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1.
Int J Obes (Lond) ; 39(3): 472-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25042863

ABSTRACT

BACKGROUND: Elevated levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) may contribute to cardiovascular disease and are associated with obstructive sleep apnea (OSA) and obesity. The relationship between OSA and obesity in determining ICAM-1 and VCAM-1 levels, and the effect of treatment, is unclear. OBJECTIVE: Our aim was to study whether positive airway pressure (PAP) usage resulted in changes in ICAM-1 and VCAM-1 after 2 years within 309 OSA patients from the Icelandic Sleep Apnea Cohort, and determine how obesity affected such changes. SUBJECTS/METHODS: The mean body mass index (BMI) was 32.4±5.1 kg m(-2); subjects had moderate-to-severe OSA (apnea-hypopnea index=45.0±20.2) and 79% were male. There were 177 full PAP users (⩾4 h per night and ⩾20 of last 28 nights), 44 partial (<4 h per night or <20 nights) and 88 nonusers. RESULTS: ICAM-1 (P<0.001) and VCAM-1 (P=0.012) change was significantly different among the PAP groups. The largest ICAM-1 differences were among the most obese subjects (P<0.001). At follow-up, nonusers had increased ICAM-1 compared with decreased levels in full users. All groups had increased VCAM-1, but nonusers had a significantly larger increase than full users. CONCLUSIONS: Within moderate-to-severe OSA patients, PAP usage prevents increases in adhesion molecules observed in nonusers after 2 years. For ICAM-1, the largest effect is in the most obese subjects. As OSA and obesity commonly coexist, the usage of PAP to limit increases in adhesion molecules may decrease the rate of progression of OSA-related cardiovascular disease.


Subject(s)
Cardiovascular Diseases/physiopathology , Cell Adhesion Molecules/blood , Continuous Positive Airway Pressure , Sleep Apnea, Obstructive/physiopathology , Body Mass Index , Cardiovascular Diseases/blood , Cardiovascular Diseases/prevention & control , Disease Progression , Female , Humans , Intercellular Adhesion Molecule-1/blood , Male , Middle Aged , Obesity , Polysomnography , Sleep Apnea, Obstructive/blood , Sleep Apnea, Obstructive/complications , Vascular Cell Adhesion Molecule-1/blood
2.
Int J Obes (Lond) ; 37(6): 835-42, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22964793

ABSTRACT

OBJECTIVES: To assess whether sleep apnea severity has an independent relationship with leptin levels in blood after adjusting for different measures of obesity and whether the relationship between obstructive sleep apnea (OSA) severity and leptin levels differs depending on obesity level. METHODS: Cross-sectional study of 452 untreated OSA patients (377 males and 75 females), in the Icelandic Sleep Apnea Cohort (ISAC), age 54.3±10.6 (mean±s.d.), body mass index (BMI) 32.7±5.3 kg m(-2) and apnea-hypopnea index 40.2±16.1 events per h. A sleep study and magnetic resonance imaging of abdominal visceral and subcutaneous fat volume were performed, as well as fasting serum morning leptin levels were measured. RESULTS: Leptin levels were more highly correlated with BMI, total abdominal and subcutaneous fat volume than visceral fat volume per se. No relationship was found between sleep apnea severity and leptin levels, assessed within three BMI groups (BMI <30, BMI 30-35 and BMI > or =35 kg m(-2)). In a multiple linear regression model, adjusted for gender, BMI explained 38.7% of the variance in leptin levels, gender explained 21.2% but OSA severity did not have a significant role and no interaction was found between OSA severity and BMI on leptin levels. However, hypertension had a significant effect on the interaction between OSA severity and obesity (P=0.04). In post-hoc analysis for nonhypertensive OSA subjects (n=249), the association between leptin levels and OSA severity explained a minor but significant variance (3.2%) in leptin levels. This relationship was greatest for nonobese nonhypertensive subjects (significant interaction with obesity level). No relationship of OSA severity and leptin levels was found for hypertensive subjects (n=199). CONCLUSION: Obesity and gender are the dominant determinants of leptin levels. OSA severity is not related to leptin levels except to a minor degree in nonhypertensive nonobese OSA subjects.


Subject(s)
Hypertension/blood , Intra-Abdominal Fat/pathology , Leptin/blood , Obesity/blood , Sleep Apnea Syndromes/blood , Subcutaneous Fat/pathology , Adult , Biomarkers/blood , Body Composition , Body Mass Index , Cohort Studies , Cross-Sectional Studies , Female , Humans , Hypertension/epidemiology , Hypertension/physiopathology , Iceland/epidemiology , Male , Middle Aged , Obesity/complications , Obesity/epidemiology , Obesity/physiopathology , Polysomnography , Severity of Illness Index , Sex Distribution , Sleep Apnea Syndromes/epidemiology , Sleep Apnea Syndromes/etiology , Sleep Apnea Syndromes/physiopathology , Surveys and Questionnaires , Time Factors
3.
Eur Respir J ; 38(2): 348-58, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21233264

ABSTRACT

The alteration of craniofacial structures has been associated with obstructive sleep apnoea (OSA). We hypothesised that: 1) a smaller mandible is a risk factor for OSA; and 2) the previously observed inferiorly positioned hyoid bone in apnoeics is associated with enlarged tongue volume. This is a case-control study using three-dimensional magnetic resonance imaging cephalometry. 55 apneics and 55 controls were matched for age, sex and race. The analysis was stratified by sex and controlled for age, race, height, neck visceral fat, skeletal type and tongue volume. We found that a 1-sd increase in mandibular length and depth were associated with decreased risk of sleep apnoea (OR 0.52, 95% CI 0.28-0.99 and OR 0.46, 95% CI 0.23-0.91, respectively) in males but not in females. Greater hyoid-to-nasion (OR 2.64, 95% CI 1.19-5.89 in males and OR 5.01, 95% CI 2.00-12.52 in females) and supramentale-to-hyoid (OR 2.39, 95% CI 1.12-5.14) in males and OR 3.38, 95% CI 1.49-7.68 in females) distances were associated with increased risk of OSA. The difference for hyoid position between apnoeics and controls was lost after controlling for tongue volume. Enlargement of tongue is likely to be the pathogenic factor for inferior-posterior positioning of hyoid. A small and shallow mandible is an independent risk factor for OSA in males but not in females.


Subject(s)
Craniofacial Abnormalities/complications , Sleep Apnea, Obstructive/etiology , Adult , Case-Control Studies , Cephalometry/methods , Craniofacial Abnormalities/physiopathology , Female , Humans , Hyoid Bone/abnormalities , Hyoid Bone/physiopathology , Magnetic Resonance Imaging , Male , Mandible/abnormalities , Mandible/physiopathology , Middle Aged , Organ Size , Pharynx/abnormalities , Pharynx/physiopathology , Risk Factors , Sex Factors , Sleep Apnea, Obstructive/physiopathology , Tongue/abnormalities , Tongue/physiopathology
4.
J Natl Cancer Inst ; 81(20): 1575-80, 1989 Oct 18.
Article in English | MEDLINE | ID: mdl-2795683

ABSTRACT

Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate/analysis , Bile/analysis , Carcinoembryonic Antigen/analysis , DNA, Neoplasm/analysis , Flow Cytometry , Gallbladder Neoplasms/analysis , Cell Cycle , Humans , Multivariate Analysis , Neoplasm Staging
5.
Arch Gen Psychiatry ; 44(9): 775-81, 1987 Sep.
Article in English | MEDLINE | ID: mdl-2820340

ABSTRACT

It has been suggested that limbic system-hypothalamic "overdrive" may be the underlying mechanism causing an augmented secretion of corticotropin releasing hormone (CRH), heightened adrenocortical responsiveness to corticotropin (adrenocorticotropic hormone) (ACTH), and alteration in cortisol feedback regulatory mechanisms as demonstrated by the dexamethasone suppression test. We examined pituitary and adrenocortical responses after morning administration of ovine CRH (oCRH) in 26 depressed patients and 11 healthy volunteers. Basal plasma ACTH concentrations were similar in both groups, whereas patients had a significantly diminished cumulative ACTH response after administration of oCRH. In contrast, basal total cortisol concentrations and cumulative cortisol responses to oCRH were similar in depressed patients and controls. Patients with melancholic features demonstrated the most profound ACTH blunting after oCRH, whereas patients separated according to dexamethasone suppression test results had similar ACTH and cortisol responses to oCRH. The present results extend data from prior studies utilizing oCRH in the evening and demonstrate a dysregulation of the functional integrity of the hypothalamic-pituitary-adrenocortical axis in depressive illness after a morning oCRH test at both central and peripheral hypothalamic-pituitary-adrenocortical axis sites.


Subject(s)
Adrenocorticotropic Hormone/blood , Corticotropin-Releasing Hormone , Depressive Disorder/diagnosis , Hydrocortisone/blood , Adult , Aged , Circadian Rhythm , Corticotropin-Releasing Hormone/pharmacology , Depressive Disorder/blood , Depressive Disorder/physiopathology , Dexamethasone , Diagnosis, Differential , Female , Humans , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/physiopathology , Male , Middle Aged , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/physiopathology
6.
Arch Gen Psychiatry ; 46(6): 550-4, 1989 Jun.
Article in English | MEDLINE | ID: mdl-2730279

ABSTRACT

There is evidence that excessive cortisol secretion in depressed patients might result, in part, from an enhanced adrenocortical sensitivity to corticotropin. This phenomenon has been examined using the cosyntropin (alpha1-24-corticotropin) stimulation test. Most studies have used supramaximal doses of cosyntropin administered in the morning, when adrenal sensitivity to corticotropin is at its maximum. This could partially obscure subtle differences in adrenocortical sensitivity in depression that might otherwise be evident at lower cosyntropin doses given later in the day. To test this hypothesis, we administered two consecutive cosyntropin tests on separate occasions employing a submaximal 0.05-microgram/kg dose and a maximal 0.2-microgram/kg dose. The cortisol centered cumulative response over 240 minutes was measured after each test in 12 depressed patients (7 melancholic, 5 nonmelancholic) and 6 healthy volunteers. When the difference in mean cortisol centered cumulative response values was determined, healthy controls demonstrated a significant increase in cortisol centered cumulative response, while the nonmelancholic patients had a less robust increase in cortisol centered cumulative response. In contrast, the melancholic patients demonstrated cortisol responses similar to those of the healthy subjects after each cosyntropin dose, suggesting an enhanced adrenocortical sensitivity to corticotropin. These data support the hypothesis that increased glucocorticoid secretion in depression may result from abnormalities at several sites within the hypothalamic-pituitary-adrenocortical axis.


Subject(s)
Cosyntropin , Depressive Disorder/diagnosis , Hydrocortisone/blood , Adrenal Cortex/drug effects , Circadian Rhythm , Cosyntropin/pharmacology , Depressive Disorder/blood , Depressive Disorder/physiopathology , Dose-Response Relationship, Drug , Humans
7.
Arch Intern Med ; 154(19): 2185-90, 1994 Oct 10.
Article in English | MEDLINE | ID: mdl-7944839

ABSTRACT

BACKGROUND AND METHODS: Although studies have demonstrated that medical rehabilitation patients have many complications that warrant attention, none has attempted to categorize complications by severity. This retrospective cohort study examined the incidence, types, and severity of problems that interrupt rehabilitation and the major risk factors for these events. RESULTS: Of 1075 patients, 359 (33.4%) had acute medical complications on rehabilitation considered severe enough to interrupt treatment. Of the 359 patients, 158 (44%) required an unexpected transfer off rehabilitation. The most common reasons for unexpected transfer were surgical causes (22.8%), followed by infection or fever (17.1%) and by thromboembolic events (16.5%). Logistic regression revealed that major risk factors for complications requiring transfer were a primary diagnosis of deconditioning or nontraumatic spinal cord injury (adjusted odds ratio, 2.7; confidence interval, 1.8 to 4.2), severity of initial disability (adjusted odds ratio, 1.2; confidence interval, 1.1 to 1.3 for every 10-point drop in a Modified Barthel Index), and number of comorbid conditions (adjusted odds ratio, 1.1; confidence interval, 1.0 to 1.2). Risk factors for any complication were similar, but there was an interaction between comorbidity and the degree of functional impairment; in patients who were severely functionally impaired, the number of comorbidities was not as strongly associated with the risk of complications as it was in patients who were less functionally impaired. CONCLUSION: There is a complex relationship among the type of underlying medical impairment, severity of functional limitation, comorbidity, and unanticipated medical or surgical complications that interrupt rehabilitation. The interruptions vary both in type and in severity.


Subject(s)
Fever/epidemiology , Infections/epidemiology , Patient Transfer/statistics & numerical data , Rehabilitation/statistics & numerical data , Thromboembolism/epidemiology , Activities of Daily Living , Aged , Aged, 80 and over , Cohort Studies , Comorbidity , Confidence Intervals , Female , Fever/classification , Fever/etiology , Humans , Incidence , Infections/classification , Infections/etiology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Patient Readmission/statistics & numerical data , Retrospective Studies , Risk Factors , Severity of Illness Index , Thromboembolism/classification , Thromboembolism/etiology
8.
Arch Intern Med ; 147(5): 954-7, 1987 May.
Article in English | MEDLINE | ID: mdl-3495244

ABSTRACT

A retrospective cohort study was performed to assess the relative risk of upper gastrointestinal (UGI) tract bleeding from two formulations of potassium chloride. Relevant information was obtained from 1980 through 1984 Medicaid billing data from the states of Michigan, Minnesota, Florida, and Ohio. After patients with a history of UGI tract bleeding prior to their first prescription for either of the two potassium chloride preparations under study were excluded, data were analyzed for 28,790 patients (143,512 patient-months) dispensed a microencapsulated formulation exclusively and 76,118 patients (560,341 patient-months) dispensed a wax-matrix formulation exclusively. The risk of UGI tract bleeding within 30 days after each prescription for the drug of interest was examined. After sampling from the undiseased study subjects and adjusting for multiple potential confounding variables using logistic regression, an odds ratio (95% confidence interval) of 0.67 (0.52 to 0.85) was observed.


Subject(s)
Gastrointestinal Hemorrhage/chemically induced , Potassium Chloride/adverse effects , Administration, Oral , Aged , Aged, 80 and over , Drug Compounding , Female , Humans , Male , Middle Aged , Potassium Chloride/administration & dosage , Retrospective Studies , Risk , Waxes
9.
J Bone Miner Res ; 6(8): 865-8, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1785376

ABSTRACT

Although hip fracture rates are higher in women than in men, for older men the lifetime risk of fractures of the femur is substantial. Very little is known about risk factors for hip fracture in men. A preliminary case control study was conducted comparing the medical charts of men with first hip fractures with two sets of age-matched controls. The major risk factors for hip fracture that emerged were preadmission ambulatory problems, confusion, heavy alcohol use, and low body mass. Although this study is limited to a medical chart review in a veteran population, these results confirm some of the known associations for hip fracture in women. Further studies in men are recommended.


Subject(s)
Hip Fractures/etiology , Adult , Age Factors , Aged , Aged, 80 and over , Alcohol Drinking , Body Weight , Case-Control Studies , Confusion , Hip Fractures/epidemiology , Humans , Male , Middle Aged , Odds Ratio , Regression Analysis , Risk Factors , Smoking , United States
10.
J Clin Endocrinol Metab ; 73(3): 541-8, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1874932

ABSTRACT

Early studies using the insulin tolerance test (ITT) in affective disorders reported a blunted GH response in some depressed patients. However, results from subsequent studies were less consistent. These discrepancies resulted in part from limited sample sizes causing diagnostic heterogeneity. In the present study we examined hormonal response patterns during the ITT in 25 bipolar patients (19 depressed and 6 hypomanic), 91 unipolar depressives, and 51 healthy volunteers to determine whether distinct neuroendocrine response patterns characterized specific diagnostic subgroups. We measured the glucose, GH, PRL, and cortisol responses during a 75-min ITT and observed a diminished cumulative GH response in bipolar hypomanic patients compared to bipolar depressives (P = 0.004) and healthy volunteers (P less than 0.001), and a larger cumulative GH response in bipolar depressives compared to unipolar patients (P = 0.02). No differences were observed in either PRL or cortisol responses among subject groups. The present findings suggest that GH responses during the ITT may be more complex than initially described and partially dependent upon affective disorder subtype. Thus, bipolar patients may have distinctive GH response patterns compared to those of unipolar depressives and healthy controls. Moreover, some of the difference observed in the GH response to the ITT may result from the phase of the manic-depressive illness. These data indicate differences in neuroendocrine substrates between affective disorder subtypes.


Subject(s)
Bipolar Disorder/metabolism , Blood Glucose/metabolism , Depressive Disorder/metabolism , Growth Hormone/blood , Hydrocortisone/blood , Hypoglycemia/blood , Insulin/adverse effects , Prolactin/blood , Adolescent , Adult , Bipolar Disorder/physiopathology , Depressive Disorder/physiopathology , Female , Humans , Hypoglycemia/chemically induced , Hypoglycemia/physiopathology , Male , Middle Aged
11.
Biol Psychiatry ; 28(4): 308-14, 1990 Aug 15.
Article in English | MEDLINE | ID: mdl-2204433

ABSTRACT

Abnormal growth hormone (GH) responses have been observed after several neuroendocrine challenge tests. In the present study, we examined the relationship between GH response after clonidine and insulin administration within the same subject to see if consistent response patterns were evident. Though there was a significant reduction in the mean GH response after clonidine (p = 0.0002), similar differences were not observed after insulin (p = 0.10). Furthermore, there were no apparent within-subject correlations for GH response between the clonidine and insulin challenge tests. Although the present findings indicate an inherent variability in GH response patterns after different neuroendocrine challenge tests, it appears from prior studies that GH may be more consistently blunted after clonidine in depression when compared to other GH provocative tests.


Subject(s)
Blood Glucose/metabolism , Clonidine , Depressive Disorder/diagnosis , Growth Hormone/blood , Insulin , Adult , Depressive Disorder/blood , Depressive Disorder/psychology , Female , Humans , Hydrocortisone/blood , Male , Psychiatric Status Rating Scales
12.
Biol Psychiatry ; 27(4): 447-53, 1990 Feb 15.
Article in English | MEDLINE | ID: mdl-2155671

ABSTRACT

There has been considerable interest in the possibility that some psychotropic medications may possess antiviral activity. Several clinical observations suggest that lithium may inhibit the reactivation of latent herpes simplex virus, thereby reducing the number of recurrent infections. We performed a retrospective study examining the putative antiviral activity of various psychotropic agents in 177 subjects receiving lithium prophylaxis and a comparison group of 59 subjects receiving other antidepressant drugs for affective illness. Chronic lithium administration resulted in a significant reduction in the mean rate of recurrent labial herpes infections when compared to the pretreatment period (p less than 0.001). In contrast, the mean rate of herpes infections was unchanged in patients taking other antidepressants (p = 0.53). Although the overall reduction in herpes infections was not significantly different between groups, the proportion of subjects reporting a reduction in infection rate was greater in the lithium group (71%) compared with those receiving other antidepressants (52%) (p = 0.07). These data compliment prior in vitro and clinical studies demonstrating a potential antiviral activity for lithium carbonate.


Subject(s)
Antiviral Agents , Lithium/pharmacology , Simplexvirus/drug effects , Adult , Antidepressive Agents/pharmacology , Female , Herpes Labialis/prevention & control , Humans , Lithium/therapeutic use , Lithium Carbonate , Male , Middle Aged , Mood Disorders/drug therapy , Recurrence , Retrospective Studies
13.
Biol Psychiatry ; 26(3): 265-78, 1989 Jul.
Article in English | MEDLINE | ID: mdl-2742943

ABSTRACT

Abnormalities in several hypothalamic-pituitary-target organ axes in depression may reflect alterations in central neurotransmitter receptor function. As the alpha 2-adrenergic receptor has been implicated in a variety of neuroendocrine abnormalities in depression, we assessed the role of alpha 2-adrenoceptor dysfunction in mediating response abnormalities of growth hormone, cortisol, and prolactin after intravenous clonidine administration (an alpha 2-adrenergic receptor agonist) in 18 patients with major depression (12 with melancholic features, 6 without melancholic symptoms) and 9 healthy volunteers. In particular, we examined the hypothesis that these abnormalities might be more evident in patients with DSM-III melancholic depression. After clonidine, the mean growth hormone response was significantly lower in melancholic depressives compared to controls (p = 0.02), and the shape of the growth hormone response profile was also significantly different in melancholic patients (p = 0.04). There was an overall decrease in the mean cortisol concentration after clonidine in melancholic patients and control subjects (p = 0.02), as well as a larger cumulative prolactin response in melancholic patients compared to those without melancholic features (p = 0.02). The present results confirm prior observations of a blunted growth hormone response after clonidine and suggest that alterations in alpha 2-adrenergic receptor activity might also contribute to several neuroendocrine abnormalities in patients with melancholic depression.


Subject(s)
Clonidine , Depressive Disorder/diagnosis , Growth Hormone/blood , Hydrocortisone/blood , Prolactin/blood , Adult , Depressive Disorder/blood , Depressive Disorder/psychology , Female , Humans , Male , Middle Aged
14.
Biol Psychiatry ; 19(5): 695-702, 1984 May.
Article in English | MEDLINE | ID: mdl-6428472

ABSTRACT

A diminished thyrotropin (TSH) response to the administration of thyrotropin-releasing hormone (TRH) has been widely reported in depressed patients. Repeated TRH administration at short intervals has been shown to produce a diminished TRH response in healthy subjects. In the present study, TRH (400 micrograms) was administered to ten healthy male subjects at weekly intervals for 4 weeks. The TSH response to TRH diminished steadily from 8.2 +/- 1.3 microU/ml on Trial 1 to 6.3 +/- 0.7 microU/ml on Trial 4 (p less than 0.05). No change in the prolactin response to TRH administration was observed over the four trials. Reduction in the TSH response to TRH was not correlated with basal concentrations of thyroxine, triiodothyronine, or cortisol.


Subject(s)
Depressive Disorder/diagnosis , Thyrotropin-Releasing Hormone , Thyrotropin/blood , Adult , Depressive Disorder/blood , Drug Administration Schedule , Humans , Male , Prolactin/blood
15.
Am J Psychiatry ; 145(3): 325-30, 1988 Mar.
Article in English | MEDLINE | ID: mdl-2894176

ABSTRACT

An association between affective disorders and alterations in glucose utilization has been recognized. The authors administered a 5-hour oral glucose tolerance test (GTT) to 28 depressed patients and 21 healthy volunteer control subjects and measured serum glucose as well as plasma insulin and glucagon responses. Depressed patients demonstrated significantly higher basal glucose levels, greater cumulative glucose responses after the GTT, and larger cumulative insulin responses after the GTT than control subjects. Values for cumulative glucagon did not significantly differ between groups. These findings indicate the presence of a functional state of insulin resistance during major depressive illness and suggest the presence of a more generalized biological disturbance in some depressed patients.


Subject(s)
Blood Glucose/analysis , Depressive Disorder/diagnosis , Glucose Tolerance Test/methods , Insulin Resistance , Administration, Oral , Adolescent , Adult , Aged , Depressive Disorder/blood , Female , Glucagon/blood , Glucose/administration & dosage , Humans , Hydrocortisone/blood , Insulin/blood , Male , Middle Aged , Personality Inventory , Psychiatric Status Rating Scales , Somatostatin/blood
16.
Am J Med ; 83(1): 65-71, 1987 Jul.
Article in English | MEDLINE | ID: mdl-3605183

ABSTRACT

In order to evaluate potential risk factors for the development of hospital-acquired acute renal failure, a case-control study was performed, comparing patients with hospital-acquired acute renal failure with control subjects matched on age, sex, hospital, service of admission, and baseline renal function. The same patients were then reanalyzed utilizing a cohort study design to investigate outcomes from this syndrome. The following elevated odds ratios (95 percent confidence interval) were found while simultaneously adjusting for possible confounding variables using logistic regression: volume depletion, 9.4 (2.1 to 42.8); aminoglycoside use, 5.6 (1.3 to 23.7); congestive heart failure 9.0 (2.1 to 38.9); radiocontrast exposure, 4.9 (1.2 to 19.7); and septic shock, approached infinity, p less than 0.0001. The effect of volume depletion was markedly accentuated in those with diabetes (odds ratio = 1.9) (p less than 0.05). The risk from aminoglycoside use markedly increased with increasing age (p less than 0.002). Finally, the development of hospital-acquired acute renal failure was associated with a marked increase in the risk of dying--the relative risk (95 percent confidence interval) was 6.2 (2.6 to 14.9)--and a marked increase in length of stay, from a median of 13 days in control subjects to a median of 23 days in case subjects (p = 0.005). In conclusion, hospital-acquired acute renal failure is a serious illness. Attempts to prevent it should focus on proved risk factors.


Subject(s)
Acute Kidney Injury/epidemiology , Hospitalization , Acute Kidney Injury/etiology , Acute Kidney Injury/mortality , Acute Kidney Injury/physiopathology , Creatinine/blood , Hospitals, University , Humans , Pennsylvania , Prognosis , Regression Analysis , Risk
17.
Am J Med ; 87(6): 614-20, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2589396

ABSTRACT

PURPOSE: The purpose of this study was to define risk factors for nosocomial candidemia in adult patients without leukemia at a tertiary care medical center. PATIENTS AND METHODS: All patients with nosocomial candidemia between August 1, 1981, and October 31, 1984, were included if they met strict selection criteria and did not have acute or chronic leukemia. For each case, one control was selected from among patients admitted during the same month/year and matched for hospital service and duration of hospitalization up to the first blood culture that grew Candida species. Logistic regression was used to obtain estimates of risk after simultaneously controlling for other variables. RESULTS: Candida albicans caused 24 of the 48 fungemias studied. The risk factors identified included the presence of a central line (odds ratio, 26.4; 95% confidence interval, 1.5 to 451.1); bladder catheter (13.0 1.3 to 131.4); two or more antibiotics (25.1, 2.1 to 318); azotemia (22.1, 2.2 to 223.2); transfer from another hospital (21.3, 1.7 to 274.5); diarrhea (10.2, 1.03 to 101.4); and candiduria (27.0, 1.7 to 423.5). A prior surgical procedure was associated with lowered risk (0.1, 0.01 to 0.9), suggesting perhaps that medical service patients are at higher risk than those on surgical services. Because total parenteral nutrition was always administered by means of a central line, it could not be shown to increase the risk over that conferred by a central line alone. CONCLUSIONS: This study has defined seven major risk factors for nosocomial candidemia. These findings should facilitate development of rational approaches to preventing infection and may assist clinicians in identifying those patients in whom this life-threatening complication is likely to occur.


Subject(s)
Candidiasis/etiology , Cross Infection/etiology , Adolescent , Adult , Aged , Anti-Bacterial Agents , Candidiasis/epidemiology , Candidiasis/urine , Case-Control Studies , Catheters, Indwelling/statistics & numerical data , Communicable Disease Control/statistics & numerical data , Creatinine/urine , Cross Infection/epidemiology , Cross Infection/urine , Drug Therapy, Combination/adverse effects , Female , Hospitals, University , Humans , Length of Stay , Male , Middle Aged , Odds Ratio , Patient Transfer , Pennsylvania , Regression Analysis , Risk Factors
18.
Am J Med ; 87(5): 547-52, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2816970

ABSTRACT

PURPOSE: A case-control study was performed to identify and quantify risk factors for amphotericin B-associated nephrotoxicity. PATIENTS AND METHODS: Thirty-five patients receiving intravenous amphotericin B for treatment of proven or suspected fungal infection who developed nephrotoxicity (greater than 100% increase in baseline serum creatinine to a level above the normal range) were compared with 60 control patients receiving amphotericin B who did not develop nephrotoxicity. Amphotericin B dosing variables and other potential risk factors were analyzed in a logistic regression model. RESULTS: Cases of nephrotoxicity received a significantly higher average daily dose of amphotericin B (0.49 +/- 0.18 mg/kg/day) than did controls (0.34 +/- 0.17 mg/kg/day). In a multivariate model, the risk of nephrotoxicity increased 3.7-fold for each 50-mg increase in total dose for a fixed duration of therapy and patient weight. Risk decreased by a factor of 0.4 for each extra day of therapy for a fixed total dose and weight. An increase in weight was also protective when the two other dosage variables were held constant. Each 0.10 mg/kg/day dose increment was associated with a 1.8-fold (95% confidence interval, 1.2 to 2.7) increase in the risk of nephrotoxicity. Other significant risk factors included diuretic use during amphotericin B therapy (12.5, 1.7 to 94.7), for which a linear dose-response relationship was demonstrated, and an abnormal baseline serum creatinine level (15.4, 1.4 to 173.2). CONCLUSION: Risk factors for amphotericin B-associated nephrotoxicity include higher average daily doses (approximately a doubling for each 0.10 mg/kg/day increment), diuretic use, and abnormal baseline renal function. These data suggest possible protective interventions and will aid clinicians in assessing the risk-benefit ratio of amphotericin B therapy for deep fungal infection.


Subject(s)
Amphotericin B/adverse effects , Kidney Diseases/chemically induced , Adult , Aged , Case-Control Studies , Creatinine/blood , Diuretics/administration & dosage , Dose-Response Relationship, Drug , Humans , Kidney Diseases/epidemiology , Middle Aged , Pennsylvania , Risk Factors
19.
J Nucl Med ; 35(10): 1602-8, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7931656

ABSTRACT

UNLABELLED: This study quantifies some of the outcome predictors in a group of children with primary vesicoureteral reflux who were initially managed medically. METHODS: We studied 133 patients with primary reflux for 7.1 +/- 2.2 yr. Direct vesicoureteral scintigraphy (DVS) was used to prospectively measure the absolute bladder volume at which reflux began and the maximum volume of urine refluxed into the ureters during the filling and voiding phases of their first two DVS studies. Findings were related to outcome as defined by spontaneous resolution or the eventual need for reconstructive surgery. RESULTS: Medical management eventually failed in 35% of this sample. Patients who did not begin to reflux until their bladders had been filled to more than 60% total bladder capacity had a substantially smaller risk of surgery than those who began to reflux at smaller bladder volumes. Patients who refluxed a volume of urine back into their ureters that was less than about 2% of their total bladder capacity had a substantially smaller risk of surgery than those who refluxed more than 2%. The difference between groups was significant for both DVS variables (p < 0.001). CONCLUSION: Quantitative DVS contributes to the assessment of prognosis in children with vesicoureteral reflux who are managed medically.


Subject(s)
Sodium Pertechnetate Tc 99m , Ureter/diagnostic imaging , Urinary Bladder/diagnostic imaging , Vesico-Ureteral Reflux/diagnostic imaging , Child , Child, Preschool , Female , Humans , Logistic Models , Male , Predictive Value of Tests , Prognosis , Prospective Studies , Radionuclide Imaging , Treatment Outcome , Vesico-Ureteral Reflux/epidemiology , Vesico-Ureteral Reflux/therapy
20.
Sleep ; 18(3): 158-66, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7610311

ABSTRACT

Questionnaire data from patients presenting at three sleep disorders centers were used to develop and assess a screening tool for sleep apnea based on the reporting of the frequency of various symptoms of sleep apnea and other sleep disorders plus age, body mass index (BMI) and gender. Patients were not specifically referred for suspicion of sleep apnea. Separate factor analyses of survey responses from 658, 193 and 77 respondents from the first, second and third sites, respectively, each yielded four orthogonal factors, one of which accounted for all the questions concerned with the frequency of disordered breathing during sleep. The survey was shown to be reliable in a subset of patients from one of the sites (test-retest correlation = 0.92). Survey data were then compared to a clinical measure of sleep apnea (respiratory disturbance index) obtained from polysomnography. A multivariable apnea risk index including survey responses, age, gender and BMI was estimated using multiple logistic regression in a total sample of 427 respondents from two of the sites. Predictive ability was assessed using receiver operating characteristic (ROC) curves. The area under the ROC curve was 0.79 (p < 0.0001). For BMI alone, it was 0.73, and for an index measuring the self-report of the frequency of apnea symptoms, it was 0.70. The multivariable apnea risk index has potential utility in clinical settings.


Subject(s)
Sleep Apnea Syndromes/diagnosis , Adult , Aged , Blood Pressure , Body Mass Index , Female , Health Surveys , Humans , Male , Middle Aged , Polysomnography , Prospective Studies , Respiratory Insufficiency/complications , Risk Factors , Sleep Apnea Syndromes/complications , Sleep Stages , Sleep, REM , Surveys and Questionnaires
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