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Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase are very common and effective treatments for hyperlipidemia. Epidermal cholesterol synthesis has been shown to be essential for maintaining the cutaneous barrier function. We present two patients who experienced cheilitis after beginning treatment of hyperlipidemia with simvastatin (Zocor). The rash resolved after discontinuation of medication and subsequent treatment with topical moisturizers and topical corticosteroids. We suspect that skin barrier dysfunction may occur in the mucosa from inhibitors of HMG-CoA reductase in a manner analogous to the epidermis.     

Eosinophilic mediastinitis, myositis, pleuritis, and pneumonia of cattle associated with migration of first-instar larvae of Hypoderma lineatum

Migrating first-instar larvae of Hypoderma lineatum are a frequent cause of focal inflammatory lesions in connective tissues of the mediastinum, parietal and visceral pleura, peritoneum, lungs, diaphragm, and other loci. The lesions are characterized grossly by foci of yellowish or greenish gelatinous edema and microscopically by infiltration of the edematous tissue by a dense array of eosinophils. Lesions were recognized during a period of several weeks in late spring; the timing was attributable to events in the life cycle of the fly. The larvae, which were small (approximately 1 x 4.5 mm), transparent, and unobtrusive, were recovered from lesions in 12 of 20 cattle in which careful parasitologic examination was made.     

Bipolar hemiarthroplasty for primary osteoarthritis of the hip

One hundred twenty-five bipolar hemiarthroplasties of the hip were performed at the authors' hospital. Although the procedure was performed for acute femoral neck fractures, rheumatoid arthritis, revision hemiarthroplasty, and primary osteoarthritis, only the latter is the subject of this review. A modified Harris hip score (HHS) was used to evaluate the patients both preoperatively and postoperatively. Radiographs were taken preoperatively as well as postoperatively at 2-, 4-, 6-, and 24-month intervals. A total of 68 patients underwent bipolar hemiarthroplasty for primary hip osteoarthritis. The mean preoperative HHS was 35.5 (SEM = 1.86); the mean postoperative score was 81.2 (SEM = 1.64) with an average improvement of 45.7 (SEM = 2.03). The results of this review were compared to a control group of conventional total hip arthroplasties performed at the same institution. The mean postoperative HHS for the group of conventional arthroplasties was 87.2 (SEM = 1.07). The results of this review indicate a good clinical result from bipolar hemiarthroplasty, but significantly less postoperative function when compared to conventional total hip arthroplasty.     

Tendon repair using flexor tendon splints: an experimental study

Mechanical strength of tendon repair using Dacron tendon splints across the laceration site were evaluated in human cadaver profundus tendons; the splints were placed both on the dorsal surface and internally within the tendon substance. Comparison was made to modified Kessler, Becker, and Savage repair techniques. Ultimate tensile strength was 2.55 kgf for the Kessler, 3.00 kgf for the Becker, 8.29 kgf for the Savage, 8.46 kgf for the internal tendon splint, and 8.10 kgf for the dorsal tendon splint; the Savage and both Tendon Splints techniques had significant higher tensile strength than the Kessler and Becker. Gap strength was 1.44 kgf for the Kessler, 2.22 kgf for the Becker, 2.45 kgf for the Savage, 2.05 kgf for internal tendon splint, and 3.15 kgf for the dorsal tendon splint. The dorsal tendon splint technique showed significant greater gap strength than the other four techniques. There was no significant difference in the magnitude of the gap during cyclic testing of these techniques; however, three of seven Kessler repairs failed and one of six Becker repairs failed. The results of these cadaver studies suggest that both tendon splint repair techniques are comparable to the Savage and may have sufficient strength to allow postoperative active motion against minimal resistance. Further in vivo testing is in order.     

Patterns of Cryptosporidium oocyst shedding in calves and a comparison of two diagnostic methods

Cryptosporidium spp. oocyst shedding was observed in calves from approximately 1 to 30 days of age. Oocysts were detected by either the Kinyoun acid-fast staining technique (microscopic examination--ME) or a commercially produced enzyme immunoassay EIA). Test concordance between the two detection methods was determined. The mean (+/- SD) number of days to detection of cryptosporidial oocysts was 9.52 +/- 1.92 for the ME and 9.83 +/- 3.19 for the EIA. No significant difference between the means was found (P = 0.17). The period prevalence of cryptosporidiosis was 100% in calves from 1 to 30 days of age. The overall agreement between the ME and EIA was 72%, with a kappa value of 0.42 (SE +/- 0.05). McNemar's test indicated that the proportion of tests determined positive by the two methods was not equal (P < 0.01). The findings or this study indicate moderate agreement between the two diagnostic methods, with the EIA being the more sensitive of the two. However, in most cases the herd-level determination of cryptosporidiosis requires minimal sample sizes and is more economically and easily accomplished by the ME method of detection.     

Association of CYP3A4 genotype with treatment-related leukemia

Epipodophyllotoxins are associated with leukemias characterized by translocations of the MLL gene at chromosome band 11q23 and other translocations. Cytochrome P450 (CYP) 3A metabolizes epipodophyllotoxins and other chemotherapeutic agents. CYP3A metabolism generates epipodophyllotoxin catechol and quinone metabolites, which could damage DNA. There is a polymorphism in the 5' promoter region of the CYP3A4 gene (CYP3A4-V) that might alter the metabolism of anticancer drugs. We examined 99 de novo and 30 treatment-related leukemias with a conformation-sensitive gel electrophoresis assay for the presence of the CYP3A4-V. In all treatment-related cases, there was prior exposure to one or more anticancer drugs metabolized by CYP3A. Nineteen of 99 de novo (19%) and 1 of 30 treatment-related (3%) leukemias carried the CYP3A4-V (P = 0.026; Fisher's Exact Test, FET). Nine of 42 de novo leukemias with MLL gene translocations (21%), and 0 of 22 treatment-related leukemias with MLL gene translocations carried the CYP3A4-V (P = 0. 016, FET). This relationship remained significant when 19 treatment-related leukemias with MLL gene translocations that followed epipodophyllotoxin exposure were compared with the same 42 de novo cases (P = 0.026, FET). These data suggest that individuals with CYP3A4-W genotype may be at increased risk for treatment-related leukemia and that epipodophyllotoxin metabolism by CYP3A4 may contribute to the secondary cancer risk. The CYP3A4-W genotype may increase production of potentially DNA-damaging reactive intermediates. The variant may decrease production of the epipodophyllotoxin catechol metabolite, which is the precursor of the potentially DNA-damaging quinone.     

Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain

We conducted a study of the safety of controlled-release (CR) oxycodone tablets (OxyContin Tablets) administered chronically to patients with cancer-related pain in a usual clinical setting. These patients had participated in 1 of 2 double-blind, active-control studies. Our study was an open, 3-month treatment study that included 87 patients. Patients received CR oxycodone tablets every 12 hr in a manner that reflected typical clinical practice. Supplemental immediate-release (IR) oxycodone was available PRN for breakthrough pain. Patients recorded medication use, adverse events, and evaluations of pain intensity and acceptability of therapy in a daily diary. Forty-four patients (51%) completed all 12 weeks of study; 43 patients (49%) discontinued participation. At baseline and throughout the study period, the overall mean pain-intensity score was slight to moderate. A comparison of initial and final doses showed a significant but modest increase in total daily CR oxycodone dose. An increase or decrease in titration of the oxycodone dose occurred for 66 patients (84%) at least once during the 12-week study period, primarily for increased pain. Forty-four patients (56%) did not undergo dose titration when the latter was indicated. Half of the patients used IR oxycodone rescue almost daily; the mean number of rescue doses per day was 1.5. Despite stable pain control and an increasing total daily CR oxycodone dose, the percentage of patients reporting common opioid-related adverse events decreased over the course of the study. CR oxycodone tablets administered every 12 hr were successfully used to manage cancer pain over a 12-week period. Importantly, side effects diminished over time without a concomitant change in efficacy.     

Endogenous vasodilators modulate pulmonary vascular anaphylaxis

We examined the role of endothelium-derived nitric oxide during antigen-induced contraction in pulmonary arteries isolated from actively sensitized guinea pigs. Ovalbumin (10(-2) mg/ml)-induced contraction was not sustained, and tension returned to baseline within 15 min. Pretreatment with methylene blue (10(-5) M) increased both the amplitude and the duration of the contractile response in these tissues. At 15 min, tension remained elevated and was > 70% of the peak amplitude. Removal of the endothelium with saponin (200 micrograms/ml) increased the magnitude of the contraction by > 125%; however, the duration of the response was unaffected. After pretreatment with saponin, methylene blue no longer increased the amplitude of antigen-induced contraction but its effect on the duration was unchanged. Pretreatment with nitro-L-arginine methyl ester significantly increased the magnitude of the contraction in each of the tissues. These results suggest that the response of guinea pig pulmonary arteries to antigen is modulated by two types of endogenous vasodilators, endothelium-derived nitric oxide that inhibits the initial phase of the response and an endothelium-independent relaxing factor that is guanosine 3',5'-cyclic monophosphate dependent and attenuates the duration of anaphylactic contraction.