Community Health In a Mountain Neighborhood

To test the hypothesis that during high periods of carbon monoxide (CO) pollution, persons with acute cardiovascular disease would be adversely affected, we have studied case fatality rates for patients admitted with myocardial infarction (Ml) to 35 Los Angeles hospitals during 1958. The results indicate that there is an increased Ml case fatality rate in “high”-pollution areas and that this difference is only evident during periods of relatively increased CO pollution.

At the present time, our interpretation of these findings is that an association could exist between ME case fatality rate and atmospheric CO pollution but we cannot draw any firm conclusions about causality at this time.     

Sick-listing habits among general practitioners in a Swedish county

Objective - To describe sick-listing habits in general practice, how common it is and for how long and for what diagnoses it is granted. Design - Medical audit study. Setting - Primary health care. Subjects - 53 general practitioners (GPs) registering all cases during a 2-week period when sick-listing was considered. Main outcome measures - Percentage of GP consultations that involved sick-listing, number of days of certified sick-leave, percentage of partial sick-listing, GP sex differences. Results - 9% of all consultations included a consideration about sick-listing, and in only 6% of these instances was a certificate not issued. The median length of the certified sickness period was 14 days. Musculoskeletal problems were by far the most common diagnosis. Female patients were more often partially sick-listed than males. Female GPs sick-listed a larger proportion of their patients than male GPs. Risk factors for long certification periods were in fact associated with long certification periods. Even in cases where the GP would not recommend sick-listing a certificate was issued in 87%. Conclusions - Patients appear to have a strong influence on sick-listing practice, and there are important sex differences among GPs in this practice.     

Work-related stressors and occurrence of adverse events in an ED

ObjectiveThe purpose of this study was to investigate the relationship between 12 work-related stressors and the occurrence of adverse events in an emergency department (ED).MethodsNurses and physicians, working in an ED at a Danish regional hospital, filled out a questionnaire on occurrence and emotional impact of 12 work-related stressors after each shift during a 4-week period. The questionnaire also instructed the participants to describe any adverse events that they were involved in during the shift.ResultsTwo hundred fourteen adverse events were reported during the 979 studied shifts. During the same period, only 27 adverse events were reported to the mandatory national reporting system, and only 10 of these were duplicates. A high variability of stressors and emotional impact among the different groups of participants was found. Linear regression analysis showed an association between involvement in adverse events and the occurrence and emotional impact of stressors across groups, whereas no significant association was found for age, seniority, shift type, or length.ConclusionThe study showed an association between the occurrence and impact of 12 work-related stressors and involvement in adverse events across the groups of participants. Furthermore, the study showed that most adverse events were not reported to the mandatory national reporting system.     

Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. METHODS: A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). RESULTS: After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. CONCLUSION: Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.     

Evaluation of the use of a biodegradable ureteral stent after retrograde endopyelotomy in a porcine model

PURPOSE: We evaluated the use of a poly-L-lactide-co-glycolide (PLGA) bioabsorbable ureteral stent after Acucise balloon incision (Applied Medical Resources, Rancho Santa Magarita, California) endopyelotomy in a porcine model. MATERIALS AND METHODS: After unilateral Acucise endopyelotomy in 9 female Yucatan minipigs a self-reinforced PLGA stent was placed in 5 (group 1) and a 7Fr double pigtail Percuflex stent (Boston Scientific, Natick, Massachusetts) was placed in 4 (group 2). Preoperatively, and 6 and 12 weeks postoperatively plain x-ray of the kidneys, ureters and bladder, cystography, side specific creatinine clearance and retrograde ureterography were done. The contralateral ureters served as untreated controls. The 7Fr stents were removed at 6 weeks. All animals were sacrificed at 12 weeks after bilateral flow studies. Histological specimens from 4 sites along the urinary tract were graded on a healing score of 0-normal, to 3-severe changes. RESULTS: Side specific creatinine clearance was similar to preoperative values at 6 and 12 weeks. At the 2 time points plain x-ray of the kidneys, ureters and bladder in group 1 showed retroperitoneal stent fragments in 3 of the 5 animals, which was confirmed at autopsy. Retrograde ureterography in group 1 showed mild hydronephrosis in all 5 ureters and saccular diverticula in 4, which was similar in 2 and 3 animals, respectively, in group 2. Cystography demonstrated grades 1 to 2 reflux in 2 animals at 6 weeks but none at 12 weeks in group 1 and no reflux at either time point in group 2. Flow rates and healing scores were statistically similar in the 2 groups but the latter trended toward less favorable healing of ureteral musculature with application of the absorbable stent. CONCLUSIONS: In this pilot study the use of self-reinforced PLGA biodegradable ureteral stents was feasible after Acucise endopyelotomy in a porcine model with radiographic and fluid flow results that were relatively similar to those of standard 7Fr stents but with less favorable biocompatibility.     

Reproducibility of constant-load treadmill testing with various treadmill protocols and predictability of treadmill test results in patients with intermittent claudication

BACKGROUND: Most trials on the reliability of constant-load treadmill testing use one pair of treadmill settings (speed, grade) only. The question of whether the results can be applied to tests with different settings is left open. Also, claudication distances measured with differing settings are not comparable, rendering the comparison of the results from different trials difficult. This study evaluates the reliability of constant-load testing with various workloads and compares them with claudication distances achieved with walking at normal speed on level ground but also evaluates whether metabolic equivalent (MET) normalization can be used to translate the results of different treadmill tests into each other. METHODS: Fifteen patients with claudication underwent repeated treadmill testing with different treadmill settings, including speeds of 2.0, 3.2, and 4.0 km/h (1.25, 2.0, and 2.5 mph, respectively) and grades of 0% and 12%. The walking capacity was also tested on level ground with a speed chosen by the individual patient. Results of virtual treadmill tests with all possible combinations of the speeds and the grades used were predicted from real tests, with MET normalization. The relationship between real and predicted claudication distances was tested with regression modeling. RESULTS: Reliability coefficients (RCs) for the absolute claudication distance (ACD) were superior to RCs for the initial claudication distance. RCs for ACD ranged between 0.61 and 0.95, with increasing values found with increasing workloads. The best coefficients for the regression of measured on predicted claudication distances were achieved with a model on the basis of a power function (r = 0.963). The model was only appropriate for the prediction of group mean results from clinical trials but cannot be applied to single patient data. For proof of concept, the model was tested with six published studies in which the claudication distances of a patient sample were double treadmill tested with different workloads. The result of the second test was predicted from the first test, and estimated and measured claudication distances were compared. The mean difference (all trials) was 7.9%, whereas the maximum difference amounted to 16.5%. CONCLUSION: For an optimal treadmill test reliability, higher workloads should be used and ACD should be preferred over initial claudication distance. MET normalization provides the basis for the comparability of treadmill test results achieved with different test conditions.     

Ventromedial Hypothalamic Nitric Oxide Production Is Necessary for Hypoglycemia Detection and Counterregulation

OBJECTIVE

The response of ventromedial hypothalamic (VMH) glucose-inhibited neurons to decreased glucose is impaired under conditions where the counterregulatory response (CRR) to hypoglycemia is impaired (e.g., recurrent hypoglycemia). This suggests a role for glucose-inhibited neurons in the CRR. We recently showed that decreased glucose increases nitric oxide (NO) production in cultured VMH glucose-inhibited neurons. These in vitro data led us to hypothesize that NO release from VMH glucose-inhibited neurons is critical for the CRR.

RESEARCH DESIGN AND METHODS

The CRR was evaluated in rats and mice in response to acute insulin-induced hypoglycemia and hypoglycemic clamps after modulation of brain NO signaling. The glucose sensitivity of ventromedial nucleus glucose-inhibited neurons was also assessed.

RESULTS

Hypoglycemia increased hypothalamic constitutive NO synthase (NOS) activity and neuronal NOS (nNOS) but not endothelial NOS (eNOS) phosphorylation in rats. Intracerebroventricular and VMH injection of the nonselective NOS inhibitor N^G-monomethyl-l-arginine (l-NMMA) slowed the recovery to euglycemia after hypoglycemia. VMH l-NMMA injection also increased the glucose infusion rate (GIR) and decreased epinephrine secretion during hyperinsulinemic/hypoglycemic clamp in rats. The GIR required to maintain the hypoglycemic plateau was higher in nNOS knockout than wild-type or eNOS knockout mice. Finally, VMH glucose-inhibited neurons were virtually absent in nNOS knockout mice.

CONCLUSIONS

We conclude that VMH NO production is necessary for glucose sensing in glucose-inhibited neurons and full generation of the CRR to hypoglycemia. These data suggest that potentiating NO signaling may improve the defective CRR resulting from recurrent hypoglycemia in patients using intensive insulin therapy.Intensive insulin therapy significantly reduces the onset and progression of hyperglycemia-related complications in patients with type 1 and advanced type 2 diabetes. However, intensive insulin therapy also causes a clinically adverse effect: hypoglycemia (1). Powerful neuroendocrine and autonomic counterregulatory mechanisms protect the brain from hypoglycemia (2,3). These protective mechanisms, known as the counterregulatory response (CRR) to hypoglycemia, involve the release of hormones (e.g., glucagon, epinephrine) that restore euglycemia by stimulating hepatic glucose production and inhibiting peripheral glucose uptake (3). Although the physiology of the CRR is well understood, the underlying cellular mechanisms by which the brain senses hypoglycemia and initiates the CRR remain elusive.During hypoglycemia, central and peripheral glucose sensors detect declining glucose levels (4). In the brain, the ventromedial hypothalamus, which includes the arcuate nucleus and the ventromedial nucleus (VMN), is important in the initiation of the CRR (5–7). This region contains specialized glucose-sensing neurons (GSNs). Ventromedial hypothalamic (VMH) GSN electrical activity is regulated by physiologically relevant changes in extracellular glucose levels (8–11). Glucose-excited neurons decrease, whereas glucose-inhibited neurons increase, their input resistance, membrane potential, and action potential frequency when extracellular glucose is reduced (10). Many studies suggest that VMH glucose-inhibited neurons play a critical role in the control of the CRR (4). For example, the response of VMH glucose-inhibited neurons to decreased glucose is impaired under conditions where the CRR is impaired (e.g., recurrent hypoglycemia) (12,13).Nitric oxide (NO) is a gaseous messenger produced by NO synthase (NOS). Two classes of NOS have been identified in the brain: the inducible NOS (iNOS) and the constitutive NOS, which includes the neuronal NOS (nNOS) and endothelial NOS (eNOS) isoforms (14). Hypothalamic NO is involved in the regulation of food intake and glucose homeostasis (15–18). In support of this, we have recently shown that VMH glucose-inhibited neurons produce NO via nNOS in response to decreased extracellular glucose levels (19,20). Therefore, in this study, we test the hypothesis that NO production by VMH glucose-inhibited neurons is necessary for the CRR to hypoglycemia. We tested this hypothesis using a combination of in vivo and in vitro techniques in wild-type rats and mice as well as in transgenic nNOS and eNOS knockout mice.     

The efficacy of ultrasound-guided transversus abdominis plane block in patients undergoing hysterectomy

The study objective of this prospective, double-blind randomised controlled study was to evaluate the efficacy of ultrasound guided transversus abdominis plane (TAP) block and bupivacaine infiltration of the skin and subcutaneous tissue of the wound in patients undergoing hysterectomy. Patients were randomly allocated to three groups: a control group (n = 18) and TAP block group (n = 18) received bilateral TAP blocks with saline and bupivacaine respectively, and an infiltration group (n = 19) received skin and subcutaneous wound tissue infiltration with bupivacaine at the end of surgery. After surgery patients received patient-controlled intravenous tramadol and were assessed for pain and tramadol consumption at 1, 2, 4, 6 and 24 hours. Both the TAP and infiltration groups had lower movement and rest pain scores than the control group, with lower scores in the TAP group than the infiltration group at 6 and 24 hours. Total tramadol consumption was significantly lower in the TAP group than in the other groups at all time points. We concluded that ultrasound-guided TAP block reduced rest and movement pain after total abdominal hysterectomy and was more effective than superficial wound infiltration for postoperative pain management.