Intoxicated motor vehicle passengers: an overlooked at-risk population.

HYPOTHESES: Intoxicated motor vehicle passengers are similar to intoxicated drivers in recurrent health care encounters and risk of death for 5 years after injury. Intoxicated passengers have a greater risk of death than population controls. DESIGN: Historical cohort study. SETTING: University-based level I trauma center. PARTICIPANTS: Motor vehicle crash victims admitted to a level I trauma center in 1993. MAIN OUTCOME MEASURES: Recurrent hospitalization, emergency department visits, survival analysis, and standardized mortality ratios for 5 years following injury. RESULTS: More than one quarter of intoxicated passengers and drivers had recurrent hospitalizations and emergency department visits. Intoxicated occupants were more likely to return to the hospital and the emergency department than nonintoxicated controls (odds ratios, 2.0 and 2.7, respectively). Intoxicated passengers were at increased risk of dying compared with nonintoxicated occupants (P = .008) and with the general population (standardized mortality ratio = 5.8). Intoxicated occupants were more likely to die an alcohol-related death (P< .001). CONCLUSIONS: Intoxicated passengers injured in a motor vehicle crash are similar to intoxicated drivers in recurrent hospitalizations and emergency department visits. Intoxicated passengers have an increased mortality rate in the 5 years following injury.

Cigarette smoking, alcohol consumption, and the risk of systemic lupus erythematosus: a case-control study.

OBJECTIVE: To investigate the effects of cigarette smoking and alcohol consumption on the development of systemic lupus erythematosus (SLE). METHODS: We interviewed 125 patients with SLE and 125 controls in a case-control study. Demographically similar controls randomly selected from outpatient clinics were matched to SLE cases for sex and age. Clinical data, including cigarette smoking, drinking habits, and other demographic variables, were collected by an interview-administered questionnaire. RESULTS: To minimize bias associated with reactive habits induced by disease, cigarette smoking before the diagnosis of SLE was the primary variable for subsequent analysis. Analysis of the data by multivariate conditional logistic regression revealed that both cigarette smoking before SLE diagnosis and ex-smoking before SLE diagnosis significantly increased the risk of development of SLE (OR 6.69, 95% CI 2.59, 17.28, p < 0.001; and OR 3.62, 95% CI 1.22, 10.70, p = 0.02, respectively). This association remained even when statistically controlling for the effects of family history and education, indicating an independent effect. Alcohol did not place an individual at increased risk nor did it have a protective role. CONCLUSION: The results of this study provide further evidence that cigarette smoking may be an associated risk factor for the development of SLE.

Population-based study of microinvasive adenocarcinoma of the uterine cervix.

OBJECTIVE: To analyze lymph node status and survival rates of women with microinvasive cervical adenocarcinoma (International Federation of Gynecology and Obstetrics stages IA(1) and IA(2)). METHODS: The Surveillance, Epidemiology, and End Results (SEER) Public-Use Database was used to identify cases of microinvasive cervical adenocarcinoma diagnosed between 1988 and 1997. Variables analyzed included stage, extent of surgery, lymph node status, radiation therapy, and age. Statistics included analysis of trends, analysis of variance, log-rank test, one-sided binomial confidence interval estimation, and power analysis. RESULTS: Among 301 reported cases, 131 had stage IA(1) and 170 IA(2) disease. Simple hysterectomies were done in 54 women with IA(1) and 64 with IA(2) disease and radical hysterectomies were done in 50 and 83 women, respectively. Only one of 140 women who had lymphadenectomy had a single positive lymph node. There were four tumor-related deaths (one with IA(1), and three with IA(2) disease). There were no deaths among 96 women (47, IA(1); 49, IA(2)) treated by simple hysterectomy alone. The mean follow-up was 46.5 months (range 1--119). The censored survival rate was 98.7% overall (99.2% IA(1), 98.2% IA(2)). Power analysis estimated that 720 patients would be required in each group to detect a 2% difference in survival. Using one-sided 95% confidence interval estimations, the risk-adverse events rate for IA(1) was no more than 3.57%, and 4.50% for IA(2) disease. CONCLUSION: Prognosis is excellent for microinvasive adenocarcinoma of the uterine cervix. In 96 cases (31.9%), simple hysterectomy alone proved adequate.

The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study.

OBJECTIVE: The aim of this study was to compare the age-adjusted incidence and survival for invasive adenocarcinoma and squamous cell carcinoma of the uterine cervix using population-based data. METHODS: The SEER database was used to identify all cases of cervical cancer registered between 1973 and 1996. Stage was defined as localized, regional, or distant. Age-adjusted incidence rates were analyzed statistically using the Jonchkeere-Terpstra exact test for trends. Relative and observed survival rates, respectively, were compared using z tests and log-rank tests. RESULTS: The age-adjusted incidence rates per 100,000 for all invasive cervical cancers decreased by 36.9% over 24 years [12.35 (1973-1977) vs 7.79 (1993-1996)]. Similarly, the age-adjusted incidence rates for squamous cell carcinoma declined by 41.9% [9.45 (1973-1977) vs 5.49 (1993-1996)]. In contrast, the age-adjusted incidence rates for adenocarcinoma increased by 29.1% [1.34 (1973-1977) vs 1.73 (1993-1996)]. The proportion of adenocarcinoma increased 107.4% relative to all cervical cancer, 95.2% relative to squamous cell carcinoma, and 49.3% relative to the population of women at risk [10. 8% vs 22.4% (P < 0.001), 12.4% vs 24.0% (P < 0.001), and 1.40 vs 2. 09 per 100,000 women (P < 0.001), respectively]. Observed survival rates for adenocarcinoma vs squamous cell carcinoma were poorer for regional (P = 0.04), but not localized or distant disease. CONCLUSIONS: Over the past 24 years, the incidence of all cervical cancer and squamous cell carcinoma has continued to decline. However, the proportion of adenocarcinoma relative to squamous cell carcinoma and to all cervical cancers has doubled, and the rate of adenocarcinoma per population at risk has also increased. These results suggest that current screening practices in the United States are insufficient to detect a significant proportion of adenocarcinoma precursor lesions.

Acute optic neuritis: association with paranasal sinus inflammatory changes on magnetic resonance imaging.

The authors compared the frequency of paranasal sinus inflammatory changes (SIC) on brain magnetic resonance imaging (MRI) obtained from 23 patients with new onset acute optic neuritis (ON) and 48 control patients who underwent outpatient MRI of the brain for reasons other than ON. The authors found a higher frequency of paranasal SIC in patients with ON (83%) than in controls (54%) (p = 0.02). The distribution of paranasal SIC (in ON and in controls) was maxillary (83% and 52%), ethmoid (4% and 2%), frontal (9% and 14%), and sphenoid (4% and 10%). Frequency of the maxillary SIC was significantly higher (p = 0.02) in patients with ON than in controls. Further evaluation of maxillary paranasal SIC with a grading system showed the presence of thickened mucosal lining of the sinuses (grade I) in 17% (ON) and 23% (controls), mucous retention cysts within the sinuses (grade II) in 48% (ON) and 25% (controls), and severe mucosal thickening with complete or near-complete filling of the sinus or an air-fluid level within the sinus (grade III) in 17% (ON) and 4% (controls). Combined frequency of grade II and grade III SIC was significantly higher in the ON group than in controls (p = 0.005), as was the frequency of grade III SIC alone (p = 0.02). Grade I SIC did not significantly differ between the groups. There was a trend (p = 0.09) toward a higher prevalence of bilateral sinus inflammatory changes in patients with bilateral ON. These findings suggest that ON may be associated with sinus inflammatory changes.

Lung biopsy: is it necessary?

OBJECTIVE: Lung biopsy is associated with substantial mortality rates. We reviewed our experience with this operation, primarily in patients with immunocompetence, to determine whether the results justify the continued performance of this procedure. METHODS: We conducted a retrospective review of all diagnostic lung biopsies performed at 3 university-affiliated hospitals between July 1, 1992, and December 31, 1998. RESULTS: There were 75 patients: 25 patients were treated electively, 17 were treated on an urgent basis, 27 patients on an emergency basis, and the urgency was unclear in 6 patients. Significant beneficial therapeutic changes were made in 15 of 25 elective procedures (60%), in 16 of 17 urgent procedures (94%), and in 11 of 27 emergency procedures (41%; P =.001). Significant beneficial therapeutic changes consisted of immunosuppression in 13 of 15 (87%) patients treated on an elective basis, in 9 of 16 (56%) treated on an urgent basis, and in 9 of 11 (82%) treated on an emergency basis in whom therapy was altered (P =.14). Operative death was 0 of 25 for elective operations (0%), 3 of 17 for urgent operations (18%), and 14 of 26 for emergency operations (54%). Multivariable analysis of operative death showed urgency to be the only significant predictor of death (P =.002). CONCLUSIONS: In patients with immunocompetence, elective and urgent lung biopsies have acceptable operative mortality rates and frequently result in important beneficial therapeutic changes. Consequently biopsies are appropriate in these patients. Emergency biopsies are associated with high operative mortality rates and rarely result in a therapeutic change other than immunosuppression. These patients should not undergo lung biopsy if they are in stable condition and should be treated empirically with immunosuppression without operation if their condition is deteriorating.

Is amniotic fluid analysis the key to preterm labor? A model using interleukin-6 for predicting rapid delivery.

OBJECTIVE: Our purpose was to create a model for predicting amnionitis and rapid delivery in preterm labor patients by use of amniotic fluid interleukin-6 and clinical parameters. STUDY DESIGN: Amniotic fluid was cultured and analyzed, and a clinical score (incorporating gestational age, amniotic fluid Gram stain, glucose, leukocyte esterase, and maternal serum C-reactive protein) was determined in 111 patients diagnosed with preterm labor. Statistical analysis involved t tests, chi2, logarithmic regression, and multivariate regression analysis (P < or = .05). RESULTS: The incidence of positive amniotic fluid cultures was 8.7% (9 of 103 patients). Patients with positive cultures of the amniotic fluid had a shorter delivery interval (4.8 +/- 7.5 vs 28.9 +/- 25.4 days, P < .001). Patients with elevated amniotic fluid interleukin-6 (> or = 7586 pg/ml) were more likely to have a positive amniotic fluid culture (relative risk = 8.8, 95% confidence interval = 1.6 to 47.4, P < .001) and to be delivered within 2 days (relative risk = 16.8, 95% confidence interval = 4.5 to 62.7, P < .001). Stepwise multivariate regression analysis yielded a model using interleukin-6, cervical dilatation, and gestational age (r2 = 0.63, P < .001) with a specificity of 100% for predicting delivery within 2 days of amniocentesis. CONCLUSIONS: A mathematical model using maternal amniotic fluid interleukin-6 seems to be a useful clinical tool for quantifying the interval to preterm birth for patients in preterm labor.

Effect of adjustment of maternal serum alpha-fetoprotein levels in insulin-dependent diabetes mellitus.

Our objective was to determine the effect of the 20% upward adjustment of maternal serum alphafetoprotein (MSAFP) in patients with insulin-dependent diabetes mellitus (IDDM) on the number of patients that would be classified at increased risk for pregnancy complicated by either Down syndrome (DS) or neural tube defect (NTD). We retrospectively evaluated a database containing 63,110 patients who underwent multiple serum marker screening between 14 and 22 weeks gestation; 620 patients with IDDM had measurements of MSAFP of which 479 also had measurements of beta-HCG, allowing calculation of DS risk. Increased NTD risk was defined as MSAFP >2.5 MOM while increased DS risk was defined as a calculated risk > or =1/270. One IDDM patient delivered an infant with a NTD; it was not detected on serum screening. No infants were born with DS. Of the 620 patients with MSAFP determinations, 9 had values >2.5 MOM before adjustment. After upward adjustment, 7 additional patients were identified. Sixteen patients were identified at increased risk for DS before and after adjustment. Our data suggest that the 20% upward adjustment of MSAFP increases by 78%, the number of patients who would require further evaluation for NTD's. Although we were able to identify 620 women with IDDM who underwent serum screening for NTD, the low prevalence of NTD's did not allow us to demonstrate an increased detection rate. The effect of upward adjustment of MSAFP on the number of patients categorized at increased DS risk appears to be minimal.

Risks of complication following thyroidectomy.

OBJECTIVE: Because hypoparathyroidism is a serious complication of thyroidectomy, we attempted to elucidate factors determining the risk of this postoperative outcome. SETTING: Four tertiary care hospitals in Albuquerque, New Mexico. PATIENTS: A retrospective study of 142 patients who underwent total or subtotal thyroidectomy between 1988 and 1995. MEASUREMENTS AND MAIN RESULTS: Permanent hypoparathyroidism was defined as hypocalcemic symptoms plus a requirement for oral vitamin D or calcium 6 months after thyroidectomy. Factors analyzed to determine their contribution to the risk of persistent postoperative hypoparathyroidism were the indication for thyroidectomy, performance of a preoperative thyroid needle biopsy, type of surgery, postoperative pathology, presence and stage of thyroid carcinoma, resident surgeon involvement, and specialty of the surgeon performing the procedure. Surgical specialty and stage of thyroid carcinoma were independent risk factors for persistent postoperative hypoparathyroidism by multivariate analysis. Nine (29%) of 31 patients who had thyroidectomy by otolaryngologists met criteria for permanent hypoparathyroidism, and 6 (5%) of 111 patients who had thyroidectomy by general surgeons met the same criteria (p < .001). Adjustment for the effect of stage did not eliminate the effect of specialty (p = .006), and adjustment for the effect of specialty did not eliminate the effect of stage (p = .02), on the occurrence of postoperative hypoparathyroidism. CONCLUSIONS: We conclude from our data that patients undergoing thyroidectomy by an otolaryngologist may be at a higher risk of permanent postoperative hypoparathyroidism than patients who undergo thyroidectomy by a general surgeon. This may reflect differences in case selection or surgical approach or both.

A prospective trial of risk factors for sulfonylurea-induced hypoglycemia in type 2 diabetes mellitus.

CONTEXT: Retrospective studies have identified oral sulfonylureas, age, and fasting as major risk factors for hypoglycemia in patients with type 2 diabetes. Sulfonylureas may be withheld from elderly patients out of concern for hypoglycemia. OBJECTIVE: To evaluate the hypoglycemic effects of maximum doses of once-daily second-generation sulfonylureas administered to fasting elderly patients. DESIGN: A prospective, randomized, double-blind clinical trial. SETTING: The University of New Mexico General Clinical Research Center. PATIENTS: Fifty-two sulfonylurea-treated subjects with type 2 diabetes with a mean (SD) age of 65.1 (5.7) years. INTERVENTIONS: Subjects were randomly assigned to glyburide or glipizide gastrointestinal therapeutic system (GITS). Each subject participated in three 23-hour fasting studies after the sequential administration of 1 week of placebo and 1 week of 10 mg and 1 week of 20 mg of the assigned sulfonylurea. MAIN OUTCOME MEASURES: Occurrence of hypoglycemia (defined as plasma glucose level <3.33 mmol/L [60 mg/dL]) and hormonal parameters during the final 9 hours of the 23-hour fast in patients who had taken sulfonylureas vs placebo. RESULTS: No hypoglycemia was observed during 156 fasting studies. Plasma glucose level was decreased (nadir, 4.9 mmol/L [88 mg/dL] for a 20-mg dose of glyburide vs 8.3 mmol/L [150 mg/dL] for placebo; nadir, 5.8 mmol/L [105 mg/dL] for a 20-mg dose of glipizide GITS vs 8.7 mmol/L [157 mg/dL] for placebo), and serum insulin was increased in the sulfonylurea studies compared with placebo (P<.001). Plasma glucose parameters did not differ between the 2 sulfonylureas, but C peptide concentrations were increased in the glyburide group compared with glipizide GITS in the 20-mg study (P=.05). Concentrations of epinephrine were increased in the sulfonylurea studies compared with placebo (P<.001). Epinephrine secretion increased when glucose concentration fell below the mean (SD) level of 9.10 (2.66) mmol/L (164 [48] mg/dL) in the 10-mg study and 8.77 (2.83) mmol/L (158 [51] mg/ dL) in the 20-mg study. CONCLUSIONS: Fasting was well tolerated among these elderly patients with type 2 diabetes treated with sulfonylureas. Older age should not be considered a contraindication to sulfonylurea treatment for diabetes. Stimulation of epinephrine secretion at normal or elevated plasma glucose levels appears to be the primary mechanism of protection against hypoglycemia in this study.

Digoxin-like immunoreactive substance and sodium-potassium-adenosine triphosphatase inhibition in normal pregnancy: a longitudinal study.

OBJECTIVE: To measure the levels of digoxin-like immunoreactive substance and digitalis-like factor bioactivity as manifested by sodium-potassium-adenosine triphosphatase (ATPase) inhibition throughout pregnancy. METHODS: Serum samples were collected from primigravidas in early (15 +/- 1.8 weeks), mid (26 +/- 1.2 weeks), and late (36 +/- 1.1 weeks) gestation, as well as at 6 +/- 1.1 weeks postpartum (mean +/- standard error). Digoxin-like immunoreactive substance levels were determined by radioimmunoassay and digitalis-like factor bioactivity was determined by inhibition of ATPase. Data were analyzed by means of repeated measures analysis of variance. RESULTS: In 41 women with normal pregnancy outcomes, levels of digoxin-like immunoreactive substance rose progressively and significantly (P < .001) throughout pregnancy and returned to normal levels postpartum. Inhibition of ATPase activity also rose significantly (P < .004), but not as dramatically, during pregnancy and remained elevated 6 weeks postpartum. CONCLUSION: Although digoxin-like immunoreactive substance levels rise in pregnancy, functional digitalis-like factor activity, as manifested by inhibition of ATPase, does not parallel this rise strictly, implying that digoxin-like immunoreactive substance receptors may be reset during normal pregnancy. The enhanced cardiac performance that occurs in normal pregnancy may be mediated in part by increased digitalis-like factor activity.

Assessment of stimulated and spontaneous adrenocorticotropin secretory dynamics identifies distinct components of cortisol feedback inhibition in healthy humans.

Corticosteroids inhibit ACTH secretion through diverse cellular mechanisms, including direct pituitary and indirect suprapituitary effects. Although exogenous CRH provides a useful assessment of corticotroph function, the suprapituitary component of ACTH regulation has been difficult to assess in humans. Naloxone (NAL) has been reported to stimulate ACTH secretion indirectly through the release of endogenous hypothalamic CRH, suggesting its potential application in the examination of suprapituitary regulation of ACTH secretory dynamics. We sought to examine the inhibitory effects of corticosteroids on kinetic parameters of ACTH secretion, assessed by a deconvolution method, in healthy human subjects. We also sought to directly compare the ACTH responses to serial administration of human CRH and NAL as well as spontaneously occurring ACTH pulses to distinguish pituitary and suprapituitary components of hypothalamic-pituitary-adrenal regulation. Normal healthy subjects (n = 11) received hCRH (0.4 microgram/kg) at 1800 h and then NAL (65 micrograms/kg) at 1930 h, respectively, on 3 separate study days: placebo pretreatment plus CRH/NAL stimulation, metyrapone (MET) pretreatment plus CRH/NAL, or MET alone. Plasma ACTH and serum cortisol were assessed at frequent (every 10 min) intervals during CRH/NAL or placebo infusions (1800-2100 h) on all 3 study days, and deconvolution analysis was performed to determine kinetic parameters of endogenous and stimulated ACTH secretion. Suppression of endogenous cortisol secretion with MET significantly increased both continuous (basal secretion rate) and pulsatile CRH- and NAL-stimulated ACTH bursts (P < 0.05). The increase in total ACTH secreted per burst was related to two distinct effects of cortisol regulating the amplitude (maximum secretion rate) and half-duration (P < 0.05) of secretory bursts. The ACTH responses to CRH and NAL for individual subjects were significantly and positively correlated in both placebo pretreatment plus CRH/NAL stimulation and MET pretreatment plus CRH/NAL studies (P < 0.01). MET administration disproportionately increased the ACTH response to NAL, producing a significant increase (P < 0.01) in the slope of the regression relating ACTH responses to CRH and NAL. The following conclusions were made: 1) endogenous cortisol secretion, even at levels associated with relatively low serum cortisol concentrations, exerts a significant negative feedback effect on both continuous and pulsatile ACTH secretion; 2) cortisol inhibits pulsatile ACTH secretion through distinct regulatory mechanisms that independently modulate both the mass and the duration of ACTH secretory bursts; 3) the differential sensitivity of the CRH- and NAL-stimulated ACTH responses to MET administration suggests that both pituitary and suprapituitary components of the hypothalmic-pituitary-adrenal axis are sensitive to negative regulation over a rapid or intermediate temporal domain. Endogenous cortisol modulates multiple components of dynamical ACTH secretion through composite effects that appear to be mediated through structurally and functionally distinct regulatory domains.