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Biomedical subjects

W Palmer

Publications and source records attributed to W Palmer.

At least 19 recordsLinked to original sources
PubMed2000

The discovery of non-basic atrial natriuretic peptide clearance receptor antagonists. Part 1.

The cyclic peptide ANP 4-23 and the linear peptide analogue AP-811 have been shown to be selective ANP-CR antagonists. Via alanine scanning and truncation studies we sought to determine which residues in these molecules were important in their binding to the clearance receptor and the relationship between these two molecules. These studies show that several modifications to these compounds are possible which improve physical properties of these molecules while retaining high affinity for the ANP-CR.

Amino Acid Sequence↗
PubMed2000

Spinal injuries at the University Hospital of the West Indies.

Acute spinal damage forms a small percentage of total trauma injury but it has tremendous significance because of the resultant disability, poor prognosis, economic and social cost and the burden on victims, family, taxpayers and health workers. Of fifty-five patients admitted to the University Hospital of the West Indies (UHWI), Mona, Jamaica, over a seven-year period, forty form the basis of this report. Young males accounted for most victims and 85% of the injuries were non-intentional. The cervical spine, most commonly C6, was the region most frequently injured, followed by the lumbar and the thoracic regions. On admission, the mean Glasgow Coma Score was 14.6 and the mean Modified Injury Severity Score 12.7. Five patients were admitted in Frankel Grade A, complete paraplegia. Of eighteen patients treated with steroids, only eleven had methylprednisolone and only six of these appropriately. Nine patients had surgery after a mean time of 10.1 days. The average length of hospital stay was 18.2 days. Of 35 patients whose outcomes were known, eleven improved; two patients died in hospital. With the modernization of the management of this condition, we recommend that attention be focused on prevention, pre-hospital immobilization and transport, prompt resuscitation, the standardization of written protocols and early operative intervention. Also essential is the continuing medical education of all levels of personnel and the formalization of a well-coordinated and rehearsed Spine team.

Adolescent↗
PubMed1999

Treatment of early seropositive rheumatoid arthritis with minocycline: four-year followup of a double-blind, placebo-controlled trial.

OBJECTIVE: Rheumatoid arthritis (RA) causes substantial morbidity and mortality, and current treatments are suboptimal. Recent studies have demonstrated the short-term efficacy of minocycline in the treatment of patients with early RA. This study was undertaken to compare patients treated with conventional therapy in the early phase of their RA and those treated with minocycline, after 4 years of followup. METHODS: Forty-six patients with seropositive RA of <1 year's duration had been enrolled in a double-blind study of minocycline (100 mg twice daily) versus placebo. After the blinded portion of the study (3-6 months, depending upon response), all patients were treated with conventional therapy. This report compares those patients randomized to receive placebo for 3 months and then conventional therapy for the duration of 4 years versus those originally randomized to receive minocycline. RESULTS: Twenty of the 23 original minocycline-treated patients and 18 of the 23 original placebo-treated patients were available for followup (mean 4 years). At followup, RA was in remission (American College of Rheumatology criteria) without disease-modifying antirheumatic drug (DMARD) or steroid therapy in 8 of the patients originally treated with minocycline compared with 1 patient in the placebo group (P = 0.02). Ten patients in the minocycline group versus 16 in the original placebo group currently require DMARD therapy (P = 0.02). CONCLUSION: Among patients with seropositive RA, remissions are more frequent and the need for DMARD therapy is less in those treated early in the disease course with minocycline compared with those treated with conventional therapy delayed by an average of only 3 months. Minocycline appears to be an effective therapy for early RA; further investigation into its mechanism of action is needed.

Anti-Bacterial Agents↗
PubMed1998

HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments.

OBJECTIVE: To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis. METHODS: Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401, 0404/0408, 0405, 0101, 1001, and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response. RESULTS: Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p < 0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p = 0.05). CONCLUSIONS: These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.

Adult↗
PubMed1997

Treatment of early rheumatoid arthritis with minocycline or placebo: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine if minocycline is an effective therapy for seropositive rheumatoid arthritis (RA) when used within the first year of disease. METHODS: The Rheumatoid Arthritis Investigational Network enrolled 46 patients with RA of <1 year duration into a 6-month study of minocycline (100 mg twice daily) versus placebo. All patients were rheumatoid factor positive. The primary end point of the study was successful completion of 6 months of treatment with no drug toxicity while maintaining 50% improvement in composite symptoms of arthritis. RESULTS: Eighteen of the 46 patients who were enrolled met 50% improvement criteria at 3 months, and maintained at least a 50% improvement for 6 months with no significant drug toxicity. Among them were 15 of the 23 patients (65%) treated with minocycline and 3 of 23 patients (13%) treated with placebo (P < 0.001). CONCLUSION: In patients with early seropositive RA, therapy with minocycline is superior to placebo.

Adult↗
PubMed1997

Kinematic CT of the patellofemoral joint.

OBJECTIVE: The purpose of this study was to determine if kinematic CT can be applied to the patellofemoral joint using current slip-ring CT scanner design in patients with anterior knee pain and thus a suspected patellar tracking disorder. SUBJECTS AND METHODS: Twenty knees in 18 patients with anterior knee pain were evaluated with kinematic CT. A single 10-sec exposure of the patellofemoral joint was obtained during active flexion and extension. Static nonkinematic and loaded kinematic examinations were compared with unloaded kinematic studies in a subset of patients. The changes in lateral patellofemoral angle and lateral shift were measured. Video cine viewing of patellofemoral motion was used to subjectively grade image quality and patellofemoral abnormalities by consensus. RESULTS: Kinematic CT was successfully used in all 20 knees. In nine knees studied with static nonkinematic and unloaded kinematic images, the lateral patellofemoral angle improved an average of 4" on the kinematic images. In addition, lateral shift improved by an average of 3%, an improvement that was statistically significant (p = .01). In 10 knees studied with and without loading, the lateral patellofemoral angle decreased an average of 3% with loading. No significant change was seen in lateral shift. In all patients, cine viewing was thought to be more useful than single images. Cine viewing was of good or diagnostic quality in all 20 knees studied. Lateral patellar translation during extension was detected in eight of 20 kinematic studies. Lateral patellar tilting also was detected in eight of 20 kinematic studies. Narrowing of the articular space was detected in 12 of 20 knees. Six knees were determined to be normal. CONCLUSION: Kinematic CT with slip-ring technology is a new technique that can be easily performed on the patellofemoral joint. This technique shows promise as a tool for determining the cause of anterior knee pain.

Adolescent↗
PubMed1996

Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications.

BACKGROUND: Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs. METHODS: We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary and point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity. RESULTS: Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P < 0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent), P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity. CONCLUSIONS: In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine, and hydroxychloroquine.

Adult↗
PubMed1996

Botulinum-induced muscle paralysis alters metabolic gene expression and fatigue recovery.

We evaluated the physiological, histochemical, and biochemical consequences of inhibiting contractile activity in rat skeletal muscles with botulinum toxin A (BTX). Contractile activity was entirely eliminated 12-18 h after a single, focal, intramuscular injection of BTX into the rat tibialis anterior muscle (TA). Neuromuscular transmission remained completely inhibited for 10-12 days, then slowly recovered. BTX-treated muscles exhibited a lower resistance to both high- and low-frequency fatigue at 7 and 14 days after injection, but contractile force recovered more rapidly in treated TA after fatigue. Treated TA showed a twofold increase in the activity of the triglyceride hydrolase enzyme lipoprotein lipase (LPL) and a comparable increase in the relative abundance of LPL steady-state mRNA. In contrast, there was a 28% reduction in protein levels of the muscle isozyme of glycogen phosphorylase (MGP) and a 70% decrease in relative MGP transcript levels. Similar changes in relative transcript levels of LPL and MGP were observed in the predominantly fast-twitch extensor digitorum longus after BTX injection, but relative LPL and MGP mRNA levels were not altered in predominantly slow-twitch soleus. Histochemical evidence indicated that fast-twitch glycolytic fibers had increased lipid content. These biochemical alterations were reversed 120 days after BTX treatment despite persistent atrophy.

Animals↗
PubMed1996

Efficacy of triple DMARD therapy in patients with RA with suboptimal response to methotrexate.

Rheumatoid arthritis (RA) has a profound effect on patients, producing significant morbidity and in some cases mortality. Because of this, most rheumatologists are moving to disease modifying antirheumatic drug (DMARD) therapy earlier in the course of RA. Methotrexate (MTX) has become the initial DMARD of choice for most rheumatologists. Unfortunately, treatment of RA with a single DMARD, including MTX, often results in a suboptimal response. Therefore, most rheumatologists are now using combinations of DMARD to treat patients with RA who have had incomplete responses to single DMARD therapy. The Rheumatoid Arthritis Investigational Network (RAIN) reported the results of a double blind, controlled comparison of triple drug therapy (MTX-sulfasalazine-hydroxychloroquine) against MTX alone, and against the combination of hydroxychloroquine and sulfasalazine. Twenty-eight patients who had suboptimal responses to MTX or the combination of sulfasalazine and hydroxychloroquine were then treated with triple therapy in an open label study. Fourteen had previously failed MTX therapy, and 14 had previously failed combination therapy with sulfasalazine and hydroxychloroquine. Both groups had statistically significant improvements in sedimentation rates, morning stiffness, swollen joint scores, tender joint scores, patient global status assessment, and physician global status assessment. Statistical significance was reached for all these variables for patients in both groups, but improvement was greater for the patients in the sulfasalazine-hydroxychloroquine group. Patients with RA who have had suboptimal responses to MTX, or to the combination of sulfasalazine-hydroxychloroquine, show both statistical and clinically significant improvement in multiple clinical variables when treated with the combination of MTX 17.5 mg/week, sulfasalazine 500 mg bid, and hydroxychloroquine 200 mg bid.

Adult↗
PubMed1996

Analysis of Centers for Disease Control and Prevention criteria for the eosinophilia-myalgia syndrome in a geographically defined population.

OBJECTIVE: To test whether individuals can be identified in a geographically defined population who would meet criteria for the eosinophilia-myalgia syndrome (EMS) established by the US Centers for Disease Control and Prevention (CDC), i.e, (1) eosinophil count > 1 x 10(9)/l, (2) myalgia severe enough to limit usual activities of daily living, and (3) no evidence of infection or neoplasm that could explain the first 2 findings. METHODS: To discover the number of individuals who would meet CDC criteria, the population was exhaustively searched using methods adapted from active pharmacoepidemiologic surveillance. Medical consultants and primary care practitioners were questioned as many as 5 times in a search for patients with severe myalgia. A predetermined protocol was used to screen those patients who appeared to meet CDC criteria for EMS using active surveillance methods. The study population was limited to Québec and Ontario (combined population 18,980,000) with special attention to the period July 1, 1992, to June 30, 1993. RESULTS: The prevalence of severe incapacitating myalgia was 43 per 100,000 persons, including 19 individuals with eosinophilia > 1 x 10(9)/l, who met CDC criteria for EMS. None of these individuals were reported to have taken L-tryptophan (LT). CONCLUSION: The CDC criteria for EMS are met by individuals in the general population who have never been exposed to LT.

Adult↗
PubMed1995

Continuing occurrence of eosinophilia myalgia syndrome in Canada.

Eosinophilia myalgia syndrome (EMS), was defined by the Centers for Disease Control (CDC) as eosinophilia > 1000 mm3 and incapacitating myalgia without infection or neoplasm. Studies suggested that use of L-tryptophan (L-T), was a risk factor. We conducted a pharmacoepidemiological survey in Canada where access to L-T is limited. Using the active surveillance method, a 100% sample of potentially involved specialists and a 15% sample of family physicians from Ontario and Quebec were surveyed regarding treatment of patients with severe myalgia within the past year. Follow-up amplified clinical and laboratory information. Overall response rates were 61.4%. Thirty-eight per cent of respondents reported at least one patient. Of 6423 patients assessed, 19 'definite' and 25 'possible' EMS cases were identified. Information from physicians did not suggest use of L-T in patients with definite or possible EMS. It was considered that the cases found an underestimate of the incidence of EMS. Its continuing occurrence in Canada brings causal interpretations of earlier studies into question.

Adult↗
PubMed1995

Modelling the cost effectiveness of antidepressant treatment in primary care.

The aim of this study was to estimate the cost effectiveness of nefazodone compared with imipramine or fluoxetine in treating women with major depressive disorder. Clinical decision analysis and a Markov state-transition model were used to estimate the lifetime health outcomes and medical costs of 3 antidepressant treatments. The model, which represents ideal primary care practice, compares treatment with nefazodone to treatment with either imipramine or fluoxetine. The economic analysis was based on the healthcare system of the Canadian province of Ontario, and considered only direct medical costs. Health outcomes were expressed as quality-adjusted life years (QALYs) and costs were in 1993 Canadian dollars ($Can; $Can1 = $US0.75, September 1995). Incremental cost-utility ratios were calculated comparing the relative lifetime discounted medical costs and QALYs associated with nefazodone with those of imipramine or fluoxetine. Data for constructing the model and estimating necessary parameters were derived from the medical literature, clinical trial data, and physician judgement. Data included information on: Ontario primary care physicians' clinical management of major depression; medical resource use and costs; probabilities of recurrence of depression; suicide rates; compliance rates; and health utilities. Estimates of utilities for depression-related hypothetical health states were obtained from patients with major depression (n = 70). Medical costs and QALYs were discounted to present value using a 5% rate. Sensitivity analyses tested the assumptions of the model by varying the discount rate, depression recurrence rates, compliance rates, and the duration of the model. The base case analysis found that nefazodone treatment costs $Can1447 less per patient than imipramine treatment (discounted lifetime medical costs were $Can50,664 vs $Can52,111) and increases the number of QALYs by 0.72 (13.90 vs 13.18). Nefazodone treatment costs $Can14 less than fluoxetine treatment (estimated discounted lifetime medical costs were $Can50,664 vs $Can50,678) and produces slightly more QALYs (13.90 vs 13.79). In the sensitivity analyses, the cost-effectiveness ratios comparing nefazodone with imipramine ranged from cost saving to $Can17,326 per QALY gained. The cost-effectiveness ratios comparing nefazodone with fluoxetine ranged from cost saving to $Can7327 per QALY gained. The model was most sensitive to assumptions about treatment compliance rates and recurrence rates. The findings suggest that nefazodone may be a cost-effective treatment for major depression compared with imipramine or fluoxetine. The basic findings and conclusions do not change even after modifying model parameters within reasonable ranges.

Antidepressive Agents↗
PubMed1993

Comparative trial of doxazosin and atenolol on cardiovascular risk reduction in systemic hypertension. The Alpha Beta Canada Trial Group.

The impact of treating hypertension on coronary artery disease has been less than anticipated from epidemiologic studies of cardiovascular risk factors. It has been suggested that adverse effects on lipids of traditional diuretic or beta-blocker regimens may diminish the potential benefits of antihypertensive therapy. Patients with mild to moderate systemic hypertension and normal serum lipids (n = 191) were randomly assigned to doxazosin or atenolol. After dose titration to goal diastolic blood pressure of < or = 90 mm Hg, patients continued treatment for a further 24 weeks. The principal outcome measurement was overall coronary artery disease risk using the Framingham formula. Relative risk of coronary artery disease was reduced to 92.4% of baseline (p = 0.144) for evaluable patients taking atenolol (n = 71), and to 74.6% (p = 0.0001) for patients taking doxazosin (n = 51): atenolol versus doxazosin, p = 0.0074. In patients who met the strict Framingham criteria for age, total cholesterol and high density lipoprotein cholesterol, the relative risk of coronary artery disease for patients taking atenolol (n = 23) was reduced to 86.2% of baseline (p = 0.082), and to 67.4% (p = 0.0004) for patients taking doxazosin (n = 18): atenolol versus doxazosin, p = 0.049. Alpha blockade with doxazosin was more effective than beta blockade with atenolol in reducing the risk of coronary artery disease in hypertensive patients because of the beneficial effects of doxazosin on high-density lipoprotein cholesterol. Overall withdrawal rate was greater in the alpha-blocker group because of a lower response rate and more adverse events.

Adult↗
PubMed1986

Estrogen induction of very low density apolipoprotein II synthesis, a major avian liver yolk protein, involves the recruitment of hepatocytes.

The mechanism of steroid hormone action was studied in the cockerel liver. Very low density apolipoprotein II (apo-VLDL-II), a yolk protein, is a low molecular weight apolipoprotein that is inducible by estrogen. The intracellular apo-VLDL-II messenger RNA (mRNA) concentration under various hormonal conditions was examined by a dot-blot assay. The concentration was very low in untreated cockerels (approximately 0.5 molecule per cell). It increased to 8,000 molecules per cell within 24 h of estrogen treatment and reached a maximum level of approximately 70,000 molecules per cell after 14 daily doses of estrogen. The distribution of hepatocytes harboring apo-VLDL-II and its mRNA was studied by immunohistochemistry and by in situ nucleic acid hybridization to cloned [3H]apo-VLDL-II complementary DNA (cDNA). The number of cells containing the immunoreactive protein and the hybridizable mRNA increased from extremely low (0.3% and 0.27%, respectively) to substantial (11% and 10%, respectively) at 24 h after estrogen treatment and to extremely high (94% and 92%, respectively) in maximally treated animals. Our studies indicate that, in addition to enhanced transcription and stabilization of mRNA, the recruitment of liver cells previously not engaged in the synthesis of apo-VLDL-II is an important mechanism by which the hormone induces the hepatic production of this protein. The phenomenon of recruitment and the heterogeneity of the functional capacity of individual hepatocytes to respond to estrogen may be important to our understanding of estrogen action in the liver.

Animals↗
PubMed1983

Immunoelectron microscopic study of somatostatin biosynthesis in dog pancreas.

The biosynthesis of somatostatin has been studied at the ultrastructural level in pancreatic islets by using rabbit antiserum against synthetic somatostatin. To document that the antiserum specifically bound preprosomatostatin, we have tested the ability of the antiserum to precipitate the product synthesized in vitro. Poly(A) enriched RNA isolated from catfish islets was translated in both the wheat germ extract and nuclease-treated reticulocyte lysate systems. It was found that the in vitro translation product, preprosomatostatin, could be recognized by the antibody against synthetic somatostatin. The morphological study was then performed by immunoelectron microscopy by using the Fab-peroxidase conjugate technique. In dog pancreatic islets, somatostatin immunoreactive reaction product was seen only in the delta cells. In these cells, they were detected on bound ribosomes, in the cisternae of the rough endoplasmic reticulum (ER) and Golgi apparatus, in the Golgi associated vesicles, and in secretory vesicles. These findings suggest that somatostatin precursor molecules are synthesized on bound ribosomes and discharged into the cisternae of the rough ER. They are then transported to the Golgi apparatus and transferred to the secretory vesicles for secretion. The different staining intensities in the secretory vesicles would suggest that the processing of the precursor molecules of somatostatin probably takes place in the secretory vesicles.

Animals↗