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Biomedical subjects

M L Mahowald

Publications and source records attributed to M L Mahowald.

At least 19 recordsLinked to original sources

Long term effects of intra-articular botulinum toxin A for refractory joint pain.

UNLABELLED: The purpose of this case series review is to describe our 12 month clinical experience with intra-articular injections of Botulinum toxin Type A (BoNT/A) for refractory joint pain. Eleven patients with chronic arthritis who had failed treatment with oral and/or intra-articular medications and were not surgical candidates were referred to us for management of moderate to severe refractory joint pain in 15 joints. The use of BoNT/A to treat joint pain is a non-FDA approved "off label" treatment with potential side effects. After a detailed explanation of the joint injection procedure, signed informed consent was obtained for the procedure. Fifteen joints were injected with BoNT/A (Allergan, Inc): six lower extremity joints (3 knees, 3 ankles) with 25-50 units and nine shoulders with 50-100 units. Patients were followed for one year or longer. Maximum relief of pain was measured by comparing baseline pain on a numeric rating scale (0-10) to pain at the time of maximum relief (paired t-test). Maximum improvement in function was assessed using paired t-tests for improvement in active flexion and abduction for the shoulder joint, and by the time to perform sit to stand ten times (the timed stands test, TST) for the lower extremity joints. RESULTS: Two patients were female and nine were male, aged 42-82 years. Five had osteoarthritis (OA), five had rheumatoid arthritis (RA) and one had psoriatic arthritis. All patients were on analgesic and/or anti-inflammatory medications and all joints had previous intra-articular steroid or viscosupplement injections with inadequate or unsatisfactory benefit. A clinically and statistically significant improvement was noted after IA-BoNT/A injections. The mean maximum decrease in lower extremity joint pain was 55% (p =0.02) and the 36% (p =0.044) improvement in the Timed Stands Test was noted at four to ten weeks after injection. There was a 71% mean maximum reduction in shoulder pain severity from 8.2 +/- 1.1 to 2.4 +/- 1.9 (p <0.001). Active range of motion increased 67% in flexion (from 67.8 +/- 27.6 to 113.3 +/- 46.6 degrees, p =0.001) and 42% in abduction (from 50 +/- 18.5 degrees to 71.1 +/- 23.1 degrees p =0.01). No immediate or delayed adverse effects related to BoNT/A were noted after the injection. Duration of pain relief was variable and ranged from 3 to 12 months. Five joints were re-injected with IA-Bont/A and had a similar decrease in joint pain that lasted 3 to 12 months. CONCLUSIONS: This is the first report of the long term effects of intra-articular BoNT/A injections to treat chronic joint pain and the efficacy of repeated injections. Although this study was small, and uncontrolled the results suggest that IA-BoNT/A injections are an effective and safe treatment for chronic joint pain disorders.

Adult↗

Life-threatening reaction to vancomycin given for noninfectious fever.

OBJECTIVE: To report a case of vancomycin-induced anaphylaxis (or anaphylactoid reaction) in a patient with a fever of unrecognized noninfectious origin. CASE SUMMARY: An 83-year-old white man, who was a patient of the Veterans Affairs Medical Center, developed a serious anaphylactic (or anaphylactoid) reaction while receiving intravenous vancomycin as empiric therapy for a nosocomial fever of unknown origin. The fever was subsequently proved to have been due to acute polyarticular gout rather than an infection. DISCUSSION: This patient developed respiratory distress and an increased serum troponin concentration, suggestive of a myocardial enzymatic leak as a result of vancomycin therapy. Vancomycin was given before the noninfectious cause of his fever was recognized. CONCLUSIONS: Even with cautious slow infusion, intravenous vancomycin can precipitate life-threatening infusion-related reactions in some patients. Because of this, and to reduce selective pressure for vancomycin resistance, sources of fever that do not require treatment with vancomycin should be diligently investigated prior to the institution of empiric vancomycin therapy in febrile patients, particularly when the past medical history is suggestive of an alternative diagnosis.

Aged↗

Codeine and oxycodone use in patients with chronic rheumatic disease pain.

OBJECTIVE: Opioid treatment of chronic rheumatic disease pain is controversial because of concerns regarding efficacy, toxicity, tolerance, dependence, and abuse. This study examined opioid use in a cohort of patients with pain due to defined rheumatic diseases. METHODS: Opioid use was studied retrospectively in a cohort of 644 rheumatology clinic patients. Computerized pharmacy records identified patients who had been prescribed opioids during the previous 3 years. Medical records were reviewed to determine reasons for opioid dosage escalations. Patients were interviewed to determine efficacy, frequency and types of side effects, and history of alcohol or street-drug abuse. RESULTS: Opioid prescriptions were found in the 3-year pharmacy database for 290 of 644 clinic patients: 153 for <3 consecutive months and 137 for > or =3 months. All opioid-treated patients received codeine and/or oxycodone. In this cohort, 133 patients in each opioid-treated group and 76 of the 354 non-opioid-treated control patients were studied. Opioids significantly reduced rheumatic disease pain severity scores from 8.2 to 3.6 (on a 0-10 scale) (P < 0.001). Mild side effects were reported in 38%; nausea, dyspepsia, constipation, and sedation were the most common. The mean +/-SD initial dosage was 2.1+/-1.7 30-mg codeine equivalents/day, the mean peak was 3.4+/-3.3 per day, and the mean current dose was 2.7+/-2.0 per day. Dosage escalations occurred in 32 patients and were attributable to worsening of the underlying painful condition or a medical complication thereof in all but 4 patients, who also displayed other abuse behaviors. Abuse behaviors were not more frequent in those with or without a history of abuse/ addiction. CONCLUSION: Prolonged treatment of rheumatic disease pain with codeine or oxycodone was effective in reducing pain severity and was associated with only mild toxicity. Doses were stable for prolonged periods of time, with escalations of the opioid dose almost always related to worsening of the painful condition or a complication thereof, rather than the development of tolerance to opioids. Doubts or concerns about opioid efficacy, toxicity, tolerance, and abuse or addiction should no longer be used to justify withholding opioids from patients with well-defined rheumatic disease pain.

Aged↗

Commercial wrist extensor orthoses: a descriptive study of use and preference in patients with rheumatoid arthritis.

OBJECTIVE: To describe patients' functional uses of 3 commercial wrist orthoses, to describe patients' preference patterns for the orthoses, and to clarify orthotic attributes that are viewed positively and negatively. METHODS: Using a cross-over design, 42 patients with definite rheumatoid arthritis used each of 3 commercial orthoses for one week. There was a one-week wash-out between each week of use. At the end of the study, private semi-structured interviews were conducted with each participant. Data from close-ended questions were tabulated. Open-ended data were analyzed using qualitative methods. RESULTS: Patients reported that the 3 commercial wrist orthoses reduced wrist pain similarly, but that comfort and a sense of security during functional tasks were only found if the orthoses were comfortable and well-fitting. Most subjects preferred the padded, short forearm orthosis, though a small number found it uncomfortably warm, and many complained that it was difficult to use when wearing long-sleeved garments. Common complaints about the two elastic orthoses included chafing at the thumb webspace and chafing at the proximal closures. Longer forearm length was often perceived as providing unnecessarily high levels of wrist support. CONCLUSIONS: No single orthosis suited all subjects. Satisfaction with an orthosis appears to be based not only on its therapeutic effect, but also the comfort and ease of its use. To maximize patient satisfaction and improve the likelihood of appropriate fit and comfort, several styles of commercial orthoses should be available. The current trend toward restricted clinic stocks appears contrary to both therapeutic goals and patient satisfaction.

Activities of Daily Living↗

Murine progressive ankylosis is not immunologically mediated.

OBJECTIVE: Murine progressive ankylosis is an autosomal recessive disorder in mice similar to the human spondyloarthropathies. The gene responsible for progressive ankylosis, ank, has not been identified and its product is unknown. We investigated whether the immune system plays a role in the pathogenesis of progressive ankylosis. METHODS: Reciprocal transfers of spleen or bone marrow cells or serum between ank/ank and normal mice were performed. CD4 T cells were depleted in vivo by injection with monoclonal antibody. Ank/ank; nu/nu mice were bred from double heterozygote offspring of homozygote parents. RESULTS: Disease was neither ameliorated nor induced by these immune system manipulations. CONCLUSION: We conclude that progressive ankylosis is not immune mediated. The similarities between ankylosing spondylitis and murine progressive ankylosis may be due to mechanisms producing osteogenesis in nonosseous tissues.

Adoptive Transfer↗

Finger dexterity and hand function: effect of three commercial wrist extensor orthoses on patients with rheumatoid arthritis.

OBJECTIVE: To investigate the effect of 3 commercial wrist orthoses on finger dexterity and hand function of patients with rheumatoid arthritis (RA). METHODS: Forty-two patients with definite RA participated in the cross-over study comparing 3 styles of commercial wrist orthoses. Finger dexterity and hand function of the dominant hand were assessed while splinted and unsplinted, at the initial session and after 1 week of intermittent orthosis use. Finger dexterity was assessed using two subtests from the Purdue Pegboard Test (Purdue) and hand function was assessed using the Jebsen-Taylor Hand Function Test (Jebsen-Taylor). RESULTS: Both finger dexterity and hand function were reduced by splinting; men and women were affected similarly. There was no difference in finger dexterity or hand function afforded by the 3 orthoses. Results on both the Purdue and Jebsen-Taylor tests showed a significant learning effect across time. CONCLUSIONS: The 3 commercial wrist orthoses studied reduce dexterity similarly and significantly. When commercial wrist orthoses are to be used during tasks that require maximum dexterity, this reduction should be weighed against the known benefits of splinting.

Activities of Daily Living↗

Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments. RESULTS: While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.

Adult↗

Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.

Adult↗

Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. METHODS: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.

Adult↗

Immediate and short-term effects of three commercial wrist extensor orthoses on grip strength and function in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the immediate and short-term effects of 3 commercial wrist orthoses on grip strength and function. METHODS: Thirty-six patients with definite rheumatoid arthritis participated in the randomized, controlled, cross-over design study of 3 commercial wrist extensor orthoses. Dominant-hand dynamometric grip strength was assessed at both initial and followup sessions while splinted and nonsplinted. Functional impact was assessed using a written questionnaire. RESULTS: All 3 commercial orthoses reduced grip strength when first donned. After a 1-week adjustment period, one orthosis, the Smith and Nephew Roylan D-Ring (Roylan), afforded splinted grip strength equal to that of the nonsplinted grip strength. The other 2 orthoses continued to reduce grip strength, and afforded splinted grip strength significantly below that of the Roylan. The Roylan was deemed comfortable by more subjects than the other orthoses. CONCLUSIONS: The belief that commercial orthotic use increases grip strength, either immediately or after 1 week, is not supported by this study's data. Different styles of commercial wrist orthoses appear to have differing influence on splinted grip strength.

Activities of Daily Living↗

Exercise for arthritis.

The data available indicate that ROM, strengthening and aerobic conditioning exercises are safe for patients with OA, RA or AS, despite earlier concerns that exercise might exacerbate joint symptoms or accelerate disease. Less clear are the therapeutic benefits of exercise. In patients with OA, stretching, strengthening, and aerobic conditioning programmes can improve the deficits observed in these patients. The improvements observed generally have been small, and the evidence that these individual improvements result in improved overall function is minimal. None the less, it is likely that exercise will reduce pain, improve endurance for physical activities and improve cardiovascular fitness. Study of the long-term effects of exercise in the geriatric population, for sustaining independent living and functioning, is critically important for future health care and social expenditures. In RA, strengthening and aerobic conditioning exercise programmes can increase muscle strength and cardiovascular fitness and probably improve physical function as well. Improvements demonstrated in patients with RA seem more convincing than those in patients with OA and AS; this probably represents their poorer physical status prior to exercising. For patients with AS, intensive physiotherapy brings statistically significant short-term improvements in spinal and hip ROM which are only modestly clinically significant. It is possible that spinal mobility exercises decelerate loss of mobility over the long term, but controlled studies are needed to confirm this. Improvement in respiratory function with exercise appears to be related to cardiopulmonary fitness and perhaps to improvements in diaphragmatic respiration rather than to changes in thoracic cage mobility. Given the overall safety and likely benefits of the described forms of exercise, exercise should be included in the overall treatment of patients with OA, RA or AS. Careful patient evaluation and education about exercise should be a part of the exercise programme.

Arthritis↗

Inclusion body myositis and renal cell carcinoma. Report of two cases and review of the literature.

OBJECTIVE: To describe the clinical course of 2 patients with concurrent inclusion body myositis and renal cell carcinoma and review published reports of inclusion body myositis associated with malignancy. METHODS: Prospective followup of 2 patients. Review of published case reports and series of patients with inclusion body myositis. RESULTS: Our 2 patients with inclusion body myositis and renal cell carcinoma had no improvement of strength following nephrectomy. Seven previously reported cases of inclusion body myositis and malignancy were identified and are discussed. CONCLUSION: Findings in our 2 patients suggest that there is no etiopathologic relationship between inclusion body myositis and malignancy.

Carcinoma, Renal Cell↗

Phosphocitrate prevents disease progression in murine progressive ankylosis.

OBJECTIVE: Mice with progressive ankylosis, a spontaneous arthropathy, were treated with phosphocitrate (PC) in vivo to determine the effect of PC on disease progression. METHODS: Two groups of mice with progressive ankylosis (matched for age, weight, and sex) were treated parenterally for 6 weeks with either PC or saline vehicle. RESULTS: Clinically, histologically, and microradiographically, there were significant differences in disease progression and severity in the PC-treated and the saline-treated mice. CONCLUSION: PC appears to inhibit disease progression in murine progressive ankylosis.

Animals↗

Validity and reliability of the timed-stands test for patients with rheumatoid arthritis and other chronic diseases.

The timed-stands test (TST) is a simple measure of lower extremity strength which correlates with age in healthy people. We validated the TST as a functional assessment tool against other measurements of functional capacity and comorbidity in 147 patients with rheumatoid arthritis (RA) or other chronic diseases. The TST was significantly impacted by RA disease activity and by comorbidity. Age affected TST only in patients without arthritis or life threatening disease. TST is a simple, reproducible measure of lower extremity function that was valid in this patient population.

Analysis of Variance↗

Transient inhibition of murine progressive ankylosis by indomethacin.

Murine progressive ankylosis (MPA) is an heritable disorder which produces acute arthritis and ankylosis of peripheral and axial joints similar to ankylosing spondylitis. Because indomethacin inhibits heterotopic bone formation in vivo, we studied its effects on MPA. Indomethacin was administered for 6 weeks beginning at weaning to litters from heterozygote breeder pairs. Progression curves for peripheral, spinal and thoracic joint ankylosis in treated and untreated ank/ank animals wer compared. There was no delay in ankylosis of peripheral or spinal joint ankylosis in MPA animals treated with indomethacin. interestingly, transient delay of thoracic ankylosis occurred in indomethacin treated MPA animals.

Animals↗

Calcergy in murine progressive ankylosis.

Murine progressive ankylosis (MPA) is characterized by periarticular ossification and joint ankylosis. We studied calcergy and calciphylaxis in MPA. Calcergy represents a chemical attraction between heavy metal salts and apatite followed by hydroxyapatite deposition around collagen. Mice were injected subcutaneously with FeCl2, PbAcetate, and saline, and sacrificed at intervals between 5 minutes and 14 days. Section of skin and subcutaneous tissues were stained with Von Kossa's stain. No mice developed calcifylaxis. PbAcetate produced calcergy in all mice. MPA mice exhibited calcergy qualitatively and quantitatively the same as normal mice suggesting abnormal calcergy is not responsible for joint ankylosis in MPA.

Animals↗