Inhibition of bronchoconstriction by pituitary adenylate cyclase activating polypeptide (PACAP 1-27) in guinea-pigs in vivo.

1. We studied the inhibitory effect of pituitary adenylate cyclase activating polypeptide (PACAP 1-27) on the increase in total pulmonary resistance (RL) caused either by allergen or histamine in anaesthetized, ventilated guinea-pigs. 2. PACAP 1-27 given via i.v. infusion (0.045-4.5 nmol kg-1 min-1) dose-dependently reduced the increase in RL caused by inhaled ovalbumin and histamine. At the highest dose, PACAP 1-27 prevented the increase in RL caused by ovalbumin and histamine completely. Infusion of PACAP 1-27 and the beta 2-adrenoceptor agonist, salbutamol (0.045-4.5 nmol kg-1 min-1) inhibited the increase in RL similarly, but salbutamol increased the heart rate more than PACAP 1-27. 3. PACAP 1-27 and salbutamol given via inhaled aerosol (0.1 mM, 20 breaths) significantly reduced the increase in RL caused by histamine infused i.v., whereas aerosolised sterile saline did not. Both PACAP 1-27 and salbutamol caused bronchodilator effects within 1 min of drug inhalation and these effects remained throughout the 20 min of study. 4. Because PACAP 1-27 produced significant bronchodilatation and rapid onset of sustained action in vivo and without pronounced cardiovascular side effects, we conclude that this peptide may have therapeutic potential as a bronchodilator.     

Verbal learning in Alzheimer's dementia.

Many recent findings in Western countries suggest that episodic recall is the most sensitive discriminator between patients with mild Alzheimer disease (AD) and the normal elderly, while semantic memory tends best to differentiate between moderate and severe AD patients. The present study is the first to examine in detail the episodic memory of Chinese AD patients in Hong Kong with a locally developed list learning test, comparing procedures that do or do not encourage the use of semantic organization. The performance of 28 AD patients was compared to that of 30 normal controls. AD patients did significantly worse in terms of acquisition and retention and also benefited significantly less from external organization cues. In the discriminant function analysis, the rate of forgetting in the random condition and the total retention score in the blocked condition were found to be the best predictors for differentiating between AD patients and controls. On the other hand, in the differentiation between mild and moderate AD, semantic clustering in the blocked condition was found to be the best predictor. Results of the present study were discussed in the light of the previous findings reported in the Western countries and the neuropathological changes of AD patients.     

Different mechanisms by which anti-DNA MoAbs bind to human endothelial cells and glomerular mesangial cells.

The mechanisms by which anti-DNA MoAbs derived from MRL-lpr/lpr mice, bind to human umbilical vein endothelial cells (HUVEC) and glomerular mesangial cells were studied using a cellular ELISA. DNAse-treatment of either the MoAb or HUVEC followed by reconstitution with DNA and/or histones was performed to determine whether DNA and histones mediated such binding. It was found that MoAb410 bound to HUVEC and mesangial cells in the form of preformed DNA/anti-DNA immune complex, and such binding was facilitated by histones. In contrast, MoAb 152 bound directly to cell membrane-associated DNA, and adding DNA to MoAb 152 reduced its cellular binding. DNA binds endothelial cell surface and histones enhance the binding of both MoAb 410 and MoAb 152 to HUVEC by increasing cell membrane-associated DNA. Finally, the degree of MoAb binding to HUVEC is critically influenced by the relative concentrations of antibody, DNA, and histones.     

Tobacco use following liver transplantation for alcoholic liver disease: an underestimated problem.

Alcohol and tobacco use commonly co-occur, with at least 90% of those with an alcohol problem also using tobacco. Thus, 3 years ago when we discovered higher rate of late deaths due to lung and oropharyngeal cancer in patients who had received a transplant for alcoholic liver disease (ALD), we hypothesized that these patients were continuing to expose themselves to tobacco after liver transplantation (post-LTX) and that this behavior was increasing their risk for cancer. We subsequently began a prospective investigation of post-LTX tobacco use in patients having undergone LTX for ALD (n = 172). For 33 recipients we had data starting from our first assessment at 3 months post-LTX and for this subgroup we report on the details of the timing of tobacco use resumption and the redevelopment of nicotine addiction. We found that on average more than 40% are smoking across all time periods. ALD recipients resume smoking early post-LTX, increase their consumption over time, and quickly become tobacco dependent. These data highlight an underrecognized serious health risk for these patients and demonstrate our need for more stringent clinical monitoring and intervention for tobacco use in the pre- and post-LTX periods.     

A review of incisional hernia repairs: preoperative weight loss and selective use of the mesh repair

At the Shouldice Clinic pre-operative weight loss is used prior to incisional hernia repairs. Mesh repair is selectively used, based on specific hernia characteristics. A series of 236 patients were reviewed and followed up for 36 months. Data were available on 188 patients (80%). There were 15 recurrences (8%). The number of obese patients was reduced from 67 (35.6%) to 25 (13.3%) through the weight loss program. The hernia diameter, gastrointestinal complications, and surgical site infection were significantly related to recurrence but not the type of repair, obesity, location, or previous recurrences. The risk factors of incisional hernias include size, intestinal complications and infections. A selective use has a comparable result to the exclusive use of mesh repair. Weight reduction has yet to be shown to affect the rate of recurrence, and further prospective studies are required.     

Do ethnicity and gender have an impact on pain thresholds in minor dermatologic procedures?

Background and Objectives: The perception of pain is a personal experience influenced by many factors, including genetic, ethnic and cultural issues. Understanding these perceptions is especially important in dermatologic patients undergoing minor surgical operations and who often differ in their pain response to surgical treatments. Little is known about how these differences affect the perception of experimental pain. The purpose of this study was to determine experimental pain perception differences in three distinct East Asian ethnic populations.
Methods: Pain thresholds were examined with a psychophysical computerized quantitative thermal sensory testing device (TSA 2001) in healthy volunteers recruited from three different Asian ethnic groups. Using the methods of limits, experimental pain perception threshold was measured on the forehead and volar aspect of the forearm in 49 healthy subjects. The measurements were then repeated after skin barrier perturbation with adhesive tape stripping of the stratum corneum. All three ethnic groups were analyzed separately with respect to age, gender educational level and skin type.
Results: A total of 20 Chinese, 14 Malay and 15 Indian subjects completed the study. Thermal pain thresholds were similar in all three ethnic groups before and after tape strippings. No significant differences were noted between genders.
Conclusions: Using quantitative sensory thermal testing, we demonstrated that no significant differences in pain occur between different races and genders.     

Paired kidney analysis of tacrolimus and cyclosporine microemulsion-based therapy in Chinese cadaveric renal transplant recipients

Few studies used paired kidneys for comparison between tacrolimus and cyclosporine in renal transplantation. Most of the published data used whole blood trough levels for drug monitoring. However, the use of limited sampling strategy and abbreviated formula to estimate the 12-h area under concentration-time curve (AUC(0-12)) allowed better prediction of drug exposure. Sixty-six first cadaveric renal transplant recipients receiving paired kidneys were randomized to receive either tacrolimus-based (n = 33) or cyclosporine microemulsion (Neoral)-based therapies (n = 33). Abbreviated AUC(0-12) was used for drug monitoring and dose titration. Mean follow-up duration was 2.8 +/- 2 years. The patient and graft survival were comparable. Fewer incidence of acute rejection was observed in tacrolimus group (15% vs. 27.3%) though the difference was not significant (P = 0.23). The absolute value and the rate of decline of creatinine clearance were both significantly better in tacrolimus-treated patients. Prevalence of hypertension, post-transplant diabetes mellitus, infection, and malignancy were similar in both groups. Prevalence of hypercholesterolemia (11/33 vs. 4/33) and gum hypertrophy (6/33 vs. 1/33) was more common in cyclosporine-treated patients (P = 0.04 in both parameters). This was the first prospective, randomized study with paired kidney analysis showing the renal function was significantly better in tacrolimus-treated patients than in cyclosporine-treated patients.     

Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis-tetanus vaccine in Canadian children.

OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine.     

Double-orifice mitral valve with intact atrioventricular septum: an echocardiographic study with anatomic and functional considerations.

We identified 18 patients with double-orifice mitral valve (DOMV) and intact atrioventricular (AV) septum out of 40,179 echocardiographic studies performed between 1997 and 2002 at Children's Hospital, Denver, CO. In this study we describe (1) the anatomic characteristics of the DOMV in the absence of AV septal defect, (2) the function of the mitral valve by spectral and color Doppler flow mapping, and (3) associated lesions. The topographic location of the orifices in the leaflets suggests possible embryologic mechanisms of DOMV. In this series, DOMV was most commonly associated with left-sided obstructive lesions (in 39% of patients). Spectral and color Doppler interrogation demonstrated a normal flow profile in most cases; only 2 patients had significant mitral regurgitation or stenosis. Therefore, due to the uncertain natural history of this lesion and the potential need for endocarditis prophylaxis, careful imaging of the mitral valve is recommended, particularly in the presence of left-sided obstructive lesions.