Choice test to determine potential attractants and repellents for the sheep scab mite, Psoroptes ovis (Acari: Psoroptidae).

A choice test bioassay was devised to screen compounds as potential semiochemicals (e.g., kairomones or allomones that mediate aggregation, attraction or repellence) for the obligate parasitic mite, Psoroptes ovis. The choice test used filter paper discs in a 1:4 test:control ratio and was found to be a reliable, effective and efficient method. Four mammalian lipid components were assessed as potential attractants-linoleic acid, arachidonic acid, methyl myristate and squalene-, and the insect/tick repellent DEET for potential repellence. Linoleic acid was significantly attractive to P. ovis adult females and has the potential to act as an attractant. Identification of P. ovis semiochemicals, especially attractants, would be beneficial in the development of novel control methods and tools for this species. This is essential considering the increase in resistance to the limited prophylactic chemical treatments in the UK, and the high prevalence of scab infections.

Pre-therapy inflammation and coagulation activation and long-term CD4 count responses to the initiation of antiretroviral therapy.

OBJECTIVES: Pre-antiretroviral therapy (ART) inflammation and coagulation activation predict clinical outcomes in HIV-positive individuals. We assessed whether pre-ART inflammatory marker levels predicted the CD4 count response to ART. METHODS: Analyses were based on data from the Strategic Management of Antiretroviral Therapy (SMART) trial, an international trial evaluating continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, evaluating three first-line ART regimens with at least two drug classes. For this analysis, participants had to be ART-naïve or off ART at randomization and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear models, we assessed the association between each of the biomarker levels, categorized as quartiles, and change in CD4 count from ART initiation to 24 months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline), study arm, follow-up time and other known confounders. RESULTS: Overall, 1084 individuals [659 from SMART (26% ART naïve) and 425 from FIRST] met the eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per cent of individuals were male with the mean age of 42 years. The median (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300) cells/µL in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 count in FIRST but not in SMART. In adjusted models, there was no clear relationship between changing biomarker levels and mean change in CD4 count post-ART (P for trend: CRP, P = 0.97; IL-6, P = 0.25; and D-dimer, P = 0.29). CONCLUSIONS: Pre-ART inflammation and coagulation activation do not predict CD4 count response to ART and appear to influence the risk of clinical outcomes through other mechanisms than blunting long-term CD4 count gain.

Peripheral versus central cannulation for extracorporeal membrane oxygenation: a comparison of limb ischemia and transfusion requirements.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be instituted centrally, through the right atrium and ascending aorta, or peripherally, most commonly using the femoral artery and vein. We sought to investigate the impact of the mode of cannulation on the incidence of limb ischemia, perfusion and overall morbidity. METHODS: A retrospective analysis of 50 consecutive patients over 5 years who underwent ECMO by central or peripheral cannulation was performed. RESULTS: There was no difference in the incidence of limb ischemia and end-organ perfusion when peripheral and central cannulation cohorts were compared. Central cannulation was associated with a higher incidence of bleeding from the cannulation site (64% vs. 18%, P = 0.002), blood product utilization and reoperation (66% vs. 14%, P < 0.0001). 30-day mortality was similar in both cohorts (46% peripheral, 50% central, P = 0.8). CONCLUSION: Our results suggest that there is comparable tissue perfusion and limb ischemia with both cannulation techniques. Central cannulation is associated with a higher incidence of bleeding, higher transfusion rates, a greater need for reoperation and greater resource utilization. Therefore, peripheral cannulation is safe and may be advantageous in certain clinical scenarios.

Oculoparalytic illusion: visual-field dependent spatial mislocalizations by humans partially paralyzed with curare.

In darkness, observers partially paralyzed with curare make large (greater thn 20 degrees) gaze- and dosage-dependent errors in visually localizing eye-level-horizontal and median planes, in matching the location of a sound to a light, and in pointing at a light. In illuminated, structured visual localization and pointing are accurate but errors in auditory-to-visual matches remain. Defects in extraretinal eye position information are responsible for all errors. The influence of extraretinal eye position information on visual localization is suppressed by a structured visual field but is crucial both in darkness and for intersensory localization if visual capture is prevented.

Decision Making in Fuzzy Discrete Event Systems1.

The primary goal of the study presented in this paper is to develop a novel and comprehensive approach to decision making using fuzzy discrete event systems (FDES) and to apply such an approach to real-world problems. At the theoretical front, we develop a new control architecture of FDES as a way of decision making, which includes a FDES decision model, a fuzzy objective generator for generating optimal control objectives, and a control scheme using both disablement and enforcement. We develop an online approach to dealing with the optimal control problem efficiently. As an application, we apply the approach to HIV/AIDS treatment planning, a technical challenge since AIDS is one of the most complex diseases to treat. We build a FDES decision model for HIV/AIDS treatment based on expert's knowledge, treatment guidelines, clinic trials, patient database statistics, and other available information. Our preliminary retrospective evaluation shows that the approach is capable of generating optimal control objectives for real patients in our AIDS clinic database and is able to apply our online approach to deciding an optimal treatment regimen for each patient. In the process, we have developed methods to resolve the following two new theoretical issues that have not been addressed in the literature: (1) the optimal control problem has state dependent performance index and hence it is not monotonic, (2) the state space of a FDES is infinite.

Phase I trial of docetaxel with estramustine in androgen-independent prostate cancer.

PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a > or = 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.

Acetylator phenotype and genotype in patients infected with HIV: discordance between methods for phenotype determination and genotype.

The acetylator phenotype and genotype of AIDS patients, with and without an acute illness, was compared with that of healthy control subjects (30 per group). Two probe drugs, caffeine and dapsone, were used to determine the phenotype in the acutely ill cohort. Polymerase chain reaction amplification and restriction fragment length polymorphism analysis served to distinguish between the 26 known NAT2 alleles and the 21 most common NAT1 alleles. The distribution (%) of slow:rapid acetylator phenotype seen among acutely ill AIDS patients differed with the probe substrate used: 70:30 with caffeine versus 53:47 with dapsone. Phenotype assignment differed considerably between the two methods and there were numerous discrepancies between phenotype and genotype. The NAT2 genotype distribution was 45:55 slow:rapid. Control subjects, phenotyped only with caffeine, were 67:33 slow:rapid versus 60:40 genotypically. Stable AIDS patients, phenotyped only with dapsone, were 55:45 slow:rapid versus 46:54 genotypically. Following resolution of their acute infections, 12 of the acutely ill subjects were rephenotyped with dapsone. Phenotype assignment remained unchanged in all cases. The distribution of NAT1 alleles was similar in all three groups. It is evident from the amount of discordance between caffeine phenotype and dapsone phenotype or genotype that caution should be exercised in the use of caffeine as a probe for NAT2 in acutely ill patients. It is also clear that meaningful study of the acetylation polymorphism requires both phenotypic and genotypic data.

Relationship of intraabdominal fat as measured by magnetic resonance imaging to postprandial lipemia in middle-aged subjects.

Adipose distribution has been associated with coronary artery disease and its risk factors. We previously described an association between postprandial triglyceride response (pptg response) to a standard high-fat meal and extracranial carotid atherosclerosis. This study was designed to evaluate the association between intraabdominal fat and pptg response. Twenty-nine subjects were recalled for determination of intraabdominal fat by magnetic resonance imaging (MRI). Fat was quantified according to an inversion recovery protocol previously validated and the cross-sectional area of intraabdominal fat at the umbilicus was analyzed as an independent variable. We observed a strong independent correlation between intraabdominal fat and pptg response to a fatty meal (r = 0.521, P < 0.05). Baseline triglyceride was also independently correlated with postprandial triglycerides (r = 0.631, P < 0.05). In univariate analysis, intraabdominal fat was correlated with age, sex, body mass index (BMI), waist-to-hip ratio (WHR), and dietary saturated fatty acids. The association with age and BMI persisted in multivariate analyses.

Phase I/II studies of docetaxel (Taxotere) combined with estramustine in men with hormone-refractory prostate cancer.

Evaluation of the combined regimen of estramustine and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) in men with hormone-refractory prostate cancer is in its early stages. While this combination is promising in terms of efficacy, adverse events associated with estramustine are a concern. Estramustine has been associated with side effects such as nausea, vomiting, edema, and serious vascular events. Reported here are the results of phase I and phase II trials in which 280 mg estramustine was given three times daily on days I to 5 in 21-day treatment cycles with docetaxel at varying doses. Data from patients evaluable thus far support the efficacy of this combination, both in chemotherapeutically naive patients and in those who have had prior therapy. A survival benefit from this combination appears achievable from these early studies. As significant antitumor activity can be achieved with docetaxel alone, future studies need to define the minimal dose of estramustine for this combination.

Diagnosis of pericardial effusion by computed tomography.

We assessed the diagnostic utility of computed tomography (CT) in the detection of pericardial effusion by using a dog model in which the amount and type of pericardial fluid were controlled and by obtaining CT scans on patients with suspected pericardial effusion prior to pericardiocentesis. The experimental studies showed that CT was capable of detecting pericardial effusion composed of serous fluid or saline in amounts as small as 50 ml. However, the hemopericardium was radiographically isodense with the heart and difficult to detect by CT unless the epicardial fat pad was identified or intravenous contrast enhancement of the heart was used. CT clearly demonstrated the presence of pericardial effusion in all six patients studied prior to successful pericardiocentesis or pericardiectomy. We conclude that CT is a sensitive noninvasive method which can be used for the diagnosis of pericardial effusion.

Comparison of intravenous and intranasal heroin self-administration by morphine-maintained humans.

Eight heroin-dependent individuals, maintained on divided daily doses of oral morphine, participated in a 2.5-week inpatient study comparing the effects of intranasal (IN) (placebo, 12.5, 25, 50, 100 mg) and intravenous (IV) (placebo, 6.25, 12.5, 25, 50 mg) heroin. Each morning, participants received $20 and a sample dose of heroin, and each afternoon they had the opportunity to self-administer all or part of the morning heroin dose or money amount. Participants responded under a modified progressive-ratio schedule (PR 50, 100, 200, 400, 800, 1200, 1600, 2000, 2400, 2800) during a ten-trial self-administration task. During each trial, participants could respond for 1/10th of the heroin dose or 1/10th of the money amount. The total amount of heroin and/or money chosen during the self-administration task was given at the end of the task. Thus, participants received drug and/or money twice each day: once during the morning sample session and once during the afternoon self-administration session. Participants received IV solution and IN powder simultaneously during each dosing; only one route contained active drug. Heroin produced dose-related increases in break point values by both routes of administration. Although IV heroin was approximately four-fold more potent than IN heroin, the maximal break point values for both routes were not significantly different. A similar difference in potency between the IV and IN routes was found for several ratings of subjective effects (e.g., "I feel a good drug effect," "I feel high"), but maximal subjective ratings were lower for IN compared to IV heroin. These results suggest that the reinforcing efficacy of heroin is similar by the two routes of administration, but that IN heroin is less potent than IV heroin. The results also underscore the importance of evaluating drug self-administration in the evaluation of the abuse liability of drugs.

Fc receptors on the human placenta.

The Fc receptors on the human placenta have been evaluated using hemadsorption to cryostat sections of fresh forzen placenta. Indicator cells were sheep erythrocytes sensitized with various amounts of rabbit IgG antibodies. The receptor activity of the placenta varied with the degree of sensitization of EA but quantitatively was greater at all dilutions when compared to other normal tissues.

Disseminated cutaneous and meningeal sporotrichosis in an AIDS patient.

We report the first proven case of Sporothrix meningoencephalitis in an AIDS patient. The patient had dramatic, wide-spread ulcerative and infiltrative disease with progressive meningoencephalitis in spite of amphotericin and itraconazole therapy. Sporothrix was cultured from premortem cerebrospinal fluid and seen in the meninges and in brain vessels at autopsy.

Efficacy and safety of abacavir plus lamivudine versus didanosine plus stavudine when combined with a protease inhibitor, a nonnucleoside reverse transcriptase inhibitor, or both in HIV-1 positive antiretroviral-naive persons.

PURPOSE: The combination of abacavir + lamivudine (ABC+3TC) versus didanosine + stavudine (ddI+d4T), each combined with other classes of antiretrovirals (ARVs) in ARV-naive patients, was compared for the combined endpoint of time to plasma HIV RNA >50 copies/mL (at or after the 8-month visit) or death (primary endpoint) in a nested substudy of an ongoing multicenter randomized trial. METHOD: The substudy enrolled 182 patients; mean HIV RNA and CD4+ cell counts at baseline were 5.1 log10 copies/mL and 212 cells/mm3, respectively. RESULTS: After a median follow-up of 28 months, rates of primary endpoint were 57.2 and 67.8 per 100 person-years for the ABC+3TC and ddI+d4T groups (hazard ratio [HR]=0.81, 95% confidence interval [CI] 0.58-1.14, p=.23). CONCLUSION: There was a trend for treatments containing ABC+3TC to be better than treatments containing ddI+d4T with respect to HIV RNA decreases, CD4+ cell count increases, and tolerability.

Immunologic status and lymphedema of the arm in postoperative patients with cancer of the breast.

Sixty women were evaluated regarding their immunologic status and for presence of lymphedema after surgery for breast carcinoma. Patients who had undergone radiotherapy were noted to have decreases in TLC, and increases in LIF. In addition, the patients also had an increased incidence of lymphedema after radical mastectomy.

Hickman-Broviac catheters. Indications and results.

The records of 84 patients in whom 98 Hickman-Broviac catheters were inserted were reviewed. The most common indication for catheter insertion was for administration of parenteral nutrition. Forty-four patients (52 percent) had catheters inserted for chemotherapy or combined chemotherapy and parenteranal nutrition. Thirteen patients had Hickman-Broviac catheters inserted for the administration of antibiotics. The majority of the patients (56 percent) had malignant disease. The insertion of Hickman-Broviac catheters was uncomplicated, especially through the external jugular vein. Catheter-related complications occurred in 20 percent of the patients, but none were fatal. The most common complications were thrombotic catheter occlusion and catheter related sepsis. The catheter-related sepsis rate was 8/6,308 catheter-days. These rates compare favorably with those reported by other investigators. Any patient with potential vascular access difficulty or obliterated or thrombosed veins who requires parenteral medication should be considered a candidate for insertion of a Hickman or Broviac catheter.

Extrahepatic biliary obstruction secondary to metastatic cancer.

Thirty patients with extrahepatic biliary obstruction secondary to metastatic cancer were reviewed to determine the sites of the primary tumor, diagnostic methods, therapy and success of palliation. Colon carcinoma was the most common primary tumor, and the common bile duct was most often obstructed. Both percutaneous transhepatic and surgical decompression of the biliary tract were employed. Twenty-seven (90 percent) of the patients obtained successful palliation. The length of survival averaged 270 +/- 49 days in patients treated surgically compared with 60 +/- 11 days in patients who underwent decompression by radiologic techniques. Mortality was not increased in patients undergoing operative biliary drainage. Surgical decompression may be the best method for managing patients with biliary obstruction secondary to metastatic cancer.

Revision of gastric bypass.

In this series, 90.6 percent of the patients who had revision of their original gastric bypass for failure to lose satisfactory weight had a significant additional weight loss. The postoperative complication rate was 21.4 percent, and there were no postoperative deaths. After proper evaluation of the patient, revision of a gastric bypass may be undertaken with expectation of a satisfactory result and an acceptable rate of complications.

Effect of biliary decompression on morbidity and mortality of pancreatoduodenectomy.

To evaluate the effect of levels of serum bilirubin on morbidity and mortality after pancreatoduodenectomy, a prospective study was designed to compare patients who underwent preoperative biliary decompression to those who did not. Preoperative biliary decompression decreased the mean serum bilirubin level from 15.8 to 5.8 mg/dl in one group of 10 patients (Group A). The only statistical differences between this group and the two other groups of patients (Groups B and C) who were not treated with preoperative biliary decompression was the level of serum bilirubin before pancreatoduodenectomy (5.8, 22, and 1.3 mg/dl in Groups A, B, and C, respectively). Only one death occurred in each group of patients. The numbers of nonfatal complications were comparable. These results suggest that there is no decrease in morbidity or mortality after pancreatoduodenectomy when the serum bilirubin level is decreased by preoperative biliary drainage.

Supervised exercise training improves cardiopulmonary fitness in HIV-infected persons.

We attempted to measure cardiopulmonary effects, CD4 counts, and perceived sense of well-being in 25 individuals moderately to severely immunocompromised from HIV infection (mean entry CD4 count = 144.microliters-1) before and after a 24-wk program of exercise training. Only six subjects completed the 24-wk program. All six showed evidence of a training effect. Statistically significant improvements were seen in maximal oxygen consumption (VO2max), oxygen pulse, and minute ventilation. Submaximal exercise performance improved significantly by 12 wk in the 10 individuals available for testing: decreases were seen in heart rate, rate pressure product, and rate of perceived exertion. White blood cell counts and T-lymphocyte subsets were stable at 12 and 24 wk in the subjects available for testing. High depression/anxiety scores on a mental health inventory (General Health Questionnaire) correlated with low CD4 counts. Scores did not correlate with compliance with the exercise program. There was a trend (P < 0.10) for scores to improve over time among those individuals who attended > or = 80% of scheduled exercise sessions. We conclude that exercise training is feasible and beneficial for some HIV-infected individuals.