Kappa-opioids produce significantly greater analgesia in women than in men

Sex differences in human responses to nociceptive stimuli and painful pathological conditions have generally indicated that women report higher pain levels or exhibit less tolerance than men for given stimulus intensities (reviewed in ref. 1 and 2). However, studies have not evaluated sex differences in analgesic responses. We recently reported that the opioid agonist-antagonist pentazocine, which acts predominantly at kappa-receptors, produced significantly better postoperative analgesia in females than in males in patients who underwent surgery for the removal of their third molars (wisdom teeth). In the current study, we evaluated the hypothesis that this sex difference is a characteristic of kappa-opioid agonism. In order to determine whether there are sex differences associated with kappa-opioid agonism, the analgesic efficacy of two other predominantly kappa-opioid analgesics, nalbuphine and butorphanol; was compared in males and females who underwent surgery for the removal of third molar teeth. We found that both nalbuphine and butorphanol produced significantly greater analgesia in females as compared with males. Considering our earlier findings, we conclude that kappa-opioid analgesia is greater in females than in males, probably reflecting a difference in kappa-opioid-activated endogenous pain modulating circuits.     

Coincident DiGeorge anomaly and renal agenesis and its relation to maternal diabetes

We describe 2 cases of DiGeorge anomaly with bilateral renal agenesis-one, who also had hemivertebrae, in an infant of an insulin-dependent diabetic mother (IDDM). In a review we identified 2 other instances of this combination, both in IDDMs. The currently accepted notion that DiGeorge anomaly and renal agenesis are developmental field defects, coupled with their coincidence in IDDM, suggests that this combination is an association.     

Interposition grafting for reoperation on the common femoral artery

PURPOSE: This report details our experience with common femoral artery resection and Dacron interposition grafting in the management of vascular reoperations involving the common femoral artery. DESIGN: Retrospective review. SETTING: University teaching hospital. SUBJECTS: Consecutive reoperative patients who had common femoral artery interposition grafting for arteriosclerotic occlusive disease from 1986 to 1997. INTERVENTIONS: Common femoral artery resection and interposition grafting. MAIN OUTCOME MEASURES: Operative morbidity and mortality rates and long-term patency, limb salvage, patient survival, freedom-from-graft-infection, and freedom-from-reoperation rates. RESULTS: Ninety-nine common femoral arteries (16 bilateral) were resected and replaced with Dacron interposition grafts in 83 patients (50 male, 33 female; mean age, 65 years) who had had 237 previous ipsilateral common femoral artery operations (mean, 2.4 operations; range, 1-9 operations). Simultaneous infrainguinal bypass grafts were performed in 52 operations (53%), and 60 operations (61%) were performed in patients who had had previous ipsilateral proximal bypass grafts. Operative mortality was 2%, with a 14% rate of perioperative wound complications. Mean follow-up time was 22 months. One- and 3-year assisted primary patency rates for the interposition grafts were 90% and 77%, respectively. Both 1- and 3-year life-table-determined limb salvage rates were 95%. One- and 3-year life-table-determined freedom-from-reoperation rates were 74% and 43%, respectively. One- and 3-year life-table-determined freedom-from-infection rates were 99% and 92%, respectively. One- and 3-year life-table-determined survival rates were 82% and 73%, respectively. CONCLUSIONS: Common femoral artery resection and Dacron interposition grafting are safe, and they obviate many difficulties associated with reoperative common femoral artery surgery with satisfactory long-term results.     

The mammalian cell cycle in normal and abnormal growth

Cell division, a complex array of intracellular events, occurs in a highly ordered and carefully coordinated manner. This regulation is achieved by the sequential activation and deactivation of the members of a family of serine-threonine-specific protein kinases that consist of regulatory and enzymatic subunits, the cyclins and cyclin-dependent kinases. These enzymes, in turn, regulate the activity of other proteins involved in the mitogenic pathway. Mutations in the components of the regulatory pathways can lead to aberrant growth, including malignancies.     

A model of the distribution and retention of tungsten in the human body

Expanding industrial and military uses of tungsten could result in substantially increased levels of this metal in the environment in the next few years. Although occupational experiences and available toxicological studies on laboratory animals suggest that tungsten may have a relatively low order of toxicity, the data are weak and inconclusive. There is a need not only for more systematic studies of the behavior and effects of tungsten in different animal species but also for a reliable, biologically realistic biokinetic model for tungsten in man that can be used to relate concentrations of this metal in environmental media to concentrations in tissues of exposed persons and translate results of experimental studies into terms of environmental exposures. This paper is intended as a first step toward development of such a biokinetic model. Information related to the biokinetics of tungsten in mammalian species is examined, a biologically meaningful compartmental model structure is proposed, provisional transfer rates between compartments are selected, areas are identified where additional biokinetic data on tungsten are most needed and suggestions are made for further research into the biokinetics of tungsten.     

The learning curve for laparoscopic colorectal surgery. Preliminary results from a prospective analysis of 1194 laparoscopic-assisted colectomies

BACKGROUND: Laparoscopic-assisted colectomy is an emerging technology for patients with cancer, polyps, inflammation, and other types of pathologic conditions. While previous studies have shown better outcomes for laparoscopic cholecystectomies when surgeons perform more procedures, there is no information on the relationship between surgeon volume and outcomes for laparoscopic-assisted colectomy. OBJECTIVE: To evaluate whether better clinical outcomes are found for surgeons who perform higher numbers of laparoscopic-assisted colectomies and whether such a relationship, if it exists, applies to both intraoperative and postoperative outcomes. DESIGN: Analysis of a data set of 1194 patients, operated on by 114 surgeons, from a prospective registry sponsored by the American Society of Colon and Rectal Surgeons, from May 1991 to October 1994. MAIN OUTCOME MEASURES: Completion rate, intraoperative and postoperative complications, and length of hospital stay. RESULTS: In 75% of cases, surgery was completed laparoscopically, with no difference between high-volume surgeons (> or = 40 cases) and low-volume surgeons. Length of stay (average, 6 days) did not vary according to surgeon volume. Postoperative complications occurred in 15% of cases, with a significantly lower rate for high-volume surgeons (10% vs 19%; P < .001). Intraoperative complications occurred in 5% of cases, with a nonsignificant trend toward a lower rate for high-volume surgeons (3.7% vs 6.3%). A multivariate regression analysis, adjusting for type of disease (cancer vs inflammation vs polyps) and for level of difficulty of the procedure (high vs low) showed that for high-volume surgeons there is a lower probability of both intraoperative complications (adjusted odds ratio, 0.56; 95% confidence interval, 0.32-0.97; P = .04) and postoperative complications (adjusted odds ratio, 0.48; 95% confidence interval, 0.34-0.68; P < .001). CONCLUSIONS: There is a learning curve for laparoscopic-assisted colectomy with respect to intraoperative and postoperative outcomes. As with other laparoscopic procedures, surgeons who perform higher volumes of laparoscopic-assisted colectomy have lower rates of intraoperative and postoperative complications.     

Adherence issues in clinical practice

The reproducibility of short tandem repeat (STR) amplification of aDNA extracts is limited by means of formation of artifacts during PCR. One of these artifacts, the so called allelic-dropout (failure of the amplification of alleles), may result in false-homozygote typing of a sample, if genotyping is based on the analysis of a single amplification product. 30 tooth- and bone samples collected from 17 individuals of three burial sites were investigated in a blind test. Using the polymerase chain reaction (PCR) the two independent segregating STR-loci HUMVWA and HUMTH01 were amplified. Corresponding to a mathematical estimation, multiple amplifications of each sample and genelocus were carried out. The results of this genotyping were compared intraindividually.     

The drawbacks of diagnostic diligence

More, earlier and better diagnostic work is being done nowadays, leasing to detection of abnormalities and preliminary stages that used to remain undetected; a large reservoir of subclinical disorders is found to exist. More intensive and sensitive diagnostic methods as a rule lead to higher disease prevalence figures, with the consequences of a seeming increase of disease risk, unnecessary further examinations, treatment and follow-up of individuals and overestimation of the effects of treatment. This may even start a vicious circle. More attention should be given to using diagnostic methods in such a way that the earlier and more frequent detection of disease actually profits the patient. The proof of this should be found in scientific (population) studies of the magnitude and severity of the burden of disease, the determinants of progression, the severity of abnormalities and diseases and the favourable effect of (early) treatment.