Effect of low dose daily aspirin on serum urate levels and urinary excretion in patients receiving probenecid for gouty arthritis.

OBJECTIVE: To determine if low dose daily enteric coated aspirin significantly affects the therapeutic actions of probenecid with respect to serum urate levels or urinary urate excretion. METHODS: Patients with gouty arthritis taking a stable dose of probenecid for at least 3 months were enrolled in a prospective crossover study. Twenty-four hour urinary and serum uric acid levels were measured after 14 days in patients crossed over to receive probenecid alone; probenecid and aspirin 325 mg taken concomitantly; and probenecid followed by aspirin 325 mg at 6 hours. RESULTS: Eleven patients completed the crossover study. The addition of aspirin to a stable dose of probenecid had no significant effect upon serum urate levels or 24 h urinary urate excretion (p > 0.05, paired t test). CONCLUSION: Low dose daily enteric coated aspirin does not significantly interfere with the uricosuric effects of probenecid in patients with gouty arthritis.

Onset of erosive osteoarthritis in a teenage girl.

Erosive osteoarthritis is a disorder that predominantly affects the hands of postmenopausal or middle aged women. Ages usually range from 30 to 83 years. Although the etiology of erosive osteoarthritis is not known, a lack of estrogen hormones has been implicated in the pathogenesis. We report a patient with onset of symptoms at age 16 and a diagnosis at age 21. She has aggressive inflammatory involvement of the distal interphalangeal joints and characteristic radiographic changes with central erosions. She is not postmenopausal nor does she have any conditions that are believed to be possible associations with erosive osteoarthritis. To the best of our knowledge, this is the youngest reported patient with erosive osteoarthritis in the literature.

Hydroxychloroquine in the treatment of erosive osteoarthritis.

OBJECTIVE: Hydroxychloroquine has been used successfully in the treatment of inflammatory arthritides such as rheumatoid arthritis and systemic lupus erythematosus, and less commonly in the seronegative spondyloarthropathies. Our objective was to determine the effectiveness of hydroxy-chloroquine in inflammatory or erosive osteoarthritis (OA). METHODS: We retrospectively reviewed clinical records of 8 patients prescribed hydroxychloroquine therapy whose symptoms of erosive OA were unresponsive to nonsteroidal antiinflammatory drugs (NSAID). RESULTS: Hydroxychloroquine was effective in 6 of the 8 patients treated; it was well tolerated by all patients. CONCLUSION: The use of hydroxychloroquine in patients with erosive OA unresponsive to NSAID appears promising. Prospective studies are needed to confirm our observations.

Infections of the lower extremities due to gas-forming and non-gas-forming organisms.

From 1977 to 1984, 87 above- and below-knee amputations were done on 77 patients for ischemic ulcerations and gangrene of the lower extremities. The overall three-month mortality was 14% and was mainly related to generalized atherosclerosis. Patients having infections with gas formations were more likely to be diabetic (80% vs 15%, P less than .01), have clinical sepsis and a higher preoperative WBC (19,000 vs 12,600/cu mm, P less than .01), and have a higher mortality (40% vs 12%, P less than .05) than those with infections due to non-gas-forming organisms. Mixed bacterial flora were cultured from most wounds. We conclude that infections with gas formation may be due to either clostridial or nonclostridial organisms, mortality is higher if gas accumulates and if the patient is diabetic, gas is more likely to accumulate in infected extremities of diabetic patients, and the combination of gas formation and diabetes is highly lethal.

Immune responsiveness of monkeys exposed chronically to cigarette smoke.

Eleven adult male stumptailed monkeys (Macaca arctoides) were chronically exposed to either a low dose (human equivalent of 1 pack/day) or a high dose (human equivalent of 3 packs/day) of high-tar, high-nicotine University of Kentucky reference cigarette smoke for 4-8 years. Several parameters of their immunological response were compared to six nonsmoked control animals. The results from these experiments suggest that cigarette smoking does not significantly affect the response of spleen cells to the mitogens phytohemagglutinin or lipopolysaccharide. However, spleen cells from animals subjected to the heavy dose of cigarette smoke demonstrated a significant reduction in their natural killer cell-mediated lytic activity and a decreased response to concanavalin A. These results suggest that cigarette smoking may have a differential effect on lymphocyte subpopulations, and that the effects on the immune response are related to the dose of cigarette smoke.

The safe use of cisplatin in hyperthermic isolated limb perfusion systems.

A patient presenting with aggressive squamous cell carcinoma successfully received cisplatin chemotherapy via hyperthermic, isolated limb perfusion (renal impairment ruled out systemic use). Human tumor stem cell assay identified cisplatin as the drug of choice and supports the potential benefit of this procedure in single therapeutic situations. The case illustrates the safety of cisplatin and the ability to give large doses of the nephrotoxic drug with no damage to renal function. The potential efficacy over systemic cisplatin has yet to be established except when systemic use is limited from renal dysfunction.

Anti-Tcb, an antibody that defines a red cell antigen antithetical to Tca.

A patient's serum, used as a source of anti-Goa typing serum, was found to contain a second antibody that detected a 'new' red cell antigen present in approximately 5 percent of blacks, but not yet found in Caucasians. Among blacks, the 'new' antigen shows an antithetical relationship to the high frequency antigen Tca, as evidenced by tests on eight unrelated Tc(a-) black women and the families of two of these propositi. The antigen, designated Tcb, has not been found on the red cells of Tc(a-) persons whose racial origins differ from the propositi of this report, which suggests that more than one genetic mechanism can produce the Tc(a-) phenotype. The presence of both anti-Goa and anti-Tcb in the same serum appears to be a coincidental and unrelated finding.

Glutathione status of isolated rabbit lungs. Effects of nitrofurantoin and paraquat perfusion with normoxic and hyperoxic ventilation.

Thirty-minute perfusion of isolated rabbit lungs with a Krebs-Ringer bicarbonate buffer containing 420 microM paraquat (PQ) or nitrofurantoin (NF) resulted in increases in lung oxidized glutathione (GSSG) content of 589 and 2656%, respectively, over control levels. The degree of glutathione efflux was also increased with both agents, i.e. 77 and 238% above control leakage for PQ and NF respectively. The pulmonary toxicity of both compounds is known to be heightened by conditions of hyperoxia(O2). Ventilation of lungs with 95% O2-5% CO2 did not, in itself, significantly alter glutathione efflux, GSH or GSSG levels. However, ventilation with 95% O2-5% CO2 increased lung GSSG levels in PQ-perfused lungs 225% over PQ-air-perfused lungs, a combined effect not observed with NF-O2, wherein mean GSSG levels were only 72% of that observed with NF-air. Glutathione efflux in PQ-O2-treated lungs declined somewhat (20%) compared to that observed with PQ-air, but a significant increase in the amount of glutathione efflux was seen with NF-O2-treated lungs, i.e. 120 and 310%, respectively, over that attributable to NF or O2 alone. Although the biochemical mechanisms of toxicity of these compounds are thought to be very similar, the disparate degree of GSH oxidation observed with equimolar levels of PQ and NF may indicate differences in reactivity towards glutathione and other lung sulfhydryl pools. The stimulation of the oxidative effects of PQ and NF on lung GSH due to hyperoxic ventilation may be related to the reported O2 enhancement of their toxicity.

Nifedipine for the poor-risk elderly patient with achalasia: objective response demonstrated by solid meal study.

We described an 84-year-old woman with symptomatic achalasia who refused both dilation and surgical treatment. She was treated with the calcium channel blocking drug nifedipine, with significant relief of symptoms. Objective evidence of response to the drug was confirmed by using an egg salad sandwich meal labeled with 99mTc-DTPA.

Carnitine metabolism in Macaca arctoides: the effects of dietary change and fasting on serum triglycerides, unesterified carnitine, esterified (acyl) carnitine, and beta-hydroxybutyrate.

Serum triglycerides and serum total, esterified, and free (unesterified) carnitine were measured in 21 male Macaca arctoides that were switched from a low fat (5.2% w/w), high carbohydrate diet to a high fat (15.9% w/w), low carbohydrate diet for 90 days and then returned to the original low fat diet for a subsequent 76-day period. Serum triglycerides and total carnitine levels fell significantly (p less than 0.05) during the initial 2 wk of feeding the high fat diet and the ratio of esterified/unesterified carnitine rose significantly (P less than 0.05) on the high fat diet. A return to the low fat diet reversed these changes; triglycerides rose significantly (p less than 0.05) within 3 days and the ratio of esterified/unesterified carnitine fell significantly (p less than 0.05) within 3 days and the ratio of esterified/unesterified carnitine fell significantly (p less than 0.05) during the same period. A return of total carnitine levels to those initially observed on the low fat diet was slower to develop. Fasting for 24 to 48 h resulted in increases of 65 to 75% in total serum carnitine. This increase reflected elevations of both the esterified and unesterified carnitine fractions but was largely attributable to increases in esterified carnitine which rose from 10 to 41 nmol/ml by 48 h while unesterified carnitine rose from 55 to 72 nmol/ml during the same period. In addition, the ratio of esterified/unesterified carnitine ratio rose from 0.183 +/- 0.023 to 0.583 +/- 0.069 (n = 8) with a 48-h fast and was significantly correlated with serum beta-hydroxybutyrate levels at both 24 and 48 h.

Failure of chronic cigarette smoke exposure to alter plasma lipoproteins of stumptailed macaques (Macaca arctoides).

Twenty-one 8-14 kg adult male stumptailed macaques, Macaca arctoides, were fed a standard laboratory diet and divided into 3 groups. The high-dose group and low-dose group were exposed to cigarette smoke at the human equivalent of 3 packs and 1 pack per day, respectively, 7 days per week, for 3-5 years. Eight animals served as cage an sham controls. Peak blood carboxyhemoglobin (COHb) levels measured immediately after smoking showed levels of 0.5+/- 0.1%, 3.6+/-1.0%, and 5.7+/-2.8% for sham controls, low, and high dose smokers, respectively. Hemoglobin and hematocrit values were 2-7% higher (N.S. to P less than 0.05) for smoking groups, presumably as a consequence of chronically elevated COHb levels. No significant differences were seen in total plasma cholesterol and lipoprotein cholesterol concentration measured at four intervals over period of one year. We conclude from these data that, while fed a low fat diet, chronic cigarette smoke inhalation fails to alter plasma lipoprotein levels in this animal model.

Effects of nitrofurantoin on the glutathione redox status and related enzymes in the isolated, perfused rabbit lung.

Nitrofurantoin (NF) is a urinary antimicrobial drug which causes pulmonary injury. We measured levels of total lung glutathione (TLG), a tripeptide central to cellular antioxidant defenses and xenobiotic detoxification, and enzyme activities related to maintenance and utilization of reduced glutathione (GSH) in isolated, New Zealand white rabbit lungs perfused with a Kreb's-Ringer's bicarbonate medium containing NF (420 microM). After 30 minutes there was no net difference in the level of TLG [GSH + GSSG(oxidized) + effluent GSH-GSSG] or total nonprotein sulfhydryls in NF-perfused or control lungs. However, there was a decrease in the GSH:GSSG redox ratio to 2% of control (P less than .0005) and an 87% increase in GSH-GSSG efflux (P less than .005). This increased oxidation of GSH indicates that toxicity of NF is likely oxidative in nature, possibly via redox cycling of NF in the presence of oxygen to generate activated oxygen species. Activities of glucose-6-phosphate and 6-phosphogluconate dehydrogenases, GSH reductase, and GSH S-transferase were not significantly different due to NF perfusion. GSH peroxidase activity decreased 34% (P less than .025) in NF-perfused lungs. Because all TLG, as well as total nonprotein thiol was accounted for in NF-perfused lungs, it would appear that no GSH-NF metabolite conjugation occurred. GSH metabolic conjugation in the perfused lung is easily detected when tissue-alkylating drugs or their metabolites are present.

Preservation of an infected arterial graft with combination systemic-topical antibiotic therapy.

A case is presented which illustrates the unusual ability to retain a bifurcation aortofemoral vascular graft with the graft-to-femoral-artery anastomosis involved in a groin abscess. The drainage of the abscess, debridement of devitalized tissue, and the combined application of topical and systemic antibiotic therapy was successful. Some authors report that should an anastomosis of a bifurcation vascular graft, in the vicinity of the groin, become involved in infection, the threat of anastomotic disruption and continued sepsis may lead to amputation, death, or both. It is not the purpose of this report to advocate conservative management of a vascular graft infection with suture line involvement based on anecdotal experience. However, the case reported here and the experience of other authors mentioned suggest that an attempt to treat an infected graft without its removal may be indicated in selected patients where extra anatomical revascularization would be hazardous.

Cardiac tamponade following penetrating mediastinal injuries: improved survival with early pericardiocentesis.

UNLABELLED: Cardiac tamponade was diagnosed in 197 patients admitted over 20 years (1955-1974) to the Charity Hospital of New Orleans, for emergency treatment of pentrating mediastinal injuries. Of the 197, 174 definitively treated patients followed one of three patterns of management: 96 had OR thoracotomy, 68% were unstable, and preoperative pericardiocentesis reduced mortality from 25 to 11% (p less than 0.01); 44 had emergency thoracotomy, 91% were unstable, and prethoractomy pericardiocentesis decreased mortality from 94 to 63% (p less than 0.05); 34 patients primarily with isolated stab wounds, were treated nonsurgically with pericardiocentesis and observation, only 50% were unstable and there was 15% mortality. Recurrent tamponade did not significantly increase overall or operative mortality in patients with pericardiocentesis. RECOMMENDATIONS: early, even presumptive, diagnosis of tamponade; immediate pericardial decompression via pericardiocentesis; and rapid transfer to OR for thoracotomy or sternotomy and cardiorrhaphy with continous pericardial decompression via intrapericardial catheter.

Optimal leukocyte removal from refrigerated blood with the IBM 2991 blood cell processor.

One hundred forty-six units of two to five-day-old refrigerated blood were washed with the IBM Blood Cell Processor. The ABO and Rh types of the units varied according to available inventory. This study was designed to select the best protocol from the 42 possible combinations utilizing the machine's variable red blood cell override (RCO). A one liter wash program was used. The two parameters selected for study were the per cent red blood cell recovery and the per cent white blood cell removal. The protocol of choice uses a RCO of four seconds in the first and second steps of the program. This protocol yields a washed unit with a mean red blood cell recovery of 82 per cent and a mean white cell removal of 93 per cent. Our studies indicate that the IBM Blood Cell Processor can be used to wash two to five day old refrigerated blood for the preparation of leukocyte-poor blood that would meet the Standards of the AABB.

Evaluation of tracheal incisions for tracheostomy.

Three standard tracheostomy incisions in dogs were compared to determine whether any were more likely associated with stomal stenosis. Each incision resulted in an average reduction in tracheal lumen of 25 per cent, with a 50 per cent maximum. The incision selected should depend on the conditions present.