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Biomedical subjects

C Goldsmith

Publications and source records attributed to C Goldsmith.

At least 19 recordsLinked to original sources
PubMed2000

IGF-II ameliorates the dystrophic phenotype and coordinately down-regulates programmed cell death.

Duchenne muscular dystrophy (DMD) is a fatal and crippling disease of skeletal muscle which displays increased fibre turnover and elevated levels of programmed cell death (PCD) in muscle stem cells. Previously we showed that this cell death is inhibited by the growth factor IGF-II. To determine the functional significance of PCD to the dystrophic phenotype, we used a transgene to over-express IGF-II in the mdx mouse. We found that ectopic expression of IGF-II inhibited the elevated PCD observed in skeletal muscles in the absence of functional dystrophin and significantly ameliorates the early gross histopathological changes in skeletal muscles characteristic of the dystrophic phenotype. Replacement of the dystrophin gene abolished abnormal skeletal muscle cell PCD levels in vivo in a dose-dependent manner and in dystrophic SMS cell lines cultured in vitro. Thus elevation of stem cell PCD in dystrophic skeletal muscle is a direct consequence of the loss of functional dystrophin. Together these data demonstrate that elevated skeletal muscle cell PCD is a critical component of dystrophic pathology and is inversely correlated with both dystrophin gene dosage and with muscle fibre pathology. Targeting PCD in dystrophic muscles reduces both PCD and the classical features of dystrophic pathology in the mdx mouse suggesting that IGF-II is a strong candidate for therapeutic intervention in the dystrophinopathies.

Animals↗
PubMed1999

A comparison of thoracic and lumbar epidural techniques for post-thoracoabdominal esophagectomy analgesia.

PURPOSE: To compare thoracic epidural analgesia (TEA) using a bupivacaine/fentanyl mixture and lumbar epidural analgesia (LEA) with morphine, in respect to the time to extubation and the quality of post-operative analgesia, in patients having thoracoabdominal esophagectomy. METHODS: Twenty two patients scheduled for elective thoracoabdominal esophagectomy were randomized to TEA or LEA. Postoperatively, the TEA group received Patient Controlled Epidural Analgesia (PCEA) with bupivacaine 0.125% and 5 microg x ml(BI) fentanyl, and the LEA group received PCEA with 0.2 microg x ml(BI) morphine. A blinded observer assessed criteria for tracheal extubation and the time of tracheal extubation was recorded. Early extubation was defined as tracheal extubation within four hours postoperatively. Visual analogue pain scores at rest (Static Visual Analogue Pain Scores, SVAPS) and with movement (Dynamic Visual Analogue Pain Scores, DVAPS) were recorded at 1, 6, 12, 18 and 24 hr post-extubation. Failure of the epidural protocol (FEP) was defined as a request for additional analgesia. RESULTS: Tracheal extubation was achieved in 70% of the LEA and 100% of the TEA at four hours postoperatively (P=NS). However, the TEA group achieved earlier extubation times when assessed with log rank testing (P = 0.01). By six hours post-extubation FEP had occurred in 50% of the LEA group but in none of the TEA group (P = 0.01). Mean SVAPS and DVAPS were lower in the TEA than in the LEA group at all measured times (P < 0.01). CONCLUSION: This study has demonstrated superior pain control in patients undergoing thoraco-abdominal esophagectomy treated with TEA than with LEA, particularly for pain with movement. Tracheal extubation occurred earlier in the TEA group, but this difference was not significant at four hours postoperatively.

Adult↗
PubMed1999

Identification of a new autosomal dominant limb-girdle muscular dystrophy locus on chromosome 7.

We report the identification of a new locus for autosomal dominant limb-girdle muscular dystrophy (LGMD1) on 7q. Two of five families (1047 and 1701) demonstrate evidence in favor of linkage to this region. The maximum two-point LOD score for family 1047 was 3.76 for D7S427, and that for family 1701 was 2.63 for D7S3058. Flanking markers place the LGMD1 locus between D7S2423 and D7S427, with multipoint analysis slightly favoring the 9-cM interval spanned by D7S2546 and D7S2423. Three of five families appear to be unlinked to this new locus on chromosome 7, thus establishing further heterogeneity within the LGMD1 diagnostic classification.

Alleles↗
PubMed1999

Hypothyroidism.

Explore the source record for details and available documents.

Hormone Replacement Therapy↗
PubMed1999

Evidence of avian leukosis virus subgroup E and endogenous avian virus in measles and mumps vaccines derived from chicken cells: investigation of transmission to vaccine recipients.

Reverse transcriptase (RT) activity has been detected recently in all chicken cell-derived measles and mumps vaccines. A study of a vaccine manufactured in Europe indicated that the RT is associated with particles containing endogenous avian retrovirus (EAV-0) RNA and originates from the chicken embryonic fibroblasts (CEF) used as a substrate for propagation of the vaccine. We investigated the origin of RT in measles and mumps vaccines from a U.S. manufacturer and confirm the presence of RT and EAV RNA. Additionally, we provide new evidence for the presence of avian leukosis virus (ALV) in both CEF supernatants and vaccines. ALV pol sequences were first identified in particle-associated RNA by amplification with degenerate retroviral pol primers. ALV RNA sequences from both the gag and env regions were also detected. Analysis of hypervariable region 2 of env revealed a subgroup E sequence, an endogenous-type ALV. Both CEF- and vaccine-derived RT activity could be blocked by antibodies to ALV RT. Release of ALV-like virus particles from uninoculated CEF was also documented by electron microscopy. Nonetheless, infectivity studies on susceptible 15B1 chicken cells gave no evidence of infectious ALV, which is consistent with the phenotypes of the ev loci identified in the CEF. PCR analysis of ALV and EAV proviral sequences in peripheral blood mononuclear cells from 33 children after measles and mumps vaccination yielded negative results. Our data indicate that the sources of RT activity in all RT-positive measles and mumps vaccines may not be similar and depend on the particular endogenous retroviral loci present in the chicken cell substrate used. The present data do not support transmission of either ALV or EAV to recipients of the U.S.-made vaccine and provide reassurance for current immunization policies.

Animals↗
PubMed1998

The reliability of physical examination for carpal tunnel syndrome.

The goal of this study was to determine the interobserver and intraobserver reliability of static and moving two-point discrimination, Semmes-Weinstein monofilament testing, Tinel's test, manual motor testing of abductor pollicis brevis, vibration and Phalen's test in the diagnosis of carpal tunnel syndrome. Twelve patients with suspected carpal tunnel syndrome were examined in an outpatient setting. The interobserver reliability was satisfactory for all tests except for Semmes-Weinstein monofilament testing. Intraobserver reliability was also satisfactory for all tests. Static two point discrimination had higher reliability than moving two-point discrimination. Seven tests for the diagnosis of carpal tunnel syndrome were reliable in the hands of skilled health care professionals. Hand surgeons and hand therapists examined patients more reliably than occupational health workers.

Adult↗
PubMed1998

The efficacy of spinal manipulation, amitriptyline and the combination of both therapies for the prophylaxis of migraine headache.

BACKGROUND: Migraine headache affects approximately 11 million adults in the United States. Spinal manipulation is a common alternative therapy for headaches, but its efficacy compared with standard medical therapies is unknown. OBJECTIVE: To measure the relative efficacy of amitriptyline, spinal manipulation and the combination of both therapies for the prophylaxis of migraine headache. DESIGN: A prospective, randomized, parallel-group comparison. After a 4-wk baseline period, patients were randomly assigned to 8 wk of treatment, after which there was a 4-wk follow-up period. SETTING: Chiropractic college outpatient clinic. PARTICIPANTS: A total of 218 patients with the diagnosis of migraine headache. INTERVENTIONS: An 8-wk course of therapy with spinal manipulation, amitriptyline or a combination of the two treatments. MAIN OUTCOME MEASURES: A headache index score derived from a daily headache pain diary during the last 4 wk of treatment and during the 4-wk follow-up period. RESULTS: Clinically important improvement was observed in both primary and secondary outcomes in all three study groups over time. The reduction in headache index scores during treatment compared with baseline was 49% for amitriptyline, 40% for spinal manipulation and 41% for the combined group; p = .66. During the posttreatment follow-up period the reduction from baseline was 24% for amitriptyline, 42% for spinal manipulation and 25% for the combined group; p = .05. CONCLUSION: There was no advantage to combining amitriptyline and spinal manipulation for the treatment of migraine headache. Spinal manipulation seemed to be as effective as a well-established and efficacious treatment (amitriptyline), and on the basis of a benign side effects profile, it should be considered a treatment option for patients with frequent migraine headaches.

Adolescent↗
PubMed1997

Fluoride therapy in prevention of rheumatoid arthritis induced bone loss.

OBJECTIVE: To determine the efficacy of sodium fluoride (40 mg/day) in preventing rheumatoid arthritis (RA) induced bone loss, which may lead to osteoporosis. METHODS: We conducted an 18 month, randomized, double blind, placebo controlled trial in 38 patients with RA. The primary outcome measure was the difference in the percentage change between groups in lumbar spine bone mineral density (BMD) from baseline values after 18 months of therapy. The secondary outcome measures were the differences in the percentage change between groups in femoral neck, Ward's triangle, trochanter, and total body BMD from baseline after 18 months of therapy. RESULTS: There was a significant percentage difference (SD) between groups of 6.2% (7.3%) (p = 0.0005) in lumbar spine BMD after 18 months of treatment in favor of the fluoride group. The fluoride group experienced a 5.2% (8.4%) (p = 0.0125) increase, whereas the placebo group showed a 1.0% (4.8%) (p = 0.8015) decrease in lumbar spine BMD after treatment. No significant differences were found for the femoral neck, Ward's triangle, trochanter, and total body BMD in terms of the percentage changes from baseline within each treatment group or in the differences in the degree of change between groups after therapy. Lumbar spine BMD increased in about 80% of patients treated with fluoride (responders) compared to 44% of patients treated with placebo. CONCLUSION: The results showed that fluoride therapy was well tolerated and increased vertebral bone mass in patients with RA.

Administration, Oral↗
PubMed1996

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.

OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Health Status Indicators↗
PubMed1996

Intermittent cyclic therapy with etidronate prevents corticosteroid-induced bone loss: two years of follow-up.

The purpose of this study was to evaluate the efficacy of intermittent cyclic therapy (ICT) with etidronate in preventing the loss of lumbar vertebral bone mineral density (BMD) in patients taking corticosteroids. The study population was a cohort of patients taking corticosteroids for at least two years for polymyalgia rheumatica, asthma, rheumatoid arthritis, systemic lupus erythematosus or other conditions. A tertiary care university teaching hospital-affiliated rheumatology office practice. Inclusion and exclusion criteria yielded eighty-eight patients taking corticosteroids for at least two years who had not taken estrogen or fluoride and had no causes of secondary osteoporosis. Changes relative to baseline in individual vertebral (L2-L4) BMD measurements after one and two years were compared between patients who had taken ICT with etidronate (n = 42) and those who had not (n = 46). We found that BMD in the lumbar spine increased significantly over baseline in patients who had taken ICT with etidronate, by 3.9% after one year and by 5.6% after two years, whereas it decreased by 3.7-3.8% in patients who had not. We conclude that ICT with etidronate prevents corticosteroid-induced osteoporosis and progressively ameliorates BMD over two years. Double blind trials are underway to evaluate whether this increased BMD is associated with reductions in vertebral fracture rates.

Adrenal Cortex Hormones↗
PubMed1995

American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis.

OBJECTIVE: Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. METHODS: Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. RESULTS: The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. CONCLUSION: We present a definition of improvement which we hope will be used widely in RA trials.

Adult↗
PubMed1995

Detection of bacteraemia by the continuously monitoring BacT/Alert system.

AIMS: To analyse a continuously monitoring blood culture system with respect to the time to detection of various groups of organisms, their clinical importance, and the relative efficacy of the aerobic and anaerobic bottles. METHODS: Four thousand blood cultures were monitored and the information relating to the positive cultures was noted and analysed. RESULTS: Four hundred and seventy seven blood cultures were detected as positive, 81% (387/477) of which were detected within 48 hours. The most pathogenic organisms were detected in the shortest period, less pathogenic later and those generally regarded as contaminants last. Clinically important isolates were also detected earlier. Many positive blood cultures were detected in only one bottle of the set, even those regarded as clinically important. CONCLUSIONS: The management of continuously monitoring blood culture systems could be improved by considering time to detection trends. Clinicians should be aware of the relatively rapid detection of clinically important, positive blood cultures in relation to patient treatment.

Automation↗
PubMed1994

Bacteriophage-like particle of Rochalimaea henselae.

An extracellular particle approximately 40 nM in diameter was detected in culture supernatant from the fastidious bacterium Rochalimaea henselae. This particle has at least three associated proteins and contains 14 kbp linear DNA segments that are heterogeneous in sequence. The 14 kbp DNA was also present in R. henselae cells as an extrachromosomal element for all 14 strains tested. Despite attempts to induce lysis of R. henselae, plaque formation was not observed. A similar particle, also containing 14 kbp DNA, was observed in Bartonella bacilliformis, and may be analogous to a bacteriophage that has been described elsewhere for B. bacilliformis.

Bacteriophages↗