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.     

Copper/zinc superoxide dismutase transgenic brain accumulates hydrogen peroxide after perinatal hypoxia ischemia

OBJECTIVE: This study aims to evaluate the risk of esophagectomy in the elderly compared with younger patients and to determine whether results of esophagectomy in the elderly have improved in recent years. SUMMARY BACKGROUND DATA: An increased life expectancy has led to more elderly patients presenting with carcinoma of the esophagus in recent years. Esophagectomy for carcinoma of the esophagus is associated with significant morbidity and mortality, and advanced age is often considered a relative contraindication to esophagectomy despite advances in modern surgical practice. METHODS: The perioperative outcome and long-term survival of 167 elderly patients (70 years or more) with esophagectomy for carcinoma of the esophagus were compared with findings in 570 younger patients with esophagectomy in the period 1982 to 1996. Changes in perioperative outcome and survival between 1982 to 1989 and 1990 to 1996 were separately analyzed. RESULTS: The resection rate in the elderly was 48% (167/345), lower than the 65% (570/874) resection rate in younger patients (p < 0.001). There were significantly more preoperative risk factors and postoperative medical complications in the elderly, but no significant differences were observed in surgical complications. The 30-day mortality rate was higher in the elderly (7.2%) than in younger patients (3.0%) (p = 0.02), but the hospital mortality rate was not significantly different in the elderly (18.0%) and younger age groups (14.4%) (p = 0.27). The long-term survival after curative resection in elderly patients was worse than younger patients (p = 0.01). However, when deaths from unrelated medical conditions were excluded from analysis, survival was similar between the two age groups (p = 0.23). A comparison of data for the periods 1982 to 1989 and 1990 to 1996 revealed that the resection rate had increased from 44% to 54% in the elderly, with significantly fewer postoperative complications and lower 30-day and hospital mortality rates. Long-term survival has also improved, although this has not reached a statistically significant level. CONCLUSIONS: With current surgical management, esophagectomy for carcinoma of the esophagus can be carried out with acceptable risk in the elderly, but intensive perioperative support is required. The improved results of esophagectomy in the elderly in recent years are attributed to increased experience and better perioperative management. Long-term survival was similar to that of younger patients, excluding deaths caused by unrelated medical conditions.     

The HMG-CoA reductase inhibitor atorvastatin increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs

We have previously shown in vivo that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin decreases hepatic apolipoprotein B (apoB) secretion into plasma. To test the hypothesis that atorvastatin modulates exogenous triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat load (2 g fat/kg body wt) containing retinol (50 000 IU) was given to 6 control miniature pigs and to 6 animals after 28 days of treatment with atorvastatin 3 mg. kg-1. d-1. A multicompartmental model was developed by use of SAAM II and kinetic analysis performed on the plasma retinyl palmitate (RP) data. Peak TRL (d<1.006 g/mL; Sf>20) triglyceride concentrations were decreased 29% by atorvastatin, and the time to achieve this peak was delayed (5.2 versus 2.3 hours; P<0.01). The TRL triglyceride 0- to 12-hour area under the curve was decreased by 24%. In contrast, atorvastatin treatment had no effect on peak TRL RP concentrations, time to peak, or its rate of appearance into plasma; however, the TRL RP 0- to 12-hour area under the curve was decreased by 20%. Analysis of the RP kinetic parameters revealed that the TRL fractional clearance rate was increased significantly, 1.4-fold (3.093 versus 2.276 pools/h; P=0.012), with atorvastatin treatment. The percent conversion of TRL RP from the rapid-turnover to the slow-turnover compartment was decreased by 47% with atorvastatin treatment. The TRL RP fractional clearance rate was negatively correlated with very low density lipoprotein apoB production rate measured in the fasting state (r=-0.49). Thus, although atorvastatin had no effect on intestinal TRL assembly and secretion, plasma TRL clearance was significantly increased, an effect that may relate to a decreased competition for removal processes by hepatic very low density lipoprotein.     

Factors influencing survival after gamma knife radiosurgery for patients with single and multiple brain metastases

BACKGROUND: Significant changes are restructurng the U.S. health care delivery system. National health reform is now extending itself into the public sector. Increased health and medical costs by federal and state governments are forcing a reevaluation of major entitlement programs, especially Medicaid. METHODS/RESULTS: Because Medicaid is the single largest item in many state budgets, states are now enrolling Medicaid patients into managed and coordinated care arrangements as a means to control costs and increase access to care. HMOs are not only competing for private patients but also actively seeking the Medicaid population. Nationally, almost one-fourth of all Medicaid patients are now enrolled in managed care plans. Various models and approaches have been developed by individual states. CONCLUSIONS: Because managed care enrollment in the Medicaid program has increased substantially in recent years, selected services including vision care are no longer rendered by any practitioner willing to accept Medicaid fees. Freedom of choice is now restricted to pre-selected and panel practitioners participating with the managed care program. The rules, regulations, billing procedures, fees, and program requisites will differ under managed care programs. Private optometric practitioners must consider entering economic and organizational relationships and linkages that make them attractive to managed care organizations.     

Diagnostic nasal endoscopy

Endoscopy has gained wide popularity due to its protean applications and efficacy in many surgical specialties. Diagnosis and treatment of nasal diseases have advanced in the process. However, proper training in nasal endoscopy is critical. The nose is an intricate organ fundamentally and has such proximity to other vital structures that procedural miscues can cause serious complications. This paper traces the historical development of nasal endoscopy, explains its rationale, reviews anatomic and diagnostic issues, and describes the selection of equipment and correct application of technique, emphasizing the potential for advanced diagnostic skills.     

Agonist-specific tyrosine phosphorylation of Cbl in human neutrophils

The effects of soluble and particulate agonists on the tyrosine phosphorylation levels of the proto-oncogene Cbl in human neutrophils were examined. Experimental conditions allowing the maintenance of Cbl as well as of its tyrosine phosphorylation status were first established. Their use allowed us to observe that Cbl was tyrosine phosphorylated in response to some (FcgammaRII ligation, opsonized bacteria and zymosan, granulocyte-macrophage colony-stimulating factor, monosodium urate, and calcium pyrophosphate microcrystals), but not all (fMet-Leu-Phe, interleukin-8) neutrophil agonists. Cbl was also shown to account for a varying proportion of the 120-kDa phosphoprotein(s) observed in response to the above stimuli. These data establish that Cbl is present in human neutrophils and that its level of tyrosine phosphorylation is modulated by some of these cells' agonists, and in particular by phagocytic particles. Furthermore, the signaling pathways activated by chemotactic factors and the other neutrophil stimuli tested in this investigation diverge at or downstream from the tyrosine phosphorylation of Cbl.     

Association between hyperadrenocorticism and development of calcium-containing uroliths in dogs with urolithiasis

OBJECTIVE: To determine, among dogs with urolithiasis, whether dogs that had hyperadrenocorticism would be more likely to have calcium-containing uroliths than would dogs that did not have clinical evidence of hyperadrenocorticism. DESIGN: Retrospective case-control study. ANIMALS: 20 dogs that had urolithiasis and hyperadrenocorticism and 42 breed-matched dogs that had urolithiasis but did not have clinical evidence of hyper-adrenocorticism. PROCEDURE: Signalment, urolith composition, results of bacterial culture of urine, and results of adrenal axis tests were recorded. A multivariate logistic regression model was created, including terms for age, sex, and hyperadrenocorticism. The outcome variable was presence or absence of calcium-containing uroliths. RESULTS: Among dogs with urolithiasis, those that had hyperadrenocorticism were 10 times as likely to have calcium-containing uroliths as were dogs that did not have clinical evidence of hyperadrenocorticism (odds ratio, 10.5; 95% confidence interval, 1.5 to 23.4). Neutered and sexually intact females were less likely to have calcium-containing uroliths than were neutered males (odds ratios, 0.041 [95% confidence interval, 0.0057 to 0.29] and 0.024 [95% confidence interval, 0.0012 to 0.51, respectively). CLINICAL IMPLICATIONS: Prompt diagnosis and treatment of hyperadrenocorticism may decrease prevalence of calcium-containing uroliths in dogs.     

Complex segregation analysis of leprosy in southern Vietnam

To investigate the nature of the genetic component controlling susceptibility to leprosy and its subtypes, 402 nuclear families were ascertained through a leprosy patient followed at the Dermatology Hospital in Ho Chi Minh City, Vietnam; 285 families were of Vietnamese origin and 117 were of Chinese origin with a higher proportion of lepromatous forms among Chinese patients. Segregation analyses were conducted using the model developed by Abel and Bonney [(1990) Genet Epidemiol 7:391-407], which accounted for variable age of onset and time-dependent covariates. Three phenotypes were considered: leprosy per se (all forms of leprosy together), nonlepromatous leprosy, and lepromatous leprosy. For each of this phenotype, analyses were performed on the whole sample and separately on the Vietnamese and the Chinese families. The results showed that a single Mendelian gene could not account for the familial distributions of leprosy per se and its two subtypes in the whole sample. However, these results were different according to the ethnic origin of the families. In the Vietnamese subsample, there was evidence for a codominant major gene with residual familial dependences for the leprosy per se phenotype, and borderline rejection of the Mendelian transmission hypothesis for the nonlepromatous phenotype. In Chinese families, strong rejection of Mendelian transmission was obtained in the analysis of leprosy per se, and no evidence for a familial component in the distribution of the nonlepromatous phenotype was observed. For the lepromatous phenotype, the discrimination between models was poor, and no definitive conclusion could be reached. Referring to immunological data, we suggest that these results could be explained by a heterogeneity in the definition of the lepromatous phenotype. It is likely that progress in the understanding of the genetic components involved in the expression of leprosy will come from a better definition of the phenotype under study, and immunological studies are ongoing in this population to investigate this hypothesis.