Nighttime administration of high-dose, sustained-release melatonin does not decrease nocturnal blood pressure in African-American patients: Results from a preliminary randomized, crossover trial.

OBJECTIVES: This preliminary study tested whether a high-dose, sustained-release form of melatonin reduced 24-hour blood pressure in African-Americans. DESIGN: Randomized, placebo-controlled, crossover pilot study of 40 self-defined African-American patients with essential hypertension. SETTINGS/LOCATION: Urban, academic medical center and associated outpatient clinics. INTERVENTIONS: Patients ingested either melatonin (high dose [24 mg], sustained-release formulation] or placebo in randomized order over a 4-week period. OUTCOME MEASURES: Mean nighttime and daytime systolic and diastolic blood pressures, as measured with 24-hour ambulatory blood pressure monitors. The primary outcome was mean nighttime systolic blood pressure. RESULTS: There were no statistically differences between melatonin and placebo conditions in mean nighttime or daytime systolic or diastolic blood pressures. CONCLUSIONS: In contrast with studies in other populations, this preliminary study showed that nighttime dosing of continuous-release melatonin had no significant effect on nocturnal blood pressure in African Americans with essential hypertension when compared to placebo.

A multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis c: pretreatment stratification by viral burden and genotype.

OBJECTIVES: The aim of this study was to determine prospectively whether an intensive regimen of daily, high-dose interferon would improve the response rate for the treatment of chronic hepatitis C in patients with unfavorable virological characteristics. METHODS: A total of 104 patients with chronic hepatitis C were randomized at eight centers to receive interferon alfa-2b at a dose of 5 million units (MU) daily or 3 MU t.i.w. for a period of 24 wk. Patients were prospectively randomized by low or high viral burden and stratified by genotype. HCV RNA was measured by quantitative polymerase chain reaction, and response rates were compared between the dosage regimens. RESULTS: HCV RNA levels dropped more rapidly to lower levels in the group treated with 5 MU daily. In this group, the initial virological response (IR) at wk 12 and the end-of-treatment response (ETR) at wk 24 were double that of patients treated with standard interferon (66% vs 33% and 48% vs 24%, p < 0.01). Sustained response rates were low for both dose groups (14% vs 4%, p = 0.08). Genotype-related differences in initial response rates were present in the standard dose group (63% non-1 genotype vs 24% genotype 1; p = 0.005) but not in those treated with 5 MU daily (66% vs 67%, p = NS). Using multivariate analysis, only the interferon dose was associated with IR and ETR (p = 0.002). CONCLUSIONS: Daily, high dose interferon rapidly dropped HCV RNA and increased initial and end-of-treatment response rates when compared to t.i.w. regimens. This effect, independent of viral burden and genotype, suggests that patients with unfavorable viral characteristics might benefit from an intensive regimen that promotes rapid viral clearance. These data support further study of the use of high-dose induction regimens. However, improvements in sustained response rates will require additional therapeutic maneuvers such as prolonged therapy or the adjunctive use of ribavirin.

Keratinocyte growth factor enhances glutathione redox state in rat intestinal mucosa during nutritional repletion.

Malnutrition decreases tissue levels of glutathione (GSH), a major endogenous antioxidant that detoxifies reactive oxygen species and promotes cell growth. This study determined the effects of the gut trophic peptide keratinocyte growth factor (KGF) on intestinal mucosal GSH concentrations and redox state in malnourished rats. Adult rats were food-deprived for 3 d, then consumed food ad libitum or 25% of ad libitum intake for 3 d with daily intraperitoneal administration of saline or KGF (5 mg.kg-1.d-1). Mucosal GSH and glutathione disulfide (GSSG) concentrations, crypt depth and total mucosal height were measured in the jejunum, ileum and colon. In the 25% of ad libitum-refed, saline-treated group, mucosal GSH was lower in all gut tissues (42% in jejunum, 38% in ileum, and 57% in colon), and the GSH/GSSG ratio was lower in the jejunum and ileum compared to that in the ad libitum-refed controls. KGF treatment with ad libitum refeeding increased GSH/GSSG in the jejunum, ileum and colon. Furthermore, in 25% of ad libitum refeeding, KGF normalized jejunal, ileal and colonic mucosal GSH content and significantly increased the mucosal GSH/GSSG ratio relative to rats treated with saline. Increased crypt depth and total mucosal height induced by KGF and feeding could be explained in part by increased mucosal GSH content. KGF treatment improved gut mucosal glutathione redox state in malnourished, refed rats. These data provide evidence that gut trophic hormones and food intake may independently support gut mucosal glutathione antioxidant capacity during nutritional repletion.

Prophylactic angioplasty reduces thrombosis in virgin ePTFE arteriovenous dialysis grafts with greater than 50% stenosis: subset analysis of a prospectively randomized study.

PURPOSE: To determine if prophylactic percutaneous transluminal balloon angioplasty (PTA) can extend patency in functioning virgin ePTFE arteriovenous hemodialysis grafts. MATERIALS AND METHODS: The results of a prospectively randomized study of 64 patients with greater than 50% stenosis of functioning ePTFE arteriovenous hemodialysis grafts who were blindly assigned to be treated with PTA (treatment group) or observed without treatment (control group) were subjected to statistical subset analysis. Within this group were 21 patients (virgins) who had never undergone surgery, PTA, or thrombolysis. Eight patients had been assigned to the treatment group and 13 to the control group. The virgin groups were well matched as to age, sex, and risk factors. The virgin treatment group versus virgin control group had 1.63 versus 1.46 stenoses per patient and 61.3% versus 63.3% average percentage stenosis per lesion, respectively. Stenoses were treated with PTA 27 times (average, 3.4 per patient) in the virgin treatment group. Primary study patency began at the time of randomization and ended with graft thrombosis or nonfunction. RESULTS: Among the 32 patients randomized to treatment with PTA, study patency was significantly increased (P > .0001) and the incidence of graft thrombosis significantly decreased (P = .0151) in the eight-patient virgin subset when compared with the 24-patient nonvirgin subset of the treatment group. During the 81.3 patient-dialysis-year study period, patency in the virgin-treatment versus virgin-control groups, respectively, was terminated by thrombosis in two versus nine, by death in two versus two, and cadaveric renal transplant in one versus zero. There was a statistically significant prolongation of study patency (P = .0349) and a reduction of graft thromboses, 0.10 versus 0.44 thromboses per patient-dialysis year, in the virgin-treatment group compared to the virgin-control group. CONCLUSION: Patency after PTA of ePTFE hemodialysis grafts is significantly affected by previous interventions. Prophylactic PTA of stenoses greater than 50% in functioning virgin ePTFE arteriovenous hemodialysis grafts can significantly extend their patency. PTA should be included as an important treatment option in this patient population.

Evaluation of staging lymphadenectomy in prostate cancer.

OBJECTIVES: To prospectively evaluate a clinical algorithm that predicts nodal status in patients with prostate cancer and to assess the impact on the outcome. METHODS: Between September 1988 and December 1994, 192 patients with organ-confined prostate cancer and considered surgical candidates for radical perineal prostatectomy (RPP) were stratified using the algorithm: prostate-specific antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a or lower. Patients failing any of these criteria were placed in the high-risk group and underwent a pelvic lymphadenectomy. Patients who satisfied all the criteria were placed in the low-risk group and underwent RPP without evaluation of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65) underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) without use of the algorithm and were used as a control group. Patients were monitored for at least 24 months. RESULTS: In the RPP group, 177 patients were considered low risk according to the algorithm and were not offered staging lymphadenectomy before surgery, whereas 15 patients were categorized as high risk for metastasis and underwent staging lymphadenectomy. In the RRP and lymphadenectomy group, 41 patients were considered at low risk and 24 at high risk of disease spread according to the algorithm. In the RPP group, low-risk patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8. Similarly, high-risk patients with negative lymph nodes in both groups had a similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic regression analysis showed that PSA was the most significant predictor for disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P = 0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated that Gleason score and clinical stage did not add to the prediction of recurrence over PSA alone. CONCLUSIONS: Staging lymphadenectomy can be omitted in low-risk patients without deleterious effects on the outcome as measured by PSA recurrence.

Cost efficacy of duplex surveillance and prophylactic angioplasty of arteriovenous ePTFE grafts.

Poor patency of arteriovenous ePTFE grafts remains a major clinical problem. Prophylactic balloon angioplasty of stenoses has been claimed to prolong graft patency and has been widely introduced into practice. In this manuscript we report the cost incurred in application of such a program involving graft surveillance and prophylactic angioplasty of ePTFE graft stenoses >50% diameter. All patients in a single dialysis unit with ePTFE bridge grafts were subject to a surveillance duplex ultrasound and those with a perigraft stenosis of >50% then underwent angiography. Those patients confirmed to have a stenosis >50% within the graft, were randomized to prophylactic percutaneous transluminal angioplasty (PTA) versus no intervention (observation). Patients were followed every 3 months with ultrasound and those in the treatment group with recurrent stenosis (>50%) were subject to repeat PTA. The outcome was thrombosis. Relevant charges were considered to be: initial duplex screening of the entire ePTFE dialysis group; professional and technical fees for angiography and angioplasty; follow-up duplex scanning; repeat angioplasty; and costs of lytic therapy for an intraprocedure lysis. In the treatment and observation group the 6-month patencies were 69% +/- 7% and 70% +/- 7%, respectively. Twelve-month patencies for the treatment and observation groups were 51% +/- 6% and 47% +/- 4%. There was no significant difference between these two groups (p = 0.97), with an 80% confidence limit for detection of a difference >20%. Cost for duplex screening of all patients in the dialysis unit with ePTFE grafts was $40,440 (@ $337 each x 120 patients). Total charges for initial angiography was $178. Angioplasty charges were $143,040. Cost of the follow-up duplex ultrasound scanning in the treated group was $32,352. Charges for repeat angiograms in those with recurrent stenoses were $83,682 (professional fee $1733 + $229; technical fee + $820; equipment charges x 32 x 0.94). One patient required urokinase therapy for an occlusion following PTA. The overall charge for treating the 32 patients in the treatment arm of this study was $440,834, there was net improvement in patency. A policy of generic graft surveillance and prophylactic is expensive and does not lead to improved patency. Until an effective intervention is defined by prospective randomized trial, surveillance duplex scanning cannot be justified.

Prophylactic balloon angioplasty fails to prolong the patency of expanded polytetrafluoroethylene arteriovenous grafts: results of a prospective randomized study.

PURPOSE: Maintenance of hemodialysis access grafts represents an enormous social and clinical problem. Current grafts and graft salvage techniques are inadequate. Consequently, there has been increasing interest in the use of minimally invasive catheter techniques to prophylactically treat stenoses in functioning arteriovenous grafts. Prophylactic balloon angioplasty has been widely suggested as prolonging assisted primary patency. We have performed a prospective randomized trial to compare patients who underwent percutaneous transluminal angioplasty (PTA) for graft stenoses > 50% with a control group that received no intervention. Our hypothesis was that to be efficacious a minimal benefit of 20% prolongation in patency would be necessary. METHODS: Color flow duplex scanning was used to detect > 50% stenoses in functioning expanded polytetrafluoroethylene grafts. Patients were then subjected to confirmatory angiographic evaluation. Those who had angiographic stenoses > 50% were randomized to balloon angioplasty or observation. Patients were followed-up with duplex scanning every 2 months. Statistical analysis was performed using the Kaplan-Meier technique. Although demographically the patient groups were well matched, there were more prior interventions and concurrent central stenoses in the treatment group. Outcomes were graft thrombosis, graft dysfunction that precluded dialysis, and six or more PTA procedures within 18 months. RESULTS: In the treatment and observation groups, the 6-month patency rates were 69% +/- 7% and 70% +/- 7%, respectively. The 12-month patency rates for the treatment and observation groups were 51% +/- 6% and 47% +/- 4%, respectively. There was no significant difference between these two groups (p = 0.97), with an 80% confidence limit for detection of a difference greater than 20%. CONCLUSIONS: This study demonstrates that a generic approach of PTA to treat all polytetrafluoroethylene grafts with stenoses > 50% does not prolong patency and cannot be supported.

Nonsteroidal antiinflammatory drugs are associated with both upper and lower gastrointestinal bleeding.

To evaluate the association between nonsteroidal antiinflammatory drug (NSAID) use and upper gastrointestinal bleeding (UGIB) and lower gastrointestinal bleeding (LGIB), we performed a prospective case-control study at a large inner-city hospital over a 28-month period evaluating 461 consecutive patients hospitalized for UGIB and 105 with LGIB. During the same period, 1895 in-patients evaluated by our gastroenterology consultative service served as controls. At the time of initial evaluation, all patients were asked about the use of any prescription or over-the-counter NSAID product within one week of admission. Endoscopic examination was performed in most patients with bleeding. NSAID use was almost equivalent in patients with UGIB and LGIB (60%) and significantly greater than controls [34%; P < 0.001; odds ratio (OR) 3.0; 95% CI, 2.4-3.6]. The age, race, and gender adjusted risk for LGIB associated with NSAID use was significant [adjusted OR (AOR) 2.6; 95% CI 1.7-3.9], although less than UGIB (AOR 3.2; P = 0.34). The risk associated with diverticular bleeding (N = 53, AOR 3.4; 95% CI 1.9-6.2) was higher than duodenal ulcer bleeding although not significantly (N = 97, AOR 3.0). We conclude that NSAID use is strongly associated with LGIB and from lesions not considered associated with mucosal ulceration such as diverticulosis.

Stereotactic radiosurgery of malignant and benign intracranial lesions utilizing a patient rotator.

This study examines the characteristics of the patient groups, treatment parameters, and results of therapy for 126 intracranial lesions treated with stereotactic radiosurgery utilizing a "patient rotator" and a linear accelerator. A retrospective review was conducted and data on 122 patients (21 patients with arteriovenous malformations-AVMs, 40 patients with 41 metastatic tumors, 24 patients with malignant gliomas and 37 patients with other benign lesions) were analyzed. Clinical and radiographic response was obtained from chart review and/or telephone follow-up. The average follow-up was 12.1, 13.0, 5.7, and 23.1 months in patients with AVMs, malignant gliomas, metastases, and other lesions, respectively. Median survival times (MST) of the metastatic and glioma group were 9 and 38 months, respectively. Complete or partial radiographic response at follow-up was seen in 62.5% of AVM patients, 33.3% of patients with metastases, 11.8% of patients with malignant gliomas, and 19.3% of patients with other lesions. (1) Local control of brain metastases and benign intracranial lesions can be obtained with single dose stereotactic radiosurgery. (2) The MST and local control rate for metastatic disease obtained are comparable with those in the literature. (3) The patient rotator method for stereotactic radiosurgery is an effective tool for treating selected intracranial lesions.

Long-term use of nonsteroidal antiinflammatory drugs and other chemopreventors and risk of subsequent colorectal neoplasia.

Our objective was to study the relationship between dispensed aspirin, nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs), steroidal antiinflammatory drugs (SAIDs), acetaminophen, calcium, psyllium, and multivitamin preparations and the risk for subsequent colorectal adenoma and adenocarcinoma. The design was a case-control study. The patient population was from a large municipal teaching hospital in Atlanta, Georgia. In logistic regression models, the risk of colorectal adenoma or adenocarcinoma decreased in the first two years of continuous NSAID use in a linear, time-dependent manner. The risk of colorectal neoplasia after two years of continuous NSAID use was reduced significantly (P < 0.01) as compared to nonusers. Risk reduction appeared greater for adenocarcinoma than adenoma. The use of SAIDs, calcium, multivitamins, and psyllium, as prescribed to our patient population during the mean six-year study period, conferred no measurable risk reduction. These results suggest that in prospective chemoprevention trials, a significant risk reduction can be expected after only two years of aspirin use, in doses similar to those recommended for the prevention of cardiovascular disease, or nonaspirin NSAIDs [correction of nonaspirin. NSAIDs], in doses commonly prescribed for the management of musculoskeletal pain. The results also imply that any short-term reduction in the incidence of colorectal adenoma detected in a phase II trial would underestimate the chemopreventive effect of NSAIDs on the risk of adenocarcinoma.

Elevated concentrations of dopamine sulfate in plasma of cocaine abusers.

This study investigated the effect of cocaine abuse on peripheral catecholamines. Specifically, we measured the concentration of free dopamine, dopamine sulfate, free norepinephrine, norepinephrine sulfate, free epinephrine and epinephrine sulfate in plasma samples obtained from the blood of a group of patients with cocaine addiction (N = 15). The concentrations of free and sulfoconjugated catecholamines in plasma were measured by a radioenzymatic technique. The results of this study revealed significant (P < 0.0001) elevation in plasma dopamine sulfate (8926 +/- 1204 pg/mL) of cocaine addicts upon admission to an in-patient treatment facility when compared with the level of this dopamine metabolite in plasma of control subjects (2356 +/- 121 pg/mL). Furthermore, there was a significant (P < 0.0001) relationship between elevation in plasma dopamine sulfate levels and severity of cocaine use among these patients, and in the majority of cases the plasma levels of dopamine sulfate declined appreciably in time with abstinence from cocaine. In contrast, no appreciable difference was observed in the concentrations of either free or sulfate-conjugated norepinephrine and epinephrine in plasma of cocaine addicts as compared with controls. Differences in plasma dopamine sulfate among these patients versus controls may be interpreted as a reflection of activation of extracellular dopamine metabolism associated with chronic cocaine exposure in humans.

EEG in liver transplantation: visual and computerized analysis.

We prospectively evaluated 40 liver transplant candidates (including 28 recipients) with visually scored or computerized EEG. As expected, EEG frequencies rose significantly after successful transplant (P < 0.01). For all subjects, but especially for the transplant recipients, higher frequencies on computerized EEG at baseline had a strong association with survival at 18 months (P < 0.001). A logistic regression model allowed estimation of the odds for survival and indicated less than 50% long-term survival with central-occipital mean frequencies below 7.6 c/sec. Visual EEG scores closely paralleled the quantitative results, but only the latter were amenable to formal statistical analysis. EEG had much stronger predictive value for survival than serum albumin, although albumin improved more significantly in the months after transplantation.

Quality-of-life changes and psychiatric and neurocognitive outcome after heart and liver transplantation.

A prospective study compared psychiatric, neurocognitive, and quality-of-life changes of heart and liver transplant patients. The 51 heart and 61 liver transplant candidates and recipients completed the Beck depression inventory (BDI), state-trait anxiety inventory (STAI), sickness impact profile (SIP), mini-mental state (MMS), California verbal learning test (CVLT), Wisconsin card sorting test (WCST), trailmaking test (TMT), and the impact message inventory (IMI). Data were gathered before transplant and at 3-month intervals for up to 1 year after transplant. Psychometric tests scores were correlated with electroencephalograms for the liver patients. Both groups showed significant improvements after transplant in neurocognitive functioning, depressive symptoms, and quality of life.

A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. II. Short-term effects on nitrogen metabolism, metabolic balance, and nutrition.

Patients with moderately severe or severe alcoholic hepatitis, described in a companion paper in this issue, had serial studies of energy and protein metabolism and elemental balances before and during treatment for 21 days with one of four randomly assigned regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 liters of 3.5% crystalline amino acids in 5% dextrose given by peripheral vein (PPN) plus standard therapy; and 4) a combination of the other three treatments. Dietary and intravenous intakes and weights were recorded daily, and weekly averages were calculated. Anthropometric measurements and blood studies were done weekly; blood studies included white blood cell counts and differentials, serum prealbumin, transferrin, and total protein and plasma aminograms. Four-days complete balance studies and measures of 15N,1-13C-leucine metabolism also were performed at baseline and after the treatment period. Major findings were as follows: a) Intakes of total calories and protein were significantly higher in PPN-treated than in other groups. b) All patients had positive elemental balances, both at baseline and at the end of the treatment period. However, those treated with PPN (with or without oxandrolone) had higher positive balances of nitrogen, potassium, phosphorus, and magnesium, indicating improvement in lean body mass. c) Anthropometric measurements showed no significant changes, but measures of the visceral protein compartment (serum prealbumin, transferrin, total protein, total lymphocyte count) improved significantly with time. For most of these variables, increases were significantly greater in those treated with PPN with or without oxandrolone than in the other groups. However, for prealbumin, the increase was greatest in the oxandrolone-treated group d) PPN treatment produced dramatic increases in levels of branched-chain amino acids and improvement in the ratio of plasma branched chain to aromatic amino acids. Other treatments had no effect on plasma aminograms. e) Metabolism of 15N,1-13C-leucine was normal and was not affected significantly by treatment. Therapy with PPN and/or oxandrolone was tolerated well. We conclude that PPN has favorable effects on energy and protein metabolism in florid alcoholic hepatitis; oxandrolone has lesser effects, although it may exert some additional action and particularly increases serum prealbumin levels. The results support the use of nutritional supplementation in therapy of moderately severe or severe alcoholic hepatitis.

Model of spontaneous obesity in aging male Wistar rats.

We analyzed retrospectively data from 148 chow-fed male Wistar rats killed between the age of 6 wk and 2 yr while varying in body weight from 136 to 917 g. The purpose of this study was to clarify the relationship of body weight and body lipid content with the composition and cellularity of the epididymal and retroperitoneal fat depots. A positive linear association was found between body weight and body water or fat-free dry residue, whereas total body lipid exhibited a curvilinear relationship with body weight. The weight of the epididymal pads was linearly related to body weight but not to body lipid. In contrast, retroperitoneal pad weight was exponentially related to body weight and paralleled total body lipid. A strong linear correlation was found between total body lipid and weight (r = 0.959) or depot lipid content (r = 0.967) of the retroperitoneal fat pads. In this rat model of aging and spontaneous obesity, significant regional differences exist in adipose depot composition and cellularity. A practical outcome of this study is a simple and accurate prediction of body lipid content from the gravimetric determination of the retroperitoneal fat depots.

Analysis of residents' performances on the In-Training Examination of the American Board of Anesthesiology-American Society of Anesthesiologists.

An analysis of the results of the In-Training Examination of the American Board of Anesthesiology-American Society of Anesthesiologists has been developed using a new question-categorization method and a new form of calculation, the resident index score. Resident index scores permit comparison of the performance of any program's residents with the performance of all U.S. residents who took the examination. This study analyzed examination results from eight residency programs for a five-year period, 1983-1987. Statistically significant differences in the residents' performances were found both within and among the residency programs during this time. Areas of educational strength and weakness were identified by levels of training for each program. The analyses of the individual programs' results were provided to the respective program directors on a confidential basis, and have been used to change curriculum content, modify lectures for residents, and provide structured review for residents. Similar analyses can be provided as a service to other residency program directors.

Statistical inference for infectious diseases. Risk-specific household and community transmission parameters.

A statistical model is presented for the analysis of infectious disease data from family studies in the community. The model partitions the sources of infection into those from within the household and those from the community at large. The parameters reflecting these sources of infection are estimated as functions of the risk factors. This new model is used to overcome problems associated with the lack of independence of observations in infectious disease data and negative confounding due to the association of unmeasured exposures and immunity. An example of how this new statistical model is used to provide a clearer and less confounded description of risk factor effects is presented for data from influenza A(H3N2) epidemic seasons in the Tecumseh Respiratory Illness Study. The risk factors examined are age and pre-epidemic season antibody level as measured by the hemagglutination-inhibition test, while the outcome is the infection rate. A standard analysis of the data indicates that the efficacy of protective antibodies is 70% in children and only 47% in adults. However, such an efficacy measurement is negatively confounded by past exposure which is age dependent. By means of the model, the true, unconfounded, efficacy of protective antibodies is shown to be 90% in both adults and children.

Models for the statistical analysis of infectious disease data.

The Longini-Koopman model (1982, Biometrics 38, 115-126) describes the process underlying the transmission of an infectious disease in terms of household and community level transmission probabilities. This model is generalized by allowing for different transmission probabilities that may correspond to various levels of risk factors on both the household and community levels. Two types of models are considered: (i) models for household data, where the numbers of susceptible and infected members in each household are known along with the values of household level risk factors; and (ii) models for individual data, where the infection status and risk factor level are known for each individual in the household. Although the type (i) models can be expressed as special cases of the type (ii) models, they deserve special attention as they can be represented and analyzed as log-linear models. Both types of models can be analyzed using maximum likelihood methods, while the type (i) models, when expressed as log-linear models, can also be analyzed by the weighted least squares method. Data from influenza epidemics in Tecumseh, Michigan and Seattle, Washington are used to illustrate these methods.

Resting metabolic rate: measurement reliability.

Resting metabolic rate (RMR) usually is measured by indirect calorimetry for a brief interval, and the results are then extrapolated to 24-hr resting energy production. The aim of the current study was to examine the validity of this approach by measuring the within- and between-day variability in RMR. The RMR was measured hourly in 14 healthy adults from 8:00 am to 4:00 pm after an overnight fast on two separate days. The results indicated that, during day 1, RMR remained unchanged from early morning to late afternoon, and there was no significant difference between RMR measurements 1 through 8. Based upon analysis of variance and intraclass correlation coefficients, the averages of the first and the last three RMR measurements were found to be unreliable. RMR reliability was improved by averaging all measurements taken during the day, and maximum reliability was obtained by averaging the middle three RMR measurements. A similar pattern of results was observed during day 2, although the overall trend was for the reliability of RMR measurements to improve relative to day 1. The average RMRs on days 1 and 2 were not significantly different. These results indicate that the current practice of establishing a patient's RMR based upon a single measurement potentially can lead to large errors in determining energy needs. Measurement reliability can be improved by serially measuring RMR, eliminating the initial measurement, and averaging the remaining two to three values.

Restenosis after successful coronary angioplasty in patients with single-vessel disease.

To determine risk factors for restenosis, we studied 998 patients who underwent elective coronary angioplasty (PTCA) to native coronary arteries between July 1980 and July 1984. Restenosis, defined as a luminal narrowing of greater than 50% at follow-up, was present in 302 patients (30.2%). Univariate analysis of 29 factors revealed seven factors related to restenosis: vessel dilated (circumflex coronary artery 18%, right coronary artery 27%, left anterior descending artery 34%; p less than .01), final gradient of 15 mm Hg or less compared with greater than 15 mm Hg (27% vs 38%, p less than .01), duration of angina greater than 2 months compared with angina of shorter duration (27% vs 35%, p = .01), post-PTCA stenosis of 30% or less compared with 31% to 50% (28% vs 36%, p less than .025), stable vs unstable angina (26% vs 34%, p less than .05), presence vs absence of intimal dissection (26% vs 32%, p = .07), and female gender vs male gender (25% vs 32%, p = .08). Multivariate analysis revealed five factors independently related to increased risk of restenosis in the following order of importance: PTCA in the left anterior descending artery, absence of intimal dissection immediately after PTCA, final gradient greater than 15 mm Hg, a large residual stenosis after PTCA, and unstable angina. Restenosis after PTCA is a multifactorial problem. The hemodynamic and angiographic result at the time of PTCA significantly influences long-term outcome, but additional measures aimed at reducing the rate of recurrence of atherosclerotic plaque are required.