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Biomedical subjects

S M Campbell

Publications and source records attributed to S M Campbell.

At least 19 recordsLinked to original sources

Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain.

OBJECTIVE: Fibromyalgia is a common syndrome of musculoskeletal pain and fatigue. Lacking distinctive tissue or laboratory correlations, it has often been considered a form of "psychogenic rheumatism." In the present study, the notion that the stage-4 sleep anomaly typically seen in the fibromyalgia syndrome may disrupt growth hormone secretion was tested. Because growth hormone has a very short half-life, serum levels of somatomedin C were measured; somatomedin C is the major mediator of growth hormone's anabolic actions and is a prerequisite for normal muscle homeostasis. METHODS: Serum levels of somatomedin C were measured in 70 female fibromyalgia patients and 55 healthy controls, using a peptide-specific radioimmunoassay. RESULTS: Significantly lower levels of somatomedin C were observed in the fibromyalgia patients compared with controls (mean +/- SD 124.7 +/- 47 ng/ml versus 175.2 +/- 60 ng/ml; P = 0.000001). These results could not be explained by concomitant therapy or by weight, and in a subset of 21 patients in whom this was investigated, there was no correlation with various indices of disease activity. CONCLUSION: These findings indicate that there is a distinctive disruption of the growth hormone-somatomedin C neuroendocrine axis in a majority of fibromyalgia patients. It is hypothesized that this abnormality may explain the link between disturbed sleep and predisposition to muscle pain.

Adult

A tutorial for students demonstrating adequate skills but inadequate knowledge after completing a medicine clerkship at the Oregon Health Sciences University.

Upon completing a clinical clerkship, some students demonstrate adequate clinical skills appropriate for that clerkship but do not demonstrate an adequate fund of knowledge or ability to apply their knowledge clinically. For such students, repeating all or a portion of the clerkship may not be appropriate. This study describes a tutorial provided such students after they had completed the medicine clerkship at the Oregon Health Sciences University. During a two-year period (academic years 1988-89 and 1989-90), six students were identified as needing remediation, and were enrolled in a tutorial coordinated by one faculty member with support from others. The experience was highly successful for all but one student, and the tutorial was uniformly viewed by the students who took it as one of their best experiences in medical school.

Clinical Clerkship

Symptoms of Raynaud's syndrome in patients with fibromyalgia. A study utilizing the Nielsen test, digital photoplethysmography, and measurements of platelet alpha 2-adrenergic receptors.

Twenty-nine female patients with fibromyalgia were questioned about symptoms of cold intolerance and Raynaud's syndrome; objective documentation of cold-induced vasospasm was obtained by a Nielsen test. Twelve patients (41%) had abnormal Nielsen test results, and 11 patients (38%) had elevated levels of platelet alpha 2-adrenergic receptors. There was a positive correlation between the percentage of change in finger systolic pressure on cooling (Nielsen test) and the number of alpha 2-adrenergic receptors. There was poor correlation between Raynaud's syndrome symptoms and an abnormal Nielsen test result. Digital photoplethysmography showed a normal waveform in 2 of 3 patients. We hypothesize that a subgroup of patients with fibromyalgia syndrome have an up-regulation of alpha 2-adrenergic receptors as a cause of their exaggerated reaction to cold.

Adult

"Tumoral" enthesopathy: a juxtacortical osteosarcoma simulation.

A patient with psoriatic arthritis involving the ankles and feet developed a rapidly progressive large juxtacortical bony proliferative lesion arising from the right proximal radius at the bicipital tendon insertion site. The radiographic pattern was compatible with a juxtacortical periosteal osteosarcoma. We discuss the similar radiographic findings between a surface osteosarcoma and florid inflammatory enthesopathy that was found upon biopsy.

Adult

Genotype influences the development of tolerance to nicotine in the mouse.

Previous studies have demonstrated that chronic infusion of DBA/2 inbred mice with nicotine results in a dose- and time-dependent tolerance to many of the effects elicited by a challenge dose of nicotine. This tolerance was paralleled by increases in the number of brain nicotinic receptors measured with L-[3H]nicotine and alpha-[125I]bungarotoxin binding, suggesting that receptor up-regulation may underlie tolerance to nicotine. The studies reported here assessed the development of tolerance to nicotine in five inbred mouse strains that differ markedly in sensitivity to acute doses of nicotine. Mice were infused with nicotine doses ranging between 0 and 6 mg/kg/hr for 10 days and were tested for sensitivity to nicotine using several tests 2 hr after infusion was stopped. Some mouse strains, such as the C57BL/6, developed tolerance to nicotine, as measured by shifts to the right of dose-response curves, at the lowest infusion doses, whereas other strains, such as the C3H/2 and BUB, did not develop measurable tolerance until the highest infusion doses were used. A correlation between sensitivity to acute nicotine treatment and the threshold for tolerance development was observed, suggesting that tolerance develops only after a physiological effect is elicited. All of the mouse strains exhibited a dose-dependent increase in nicotine binding in all brain regions; no marked strain differences were seen in up-regulation of this binding site. Chronic nicotine infusion also evoked increases in alpha-bungarotoxin binding, but higher doses were required to elicit this effect. Changes in this binding site were observed after treatment with nicotine doses that elicited tolerance in those mouse strains that are more resistant to an acute dose of nicotine. These results indicate that the relationship between tolerance development and brain nicotinic receptor up-regulation may not be simple.

Animals

The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee.

To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in greater than or equal to 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned.

Adult

Indirect inhibition of myocyte RNA and protein synthesis by interleukin-1.

Soluble mediators of the inflammatory response may directly influence myocardial function and metabolism in the absence of myocardial cell necrosis. Previous reported experimental data have demonstrated that the monokine interleukin-1 (IL-1) can produce myocardial depression and may influence muscle protein metabolism. To further investigate this hypothesis, IL-1 was added to neonatal rat cardiac muscle cell (MC) cultures with and without additional rat cardiac non-muscle cells (NMC). Incorporation of 3H-uridine or 14C-phenylalanine into acid-insoluble material was utilized as a measure of RNA or protein synthesis. IL-1 in concentrations of up to 500 units/ml had no effect on MC RNA or protein synthesis. When NMC were added to the MC culture, IL-1 exhibited a concentration-dependent inhibition of both RNA and protein synthesis, with effects apparent at concentrations as low as 5 units/ml. Supernatants from IL-1-treated NMC cultures exerted a dose dependent reduction on the incorporation of radiolabeled precursor into MC cultures, suggesting production of a soluble substance mediating the IL-1 effect. Supernatants from IL-1 treated rat skin fibroblasts or rat skeletal muscle myoblasts increased MC radiolabeled precursor incorporation slightly, in contrast to the decrease seen with NMC supernatant. Furthermore, IL-1 treated NMC supernatant had no inhibitory effect on skeletal myoblasts. We conclude that IL-1 decreases protein and RNA synthesis in MC cultures through a second mediator elaborated from the NMC population.

Animals

A comparison of sensitivity to oxotremorine and muscarinic receptors in LS and SS mice.

Several studies have suggested that ethanol interacts with muscarinic cholinergic systems in the brain. In order to assess whether muscarinic systems regulate sensitivity to ethanol, the effects of oxotremorine pretreatment on sensitivity to ethanol were determined in the long-sleep (LS) and short-sleep (SS) mice, which were selectively bred for differential sensitivity to ethanol. In addition, the relative sensitivity of these two lines to intraperitoneally (ip) injected oxotremorine and total muscarinic receptors, as measured by quinuclidinyl benzilate (QNB) binding, M1 receptor subtypes, as measured by pirenzepine (PZ) binding, and ratios of high and low agonist affinity were measured in seven brain regions. SS mice were more sensitive to oxotremorine-induced increases in sensitivity to ethanol but the LS mice were more sensitive to the effects elicited by ip oxotremorine injection. Because the effects of oxotremorine were blocked by scopolamine but not by methylscopolamine, it is likely that the effects of oxotremorine that were measured are centrally mediated. QNB binding did not differ between the LS and SS mice except for cortex where the SS mice exhibited slightly larger numbers. The mouse lines did not differ in the number of M1 receptors or in ratio of high to low affinity agonist sites. Therefore, it does not seem likely that differences in receptor numbers are important in regulating the differential sensitivities of the LS and SS mice to oxotremorine or ethanol. Differences in receptor coupling processes may be critically involved.

Animals

Postoperative jejunal feedings following complicated pancreatitis.

Some surgeons avoid placing a jejunostomy in patients with complications, fearing either exacerbation of the disease during enteral feedings or complications from the jejunostomies. Eleven patients with hemorrhagic pancreatitis (four), pancreatic abscess (five), or infected pseudocyst (two) underwent placements of needle (five) or Red Robinson (six) jejunal catheters during laparotomy. Five patients had been given 30.8 +/- 16 liters of TPN over 25 +/- 12 days preoperatively. Only two patients received TPN postoperatively because of progressive sepsis with enteral intolerance to feedings. One of these patients developed a jejunal leak near the placement of the Red Robinson catheter. Both patients died of complications from their pancreatic disease. The remaining nine patients received 35.6 +/- 8.6 liters of enteral feedings over 31 +/- 6.8 days before resuming oral intake. Glucosuria and hyperglycemia were common, but easily managed. No catheters were lost, and diarrhea necessitating slowing and diluting the diet was unusual after the first week. Enteral feeding did not elevate amylase values. Therefore, jejunal feedings can be given safely in patients with severe acute pancreatic disease to provide prolonged nutrition without aggravating the disease.

Adult

Variation of nicotinic binding sites among inbred strains.

The specific binding of L-nicotine and alpha-bungarotoxin, two ligands which label different populations of putative nicotinic receptors, was determined in eight brain regions of 19 inbred mouse strains. The dissociation constants for L-nicotine (average = 2.26 nM) and alpha-bungarotoxin (average = 0.31 nM) did not vary significantly among the brain regions or strains. In contrast, significant variability among the maximal binding sites was observed between regions and among the strains within a region. Significant differences in L-nicotine binding were observed among the strains in midbrain, hindbrain, hippocampus, hypothalamus and colliculi, while little variability was noted in cortex or cerebellum. In general, those strains that had high L-nicotine binding in one region had high nicotine binding in the other regions. The strains clustered into two large groups: one group expressing relatively low binding and a second group expressing relatively high binding. Significant differences in alpha-bungarotoxin binding were observed in seven of the eight regions measured and, in general, those strains with high binding in one region tended to have high binding in the other regions. The strains clustered into three groups: those with low binding (DBA/1 and DBA/2), those with high binding (ST/b alone) and those with intermediate binding (the remaining 16 strains). The amount of binding of the two ligands did not correlate with each other. Comparison of nicotinic ligand binding with physiological response to nicotine suggests a relationship of L-nicotine binding with several responses observed after injection of low doses of nicotine and a relationship between alpha-bungarotoxin binding and nicotine-induced seizures.

Animals

Stimulation of spermatocyte development in prepubertal rats by the Sertoli cell steroid, 3 alpha-hydroxy-4-pregnen-20-one.

The effect of 3 alpha-hydroxy-4-pregnen-3-one (3HP), a Sertoli cell steroid, on spermatogenesis was examined in normal and gonadotropin-suppressed rats, through s.c. as well as direct intratesticular injections. Early experiments employing normal prepubertal male rats indicated that 3HP, when administered at 65 micrograms/100 g BW daily for 15 days, was capable of stimulating pachytene spermatocyte number to 149% of untreated control numbers. It was of interest to determine if this effect could be amplified in gonadotropin-suppressed animals. Neonatally estrogenized rats (500 micrograms estradiol benzoate in 0.1 ml oil at 2 days) were treated on alternate days with 3HP (100 micrograms/100 g BW) for 3 wk, starting at 7 days of age. This treatment significantly increased the number of spermatocytes per tubule cross section from 17.3 +/- 1.9 (in estradiol benzoate-only animals) to 47.1 +/- 7.9 (p less than 0.01). In a similar study, 100 micrograms/100 g BW of testosterone propionate could stimulate spermatocyte number to only 15.1 +/- 2.2 cells per tubule cross section versus estradiol benzoate-only numbers. A single intratesticular injection of 3HP (2 ng in 2.0 microliters oil) in Methallibure-treated rats resulted in a significant increase in late pachytene spermatocyte numbers from 0.77 +/- 0.12 in Methallibure-only-treated rats to 1.70 +/- 0.10 (p less than 0.001) cells per tubule cross section in 28-day-old rats. However, in this study, no other progesterone metabolite or androgenic steroid (testosterone, 5 alpha-dihydrotestosterone, or 5 alpha-androstan-3 alpha, 17 beta-diol) tested was capable of this level of germ cell stimulation. In conclusion, 3HP appears to have a direct effect on germ cell development within the testis at levels much lower than those shown to be effective for androgens. It does not appear that this effect is mediated through the conversion of 3HP to any C21 or C19 steroids, and appears to be the first report of a Sertoli cell steroid with a possible role in the process of mammalian spermatogenesis.

20-alpha-Dihydroprogesterone

Synovial fluid lymphocytes in eosinophilic fasciitis.

Arthritis is an uncommon manifestation of eosinophilic fasciitis. We report a patient who developed arthritis of his left knee, followed 2 weeks later by skin lesions which evolved into histologically proven eosinophilic fasciitis. Synovianalysis on 2 occasions demonstrated a mildly inflammatory fluid with more than 90% lymphocytes. These lymphocytes were shown to be primarily activated suppressor/cytotoxic T cells.

Adult

Regional myofascial pain syndromes.

MPS are regional pain syndromes characterized by a tender trigger point in muscle (sometimes with an accompanying palpable abnormality in consistency) producing pain in a characteristic reference zone. There is abundant evidence supporting MPS as an important cause of regional musculoskeletal pain, and a small but growing body of quantitative clinical and experimental data. The pathogenesis is unknown, but probably involves both a peripheral (muscle) and central (spinal cord) mechanism. Several modes of therapy have been proposed as effective. MPS may be related to fibrositis, but conclusive evidence is lacking.

Humans

A comparison of cyclobenzaprine and placebo in the management of fibrositis. A double-blind controlled study.

The efficacy of cyclobenzaprine (Flexeril), as compared with placebo, was tested in a 12-week, double-blind, controlled trial of 120 patients with fibrositis. Of the patients who received placebo, 52% dropped out due to lack of efficacy of the drug, compared with 16% of patients taking cyclobenzaprine. The dropout rate due to adverse reactions was similar in the 2 groups. Patients taking cyclobenzaprine experienced a significant decrease in the severity of pain and a significant increase in the quality of sleep. There was a trend toward improvement in the symptoms of fatigue, but morning stiffness was not alleviated. These improvements in symptoms were associated with a significant reduction in the total number of tender points and in muscle tightness. Our findings indicate that cyclobenzaprine is a useful adjunct in treating patients with the fibrositis syndrome.

Adult

A clonal derivative of mammary epithelial cell line COMMA-D retains stem cell characteristics of unique morphological and functional heterogeneity.

The COMMA-D cell line derived from mammary epithelial cells of midpregnant mice was shown previously to be heterogeneous as determined by phase-contrast microscopy, immunocytochemical staining, DNA content, and oncogenic potential (K.D. Danielson et al. (1984) Proc. Natl. Acad. Sci. USA 81, 3756; D. Medina et al. (1986) J. Natl. Cancer Inst. 76, 1143). Clonal subpopulations of COMMA-D cells have now been isolated by both transfection and selection using a dominant-selectable gene transfer vector and by limiting dilution. Despite their clonal origin, these subpopulations in many cases retained the heterogeneity of the parental COMMA-D line. Of 18 clonal lines assayed, only 5 were able to express beta-casein mRNA. Pooled populations of G418-resistant cells expressed substantially higher levels of beta-casein mRNA than the clonal lines. One of the expressing clonal lines, BNW-7, was characterized further, using immunocytochemical techniques. Approximately 10% of BNW-7 cells expressed casein under the appropriate hormonal and cell-substratum conditions by indirect immunofluorescent staining. Casein immunoperoxidase staining of BNW-7 cells on floating collagen gels revealed that casein-producing cells were localized in small alveolar structures, which were formed in a non-hormone-dependent fashion. The cells in these alveolar structures were cuboidal with basally located nuclei, expressed keratin intermediate filament proteins preferentially, and comprised approximately 18% of the total cells. Cells elsewhere on the surface of the gel displayed a flattened morphology, and expressed vimentin intermediate filament proteins preferentially. A proportion of COMMA-D cells, therefore, appeared to have some of the characteristics of mammary stem cells, and retained the ability to differentiate and form phenotypically heterogeneous cell populations in vitro.

Animals