Human joint performance and the roughness of articular cartilage

The Doppler technique has been used to evaluate venous reflux in the spermatic cord. Valsalva-induced reflux occurred on the left side in 83% and on the right side in 59% of 118 patients without clinical varicoceles and there was no difference in incidence between fertile and infertile men. The significance of Valsalva-induced reflux should be questioned. Greater importance should be attributed to the spontaneous venous reflux that occurred during quiet respiration in the majority of patients with varicoceles. Seven velocity waveform patterns are described and these are thought to represent increasing degrees of internal spermatic vein reflux and provide a basis on which it is possible to grade varicoceles. The Doppler grades correlated with the size of the varicocele, and with the internal spermatic vein diameter and testosterone concentrations.     

Reversal of pretreatment hypotension and control of hemorrhage in trauma patients by a simple device

The injection of a suspension of Walker 256 carcinoma cells into the carotid artery of rats produced a model of hematogenously spread cerebral metastases. Most animals died from massive extracerebral tumors of the head and jaw; brain tumors were present in only one-quarter. External carotid artery ligation prior to tumor inoculation did not increase the incidence of fatal brain tumor. When cyclophosphamide, 15 mg/kg, was injected as a single dose on the fourteenth day after tumor inoculation, most of the extracerebral tumor disappeared. Fifty percent of the animals so treated were cured of tumor, but 90% of the remainder died of large intracerebral tumors. Severe cytopathic changes resulting from cyclophosphamide were present in extracerebral or choroid plexus tumors but were mild or nonexistent in intracerebral tumors. These selective effects of cyclophosphamide suggest that water-soluble agents are less effective against tumor in the brain than against extracerebral tumors despite the fact that metastatic tumor breaks down the blood-brain barrier.     

RNA tertiary structure mediation by adenosine platforms

The crystal structure of a group I intron domain reveals an unexpected motif that mediates both intra- and intermolecular interactions. At three separate locations in the 160-nucleotide domain, adjacent adenosines in the sequence lie side-by-side and form a pseudo-base pair within a helix. This adenosine platform opens the minor groove for base stacking or base pairing with nucleotides from a noncontiguous RNA strand. The platform motif has a distinctive chemical modification signature that may enable its detection in other structured RNAs. The ability of this motif to facilitate higher order folding provides one explanation for the abundance of adenosine residues in internal loops of many RNAs.     

Gonadal steroids have paradoxical effects on brain oxytocin receptors

Specific brain receptors for oxytocin have been described in several mammalian species. The distribution of these receptors differs greatly across species and in the rat, receptor binding in specific brain regions appears to depend upon gonadal steroids. This study used in vitro receptor autoradiography to examine the effects of testosterone on oxytocin receptor binding in the mouse forebrain. Three groups of male mice were compared: castrates treated with blank capsules, castrates treated with testosterone filled capsules, and intact males. Irrespective of steroid treatment, the distribution of oxytocin receptors in mouse forebrain differed markedly from patterns previously described in the rat. In addition to these species differences in receptor distribution, testosterone had effects in the mouse which differed from the induction of receptors previously reported in the rat. In the mouse ventromedial nucleus of the hypothalamus, binding in the untreated castrate males was approximately double that observed in either the intact or the testosterone-treated castrates. In other regions of the mouse brain, such as the intermediate zone of the lateral septum, binding to oxytocin receptors was increased with testosterone treatment. These results suggest that the brain oxytocin receptor varies across species not only in its distribution but also in its regional regulation by gonadal steroids. These apparently paradoxical changes in oxytocin receptor binding may result from either direct or indirect effects of gonadal steroids in mouse brain.     

Predictors of long-term smoking cessation in head and neck cancer patients

Cigarette smoking is a major risk factor for head and neck cancer, and individuals who continue to smoke past diagnosis and treatment are at elevated risk for further disease. In a randomized controlled trial, a state of the art provider-delivered smoking cessation intervention was compared to a usual care advice control condition. The intervention consisted of surgeon- or dentist-delivered advice to stop smoking, a contracted quit date, tailored written materials, and booster advice sessions. Subjects were 186 patients with newly diagnosed first primary squamous cell carcinomas of the upper aerodigestive tract who had smoked cigarettes within the past year. At randomization, 88.2% of subjects were current smokers. At 12-month follow-up, 70.2% of subjects completing the trial (n = 114) were continuous abstainers; among baseline smokers alone the continuous abstinence (CA) rate was 64.6%. The cotinine validation rate at 12 months was 89.6%. Modeling techniques were utilized in order to derive expected CA rates, which included noncompleter subjects (n = 72). The CA rate expected at 1 year for the entire patient population was 64.2%, and for smokers alone the expected CA rate was 59.4%. Logistic regression analysis carried out on baseline smokers identified predictors of 12-month CA status. These included medical treatment, stage of change, age, nicotine dependence, and race. The intervention effect was not significant, although the sign of the effect was positive. Based on these findings, we recommend systematic brief advice to stop smoking for head and neck cancer patients, with a stepped care approach for patients less able to quit.     

Are supplementary services provided during methadone maintenance really cost-effective?

OBJECTIVE: Previous research has suggested that support services supplementing methadone maintenance programs vary in their cost-effectiveness. This study examined the cost-effectiveness of varying levels of supplementary support services to determine whether the relative cost-effectiveness of alternative levels of support is sustained over time. METHOD: A group of 100 methadone-maintained opiate users were randomly assigned to three treatment groups receiving different levels of support services during a 24-week clinical trial. One group received methadone treatment with a minimum of counseling, the second received methadone plus more intensive counseling, and the third received methadone plus enhanced counseling, medical, and psychosocial services. The results at the end of the trial period have been published elsewhere. This article reports the results of an analysis at a 6-month follow-up. RESULTS: The follow-up analysis reaffirmed the preliminary findings that the methadone plus counseling level provided the most cost-effective implementation of the treatment program. At 12 months, the annual cost per abstinent client was $16,485, $9,804, and $11,818 for the low, intermediate, and high levels of support, respectively. Abstinence rates were highest, but modestly so, for the group receiving the high-intensity, high-cost methadone with enhanced services intervention. CONCLUSIONS: This study suggests that large amounts of support to methadone-maintained clients are not cost-effective, but it also demonstrates that moderate amounts of support are better than minimal amounts. As funding for these programs is reduced, these findings suggest a floor below which supplementary support should not fall.     

Buprenorphine versus methadone maintenance for opioid dependence

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)