Glucose utilization during interictal intervals in an epilepsy model induced by pilocarpine: a qualitative study

OBJECTIVE: To compare the antibiotic susceptibility of bacterial isolates from patients in the surgical intensive care unit (SICU) with hospital-wide bacterial susceptibility. DESIGN: Retrospective cohort analytic study. SETTING: Eight-bed SICU in a university-affiliated teaching hospital. PATIENTS: All hospitalized patients with culture results positive for microorganisms. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Antibiotic susceptibility data were collected retrospectively for all bacterial isolates from SICU patients during July 1, 1994, to June 30, 1995. All duplicate and surveillance cultures were eliminated from the data set. Susceptibility testing was conducted using our standard laboratory methods. Results were compared with the hospital-wide antibiogram (HWA) for the same time period. Comparisons were made using the chi(2) test with Yates correction or the Fisher exact test, as appropriate. Staphylococcus aureus (HWA, n=494; SICU, n=71) was significantly less susceptible to oxacillin (51% vs 28%; P<.001), ciprofloxacin (50% vs 25%; P<.001), erythromycin (46% vs 23%; P<.001), and clindamycin (51% vs 27%; P<.001) in the SICU. Coagulase-negative staphylococci (HWA, n=339; SICU, n=37) were significantly less susceptible to oxacillin (33% vs 16%; P=.04) and clindamycin (57% vs 34%; P=.02). Pseudomonas aeruginosa (HWA, n=513; SICU, n=96) was less susceptible to imipenem (85% vs 74%, P=.01) and more susceptible to ticarcillin-clavulanic acid (88% vs 100%, P<.001) in the SICU. Escherichia coli (HWA, n=474; SICU, n=36) was more susceptible to most penicillin-derivative antibiotics in the SICU (ampicillin [68% vs 83%, P=.06], ticarcillin [65% vs 86%, P=.01], mezlocillin [76% vs 95%, P=.01], and ticarcillin-clavulanic acid [88% vs 100%, P=.02]). CONCLUSIONS: The 2 most commonly isolated bacterial pathogens in the SICU (S aureus and P aeruginosa) had significantly different susceptibility patterns compared with the HWA. Surprisingly, E coli isolated in the SICU tended to be more susceptible to penicillin-derivative antibiotics. These data indicate that empiric antibiotic choices in the SICU may be better guided by unit-specific antibiograms.     

Expression and recovery of functional G-protein-coupled receptors using baculovirus expression systems

BACKGROUND: Enterococcus faecium has received increased attention, primarily due to the emergence of vancomycin resistance. The purpose of this investigation was to study the epidemiological characteristics of vancomycin-resistant E faecium (VRE) bacteremia and to determine the clinical impact of vancomycin resistance on the outcome of patients with this infection. METHODS: We retrospectively analyzed the clinical features and outcome of 53 patients with E faecium bacteremia. RESULTS: From January 1992 until December 1995, there were 32 episodes of bacteremia caused by vancomycin-susceptible E faecium (VSE) and 21 caused by VRE. An intra-abdominal site was the most common source of bacteremia in both groups. All of the VRE and 78% of VSE bacteremia cases were nosocomially acquired. Previous administration of vancomycin was associated with VRE bacteremia (P<.001), as were indwelling bladder catheters (P=.01). Fifty-nine percent of the patients with VSE bacteremia survived vs 24% with VRE (P=.009), despite similar severity-of-illness scores. In 62% of the patients with VRE sepsis, death was related to the bacteremia (P=.01). Patients infected with VRE had longer hospitalizations than those with VSE (34.8 vs 16.7 days, respectively) (P=.004), were more likely to be on the medical service (P=.03), and on the average, had hospitalization costs of more than $27,000 per episode than did patients with VSE bloodstream infection ($83,897 vs $56,707, respectively) (P=.04). CONCLUSIONS: Vancomycin-resistant E faecium bacteremia is a complication of prolonged hospitalization in debilitated patients. Vancomycin resistance has a negative impact on survival in patients with E faecium bacteremia and leads to higher health care costs.     

Influences of gender and social class on adolescents' perceptions of health

OBJECTIVE: To explore how gender and social class affect perceptions of health status among 16-year-old adolescents. DESIGN: Cross-sectional survey. SETTING: University psychology laboratory. PARTICIPANS: Fifty upper-middle-class and 48 working-class adolescents stratified by gender. MAIN OUTCOME MEASURES: The general health perceptions (GHP) scale of the Medical Outcomes Survey 36-Item Short Form Health Survey (SF-36). The other self-reported health status domains and 3 measures of different aspects of psychological well-being were included as covariates in analysis of variance models. RESULTS: Upper-middle-class females reported the lowest and upper-middle-class males the highest GHP (76.7 vs 88.4, P=.003). A multivariate regression model (adjusted R2=0.08) revealed significant gender (P=.03) differences in GHP, but not a social class effect, and an interaction effect between gender and class (P=.01). With addition of psychological well-being covariates (P<.001), gender remained significant (P=.04) and a significant portion of the interaction effect (P=.13) was explained. When the self-reported physical health status scales (P<.001) were added to the model (adjusted R2=0.51), gender remained significant (P=.03) and the interaction effect was partially explained (P=.07). CONCLUSIONS: Gender is a crucial factor in understanding the complex relationships between sociostructural inequalities and health differentials. These data suggest that psychological well-being and self-reported physical health status mediate the effects of gender and the gender and social class interaction in explaining variation in GHP. Contrary to the social class gradient hypothesis, upper-middle-class females reported the lowest GHP. These results suggest that the paradigms applicable to early childhood and adulthood may not be appropriate to understand the complex dynamics of adolescence.     

Prolonged beneficial effects of a home-based intervention on unplanned readmissions and mortality among patients with congestive heart failure

BACKGROUND: A single home-based intervention (HBI) applied immediately after hospital discharge in a cohort of "high-risk" patients with congestive heart failure has been shown to decrease numbers of unplanned readmissions plus out-of-hospital deaths during a period of 6 months. The duration of this beneficial effect remains uncertain. METHODS: Hospitalized patients with congestive heart failure who had been randomly assigned to receive either usual care (n=48) or HBI 1 week after discharge (n=49) were subject to an extended follow-up of 18 months. The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths. Secondary end points included total hospital stay, frequency of multiple readmissions, cost of hospital-based care, and total mortality. RESULTS: During 18-month follow-up, HBI patients had fewer unplanned readmissions (64 vs 125; P=.02) and out-of-hospital deaths (2 vs 9; P=.02), representing 1.4+/-1.3 vs 2.7+/-2.8 events per HBI and usual-care patient, respectively (P=.03). The HBI patients also had fewer days of hospitalization (2.5+/-2.7 vs 4.5+/-4.8 per patient; P=.004) and, once readmitted, were less likely to experience 4 or more readmissions (3/31 vs 12/38; P=.03). Hospital-based costs were significantly lower among HBI patients (Aust $5100 vs Aust $10600 per patient; P=.02). Unplanned readmission was positively correlated with 14 days or more of unplanned readmission in the 6 months before study entry (odds ratio [OR], 5.4; P=.006). Positive correlates of death were (1) non-English speaking (OR, 4.9; P=.008), (2) 14 days or more of unplanned readmission in the 6 months before study entry (OR, 4.9; P=.008), and (3) left ventricular ejection fraction of 40% or less (OR, 3.0; P=.03); conversely, assignment to HBI was a negative correlate (OR, 0.3; P=.02). CONCLUSIONS: In this controlled study, among a cohort of high-risk patients with congestive heart failure, beneficial effects of a postdischarge HBI were sustained for at least 18 months, with a significant reduction in unplanned readmissions, total hospital stay, hospital-based costs, and mortality.     

Symptoms of depression in residents: a South Carolina Family Practice Research Consortium study

OBJECTIVES: To test the hypothesis that loss of polymorphonuclear neutrophil tumor necrosis factor alpha (TNF-alpha) receptors during transmigration renders the exudate neutrophil refractory to TNF-alpha-mediated stimulation of apoptosis; and to investigate the surface expression of Fas on both circulating and exudate neutrophils. DESIGN: A prospective cohort study. SETTING: Surgical laboratory of a tertiary care hospital. PARTICIPANTS: Twenty-one healthy human volunteers. INTERVENTIONS: All subjects had circulating neutrophils and exudate neutrophils collected by venipuncture and skin window methods, respectively. MAIN OUTCOME MEASURES: Circulating and exudate neutrophils were incubated in culture medium (1.0x10(6) neutrophils per milliliter) alone or with TNF-alpha (100 ng/mL). Apoptosis was evaluated by flow cytometry (annexin V-fluorescein isothiocyanate and propidium iodide). Tumor necrosis factor alpha-phycoerythrin and anti-human Fas-fluorescein isothiocyanate were used to evaluate neutrophil TNF-alpha receptors and surface expression of Fas. RESULTS: Exudate neutrophils had a significant delay in apoptosis rates when compared with circulating neutrophils. The percentage of neutrophils expressing TNF-alpha receptors was significantly diminished after exudation (80%+/-15% vs 33%+/-9%; P<.001), as was the median channel number of TNF-alpha phycoerythrin fluorescence (8.1+/-1.6 vs 5.2+/-0.5; P=.001). However, the expression of Fas was unchanged after transmigration (percentage positive for Fas: 98.7%+/-0.7% vs 92.8%+/-3.4%, P=.89; Fas antibody-fluorescein isothiocyanate median channel fluorescence: 12.2+/-1.1 vs 13.1+/-1.2; P=.80). Exposure of exudate neutrophils to TNF-alpha failed to increase their rate of apoptosis. CONCLUSIONS: Exudate polymorphonuclear neutrophils are confirmed to have delayed apoptosis. Loss of TNF-alpha receptors during transmigration is necessary for neutrophil survival in the extravascular inflammatory milieu.     

Cryopreserved arterial allografts in the treatment of major vascular infection: a comparison with conventional surgical techniques

OBJECTIVE: Recent findings with cryopreserved heart valve allografts in the treatment of infectious endocarditis suggest that the use of cryopreserved arterial allografts may improve the outcome in patients with vascular infections. METHODS: Seventy-two patients with mycotic aneurysms (n = 29) or infected vascular prostheses (n = 43) of the thoracic (n = 26) or abdominal aorta (n = 46) were treated with in situ repair and extra-anatomic reconstruction using prosthetic material (n = 38) or implantation of a cryopreserved arterial allograft (n = 34). Disease-related survival and survival free of reoperation were assessed. Morbidity, cumulative lengths of intensive care, hospitalization, antibiotic treatment, and costs were calculated per year of follow-up. RESULTS: The use of cryopreserved arterial allografts was superior to conventional surgery in terms of disease-related survival (P =.008), disease-related survival free of reoperation (P =.0001), duration of intensive care per year of follow-up (median 1 vs 11 days; range 1 to 42 vs 2 to 120 days; P =.001), hospitalization (14 vs 30 days; range 7 to 150 vs 15 to 240 days; P =.002), duration of postoperative antibiotic therapy (21 vs 40 days; range 21 to 90 vs 60 to 365 days; P =.002), incidence of complications (24% vs 63%; P =.005), and elimination of infection (91% vs 53%; P =.001). In addition, costs were 40% lower in the group treated by allografts (P =.005). CONCLUSIONS: The use of cryopreserved arterial allografts is a more effective treatment for mycotic aneurysms and infected vascular prostheses than conventional surgical techniques.     

Five-year retention of the classically conditioned eyeblink response in young adult, middle-aged, and older humans

OBJECTIVE: To describe the clinical profile of demyelinating optic neuritis in African Americans. METHODS: The medical records of all patients with a diagnosis of optic neuritis examined at the Neuro-Ophthalmology Unit at the Emory University Eye Center (Emory) and at the Grady Memorial Hospital Eye Clinic (Grady), Atlanta, Ga, between 1989 and 1996 were retrospectively reviewed. PATIENTS: African American and white patients, aged 15 through 55 years, with a single initial episode of acute optic neuritis of unknown or demyelinative origin were included in the study. Study patients included 23 African American patients and 56 white patients examined at Emory as well as 10 African American patients examined at Grady. RESULTS: There were no significant differences among the African American study patients, the white study patients, and patients from the Optic Neuritis Treatment Trial (ONTT) regarding sex (P=.36), age (P=.73), or the presence of disc edema (P=.40), lesions found on magnetic resonance imaging (P=.43), or multiple sclerosis (P=.54) at the onset of an initial episode of optic neuritis. The Emory African American patients presented with more frequent severe visual loss (13 [93%] of 14 patients with a visual acuity < or =20/200) compared with Emory white patients (12 [39%] of 31 patients; P=.002) and with ONTT patients (161 [36%] of 448 patients; P<.001). At follow-up examination of at least 1 year, Emory African American patients had worse vision (9 [39%] of 23 patients <20/40, and 4 [17%] of 23 patients < or =20/200) compared with Emory white patients (5 [8%] of 63 patients <20/40, P=.001; 3 [5%] of 63 patients < or =20/200, P=.08), and with ONTT patients (29 [7%] of 409 patients <20/ 40, P=.0001; 12 [3%] of 409 patients < or =20/200, P=.01). Compared with ONTT patients, the Emory African American patients combined with the Grady African American patients had more frequent severe visual loss (visual acuity < or =20/200) at presentation (18 [90%] of 20 patients vs 161 [36%] of 448 patients; P<.001) and at follow-up examination of at least 1 year (6 [18%] of 33 patients vs 12 [3%] of 409 patients; P=.002). Seven (58%) of 12 African American patients with multiple sclerosis had a "neuromyelitis optica" presentation defined by the presence of neurological deficits limited to the optic nerves and spinal cord. CONCLUSIONS: The African American study patients with a single episode of demyelinating optic neuritis had visual acuities more severely affected at onset and after 1 year of follow-up compared with the white study patients and with patients in the ONTT. In the African American patients, multiple sclerosis occurred most frequently in a "neuromyelitis optica" form.     

Doxycycline is a cost-effective therapy for hospitalized patients with community-acquired pneumonia

BACKGROUND: Doxycycline has a high degree of activity against many common respiratory pathogens and has been used in the outpatient management of lower respiratory tract infections, including pneumonia. OBJECTIVE: To evaluate the efficacy of intravenous doxycycline as empirical treatment in hospitalized patients with mild to moderately severe community-acquired pneumonia. PATIENTS AND METHODS: We conducted a randomized prospective trial to compare the efficacy of intravenous doxycycline with other routinely used antibiotic regimens in 87 patients admitted with the diagnosis of community-acquired pneumonia. Forty-three patients were randomized to receive 100 mg of doxycycline intravenously every 12 hours while 44 patients received other antibiotic(s) (control group). The 2 patient groups were comparable in their clinical and laboratory profiles. RESULTS: The mean+/-SD interval between starting an antibiotic and the clinical response was 2.21+/-2.61 days in the doxycycline group compared with 3.84+/-6.39 days in the control group (P = .001). The mean+/-SD length of hospitalization was 4.14+/-3.08 days in the doxycycline group compared with 6.14+/-6.65 days in the control group (P = .04). The median cost of hospitalization was $5126 in the doxycycline group compared with $6528 in the control group (P = .04). The median cost of antibiotic therapy in the doxycycline-treated patients ($33) was significantly lower than in the control group ($170.90) (P<.001). Doxycycline was as efficacious as the other regimens chosen for the treatment of community-acquired pneumonia. CONCLUSION: Doxycycline is an effective and inexpensive therapy for the empirical treatment of hospitalized patients with mild to moderately severe community-acquired pneumonia.     

Oxidative stress and advancing age: results in healthy centenarians

OBJECTIVE: Our study aims at investigating the degree of oxidative stress in centenarians DESIGN: Indices of oxidative stress (reaction products of malondialdehyde with thiobarbituric acid (TBARS) and lipid hydroperoxides (LPO)), and plasma concentrations of antioxidant defenses (plasma vitamin E and C concentrations and reduced/oxidized glutathione ratio (GSH/GSSG)) were determined. SUBJECTS: Eighty-two subjects volunteered for the study. They were divided into three groups: (1) adults (<50 years of age, n=30); (2) aged subjects (70-99 years, n=30); (3) centenarians (age > or=100 years, n=22). MEASUREMENTS: TBARS and LPO, plasma vitamin E and C concentrations, and plasma GSH/GSSG ratio were determined. Insulin action was assessed by euglycemic hyperinsulinemic glucose clamp. MAIN RESULTS: TBARS (0.44+/-0.07 vs 0.31+/-.05 nmol malondialdehyde/mL plasma, P=.020) and LPO (0.36+/-0.05 vs 0.31+/-.04 micromol/L, P=.050) were lower in centenarians than in aged subjects. In contrast, plasma GSH/GSSG ratio (0.82+/-0.09 vs 1.17+/-.06, P=.010), vitamin C (72.3+/-4.6 vs 59.4+/-3.8 micromol/L P=.010), and vitamin E (29.1+/-2.2 vs 24.4+/-2.3 micromol/L P=.050) concentrations were more elevated in centenarians than in aged subjects. Differences in daily vegetable intake, in fasting plasma glucose and free fatty acid (FFA) concentrations, and in insulin action are significant determinants of degree of oxidative stress. A specific genetic background in centenarians might also provide a possible explanation. CONCLUSIONS: The degree of oxidative stress is lower in healthy centenarians than in aged subjects.     

Insulin sensitivity, insulin action, and fibrinolysis activity in nondiabetic and diabetic obese subjects

Because inconsistencies occur with regard to the relative contribution of insulin to the hypofibrinolysis characteristic of obesity and diabetes, we explored the relationship between insulin and fibrinolysis, assessing both insulin sensitivity and insulin action. Seventeen markedly obese subjects (body mass index [BMI], 34.0+/-1.6 kg/m2; 12 nondiabetic and five diabetic) were studied using the three-step euglycemic-hyperinsulinemic clamp technique. Since the circadian rhythm of the fibrinolytic system may obscure a true effect of insulin, variations in fibrinolysis parameters observed during the glucose clamp were compared with those occurring spontaneously because of the circadian rhythm. Compared with six normal-weight subjects (BMI, 21.0+/-0.9 kg/m2), all obese subjects exhibited basal hyperinsulinism (fasting plasma insulin, 16.0+/-1.4 v 9.8+/-1.3 microU/microL, P < .001; fasting plasma C-peptide, 1.4+/-0.2 v 0.5+/-0.2 ng/mL, P < .001), hypofibrinolysis (euglobulin lysis time [ELT], 378+/-29 v 222+/-31 minutes, P=.01; tissue plasminogen activator [tPA] antigen, 7.8+/-0.9 v 4.2+/-0.5 ng/mL, P=.04; plasminogen activator inhibitor type 1 [PAI-1] activity, 22.2+/-2.5 v3.9+/-0.6 AU/mL, P=.004), and marked insulin resistance (M value, ie, the maximal glucose disposal rate, 9.1+/-0.6 v 18.6+/-0.8 mg/(kg x min), P < .001). The M value correlated inversely with tPA antigen (r=-.46, P=.05). During insulin infusion, values for fibrinolysis parameters decreased, but were not different compared with variations due to the circadian rhythm. In conclusion, our findings together with previously reported data reinforce the idea that chronic hyperinsulinism is linked to hypofibrinolysis, but insulin does not seem to acutely regulate the fibrinolysis system.     

Isolation-stress-induced facilitation of passive avoidance memory in the day-old chick

Left ventricular (LV) midwall shortening (MWS) is subnormal in relation to LV circumferential end-systolic stress (ESS) (ESS-corrected MWS) in many hypertensive patients with normal LV chamber function and predicts subsequent morbidity and mortality. However, little is known of the relations of LV midwall function to demographic and metabolic variables or to arterial geometry. Asymptomatic, unmedicated normotensive (n=366) or hypertensive (n=282) adults were assessed with echocardiography and carotid ultrasound. In normal adults, lower LV MWS and ESS-corrected MWS, an index of LV contractility, were related independently to high total peripheral resistance, high heart rate, and male gender (all P<.00001), lower serum HDL cholesterol (P=.001) and diastolic pressure (P=.003), and for ESS-corrected MWS only, arterial relative wall thickness (RWT, P=.03). Among hypertensive patients, lower values for both midwall function indices were associated independently with higher peripheral resistance (P<.00001), heart rate (P<.00005), body mass index (P<.01), and arterial RWT (P=.04), as well as male gender (P<.0002). In the entire population, lower LV MWS was independently related to higher peripheral resistance, heart rate (both P<.00001), body mass index (P=.0006) and arterial RWT (P=.009); male gender (P<.00001); and lower age (P=.004), diastolic pressure (P=.042), and systolic carotid artery expansion (P=.032). Lower ESS-corrected MWS in the entire population was independently associated with higher peripheral resistance and heart rate (both P<.00001), body mass index (P=.0006), arterial RWT (P=.004); male gender; and lower diastolic pressure (both P<.00001), age (P<.00005), arterial expansion in systole (P=.006), and serum HDL cholesterol levels (P=.04). Among a subset (n=60), ESS-corrected MWS was positively related to apolipoprotein A1 (P=.004) and negatively to hemoglobin A1c (P<.01). Thus, higher LV midwall function is associated with female gender and more favorable profiles of hemodynamics, metabolic pattern, and arterial structure and function.     

Assessing outcomes, costs, and benefits of emerging technology for minimally invasive saphenous vein in situ distal arterial bypasses

BACKGROUND: Instrumentation for a minimally invasive angioscopic in situ peripheral arterial bypass (MIAB) with catheter-directed side-branch occlusion has recently been approved for use. Despite the attractiveness of this approach (2 short incisions), benefits such as lower morbidity and shorter hospitalizations remain undocumented. To justify wide acceptance, minimally invasive surgical techniques must match conventional procedures in durability and cost while enhancing patient comfort. Often such comparisons are difficult during the implementation phase of a new procedure. OBJECTIVE: To compare the outcomes of the MIAB procedures with a concurrent group of patients undergoing conventional in situ bypass procedures. DESIGN: Retrospective review. SETTING: University medical center. PATIENT: The first 20 consecutive MIAB procedures in 19 patients performed between August 1, 1995, and July 31, 1997, were compared with 19 contemporaneous consecutive conventional in situ bypass procedures performed at the same institution. MAIN OUTCOME MEASURES: Operative time, postoperative length of stay, hospital costs, complications, primary assisted and secondary patency, limb salvage, and survival. RESULTS: The patient groups were comparable with respect to age, sex, incidence of smoking, coronary artery disease, hypertension, diabetes, renal failure, cerebrovascular disease, indication, and distal anastomosis level. The median operative time was significantly greater for the MIAB group (6.6 hours vs 5.7 hours; P=.009), and intraoperative completion arteriography more frequently showed retained arteriovenous fistulas in the MIAB group (55% vs 21%; P=.05). The median postoperative length of stay and total cost were 6.5 days and $18,000 for the MIAB group and 8 days and $27,800 for the conventional group (P > or = .05). There were no significant differences in major complications (10% in the MIAB group vs 11% in the conventional group), wound complications (10% vs 11%, respectively), primary assisted patency at 1 year (68%+/-11% vs 78%+/-10%, respectively), secondary patency at 1 year (79%+/-10% vs 88%+/-8%, respectively), limb salvage at 1 year (85%+/-10% vs 94%+/-6%, respectively), or patient survival at 1 year (89%+/-8% vs 61%+/-13%, respectively). CONCLUSION: Patients undergoing the MIAB procedure avoided lengthy vein exposure incisions without sacrificing short-term results. There was a trend toward decreased hospital stay and cost, which may be further realized as the clinical experience broadens. Although longer follow-up and larger cohorts will always be required to define durability, immediate access to outcomes and costs on small numbers of patients facilitates the early assessment of emerging technology.     

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.     

Effect of psychotherapy on the course of Crohn''s disease. Results of the German prospective multicenter psychotherapy treatment study on Crohn''s disease. German Study Group on Psychosocial Intervention in Crohn''s Disease

OBJECTIVES: To determine whether a combination of ciprofloxacin hydrochloride and metronidazole hydrochloride would be as effective or more effective than a combination of gentamicin sulfate and metronidazole hydrochloride for preventing infection in patients with penetrating abdominal trauma, to evaluate the factors associated with increased risk of infection, and to determine the serum peak and trough levels of gentamicin with the dosage regimen of 2.5 mg/kg every 12 hours. DESIGN: Randomized double-blind study. SETTING: Level I trauma center. PATIENTS: Eighty-four patients with penetrating intra-abdominal injuries (gunshot wound, 69; stab wound, 15) thought to require laparotomy. INTERVENTIONS: The patients were randomized during treatment in the emergency department to be given a combination of ciprofloxacin hydrochloride, 400 mg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours, or a combination of gentamicin sulfate, 2.5 mg/kg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours. RESULTS: Of 68 patients with intra-abdominal injuries who could be observed for at least 48 hours after laparotomy, posttraumatic infections developed in 12 (18%), and nosocomial infections developed in 6 (9%). The incidence of posttraumatic infections in patients who were given gentamicin and metronidazole (5/33 [15%]) was not significantly lower than the incidence in patients who were given ciprofloxacin and metronidazole (7 of 35 [20%]; P=.75). The presence of any infection increased the mean+/-SD length of hospital stay from 8.7+/-3.5 days to 23.3+/-10.9 days and increased the mean+/-SD hospital charges from $24 507+/-$9860 to $104920+/-$49083 (P<.001). Univariate analysis showed the factors most significantly associated with infection were as follows: (1) the use of blood transfusions (P<.001), (2) the penetrating abdominal trauma index of 35 or more (P<.002), (3) injury to the colon requiring a colostomy (P=.004), and (4) a trauma score of less than 12 (P<.02). Multivariate analysis showed the only significant factor was the receipt of blood transfusions (F=10.165; P<.005). CONCLUSIONS: Ciprofloxacin and gentamicin, each in combination with metronidazole, were equivalent in their ability to prevent infections after penetrating abdominal trauma; other factors, especially the receipt of blood transfusions, had much more effect on the incidence of infection. Infection greatly increases the length of hospital stay and hospital charges. The use of an increased dosing regimen of 2.5 mg/kg every 12 hours of gentamicin sulfate was effective at obtaining a therapeutic peak serum concentration.     

The tocolytic effect of catecholamines in the gravid rat uterus

OBJECTIVE: The aim of the study was to determine the most cost-effective delivery management of vertex and nonvertex twin pair gestations. STUDY DESIGN: Two hundred sixty-six consecutive twin gestations were followed up prospectively in a special antepartum Twins Clinic directed by the Maternal-Fetal Medicine Division. Maternal demographic, obstetric, and neonatal data were compiled prospectively. Information regarding 84 vertex and nonvertex twin pair gestations was extracted for review. Comparison groups included 41 twin pairs managed by spontaneous vaginal delivery and breech extraction (group A), 19 twin pairs managed by spontaneous vaginal delivery and external cephalic version (group B), and 24 twin pairs managed by primary cesarean delivery (group C). In-hospital financial data were retrieved and adjusted for inflation to 1996 constant dollars (data from a single institution allow comparison of charges). The Kruskal-Wallis chi2 test, the Fisher exact test, and analysis of variance were used for statistical analysis. RESULTS: The 3 groups did not differ with respect to maternal demographics, medical complications, gestational age, birth weight, fetal sex, or intrauterine growth restriction. Maternal and neonatal hospital charges were both significantly lower (P = .01 and P = .0001, respectively) in the breech extraction group A ($5890 +/- $2304 and $3526 +/- $5017, respectively) than in either group B ($8638 +/- $4175 and $11,754 +/- $15,457, respectively) or group C ($7,608 +/- $3,256 and $36,994 +/- $54,318, respectively). Although maternal morbidity was similar among the 3 groups, length of stay was shorter for mothers in group A. The infants delivered by spontaneous vaginal delivery and breech extraction (group A) had significantly lower rates of pulmonary disease (7% vs 24% vs 31% for groups A, B, and C, respectively; P = .002) and neonatal infectious disease (1% vs 0% vs 16%; P = .0005). These infants required the use of a ventilator less frequently (5% vs 12% vs 24%; P = .01), were more likely to be admitted to the normal newborn nursery (71% vs 51% vs 50%; P = .0001), and had a significantly shorter length of hospitalization (4.8 vs 12.4 vs 17.8 days; P = .0001). CONCLUSIONS: There is no medical consensus regarding delivery management for vertex and nonvertex presenting twin pairs. When hospital charges are examined with clinical data, however, breech extraction of the nonvertex second twin is the most cost-effective delivery management strategy.     

Histologic localization of indocyanine green dye in aging primate and human ocular tissues with clinical angiographic correlation

OBJECTIVE: Because C5a induces tissue injury by activating polymorphonuclear leukocytes, the hypothesis was that inhibition of C5a activity would reduce cardioplegia-related injury. METHODS: Pigs were placed on cardiopulmonary bypass. The hearts were arrested for 1 hour with hyperkalemic cardioplegia. Pigs were then separated from bypass, and the hearts were reperfused for 2 hours. Anti-porcine C5a monoclonal antibody (1.6 mg/kg, intravenously; n = 6) was administered 20 minutes before the onset of cardiopulmonary bypass. Six pigs received saline solution vehicle. Reactivity of coronary arterioles was studied in vitro with videomicroscopy. Microvessels from uninstrumented pigs served as controls for vascular studies. RESULTS: Endothelium-dependent relaxation to adenosine diphosphate (percent relaxation of precontraction) was reduced after cardioplegic reperfusion (63% +/- 14% vs 77% +/- 10% in control at 10 micromol/L; P =.01). This impairment in endothelium-dependent relaxation was improved with anti-porcine C5a monoclonal antibody (80% +/- 22%; P =.01 vs saline solution), as was the impaired endothelium-dependent relaxation to clonidine (64% +/- 12% control; 26% +/- 17% saline solution; 55% +/- 24% anti-porcine C5a monoclonal antibody at 10 micromol/L; P =.01 saline solution vs control or anti-porcine C5a monoclonal antibody). Myeloperoxidase activity was significantly decreased (0.2 +/- 0.2 units/g protein; P =.04) in the anti-porcine C5a monoclonal antibody group compared with 5.2 +/- 2.7 in the saline solution group. CH50 2 hours after bypass was not statistically different (0.57 +/- 0.41 unit and 0.65 +/- 0.41 unit, respectively) between the anti-porcine C5a monoclonal antibody and saline solution groups. Despite less myocardial polymorphonuclear leukocyte infiltration after C5a inhibition, maximum rate of rise of left ventricular pressure, percent segmental shortening, and blood flow through the left anterior descending coronary artery were similar in the anti-porcine C5a monoclonal antibody and saline solution groups. CONCLUSIONS: Inhibition of C5a limits neutrophil-mediated impairment of endothelium-dependent relaxation after cardiopulmonary bypass and cardioplegic reperfusion, but it has no effect on short-term myocardial functional preservation.     

Plasma levels of activated protein C in healthy subjects and patients with previous venous thromboembolism: relationships with plasma homocysteine levels

BACKGROUND/PURPOSE: In the pediatric population, appendicitis remains the most common surgical emergency encountered. The purpose of this study was to determine the impact of an evidence-based clinical pathway for acute appendicitis on patient care as well as hospital and home care costs at the authors' pediatric institution. METHODS: A prospective evaluation was conducted of an appendicitis clinical pathway (June 1996 through November 1996) compared with historical control patients (June 1994 through November 1994) not cared for by the pathway. RESULTS: Data (average +/- SD) for 120 pathway (P) patients were compared with 122 control (C) patients. Age (11.5 +/- 3.6 years for C v 11.2 +/- 3.9 years for P), rates of negative appendectomy (12.3% for C v 9.2% for P) and perforation (26.2% for C v 18.3% for P) were similar. Pathway patients with nonperforated appendicitis were more often discharged from the hospital within 24 hours (48% for C v 67% for P; P = .014) with lower hospital costs ($4,095 +/- $1,280 for C v $3,638 +/- $1,633 for P; P = .001). Pathway patients with perforated appendicitis had shorter hospitalization (185.2 +/- 59 hours for C v 113 +/- 44 hours for P; P = .0001) and lower hospital costs ($11,175 +/- $3,893 for C v $7,823 +/- $2,366 for P; P = .0001). CONCLUSION: An evidence-based appendicitis pathway decreased duration of hospitalization and cost without adversely affecting diagnosis or therapy. Clinical pathways for surgical diagnoses may prove useful as a means to minimize costs without compromising patient care.     

Lack of interaction between glipizide and co-trimoxazole

To identify the effects of co-trimoxazole on the elimination and disposition kinetics of glipizide, eight healthy male volunteers were studied in an unblinded, randomized, cross-over trial with two phases (no treatment or co-trimoxazole 160/800 mg twice a day). During each phase, subjects were treated at home for 7 days with one of the treatment regimens, followed by a 24-hour hospitalization for a single-dose challenge with 10-mg oral glipizide and detailed blood studies. A 7-day washout period was interspersed between the phases. Pharmacokinetic and pharmacodynamic parameters were determined and compared using the Student's t-test for paired observations. Glipizide area under the curve (AUC), clearance, and half life for treatment and control phases were 5758 +/- 1874 versus 5176 +/- 1505 micrograms/L/hour (P = .21), 0.41 +/- 0.15 versus 0.45 +/- 0.14 mL/min/kg (P = .27), and 5.13 +/- 2.10 versus 3.95 +/- 1.37 hours (P = .04), respectively. Twenty-four-hour glucose AUCs for treatment and control phases were 112.24 +/- 8.76 versus 114.86 +/- 11.98 mmol/L/hour (P = .55), respectively. The only parameter reaching statistical significance was glipizide half life, but the difference is of doubtful clinical significance because of difficulty in identifying a clear elimination phase in several subjects. It is concluded that co-trimoxazole administration did not significantly alter glipizide disposition and elimination kinetics in this study population.     

Predictors of mortality in the prospective Dubbo study of Australian elderly

BACKGROUND: A study was undertaken to examine the relationship between first-contact care, an essential feature of primary care, and expenditures for frequent ambulatory episodes of care in a nationally representative sample. METHODS: A nonconcurrent cohort study was conducted using data from the 1987 National Medical Expenditure Survey. Ambulatory claims data of respondents with an identified primary care source were used to develop 20,282 episodes of care for 24 preventive and acute illness conditions. The study examined the relationship of first-contact care, defined as the use of an identified primary care source for the first visit in an episode, and ambulatory episode-of-care expenditures. RESULTS: Episodes that began with visits to an individual's primary care clinician, as opposed to other sources of care, were associated with reductions in expenditures of 53% overall ($63 vs 134, P<.001), 62% for acute illnesses ($62 vs $164, P<.001), and 20 for preventive care ($64 vs $80, P<.001). For 23 of the 24 health problems studied, first-contact care was associated with reductions in expenditures. Multivariate regression analyses that controlled for sociodemographic characteristics, health status, case-mix, length of the episode, and number of visits to the emergency room did not substantively alter these results. CONCLUSIONS: First-contact care was associated with reductions in ambulatory episode-of-care expenditures of over 50% in a nationally representative sample. These findings suggest that systems of care may reduce ambulatory expenditures.