Serotonin availability in rat colon is reduced during a Western diet model of obesity.

Constipation and slowed transit are associated with diet-induced obesity, although the mechanisms by which this occurs are unclear. Enterochromaffin (EC) cells within the intestinal epithelium respond to mechanical stimulation with the release of serotonin [5-hydroxytryptamine (5-HT)], which promotes transit. Thus our aim was to characterize 5-HT availability in the rat colon of a physiologically relevant model of diet-induced obesity. EC cell numbers were determined immunohistochemically in chow-fed (CF) and Western diet-fed (WD) rats, while electrochemical methods were used to measure mechanically evoked (peak) and steady-state (SS) 5-HT levels. Fluoxetine was used to block the 5-HT reuptake transporter (SERT), and the levels of mRNA for tryptophan hydroxylase 1 and SERT were determined by quantitative PCR, and SERT protein was determined by Western blot. In WD rats, there was a significant decrease in the total number of EC cells per crypt (0.86 ± 0.06 and 0.71 ± 0.05 in CF and WD, respectively), which was supported by a reduction in the levels of 5-HT in WD rats (2.9 ± 1.0 and 10.5 ± 2.6 µM at SS and peak, respectively) compared with CF rats (7.3 ± 0.4 and 18.4 ± 3.4 µM at SS and peak, respectively). SERT-dependent uptake of 5-HT was unchanged, which was supported by a lack of change in SERT protein levels. In WD rats, there was no change in tryptophan hydroxylase 1 mRNA but an increase in SERT mRNA. In conclusion, our data show that foods typical of a WD are associated with decreased 5-HT availability in rat colon. Decreased 5-HT availability is driven primarily by a reduction in the numbers and/or 5-HT content of EC cells, which are likely to be associated with decreased intestinal motility in vivo.

Prevalence of hepatitis B virus infection among persons with diagnosed diabetes mellitus in the United States, 1999-2010.

The prevalence of hepatitis B virus (HBV) infection among persons with diabetes has not been assessed among the US population, despite increasing reports of HBV transmission in institutional care settings. Using national survey data, we found a 60% higher prevalence of HBV infection among persons with (vs without) diagnosed diabetes.

Endothelium-independent constriction of isolated, pressurized arterioles by Nomega-nitro-L-arginine methyl ester (L-NAME).

BACKGROUND AND PURPOSE: Nitric oxide synthase (NOS) inhibitors cause vasoconstriction in pressurized arterioles with myogenic tone. This suggests either tonic production of NO modulates myogenic tone or a direct, NOS-independent effect of the NOS inhibitors. The nature of the contractile effect of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) on pressurised arterioles was investigated. EXPERIMENTAL APPROACH: Segments of rat cremaster muscle first-order arteriole were cannulated on glass micropipettes and maintained at an intraluminal pressure of 50, 70 or 120 mmHg. KEY RESULTS: L-NAME and the related compound L-NA (100 microM) constricted pressurized vessels with myogenic tone. Removal of the endothelium did not cause constriction or alter myogenic tone, however the constrictor effect of L-NAME persisted. The constrictor effect of L-NAME was abolished by L-arginine (1 mM). Other NO and cGMP pathway inhibitors, including the nNOS inhibitor 7-nitroindazole (100 muM), the NO scavenger carboxy-PTIO (100 microM), the guanylate cyclase inhibitor ODQ (10 microM) and the cGMP inhibitor Rp-8CPT-cGMPS (10 microM) did not cause constriction of the arterioles. L-NAME caused a small (3-4 mV) but not statistically significant depolarization of the arteriolar smooth muscle at both pressures. The constrictor effect was not prevented by the K(+)-channel antagonist tetraethyl ammonium (TEA, 1 mM) or the K(ATP) channel antagonist glibenclamide (1 microM). CONCLUSIONS AND IMPLICATIONS: These observations demonstrate that L-NAME causes an endothelium- and NOS-independent contraction of vascular smooth muscle in isolated skeletal muscle arterioles. It is suggested that the underlying mechanism relates to an arginine binding interaction.

Progressive vascular remodelling, endothelial dysfunction and stiffness in mesenteric resistance arteries in a rodent model of chronic kidney disease.

Chronic kidney disease (CKD) and hypertension are co-morbid conditions both associated with altered resistance artery structure, biomechanics and function. We examined these characteristics in mesenteric artery together with renal function and systolic blood pressure (SBP) changes in the Lewis polycystic kidney (LPK) rat model of CKD. Animals were studied at early (6-weeks), intermediate (12-weeks), and late (18-weeks) time-points (n=21), relative to age-matched Lewis controls (n=29). At 12 and 18-weeks, LPK arteries exhibited eutrophic and hypertrophic inward remodelling characterised by thickened medial smooth muscle, decreased lumen diameter, and unchanged or increased media cross-sectional area, respectively. At these later time points, endothelium-dependent vasorelaxation was also compromised, associated with impaired endothelium-dependent hyperpolarisation and reduced nitric oxide synthase activity. Stiffness, elastic-modulus/stress slopes and collagen/elastin ratios were increased in 6 and 18-week-old-LPK, in contrast to greater arterial compliance at 12weeks. Multiple linear regression analysis highlighted SBP as the main predictor of wall-lumen ratio (r=0.536, P<0.001 n=46 pairs). Concentration-response curves revealed increased sensitivity to phenylephrine but not potassium chloride in 18-week-LPK. Our results indicate that impairment in LPK resistance vasculature is evident at 6weeks, and worsens with hypertension and progression of renal disease.

Beta-adrenoceptor blockade and sympathetic neurotransmission in the pithed rat.

The effects of the beta 1-adrenoceptor blocking drug atenolol and the beta 2-adrenoceptor blocking drug ICI 118551 (ICI, Melbourne, Australia) on noradrenaline release and blood pressure were investigated using the pithed rat, which was subjected to continuous electrical stimulation of the spinal sympathetic outflow (pulses at 3 Hz). This stimulation increased blood pressure but not heart rate. The noradrenaline release rate was calculated by infusing [3H] noradrenaline and measuring the steady-state concentrations of both endogenous and infused noradrenaline. Atenolol (0.2 mg/kg bolus plus 0.1 mg/kg per h, intra-arterially) had no effect on the noradrenaline release rate or heart rate, but significantly decreased blood pressure. On the other hand, ICI 118551 (0.2 mg/kg bolus plus 0.1 mg/kg per h. intra-arterially) had no significant effect on blood pressure or heart rate, but did inhibit the noradrenaline release rate. The sympathoinhibitory effect of ICI 118551 was not observed in animals which had been adrenal medullectomized, suggesting that its effect on noradrenaline release was due to blockade of activation of facilitatory prejunctional beta 2-adrenoceptors by adrenaline. The reduced noradrenaline release in the presence of ICI 118551 was not accompanied by a reduction in blood pressure. This may be because ICI 118551 also blocked vasodilatory beta 2-adrenoceptors on vascular smooth muscle. Indeed, in unstimulated pithed rats, infusions of adrenaline which were non-pressor were found to be pressor after ICI 118551 was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Shigella vaginitis: report of 38 patients and review of the literature.

Thirty-eight cases of Shigella vaginitis were identified in a retrospective review of records kept over the past 14 years. The cases of vaginitis were due to three subgroups of Shigella. Vaginitis varied in severity and duration, persisting for several months in some instances. In 47% of the cases, there was associated bloody vaginal discharge. Only two children had diarrhea temporally associated with vaginitis, but six others had had diarrhea. Many treatment modalities were used. Systemic antibiotic therapy appeared more effective than topical antimicrobials in the few patients who could be evaluated. Review of the literature revealed 32 additional cases, including four in adult women.

Prospective surveillance of Haemophilus influenzae type b disease in Dallas County, Texas, and in Minnesota.

Among children less than 12 years of age residing in Dallas County, Texas, and in the state of Minnesota we conducted prospective, active surveillance of invasive Haemophilus influenzae disease. During 18 months, 616 cases were identified, of which 600 were caused by type b organisms. The annual incidence of disease was significantly greater in Dallas than in Minnesota (109 v 68/100,000 children younger than 5 years of age, P less than .001) and was greater in Dallas, even when rates for white children in the two regions were compared (P less than .001). Other regional differences were observed. In Dallas, a larger proportion of cases were in children attending day-care centers (27% compared with 12% in Minnesota, P less than .001) and more patients attended day care for greater than 40 h/wk (56% compared with 30% in Minnesota, P less than .001). Outer membrane protein subtyping of isolates revealed that in Dallas 6U isolates were associated significantly with cases in black children who attended day care. In Minnesota, but not in Dallas, isolates with subtype 1H were associated significantly with cases in children in day care. These data indicate that there are regional differences in the epidemiology of type b Haemophilus disease that may relate to differences in strains, day-care practices, or other unknown cultural or environmental factors. Finally, because only 15% of systemic Haemophilus disease in these regions occurred in children in the age groups recommended for vaccination (24 to 59 months), the new Haemophilus type b polysaccharide vaccine is expected to have a limited impact on the overall incidence of disease.

Prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are sensitive to N-ethylmaleimide, but not pertussis toxin.

1. The identity of the G-proteins involved in prejunctional alpha 2-adrenoceptor signal transduction in mouse atria was examined by use of the G-protein inactivators N-ethylmaleimide and pertussis toxin. 2. The alpha 2-adrenoceptor partial agonist clonidine (0.03 microM) inhibited the electrical stimulation-induced (S-I) outflow of radioactivity from mouse atria which were incubated with [3H]-noradrenaline and stimulated at 5 Hz. The partial alpha 2-adrenoceptor agonist St 363 (10 microM) inhibited the S-I outflow of radioactivity at the lower stimulation frequency of 2.5 Hz. The inhibitory effects of these compounds were not altered in mice pretreated with pertussis toxin (1.5 micrograms, i.v.). 3. The alpha 2-adrenoceptor antagonist, idazoxan (0.1 microM), increased the S-I outflow of radioactivity from mouse atria stimulated at 5 Hz, and this effect was not altered in atria from mice pretreated with pertussis toxin. 4. The inhibitory effects of clonidine and St 363 and the facilitatory effect of idazoxan on the S-I outflow of radioactivity from mouse atria were significantly less in atria incubated with N-ethylmaleimide (NEM, 3 microM) for 60 min before the [3H]-noradrenaline incubation. 5. The results suggest that prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are NEM-sensitive, but pertussis toxin insensitive.

Effects of mibefradil and nifedipine on arteriolar myogenic responsiveness and intracellular Ca(2+).

1. Ca(2+) entry mechanisms underlying spontaneous arteriolar tone and acute myogenic reactivity remain uncertain. These studies aimed to compare the effects of nifedipine and the putative T-channel blocker, mibefradil, on arteriolar myogenic responsiveness and intracellular Ca(2+) (Ca(2+)(i)). 2. First order cremaster muscle arterioles (1A) were isolated from rats, cannulated, pressurized to 70 mmHg in the absence of intraluminal flow, and mechanical responses studied by video microscopy. The Ca(2+)(i) was measured using fluorescence imaging of Fura 2 loaded arterioles. 3. Both nifedipine and mibefradil showed dose-dependent inhibition of spontaneous myogenic tone (at 70 mmHg; pEC(50) 7.04+/-0.17 vs 6.65+/-0.20 respectively, n=6 for both, n.s.) and KCl-induced vasoconstriction (at 70 mmHg; pEC(50) 6.93+/-0. 38 vs 6.45+/-0.27 respectively, n=6 for both, n.s.). 4. In arterioles maintained at 50 mmHg, nifedipine (10(-7) and 10(-5) M) caused a concentration dependent reduction in Ca(2+)(i), however, mibefradil (10(-7) and 10(-5) M) had no effect. Furthermore nifedipine significantly attenuated the increase in Ca(2+)(i) associated with an acute pressure step (50 - 120 mmHg) whereas mibefradil was considerably less effective. 5. Mibefradil (10(-7) M) significantly attenuated contractile responses to 60 mM KCl without altering the KCl-induced increase in Ca(2+)(i), in contrast to nifedipine (10(-7) M) which reduced both Ca(2+)(i) and contraction. 6. Membrane potential of arterioles with spontaneous myogenic tone (70 mmHg) was -41.5+/-1. 0 mV. Nifedipine (10(-7) or 10(-5) M) had no effect on membrane potential, however mibefradil (10(-5) M) caused significant depolarization. 7. In summary, both mibefradil and nifedipine inhibit arteriolar spontaneous tone and acute myogenic reactivity. While there may be overlap in the mechanisms by which these agents inhibit tone, differences in effects on membrane potential and intracellular Ca(2+) levels suggest mibefradil exhibits actions other than blockade of Ca(2+) entry in skeletal muscle arterioles.

Noradrenaline release and the effect of endogenous activation of the phospholipase C/protein kinase C signalling pathway in rat atria.

1. It has been proposed that protein kinase C (PKC) in sympathetic nerves is activated during action-potential evoked release of noradrenaline and helps maintain transmitter output. We studied this phenomenon further in rat atria radiolabelled with [3H]-noradrenaline. 2. Noradrenaline release was elevated by continuous electrical stimulation of the atria for 10 min at either 5 or 10 Hz. Two inhibitors of PKC, polymyxin B (21 microM) and Ro 318220 (3 microM), markedly inhibited the release of noradrenaline but only at the higher stimulation frequency. 3. Further experiments were conducted with 10 Hz stimulation but for shorter train durations. In this case polymyxin B inhibited noradrenaline release during a 10 or 15 s train of impulses but not during a 5 s train. This suggests that PKC effects are induced during the stimulation train by some process. 4. The diacylglycerol kinase inhibitor R59949 (10 microM), which prevents the breakdown of diacylglycerol, enhanced noradrenaline release elicited by stimulation at 10 Hz for 10 or 15 s. This effect was not seen if polymyxin B was present and suggests that diacylglycerol is the endogenous activator of PKC. 5. The source of the diacylglycerol may be through phospholipase C pathways, since the phospholipase C inhibitor U73122 (3 microM) inhibited noradrenaline release at 10 Hz for 10 s and the effect was not seen if polymyxin B was also present. 6. It is unlikely that phospholipase D is the source of diacylglycerol. Although the phospholipase D inhibitor wortmannin (1 microM) inhibited noradrenaline release, this effect was still observed in the presence of polymyxin B. Furthermore ethanol, which inhibits diacylglycerol formation by phospholipase D, had no effect on noradrenaline release. 7. We therefore suggest that during a train of high frequency pulses phospholipase C is activated and this results in the production of diacylglycerol which in turn activates PKC. This enables the neurones to maintain transmitter release at a high level.

Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery.

1. Small strips from third-order branches of rabbit mesenteric artery (approximately 150-200 microM wide) contracted in response to noradrenaline (10 microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a single, transient contraction in artery strips, while 5-HT (10 microM) failed to induce any response. 2. In strips of mesenteric artery which had been permeabilized with Staphylococcus alpha-toxin and bathed in Ca(2+)-free mock intracellular solution, noradrenaline (10 microM), caffeine (10 mM) and D-myo-inositol (1,4,5)-trisphosphate (IP3, 100 microM), but not 5-HT (10 or 100 microM) induced a transient contraction. In contrast to the non-permeabilized strips, contractions to noradrenaline, caffeine and IP3 were restored by prior incubation (10 min) in solution containing 0.08 microM Ca2+. The contractions to noradrenaline and IP3 in permeabilized muscle strips required the presence of 100 microM guanosine 5'-triphosphate (GTP), although in the absence of Ca2+. GTP alone did not induce contraction. 3. Exposure of permeabilized mesenteric artery strips to IP3 significantly reduced the subsequent contractile responses to caffeine. Contractile responses to caffeine and IP3 were abolished by the Ca(2+)-ATPase inhibitor, thapsigargin (1 microM). 4. Ca2+ (0.1-10 microM) induced concentration-dependent contraction in permeabilized artery strips. In strips which were submaximally contracted with 0.5 microM Ca2+/100 microM GTP, the subsequent addition of 5-HT (10 microM) stimulated further contraction. The protein kinase C inhibitor, H-7 (1 microM) abolished the 5-HT/GTP-induced contraction, but did not alter the contraction to Ca2+. 5. In non-permeabilized, endothelium-denuded segments of rabbit mesenteric artery bathed in Ca2+-replete Krebs solution, noradrenaline (10 microM) stimulated a rapid, transient accumulation of IP3. 5-HT(100 microM) failed to stimulate IP3 accumulation during exposure periods of up to 5 min. 5-HT (100 microM)did stimulate IP3 accumulation if the external K+ concentration was raised (to around 25 mM). This concentration of K+ alone did not stimulate IP3 production and the 5-HT-stimulated IP3 accumulation in the presence of elevated extracellular [K+] was abolished by the alpha l-adrenoceptor antagonist, prazosin(O.1 microM).6. These results suggest that intracellular Ca2+ release does not play an important role in 5-HT-induced smooth muscle contraction in the rabbit mesenteric artery. This is despite the fact that a significant intracellular Ca2+ pool is present in these cells, which can be discharged by either noradrenaline or IP3.However, 5-HT did stimulate smooth muscle contraction in the presence of raised intracellular calcium,suggesting that a component of the contraction to 5-HT will reflect an increase in myofilament Ca2+sensitivity, possibly due to the activation of protein kinase C.

Factors associated with unnecessary immunization given to children.

OBJECTIVE: To determine the factors associated with unnecessary immunization during the pre-school years. METHODS: Children were selected from birth certificates and their parents were interviewed to identify all immunizations to 72 months of age. The immunizations were verified. RESULTS: Of 187 children studied 34 (18%) received unnecessary immunization. Unnecessary immunization was strongly associated with ever receiving immunization in a large system of public clinics (designated "Public A") (33%) compared with other providers (5%) (P < 0.00001). Among children immunized in Public A, unnecessary immunization was associated with the parent having an incomplete or no copy of the child's immunization record (P = 0.007) and with not being up to date for immunizations at 24 months of age (P = 0.04). Complete documentation of immunizations either in the Public. A record or in the parent's copy of the record was associated with a 4% rate of unnecessary immunization; incomplete or no documentation in both the Public A and the parent's record was associated with a 45% rate of unnecessary immunization (P = 0.001). CONCLUSIONS: Access to a complete immunization record, be it the provider's, the parent's or ideally both, decreases substantially a child's risk of unnecessary immunization.

Meningococcal disease in Dallas County, Texas: results of a six-year population-based study.

OBJECTIVE: Neisseria meningitidis is an important cause of serious bacterial infection in children and adults in the US. From 1992 to 1997 invasive disease caused by N. meningitidis was studied among 1.9 million residents of Dallas County, TX METHODS: The demographic characteristics and diagnoses of 151 patients were identified through active, population-based surveillance and review of medical records. Serogroups were determined for strains infecting 129 (85%) patients. RESULTS: The average annualized incidence rate was 1.3 cases per 100,000 person years and was highest for children <1 year (13 cases/100,000 person years). Older patients (50+ years old) were more likely to present with pneumonia and less likely to present with meningitis than younger patients. Neither the fatality rate nor the duration of hospitalization for surviving patients was associated with age. Among patients with a known serogroup, serogroup C disease was found in 35% of cases <1 year old, 64% of those 1 to 49 years old and 44% of those 50+ years old. Serogroup B strains were isolated from 26% of patients <1 year, 17% of patients 1 to 49 years old and none of the patients 50+ years old. Serogroup Y disease increased from 22% to 35% of cases between 1992 and 1997 (P = 0.03). This serogroup was identified in 26% of patients <1 year old, 17% of patients 1 to 49 years old and in 50% of patients 50+ years old. Serogroup C and Y accounted for 61% of cases in children <1 year old and for 79% of cases in all age groups. CONCLUSION: The results underscore the importance of conjugate vaccines for serogroups C and Y.

Haemophilus influenzae type b in respiratory secretions.

Oral and respiratory secretions of 31 children who were healthy or had mild upper respiratory infection, and who had a positive throat culture for Haemophilus influenzae type b, were cultured to determine which secretions contain this organism and how long it can be recovered from fomites. Rhinorrhea was present in 11 of 31 (34%) children and nasal mucus was positive for H. influenzae type b in 10 (91%). In 5 of these children the concentration of H. influenzae type b in nasal mucus was 10(4) to 10(7) colony-forming units/ml3. H. influenzae type b in nasal mucus applied to fomites were recovered for 12 hours. Cultures of saliva and cough secretions compared with nasal mucus were less often positive (3 of 31, P less than 0.001; 3 of 25, P less than 0.001, respectively) and contained fewer H. influenzae type b (5 and 15 colony-forming units, respectively). H. influenzae type b was recovered from the hand of 2 of 27 (7%) children; both children had positive cultures of saliva. These data indicate that H. influenzae type b can be found in oral and respiratory secretions of pharyngeal carriers and can contaminate children's hands. Nasal mucus was the most consistently positive secretion and contained the largest number of bacteria. Careful management of nasal mucus secretions is warranted in settings where transmission could occur to susceptible children.

Second episodes of Haemophilus influenzae type b disease following rifampin prophylaxis of the index patients.

Patients treated for Haemophilus influenzae type b disease frequently remain nasopharyngeal carriers of that organism and fail to develop protective concentrations of serum antibody. It has been suggested that rifampin prophylaxis of the index patient may prevent recurrence of disease by eliminating type b Haemophilus carriage. We report nine children who developed second episodes of disease 1 week or more after receiving rifampin prophylaxis. The median interval between the last dose of rifampin and admission to the hospital for the second episode was 70 days (range, 9 to 138). Analysis of biotypes and outer membrane protein polyacrylamide gel electrophoresis patterns of paired isolates from eight cases revealed that the second episodes in two of the children were caused by acquisition of new type b Haemophilus strains, whereas the second episodes in the remaining six children were caused by isolates which were indistinguishable from the respective isolates from the first episodes. Rifampin prophylaxis of the index patient may prevent some episodes of recurrent disease. However, in some patients who have received prophylaxis, second episodes can occur, probably as a result of reacquisition of the organism from contacts who did not receive rifampin or from acquisition of new type b strains.

Estimating immunization coverage from school-based childhood immunization records.

To determine the accuracy of school-based childhood immunization records and to describe the effects of their use on estimates of community-wide immunization coverage, we verified the immunizations to 72 months of age for children born in 1986 to residents in Dallas County, TX, and in Minnesota. Verified immunizations were compared with those documented in the school record. Major transcription errors accounted for fewer than 1% of discrepancies between school and provider records. For 99 subjects with 987 verified immunizations in Minnesota, age-appropriate immunization coverage estimated from the school records was within two percent of actual coverage. For 86 subjects with 981 verified immunizations in Dallas County, age-appropriate immunization coverage from the school records underestimated actual coverage by as much as 21%. The primary factor explaining the underestimate in Dallas was incomplete school immunization records for 33 (38%) subjects and 126 (13%) immunizations. Selective recording of immunizations related to the minimum state requirements in Texas contributed to incomplete school records in Dallas County. Verification of the completeness of records selected to estimate immunization coverage is essential if the estimates are used to monitor trends or to make public policy decisions.

Pediatric clinical clerkships are associated with an excess risk of acute infection.

OBJECTIVE: To determine the incidence of acute respiratory and gastrointestinal tract illness and associated absence by third-year medical students during pediatric and nonpediatric (control) clinical clerkships. DESIGN: A self-administered questionnaire was completed by students after the first 4 weeks of two pediatric clerkships (inpatient and outpatient) and two non-pediatric clerkships (obstetrics-gynecology and psychiatry). Information was obtained on the symptoms of acute respiratory and gastrointestinal tract illness and related absences. ANALYSIS: Results from each student's pediatric clerkship were compared with the results from the same student's control clerkship by means of matched-pair analysis. SUBJECTS: Students who made up the junior class at the University of Texas Southwestern Medical School at Dallas, July 1, 1990, to June 30, 1991. RESULTS: Of 177 students (77%) who completed questionnaires after one pediatric and one control clerkship, 108 students (61%) had had an acute illness while on pediatric clerkships in contrast to 69 students (39%) on control clerkships (odds ratio, 3.3; 95% confidence interval, 2.0 to 5.4; P < .001). More students were absent for illness during pediatric than control clerkships (23 [13%] vs nine [5%], respectively; odds ratio, 2.7; 95% confidence interval, 1.2 to 6.2; P = .02). The higher risk of illness during pediatric clerkships was not related to the order of the pediatric or control clerkship, the order of inpatient and outpatient pediatrics, or the season of the year. CONCLUSION: Pediatric clinical clerkships in the third year of medical school were associated with excess morbidity from acute infectious illness. Studies are needed to determine whether emphasizing infection control practices decrease this morbidity and any resulting nosocomial spread to patients.

Use of rapidly generated results in patient management.

The usefulness of a rapid diagnostic test in patient management depends on the sensitivity of the test, the clinical consequences of false-negative or false-positive results, the ease and cost of performance, and the timely availability of results. A test that is sensitive, specific, inexpensive, and rapid is presumed to be useful clinically. However, there has been surprisingly little effort to measure the actual impact of the results on patient care. Since antigen detection for Haemophilus influenzae type b disease has been available for more than a decade, it will be used as a model to illustrate several factors that help determine the benefits, limitations, and pitfalls of antigen detection in the management of patients with serious bacterial infections. Herein we will compare the use of antigen detection in meningitis with that in other Haemophilus influenzae type b diseases. We also will review our experience with the impact of rapid diagnosis on the treatment of bacterial meningitis. Finally, other factors that influence the usefulness of antigen detection on patient care will be explored by comparing the potential consequences of laboratory error on the management of patients with Haemophilus influenzae type b infections with that of management of other kinds of infections, such as streptococcal pharyngitis, sexually transmitted diseases, and viral respiratory infections.

Modulation of noradrenaline release in slices of rat kidney cortex through alpha 1- and alpha 2-adrenoceptors.

Slices of rat kidney cortex were incubated in [3H]noradrenaline, then placed in a flow cell and subjected to electrical field stimulation. At a stimulation frequency of 5 Hz, both the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the alpha 1-adrenoceptor antagonist prazosin (0.1 microM) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity from the slice. However, neither clonidine (0.1 microM) nor methoxamine (10 microM), alpha 2- and alpha 1-agonists respectively, affected the S-I outflow of radioactivity at this stimulation frequency. At a lower stimulation frequency (1 Hz), the S-I outflow of radioactivity was not affected by idazoxan or prazosin, but was inhibited by both clonidine and methoxamine. The effect of clonidine was prevented by idazoxan (0.1 microM), but not by prazosin (0.1 microM). The effect of methoxamine was abolished by prazosin (0.1 microM), but not by idazoxan (0.1 microM). The inhibitory effect of methoxamine was not prevented by the prostaglandin synthesis inhibitor indomethacin (10 microM) or the adenosine receptor antagonist 8-phenyltheophylline (1 microM) and thus was not mediated by either prostaglandins or adenosine. The results suggest that both prejunctional alpha 1- and alpha 2-adrenoceptors are directly involved in modulation of noradrenaline release from the renal sympathetic nerves of the rat.

Pertussis toxin differentiates between alpha 1- and alpha 2-adrenoceptor-mediated inhibition of noradrenaline release from rat kidney cortex.

In slices of rat kidney cortex incubated in [3H]noradrenaline, the alpha 1-adrenoceptor agonist methoxamine (10 microM), the alpha 2-adrenoceptor agonist clonidine (0.1 microM), as well as adenosine (10 microM), inhibited the electrical stimulation-induced (S-I) outflow of radioactivity, at a stimulation frequency of 1 Hz. Prior treatment of rats with pertussis toxin (25 micrograms/kg i.v.), which abolished the negative inotropic effect of carbachol (10 microM) on isolated atria, prevented the inhibition caused by methoxamine, but not that caused by clonidine or adenosine. At a stimulation frequency of 5 Hz, the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the prostaglandin synthesis inhibitor indomethacin (10 microM) both facilitated the S-I outflow of radioactivity, and neither of these effects were altered by pertussis toxin. These results suggest that a pertussis toxin sensitive G-protein is involved in alpha 1-adrenoceptor inhibition of noradrenaline release, but not in alpha 2-adrenoceptor, adenosine or prostaglandin inhibition.