Effect of Vorapaxar Alone and in Combination with Aspirin on Bleeding Time and Platelet Aggregation in Healthy Adult Subjects.

The effect of the protease-activated receptor-1 (PAR-1) antagonist vorapaxar on human bleeding time is not known. This was a randomized, two-period, open-label trial in healthy men (n = 31) and women (n = 5). In period 1, subjects received 81 mg aspirin q.d. or a vorapaxar regimen achieving steady-state plasma concentrations equivalent to chronic 2.5 mg q.d. doses, for 7 days. In period 2, each group added 7 days of the therapy alternate to that of period 1 without washout. Bleeding time and platelet aggregation using arachidonic acid, ADP, and TRAP agonists were assessed. Bleeding time geometric mean ratio (90% CI) for vorapaxar/baseline was 1.01 (0.88-1.15), aspirin/baseline was 1.32 (1.15-1.51), vorapaxar + aspirin/vorapaxar was 1.47 (1.26-1.70), and vorapaxar + aspirin/aspirin was 1.12 (0.96-1.30). Unlike aspirin, vorapaxar did not prolong bleeding time compared with baseline. Bleeding time following administration of vorapaxar with aspirin was similar to that following aspirin alone.

Benzodiazepine modulation of opiate reward.

Case studies reveal that opiate addicts often premedicate themselves with benzodiazepine (BDZ) tranquilizers prior to taking their opiate. It has been hypothesized that such actions occur because the BDZ enhances the euphoric or reinforcing properties of the opiate. The present study tested this hypothesis in the animal laboratory. Sprague-Dawley rats were used to examine whether the magnitude of conditioned preferences for a distinctive environment associated with intravenous heroin delivery would be augmented by intraperitoneal alprazolam pretreatment. Results demonstrated that alprazolam produced a leftward shift of the heroin dose-response curve in the conditioned place preference test. The data obtained are consistent with the view that BDZs can augment the affective response to heroin in laboratory animals.

Staging and managing lung tumors using F-18 FDG coincidence detection.

PURPOSE: Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomographic (PET) imaging can be a vital tool in the evaluation and preoperative staging of pulmonary neoplasms. Imaging studies on the gamma camera using coincidence PET (co-PET) were introduced recently into clinical practice. This prospective study assessed the efficacy of co-PET for identifying primary tumors, mediastinal lymph node involvement, the presence of distant spread, the effect on disease staging, and influence on disease management. PATIENTS AND METHODS: Sixty consecutive patients with 61 lung tumors were enrolled in the study (36 men, 24 women; age range, 32-87 years; mean age, 67 years). Histopathologic confirmation was obtained in 58 patients (59 tumors). RESULTS: In assessments of a primary lesion to establish its malignant or benign nature, the sensitivity rate of co-PET was 96% (53 of 55 lesions), the specificity rate was 83% (5 of 6 lesions), and the accuracy rate was 95% (58 of 61 lesions). In the co-PET assessment of lymph node involvement in which histopathologic confirmation was obtained (n = 32), the sensitivity rate was 89% (8 of 9 lesions), the specificity rate was 91% (21 of 23 lesions), and the accuracy rate was 91% (29 of 32 lesions). Previously unknown distant metastases were correctly identified in eight patients, but five false-positive lesions were detected in the brain. Disease staging was correctly altered in 20 patients (33%), and disease management plans were changed in 20 patients (33%) based on the co-PET findings. Unnecessary surgery was obviated in six patients (10%). One patient was given the chance for curative treatment based on the findings of the co-PET study. CONCLUSION: The evaluation of patients with lung neoplasms using F-18 FDG coincidence detection appears to be reliable.

Bacteriological method for detecting small intestinal hypomotility.

OBJECTIVE: Small intestinal hypomotility is an important cause of small intestinal bacterial overgrowth, yet assessment of small intestinal motility in this setting is problematic. This study was performed to investigate the validity of a bacteriological method for detecting small intestinal hypomotility. METHODS: Twenty-five subjects without previous gastric surgery were studied with (i) concurrent bacteriological analyses of fasting saliva and gastric and proximal small intestinal aspirates, (ii) measurement of gastric pH, and (iii) scintigraphic assessment of small intestinal transit rates of a liquid test meal. The reproducibility of bacteriological analyses of saliva and small intestinal secretions was determined in 12 subjects. RESULTS: Serial bacteriological analyses of saliva and proximal small intestinal secretions yielded reproducible results over time periods of up to 1 month. Eleven subjects were deemed to harbor Enterobacteriaceae of nonsalivary origin in proximal small intestinal secretions. Orocaecal transit, but not gastric emptying, of a liquid test meal was significantly delayed in this group (p = 0.002 and p = 0.84, respectively), suggesting the presence of small intestinal hypomotility. Impaired gastric acidity unlikely confounded assessment of the origin of small intestinal Enterobacteriaceae in any instance. CONCLUSIONS: The presence of Enterobacteriaceae of nonsalivary origin in proximal small intestinal secretions may be taken to reflect the presence of small intestinal hypomotility. The presence of impaired gastric acidity does not confound this approach. Because small intestinal intubation and culture of aspirate are required anyway to accurately diagnose small intestinal bacterial overgrowth, the simple addition of concurrent bacteriological analysis of saliva may allow small intestinal hypomotility to be detected at the same time as the presence or absence of small intestinal bacterial overgrowth itself is established, thus streamlining the investigation of subjects for this disorder and its possible causes.

The lactulose breath hydrogen test and small intestinal bacterial overgrowth.

OBJECTIVES: To i) document the sensitivity and specificity of a combined scintigraphic/lactulose breath hydrogen test for small intestinal bacterial overgrowth and ii) investigate the validity of currently accepted definitions of an abnormal lactulose breath hydrogen test based on "double peaks" in breath hydrogen concentrations. METHODS: Twenty-eight subjects were investigated with culture of proximal small intestinal aspirate and a 10-g lactulose breath hydrogen test combined with scintigraphy. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of overgrowth flora to ferment lactulose were determined. RESULTS: Sensitivity (16.7%) and specificity (70.0%) of the lactulose breath hydrogen test alone for small intestinal bacterial overgrowth were poor. Combination with scintigraphy resulted in 100% specificity, because double peaks in serial breath hydrogen concentrations may occur as a result of lactulose fermentation by cecal bacteria. Sensitivity increased to 38.9% with scintigraphy, because a single rise in breath hydrogen concentrations, commencing before the test meal reaches the cecum, may occur in this disorder. Sensitivity remained suboptimal irrespective of the definition of small intestinal bacterial overgrowth used, the nature of the overgrowth flora, favorable luminal pH, the presence of concurrent gastric bacterial overgrowth, or the in vitro ability of the overgrowth flora to ferment lactulose. CONCLUSIONS: Definitions of an abnormal lactulose breath hydrogen test based on the occurrence of double peaks in breath hydrogen concentrations are inappropriate. Not even the addition of scintigraphy renders this test a clinically useful alternative to culture of aspirate for diagnosing small intestinal bacterial overgrowth.

Anxiety in community-based AIDS caregivers before and after personal construct counseling.

Personal construct counseling was provided for voluntary AIDS caregivers based in the community, with the goal of reducing their anxiety levels. Seventy-five caregivers participated in the project, 33 of whom received counseling. They were interviewed on three occasions--before, immediately after, and 3 months after counseling. Their responses to an open-ended question were subjected to six subscales of a content analysis scale in order to measure levels of anxiety from six different sources. At time 2, the anxiety of the counseled caregivers was significantly less than that of those not counseled, specifically their anxiety about bodily mutilation and guilt. These differences were not sustained at time 3 because the anxiety of those not counseled dropped. Some criticisms of the project are examined before the meaning of these findings for meeting the mental health needs of AIDS caregivers is discussed.

Dying in palliative care units and in hospital: a comparison of the quality of life of terminal cancer patients.

A comparison of the quality of life of terminal cancer patients in two palliative care units with that of those in a general hospital is reported here. Quality of life was considered as a multidimensional concept. It was assessed for the 182 patients by applying content analysis scales to transcripts of their responses to part of a standardized interview. A personal construct model of dying provided the specific hypotheses about differences in quality of life. Patients in specialized palliative care units were, as predicted, found to differ from those dying in hospital, showing less indirectly expressed anger but more positive feelings. They also reported more anxiety about death but less anxiety about isolation and general anxiety, and fewer influential and nonspecified shared relationships. Against prediction, the patients in the two specialized units were also found to differ from each other, those in the smaller unit showing more directly expressed anger and helplessness than those in the larger unit.

An improved radionuclide technique for the detection of altered pulmonary permeability.

Technegas, an ultra-fine dry aerosol with prolonged retention in the lungs, can be modified by altering the atmosphere in which the carbon particles are generated. The modified Technegas has much faster clearance from the lung. The half-time pulmonary clearances with modified Technegas were compared to those obtained with conventional 99mTc DTPA aerosol in 50 patients. Interstitial lung disease was suspected in 12 while 38 were infected with the human immunodeficiency virus and suspected of having opportunistic lung infection. In 22 nonsmokers in whom no evidence of active pulmonary pathology was demonstrable, the mean half-time with DTPA was 52.5 min whereas the mean half-time with modified aerosol was 10.1 min. The mean half-time in 14 smokers in whom there was also no evidence of active pulmonary disease was 28.3 min with DTPA and 7.0 min with the modified method. In the 14 patients in whom altered pulmonary permeability was demonstrated by a short DTPA half-time (mean 4.8 min) there was also an accelerated half-time with modified Technegas (mean 2.5 min). It is concluded that the modified Technegas procedure offers a simple but accurate method of identifying individuals having opportunistic infection or other diffuse lung pathology.

Psychological frailness and strength in an AIDS-affected community: a study of seropositive gay men and voluntary caregivers.

Addressed both the psychological frailness and strength in an AIDS-affected community. The gay community in Sydney, Australia, was represented by men who were seropositive (n = 60) and voluntary caregivers (n = 60). They were compared with two samples of men outside the gay community, who were ill with non-AIDS-related medical conditions (n = 30), and well (n = 30). Their psychological frailness and strength were measured by content analysis scales. Both the seropositive men and the caregivers showed the frailness of anxiety, indirectly expressed anger and helplessness, but also the compensating strength of greater personal competence and good feeling relative to the other men. The men who were seropositive or had other illnesses showed the predicted frailness of anxiety and depression but neither indirectly expressed anger nor helplessness. The seropositive men and caregivers of the gay community differed from each other only in the high levels of depression of the former.

Optimising technetium 99m diethylene triamine penta-acetate lung clearance in patients with the acquired immunodeficiency syndrome.

Pneumocystis carinii pneumonia (PCP) has become a major cause of morbidity and mortality due to infectious diseases, largely as a result of the acquired immunodeficiency syndrome (AIDS) epidemic. Since the mortality from recurrent infection is between 40% and 60%, early diagnosis and therapy are the keys to survival. The role of technetium 99m diethylene triamine penta-acetate (DTPA) aerosol pulmonary clearance was studied in 81 patients with AIDS. The mathematical technique of curve stripping was found to be the optimal method of analysis and to provide an overall sensitivity of 94% for the detection of interstitial pneumonitis. The procedure was superior to standard pathology parameters and radiography and more convenient than gallium 67 scintigraphy.

The emotional reactions of HIV antibody positive men.

This study was concerned with the emotional reaction of men who are HIV antibody positive, and with whether their expression of enjoyment is better viewed as the result of rigid defending or flexible coping. A sample of these men was matched with samples of patients with other major illnesses and well controls. Enjoyment was found to be more frequently expressed in the two ill samples, as were anxiety, depression and helplessness. The HIV antibody positive patients expressed more anger, and yet more competence, than the other patients. These patterns of emotional reaction proved to be modified by different levels of enjoyment in a manner more indicative of coping than defending, because depressive emotions appeared to be reduced when some enjoyment of life was apparent. The implications of these findings for health professionals working with people who are HIV antibody positive are discussed.