3-Diazopyrroles. Part 5 (1). Antibacterial activity of 3-diazo-2-phenylpyrroles.

3-Diazo-2-phenylpyrroles 3a-g showed antimicrobial activity against Gram-positive bacteria, whereas against Gram-negative strains the inhibitory activity is limited to derivatives 3a and 3c. The substituents at 4 and 5 positions strongly influence the inhibitory activity, but the presence of the diazo group is crucial for appearance of activity.     

A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia.

BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia. To determine if synapsin III plays a role in this disease, we searched for polymorphisms in this gene in patients with schizophrenia and controls. METHODS: The synapsin III gene was initially sequenced from 10 individuals with schizophrenia to identify polymorphisms. Association analysis was then performed using 118 individuals with schizophrenia and 330 population controls. Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32. RESULTS: A rare, missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia than in controls (p =.0048). The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. Phosphorylation at Ser470 was increased during neonatal development and in response to neurotrophin-3 in cultured hippocampal neurons. CONCLUSIONS: Our observations suggest an association of a rare polymorphism in synapsin III with schizophrenia, but further studies will be required to clarify its role in this disease.     

Access to primary health care for Australian young people: service provider perspectives.

BACKGROUND: To adequately address the complex health needs of young people, their access to services, and the quality of services received, must be improved. AIMS: To explore the barriers to service provision for young people and to identify the training needs of primary healthcare service providers in New South Wales (NSW), Australia. DESIGN OF STUDY: A cross-sectional, qualitative study of the perspectives of a range of health service providers. SETTING: A range of primary healthcare organisations across NSW. METHODS: Samples of general practitioners (GPs), youth health workers, youth health coordinators, and community health centre staff were drawn from urban and rural clusters across NSW. Focus groups and interviews were used to identify barriers to service provision and the training needs of service providers. Data were tape recorded, transcribed, and analysed. RESULTS: Barriers to service provision among GPs and community health centre staff included inadequate time, flexibility, skills, and confidence in working with young people, and poor linkages with other relevant services. Training needs included better knowledge of and skills in adolescent health requirements, working with adolescents, and working with other services. Barriers to service provision for youth health workers and coordinators included lack of financial resources and infrastructure. There were few linkages between groups of service providers. CONCLUSION: Models of service provision that allow stronger linkages between service providers, sufficient time for consultation with young people, adequate training and support of health professionals, and flexibility of service provision, including outreach, should be explored and evaluated.     

Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone.

The authors conducted a retrospective analysis of 1178 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. The minimum follow-up time was 3 years. The 10-year actuarial pelvic failure rate in Stage IB was 6% for tumors less than 3 cm, 15% for tumors 3 to 5 cm, and 30% for tumors more than 5 cm (P = 0.0018). The 10-year actuarial pelvic failure rate in Stage IIA was 10% for tumors less than 3 cm, 28% for tumors 3 to 5 cm, and 20% for tumors more than 5 cm (P = 0.09). Stage IIB unilateral nonbulky tumors (less than 5 cm) had a 20% pelvic failure rate compared with 28% for bilateral lesions and 35% for unilateral bulky tumors (more than 5 cm) (P = 0.35). In Stage IIB, pelvic failures were greater when disease extended into the lateral parametrium (30%) compared with medial parametrial involvement only (17%) (P = 0.01). In Stage III unilateral nonbulky tumors, the pelvic failure rate was 28% compared with 45% to 50% for unilateral bulky lesions (P = 0.002). Bilateral parametrial disease in Stage IIB did not increase the pelvic failure rate (21% in both subgroups) (P = 0.83), whereas in Stage III, bilateral parametrial involvement was associated with a 48% pelvic failure rate versus 28% for unilateral extension (P less than or equal to 0.01). Five-year disease-free survival (DFS) rates for IB tumors less than or equal to 3 cm was 90% versus 67% for tumors more than 3 cm (P = 0.01). In Stage IIA tumors less than or equal to 3 cm, 5-year DFS was 70% versus 45% for tumors more than 3 cm. Patients with Stage IIB nonbulky tumors (less than or equal to 5 cm in diameter) had better 10-year DFS (65% to 70%) compared with those with bilateral bulky tumors (45% to 55%) (P = 0.10). Stage III patients with unilateral nonbulky tumors had a 55% 10-year DFS compared with 35% to 40% for bulky tumors or bilateral parametrial involvement (P = 0.002). The authors concluded that clinical stage and size of tumor are critical factors in the prognosis, therapy selection, and evaluation of results in carcinoma of the uterine cervix.     

Maternal serum caffeine metabolites and small-for-gestational age birth.

To determine whether the third-trimester maternal serum concentration of paraxanthine, caffeine's primary metabolite, is associated with delivery of a small-for-gestational age infant (birth weight less than the 10th percentile for gestational age, gender, and ethnicity) and whether this association differs by smoking, the authors studied 2,515 women who participated in the Collaborative Perinatal Project from 1959 to 1966. The women provided a third-trimester serum sample and had been controls for a nested case-control study of spontaneous abortion. The mean serum paraxanthine concentration was greater in women who gave birth to small-for-gestational age infants (754 ng/ml) than to appropriately grown infants (653 ng/ml, p = 0.02). However, the linear trend for increasing serum paraxanthine concentration to be associated with increasing risk of small-for-gestational age birth was confined to women who also smoked (p = 0.03). There was no association between paraxanthine and fetal growth in nonsmokers (p = 0.48). Adjustment for maternal age, pre-pregnant weight, education, parity, ethnicity, and the number of cigarettes smoked per day did not alter the results substantially, although the p value for trend among smokers increased to 0.07. The authors conclude that maternal third-trimester serum paraxanthine concentration, which reflects caffeine consumption, was associated with a higher risk of reduced fetal growth, particularly among women who smoked.     

Sympathoadrenal excitation and inhibition by lower brainstem stimulation in cats

Effects of stimulation of brainstem sites on hemodynamics and plasma catecholamine levels were assessed in cats under chloralose-urethane anesthesia. Pressor areas of the dorsal medulla (DM) and ventrolateral medulla (VLM) and the depressor area of the paramedian reticular nucleus (PRN) were stimulated electrically using a monopolar electrode, or chemically using sodium glutamate microinjection. Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in caval blood above the adrenal veins. Electrical stimulation of the DM and VLM produced increases in blood pressure and in plasma NE and EPI levels that were enhanced after acute vagotomies. The NE and EPI responses were attenuated after acute, bilateral adrenalectomies, confirming augmented adrenomedullary secretion, whereas the pressor responses were intact. Injection of sodium glutamate into the same pressor regions of the DM or VLM also produced pressor responses and elevated plasma catecholamine levels, indicating that the responses resulted from activation of neuronal perikarya. Stimulation of the PRN attenuated pressor and catecholamine responses during stimulation of the DM and VLM. The results indicate that pressor responses during stimulation of the DM and VLM are due at least partly to activation of perikarya in these regions, are associated with but not dependent on adrenomedullary activation, and are enhanced after vagotomy; and that neurons of the PRN exert inhibitory modulation of the pressor and adrenomedullary responses during stimulation of VLM and DM.     

Postoperative Cognitive Dysfunction in Middle-aged Patients

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.