INTRODUCTION: Rofecoxib, a cyclooxygenase 2 inhibitor (sometimes known as a specific cyclooxygenase 2 inhibitor or Coxib), is used in osteoarthritis (OA). Published information indicates rofecoxib's improved gastrointestinal safety profile over nonselective nonsteroidal anti-inflammatory agents (NSAIDs). OBJECTIVE: To evaluate the efficacy and safety of rofecoxib in treating OA in 2 studies. METHODS: Two randomized, double-blind, parallel-group studies in patients with OA of the knee or hip were conducted using identical entry criteria and end points. A 6-week placebo-controlled trial in 736 patients compared 12.5 and 25 mg of rofecoxib once daily with 800 mg of ibuprofen 3 times daily, and a 1-year study compared 12.5 and 25 mg of rofecoxib once daily with 50 mg of diclofenac 3 times daily in 693 patients. RESULTS: Rofecoxib, at 12.5 and 25 mg, demonstrated efficacy clinically comparable with ibuprofen, assessed by 3 primary end points according to predefined comparability criteria. Both rofecoxib doses and ibuprofen provided significantly greater efficacy than placebo on all primary end points at 6 weeks. Both rofecoxib doses and diclofenac showed similar efficacy over 1 year. All treatments were well tolerated. CONCLUSIONS: Rofecoxib is effective in treating OA with once-daily dosing for 6 weeks and 1 year. Rofecoxib was generally safe and well-tolerated in OA patients for 6 weeks and 1 year. Arch Fam Med. 2000;9:1124-1134

Adult↗

PubMedDate not supplied

Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients.

The pharmacokinetics of midazolam and of its main metabolite, 1-hydroxymidazolam, were investigated in intensive care patients after intravenous bolus of 0.2 mg/kg followed by a 0.1 mg/kg/h intravenous infusion of midazolam over 2 hours. A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found. The mean values of elimination half life and volume of distribution, 4.5 +/- 5.4 h and 1.7 +/- 0.7 l/kg respectively, were higher than those reported in healthy subjects. Total plasma clearance was significantly increased in patients taking drugs that induce hepatic metabolism. Significant concentrations of the unconjugated form of 1-hydroxymidazolam were recovered in plasma. The volume of distribution and the elimination half life of the metabolite were higher than those of the parent drug. These results show that 1-hydroxymidazolam might contribute to the pharmacodynamic effect of midazolam and consequently must be taken into account during pharmacokinetic and pharmacodynamic studies.

Adolescent↗

PubMedDate not supplied

Accuracy of biopsy techniques for limb and limb girdle soft tissue tumors.

BACKGROUND: The biopsy method of choice for soft tissue sarcomas (STS) of the limb and limb girdle is controversial. There have been no randomized controlled trials that compare incision biopsy with Tru-cut biopsy. We present a large series, which includes an analysis of the effectiveness of Tru-cut core biopsy both in a tertiary referral center as well as from many referring hospitals. This is compared with the other methods of biopsy of all soft tissue tumors (STT) referred to this institution. METHODS: A retrospective review of all patients who were referred to Royal Marsden Hospital NHS Trust (RMH) from 1989 to 1998. RESULTS: There were 570 patients (576 lesions) identified. Overall Tru-cut biopsy differentiated benign from malignant tumors with a sensitivity of 99.4%, specificity 98.7%, positive predictive value 99.4%, and negative predictive value 98.7% with similar results for RMH and referral hospitals. Tru-cut identified both tumor subtype and grade in approximately 80% of STS. Incision biopsy had similar sensitivity and specificity for differentiating benign from malignant STT as well as subtype of STS but was less accurate for grade assessment. Tumors from patients who were referred after enucleation had a median maximum tumor diameter (MTD) of 4.9 cm, whereas median MTD of tumors diagnosed at referring hospitals by Tru-cut biopsy was 10.6 cm. (P < 0.001). CONCLUSION: Tru-cut biopsy is highly sensitive and specific in the diagnosis of STT as well as subtyping and grading of STS. It is equally effective as incision biopsy in all these parameters and has a lesser morbidity. The failure to use Tru-cut biopsy is most likely because of the possibility that STS is not suspected in patients with small tumors even when they are deep to the investing fascia.

Biopsy, Needle↗

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Modified staging system for extremity soft tissue sarcomas.

BACKGROUND: The establishment of a universally acceptable staging system for soft tissue sarcomas has been hampered by the low incidence, various grading systems, and lack of consensus regarding the value of different prognostic factors. We aimed to evaluate prognostic factors in patients with extremity soft tissue sarcomas and to test the validity of the AJCC/UICC staging system. METHODS: Prospectively collected data from 316 previously untreated patients with primary extremity soft tissue sarcomas treated at a single institution between 1989 and 1995 were studied. The influence of clinical and pathological factors on local recurrence, distant metastasis, and disease-specific survival was analyzed by univariate and multivariate techniques. RESULTS: Large tumor size and high histological grade were independent adverse prognostic factors for distant metastasis. Large size, high grade, and positive microscopic surgical margins were independent adverse prognostic factors, and liposarcoma histology was an independent favorable prognostic factor for disease-specific survival. Within each histological grade, there was a progressive decline in survival with increasing tumor size, as reflected by an almost linear increase in hazard ratios. Similarly, there was a progressive fall in survival with increasing grade within each size group (<5 cm, 5 to 10 cm, 10 to 15 cm, and > 15 cm). AJCC staging did not correlate well with prognosis. Survival for intermediate-grade tumors smaller than 5 cm (stage IIA) was better than that for low-grade tumors larger than 5 cm (stage IB) (86% vs. 73%). Survival for high-grade tumors smaller than 5 cm (stage IIIA) was better than that for intermediate-grade tumors larger than 5 cm (stage IIB) (72% vs. 57%). A modified staging system was formulated based on the additive influence of size and grade on the estimated hazard ratios for disease-specific survival, as follows: stage IA, G1T1; stage IB, G1T2 or G2T1; stage IIA, G1T3 or G2T2 or G3T1; stage IIB, G1T4 or G2T3 or G3T2; stage IIIA, G2T4 or G3T3; stage IIIB, G3T4; and stage IV, M1 (G1, G2, G3 = low, intermediate, and high grade; T1, T2, T3, T4 = tumor size < 5 cm, 5-10 cm, 10-15 cm, and > 15 cm, respectively). The 5-year disease-specific survivals of stages IA, IB, IIA, IIB, IIIA, and IIIB were 100%, 83%, 74%, 61%, 39%, and 18%, respectively. The 5-year disease-specific survival for stages I, II, III, and IV were 90%, 67%, 31%, and 6% respectively. The survival difference between each stage was statistically significant (P < .001). CONCLUSION: Histological grade and tumor size are equally important determinants of distant metastases and survival. The AJCC/UICC staging system is based primarily on the grade of the tumor, with size used to subgroup each stage. A staging system for extremity soft tissue sarcomas with equal emphasis on grade and size is proposed that correlates extremely well with prognosis.

Adolescent↗

PubMedDate not supplied

MSH peptides are present in mammalian skin.

Immunoreactive alpha-MSH was found in human skin and the skin of numerous other mammals. After hypophysectomy the concentration of alpha-MSH in rat skin showed little change suggesting that the pituitary is not the source of this MSH. In human skin the highest concentration was found in the epidermis and HPLC revealed four peaks of immunoreactive alpha-MSH. Two of these co-eluted with mono- and des-acetyl alpha-MSH standards. An earlier peak probably represented an oxidized MSH and a later running peak, diacetylated alpha-MSH. Although no differences were found in alpha-MSH content of skin from albino and pigmented rats or between involved and non-involved epidermis of patients with vitiligo, its predominance in human epidermis could suggest a relationship with the melanocyte or its melanin. Whether alpha-MSH in the skin has any pigmentary significance or any other role has yet to be established.

Animals↗

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Pituitary-gonadal function during sleep in men with erectile impotence and normal controls.

Studies of pituitary-gonadal function in men with erectile disorders have provided conflicting findings. This study compares blood LH and testosterone during sleep in 17 physically healthy men with erectile impotence and 12 matched normal controls, and relates hormonal variations to stages of sleep and penile tumescence. Subjects, aged 23-36 were studied in a sleep laboratory for 3-6 nights with the last two nights devoted to sequential blood sampling every 20 minutes. Five men had never been able to achieve intercourse (primary impotent group) and 12 suffered from a life-long history of intermittent erectile failures (secondary-impotent group). There were no significant differences in sleep duration and REM time among the impotent groups and normal controls. Primary-impotent men showed half as many full tumescent episodes as secondary-impotent men and controls, and spent significantly less time above 80% of full tumescence. The secondary-impotent group did not differ in nocturnal penile tumescent measures from controls. There was a pattern of irregularly occurring fluctuations in plasma LH and testosterone with no differences among groups in frequency and amount of peak hormonal increases. Normal subjects had significantly higher mean testosterone concentrations during REM sleep than during other sleep stages, and during full tumescence than during partial and nontumescent periods. A direct causal relation between REM-related activity and circulating testosterone was not supported by the observation that the hormonal levels during REM sleep and during full tumescence did not differ statistically from the levels measured during adjacent time periods. As with normal subjects, the secondary-impotent group exhibited higher testosterone levels during REM sleep and full tumescence; by contrast, the primary-impotent group did not show significant hormonal differences across stages of sleep and tumescent/ nontumescent periods. These data are discussed with respect to the possible existence of subgroups of impotent men without known organic pathology than may be characterized by psychophysiologic and endocrine differences during sleep.

Adult↗

PubMedDate not supplied

Pulmonary masses presenting 11 years after abdominal surgery.

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Adult↗

PubMedDate not supplied

The spectrum of beta-thalassaemia mutations in the Lebanon.

We screened 110 DNA samples from carriers of beta-thalassaemia, using the ARMS-PCR technique with primers for common Mediterranean mutations. Unidentified samples were subjected to a heteroduplex analysis with Universal Heteroduplex Generators covering the beta-globin gene, followed by DNA sequencing. In total, 16 different mutations were detected, the most frequent being IVSI-110 (40%), followed by other common Mediterranean mutations (IVSI-1, IVSII-1, IVSI-6). Other mutations detected were of Lebanese, Turkish, Iranian, Kurdish, Bulgarian and Asian Indian origin. The most heterogeneous religious group seems to be the Sunni Muslims, with 13 mutations, while only 2 mutations were detected among the Christian Maronites. Results from this study are compared with those from other Mediterranean and neighbouring countries.

Community Medicine↗