Desaggregation of PAF-acether-aggregated platelets by verapamil and TMB-8 with reversal of phosphorylation of 40K and 20K proteins

Verapamil at a concentration of 10(-4) M inhibited aggregation and release of [3H]5HT induced by platelet activating factor (PAF-acether, PAF) in rabbit platelet-rich plasma and washed labelled platelets. When added to platelets previously aggregated by PAF-acether verapamil caused them to desaggregate at doses as low as 2 X 10(-6) M. The desaggregated platelets were refractory to further additions of similar doses of PAF-acether but could further be aggregated by A23187. Simultaneous to full aggregation PAF-acether caused phosphorylation of 40K and 20K proteins in particular. Addition of verapamil at the concentration of 2 X 10(-6) M to platelets already aggregated by PAF-acether resulted in dephosphorylation of 40K protein and reduction of phosphorylation of 20K protein to the level of control parallel to desaggregation. TMB-8 (10(-3) M) also caused desaggregation and reversal of phosphorylation of 40K and 20K proteins. When A23187 was added to verapamil desaggregated platelets, 40K and 20K proteins were rephosphorylated. The extracellular calcium antagonists EGTA or La3+, when added to PAF-acether aggregated platelets, did not abolish the phosphorylation of 40K and 20K proteins. The experiments suggest that inhibition of intracellular calcium-dependent reactions is involved in the desaggregatory action of verapamil.     

Investigation of rectal bleeding in children

Rectal bleeding is a common symptom in children, however the range of diagnoses is large and varied, with most being non-life threatening. Occasionally, however, this symptom is a sign of major morbidity, which, if not diagnosed urgently, may lead to either death or long-term morbidity. Major factors in respect of diagnosis are that of age and mode of presentation. This review will look at the surgical differential diagnoses based on age, ranging from prematurity to teenager, presentation and the investigations that are appropriate. The article will then finish with an algorithm to help direct the clinician towards the appropriate investigation.     

Antiretroviral medication compliance in patients with AIDS

The paradigm of AIDS patient care has evolved to that of a chronic disease that is manageable with combination antiretroviral therapy. Intermittent adherence to antiretroviral regimens, however, has been associated with the selection of HIV mutations, resulting in drug-resistant virus. Medication compliance has become a vital component in the care of HIV-infected patients. This study was designed to assess the degree of medication compliance with zidovudine (ZDV) over a 2-month period among a convenience sample of 23 ambulatory patients with HIV infection. Enrollment took place during February to March 1995, when monotherapy with ZDV was considered the standard of care. Medication compliance was assessed by three methods: patient self-report determined by questionnaire, pharmacy refill records from the 3 months immediately before entry in the study, and an electronic monitoring system (Medication Event Management Systems [MEMS], Aprex Corp., Fremont, CA), which records the date and time of each opening of the medication vials. MEMS was utilized among a subgroup of eight participants over a 2-month period. Despite greater than 95% (22 of 23) of the subjects reporting that they believed ZDV was life prolonging, a majority took < or = 75% of the prescribed doses of ZDV as identified by both refill and MEMS methods. The mean percentage compliance over a 2-month period of observation for MEMS and pharmacy refill record review methods was 66% and 78%, respectively (p = 0.294). Among the subgroup of eight in the MEMS evaluation, 88% reported taking their ZDV according to the directions, all of the time. These results demonstrate that reliance upon patient self-report of medication compliance is less accurate than MEMS or pharmacy refill records, and that reliance on self-reporting could lead to erroneous assumptions of the patient's true drug compliance. In addition, the study suggests that pharmacy refill records may provide a method of assessing compliance that is equivalent to MEMS but is less experimental, and can easily be followed and interpreted by pharmacists and other clinicians caring for patients infected with HIV. Most importantly, relatively poor compliance rates demonstrated by MEMS raises serious concern for widespread development of HIV resistance to the more complicated, multiple-drug regimens in present use.     

Antisocial Personality Disorder and Alcohol-Induced Aggression

This study compared the effects of alcohol on aggressive responding between subjects with antisocial personality disorder (ASPD) and subjects without ASPD. Eighteen alcohol drinking subjects (10 subjects without ASPD and 8 subjects with ASPD) underwent testing on a laboratory measure of aggression, the Point Subtraction Aggression Paradigm, after consumption of placebo and three doses of alcohol (0.25 g/kg, 0.5 g/kg, and 1.0 g/kg). There was a significant difference in the effect of alcohol on aggressive responding on the Point Subtraction Aggression Paradigm between subjects with ASPD and subjects without ASPD. Subjects with ASPD had a greater increase in aggressive responding after alcohol, compared with non-ASPD subjects. There was no difference between the two groups in the effect of alcohol on monetary-reinforced responding.     

Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy

BACKGROUND:

The prevalence of chronic kidney disease (CKD) in patients with upper tract urothelial carcinoma (UTUC) is poorly defined, both before and after nephrouretectomy. Although multimodal treatment paradigms for UTUC are under‐developed, this has important implications on patients' ability to receive cisplatin‐based combination chemotherapy (CBCC).

METHODS:

Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula in 336 patients with UTUC, who were treated at the Cleveland Clinic by nephroureterectomy since 1992. An eGFR cutoff of 60 mL/min/1.73 m² was used to determine the presence of CKD and eligibility for CBCC.

RESULTS:

Median age was 72 years and median preoperative eGFR was 59 mL/min/1.73m². Before nephroureterectomy, only 48% of patients were eligible to receive CBCC and this decreased to 22% postoperatively (P < .001). In the 144 patients with pT2‐pT4 and/or pN1‐pN3 disease who are suitable to receive CBCC, these proportions were 40% and 24%, respectively (P = .009). Although 50 patients overall received some form of perioperative chemotherapy, only 3 and 11 patients received neoadjuvant and adjuvant CBCC, respectively.

CONCLUSIONS:

CKD is prevalent in the UTUC population and a minority of patients has an optimal eGFR to receive neoadjuvant CBCC. Nephrouretectomy may eliminate CBCC as a therapeutic option in 49% of high‐risk patients if it is deferred to the adjuvant setting. Multimodal treatment strategies for UTUC should focus on neoadjuvant chemotherapy, as few patients are eligible for adjuvant CBCC because of the substantial decline in eGFR caused by nephroureterectomy. Cancer 2010. © 2010 American Cancer Society.     

Human immunodeficiency virus seroprevalence among blood product recipients in San Francisco before transfusion

To determine the incidence of transfusion-associated human immunodeficiency virus (HIV) infection after routine screening of donated blood, a pilot study estimated the pretransfusion prevalence of HIV infection among blood product recipients in San Francisco. Among the 911 nonduplicate pretransfusion specimens from recipients without a clinical history of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC), the overall prevalence of antibody to HIV was 2.9 percent (5.2% among males and 0.6% among females; p = 0.00002). If recipients in specifically defined or possible high-risk groups (n = 348) were excluded, a seropositivity rate of 1.8 percent (10/563) was detected, with all the positives occurring in men (10/242, 4.1%) and none in women (0/321, 0%). This demonstrated prevalence of HIV infection among blood product recipients in San Francisco before transfusion was substantially higher than the known 0.02 to 0.04 percent prevalence in the donor population. Therefore, the population of women without known risk for AIDS is the best in which to assess the risk of HIV infection in patients who are currently receiving seronegative blood transfusions.     

Roles, work, health perceptions and health resources of women: a study in an Egyptian delta hamlet.

Women's health needs can only be described and programs to address them implemented with an understanding of women's multiple roles and responsibilities. A life-cycle approach to examining women's roles and responsibilities provides a useful framework to achieve such understanding. This paper describes the results of a study conducted in a rural village in Egypt that examines the daily life experiences of women, their work, their family responsibilities, their health perceptions and their health resources. We argue that programs designed to address women's health needs must consider these critical aspects of their lives. This argument is based on the premise that women's health needs have been neglected and efforts to ameliorate this situation should be a top priority in the international health care agenda of the 1990s.     

Resuscitation from prolonged cardiac arrest with high-dose intravenous magnesium sulfate

We present evidence of resuscitation from prolonged (70-min) cardiac arrest, temporally associated with administration of 8 g intravenous (IV) magnesium sulfate (MgSO₄). A patient undergoing liposuction surgery developed bradycardia and a fall in oxygen tension after reversal of general anesthesia with physostigmine. The electrocardiogram (ECG) rhythm degenerated to ventricular asystole, which was refractory to standard therapy, including multiple boluses of epinephrine, atropine, wide-open dopamine, and attempts at right heart pacing. External cardiopulmonary resuscitation (CPR) was continuously maintained with the patient intubated on 100% oxygen. Multiple electric countershocks (× 7) and lidocaine were also administered when ventricular tachycardia/ventricular fibrillation (VTNF) occurred, but without clinical success. Approximately one hour into the resuscitation, after all of the above occurred, 8 g IV MgSO₄ was given and countershock repeated. Whereas the 7 previous countershocks had resulted in unsuccessful conversion of VT/VF to a pulseless rhythm (END), the 8th countershock (applied immediately after two 4 g boluses of IV MgSO₄) resulted in a stable pulse and normal sinus rhythm developing within 4 minutes. The patient recovered without neurologic deficit.