Distribution and function of cholinergic receptors in the sheep detrusor muscle

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.     

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.     

Adenocarcinoma at an ileostomy site after colectomy for ulcerative colitis

In this article we present the tenth case, according to the literature, of adenocarcinoma occurring at a long standing ileostomy originally performed for ulcerative colitis. Study of this and previous cases demonstrates common factors such as a previous history of ulcerative colitis, a long interval until the appearance of symptoms, together with a similar clinical and pathological characterisation with invasion of neighbouring skin layers close to the ileostomy. Several pathogenic hypotheses are considered. We believe that local excision in oder to obtain the diagnosis is a better option than a sampling biopsy and that surgery should include a wide resection of the abdominal wall and intestine in order to comply with therapeutic criteria in malignant disease.     

Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.     

The cardioprotective action of nifedipine during short-term transient ischemia

To determine the therapeutic activity on regional myocardial function of nifedipine intravenous administration (0.16 mg/kg) during short term myocardial induced ischemia, we used 6 mongrel dogs anesthetized and intubated those who we have implanted 3 pairs of ultrasonic crystals in the subendocardial layer. Utilizing an open chest canine model we performed total 1 minute and partial 2 minutes 30 seconds alternative obstructions, controlled with electromagnetic flowmeters in the anterior descending (AD) and circumflex (Cx) coronary arteries before and after drug administration. During the 70-80% obstructions we have shown a significant improvement in segment shortening, reduced by ischemia, in the ischemic and peri-ischemic zone. The ischemic markers, per cent increment of end diastolic length (% IEDL) and per cent increment of end systolic length (% IESL), have shown significant improvement during partial obstructions in the ischemic and peri-ischemic zone. After total obstructions the improvement on regional myocardial function is less marked and limited to ischemic zone.     

Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo,Malawi

In Thyolo district, Malawi, an operational research study is being conducted on the efficacy and feasibility of co-trimoxazole prophylaxis in preventing deaths in HIV-positive patients with tuberculosis (TB). A series of cross-sectional studies were carried out to determine i) whether faecal Escherichia coli (E.coli) resistance to co-trimoxazole in TB patients changed with time and ii) whether the resistance pattern was different in HIV positive TB patients who were taking co-trimoxazole prophylaxis. Co-trimoxazole resistance among E.coli isolates in TB patients at the time of registration was 60% in 1999 and 77% in 2001 (p<0.01). Resistance was 89% among HIV-infected TB patients (receiving co-trimoxazole), while in HIV negative patients (receiving anti-TB therapy alone) it was 62% (p<0.001). The study shows a significant increase of E.coli resistance to co-trimoxazole in TB patients which is particularly prominent in HIV infected patients on co-trimoxazole prophylaxis. Since a high degree of plasmid-mediated transfer of resistance exists between E.coli and the Salmonella species, these findings could herald limitations on the short and long term benefits to be anticipated from the use of co-trimoxazole prophylaxis in preventing non-typhoidal salmonella bacteraemia and enteritis in HIV infected TB patients in Malawi.     

Secondary surfactant deficiencies in extremely low birth weight premature infants.]

Primary deficiency of surfactant is responsible for the respiratory distress syndrome and concerns premature neonates born before 33 weeks of gestation. However, newborns may develop respiratory disorders related to a secondary deficiency or dysfunction of surfactant. We report the course of three extremely low birth weight premature infants who experienced clinical respiratory decompensation at two weeks and showed a marked improvement after exogenous natural surfactant administration.     

Oral tolerance impairment in mice with staphylococci-induced wasting syndrome.

The effects of staphylococci-induced experimental wasting disease on the immune response of 1 month old CD1 mice were investigated. Animals were separated into different subgroups in order to study their cellular immune competence. Malnutrition of wasted mice was associated with anorexia, diarrhea and weakness. Footpad-injected splenic cells produced normal graft vs. host (GvH) reactions in the popliteal lymph nodes of F1 hybrids. In other experiments, the SRBC intragastric feeding of wasted mice did not cause a tolerant anti-erythrocyte humoral immune response. Three weeks after the staphylococci injections, convalescent erythrocyte-fed wasted mice exhibited an anti-SRBC PFC production similar to that observed in non-tolerant immunized control healthy mice. In return, healthy SRBC-fed control mice showed the specific attenuation of antibody response characteristics of oral tolerance. Differences were found between the immune competence of the undernourished staphylococci-treated wasted mice and those shown by other authors in protein-depleted mice.     

Hodgkin disease: CT of the thymus

The computed tomography (CT) scans in two groups of patients with Hodgkin disease were reviewed to determine the frequency of thymic enlargement. In 50 CT scans from 50 patients with evidence of thoracic disease on CT scans who were examined for primary staging, the thymus was enlarged in 15 of 50 (30%). Fifty CT scans were obtained from 44 patients at the time of 50 separate episodes of known or suspected relapse. Relapse occurred in the mediastinum in 12 episodes, lung parenchyma in five, and both sites in one. Thymic enlargement thought to be due to involvement by disease was present in seven of 18 (38%). Mediastinal disease was associated with thymic enlargement in all but one patient in whom a thymic cyst developed after radiation therapy. Differentiation of thymic enlargement from enlarged superior mediastinal lymph nodes was easily made in all but two patients. Thymic enlargement in the absence of lymph node enlargement may indicate a different disease, since isolated Hodgkin disease of the thymus is uncommon. Primary thymic tumor should be considered initially, whereas after treatment, rebound hyperplasia of the thymus may be the cause of enlargement.