2). However, cellular activation requires higher concentrations of IL-2 than are achieved with low-dose therapy. The objective of the current trial was to determine the toxicity and immunological effects of periodic subcutaneous intermediate-dose IL-2 pulses in patients receiving daily low-dose therapy. A group of 19 patients were treated with daily subcutaneous low-dose IL-2 at 1.25 x 10(6) International Units (1.25 MIU) m(-2) day(-1). After 4-6 weeks, patients received escalating 3-day intermediate-dose IL-2 pulses administered as single daily subcutaneous injections, repeated at 2-week intervals. The maximum tolerated pulse dose was 15 MIU m(-2) day(-1), with transient hypotension, fatigue, and nausea/vomiting dose-limiting. Subcutaneous IL-2 resulted in in vivo expansion of CD56+ NK cells (796+/-210%) and CD56bright natural killer (NK) cells (3247+/-1382%). Expanded NK cells coexpressed CD16, and showed lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity in vitro. Intermediate-dose pulsing resulted in serum IL-2 concentrations above 100 pM. Cellular activation was suggested by rapid margination of NK cells following pulsing, coincident with peak IL-2 levels, with return to baseline by 24 h. In.addition, interferon gamma production in response to lipopolysaccharide was augmented. Subcutaneous daily low-dose IL-2 with intermediate-dose pulsing is a well-tolerated outpatient regimen that results in in vivo expansion and potential activation of NK cells, with possible application in the treatment of malignancy and immunodeficiency.

Adult↗

Effect of venlafaxine on pineal melatonin and noradrenaline in the male rat.

Studies in vitro indicate that the antidepressant drug, venlafaxine (VEN), inhibits the reuptake of both serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NA) but has little activity on other neurotransmitter receptors. There are, however, few studies on the effects of VEN on monoamine neurotransmission in vivo. In the present study we examined the effect of VEN treatment on the melatonin content of the rat pineal gland because the synthesis of melatonin is regulated by the release of NA onto pinealocyte beta-adrenoceptors. Acute treatment with higher doses (15 mg/kg) of VEN significantly increased pineal melatonin and NA but this effect was attenuated by subchronic treatment. These data are consistent with in vitro data suggesting that VEN increases NA neurotransmission at higher doses and that repeated treatment can desensitize pinealocyte beta-adrenoceptors.

Animals↗

Design and development of a computer-based clinical referral system for use within a physician hospital organization.

The process of creating a clinical referral for a patient and the transfer of information from the primary care physician to the specialist and back again is a key component in the struggle to deliver less costly and more effective clinical care. We have created a computer-based clinical referral application which facilitates 1) identifying an appropriate specialist; 2) collecting the clinical, demographic, and financial data required to generate a referral; and 3) transferring the information between the specialist and the primary care physician. Preliminary results indicate that the new computer-based process is faster.

Ambulatory Care Information Systems↗