Electron microscopy study of refractory ceramic fibers.

In epidemiological studies designed to identify potential health risks of exposures to synthetic vitreous fibers, the characterization of airborne fiber dimensions may be essential for assessing mechanisms of fiber toxicity. Toward this end, air sampling was conducted as part of an industry-wide study of workers potentially exposed to airborne fibrous dusts during the manufacture of refractory ceramic fibers (RCF) and RCF products. Analyses of a subset of samples obtained on the sample filter as well as on the conductive sampling cowl were performed using both scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to characterize dimensions of airborne fibers. Comparison was made of bivariate fiber size distributions (length and diameter) from air samples analyzed by SEM and by TEM techniques. Results of the analyses indicate that RCF size distributions include fibers small enough in diameter (< 0.25 microm) to be unresolved by SEM. However, longer fibers (> 60 microm) may go undetected by TEM, as evidenced by the proportion of fibers in this category for TEM and SEM analyses (1% and 5%, respectively). Limitations of the microscopic techniques and differences in fiber-sizing rules for each method are believed to have contributed to the variation among fiber-sizing results. It was concluded from these data that further attempts to characterize RCF exposure in manufacturing and related operations should include analysis by TEM and SEM, since the smallest diameter fibers are not resolved with SEM and the fibers of longer length are not sized by TEM.

A feeding protocol for healthy preterm infants that shortens time to oral feeding.

OBJECTIVE: To test the hypothesis that healthy preterm infants randomly assigned to a semi-demand feeding protocol would require fewer days to attain oral feeding and have a satisfactory weight gain compared with control infants receiving standard care. STUDY DESIGN: In 2 neonatal intensive care nurseries, 81 infants 32 to < or = 34 weeks' postconceptional age were randomly assigned to the control (n = 41) or experimental (n = 40) protocol for transition from gavage to oral feedings. The control protocol followed the standard practice of gradually increasing scheduled oral feedings, whereas the experimental protocol used a semi-demand feeding method contingent on infant behavior. Analysis of variance techniques were used to compare the study groups for number of days to attain oral feeding and weight gain. RESULTS: The semi-demand method shortened the time for infants to achieve oral feeding by 5 days (P < .001). There were no differences in weight gain between the study groups, and both groups had satisfactory weight gain. CONCLUSION: The semi-demand method for the transition from gavage to oral feeding in healthy, preterm infants 32 to < or = 34 weeks postconceptional age promotes faster attainment of oral feeding and does not compromise their weight gain.

Vesicoureteral reflux: subpopulations of patients defined by clinical variables.

BACKGROUND: The first imaging evaluation of the child with urinary tract infection (UTI) is often the same for all children, regardless of the child's clinical presentation. However, this approach is simplistic and ignores considerable differences in the frequency of abnormal pathophysiology in different subpopulations of children with UTI. OBJECTIVE: Six clinical variables are evaluated as predictors of vesicoureteral reflux (VUR) in a large series of girls with UTI. MATERIALS AND METHODS: Data were collected from a consecutive series of 919 girls undergoing a first imaging evaluation for UTI. Six input variables were used: age, maximum body temperature (T(max)), number of UTIs, hospitalization, family history of childhood UTI, and rapidity of response to antibiotic therapy. The dependent variable was VUR. Data were enumerated and analyzed by logistic regression and the chi-square test. RESULTS: VUR was present in 28.8 %. The percentage with VUR varied from 56.1 % for age < 6 months and T(max) L 38.5 degrees C to 13.0 % for age L 10 years and T(max) < 38.5 degrees C. The frequency of VUR was significantly lower in girls with T(max) < 38.5 degrees C in most age groups. Logistic regression demonstrated, when all clinical variables were taken together, that only age and T(max) were independent predictors of VUR. CONCLUSIONS: Girls with UTI should not be considered to be a homogeneous group. The frequency of VUR is related to T(max) and inversely to age. Data about these subpopulations should be used in deciding which girls should undergo cystography.

Cyclic cystography: diagnostic yield in selected pediatric populations.

PURPOSE: To test the hypothesis that the diagnostic yield of cyclic cystography is related to the prevalence of vesicoureteral reflux (VUR) in the population being evaluated. MATERIALS AND METHODS: Two groups of children were examined prospectively: 124 with severe urinary tract infection, defined as patient hospitalization or a maximum temperature greater than 39.5 degrees C, and 135 with previously diagnosed VUR. Nuclear cystography was performed in 249 patients, and fluoroscopic cystography was performed in 10. If VUR was not seen during the first cycle of bladder filling and voiding, a second cycle was performed. RESULTS: VUR was present during cycle 1 in 40 (32%) of 124 patients with severe urinary tract infection and 90 (67%) of 135 children in the VUR follow-up group (P < .001). VUR was demonstrated during cycle 2 in seven (9%) of 76 of the severe urinary tract infection group and eight (24%) of 34 of the VUR follow-up group (P = .045). Of 15 patients with VUR during cycle 2, two had grade III VUR and 13 had grade I or II VUR. CONCLUSION: The second cycle of cyclic cystography has a higher diagnostic yield in patients undergoing VUR follow-up than in patients with severe urinary tract infection. The decision to perform a second cycle of bladder filling and voiding should take into account the pretest probability of VUR in the child being examined.

Correlation of the C677T MTHFR genotype with homocysteine levels in children with sickle cell disease.

Recently, a mild to moderate elevation in the plasma homocysteine (Hcy) level has been found to be an important risk factor for stroke. Homozygosity for a common mutation (C677T) in the gene encoding for the enzyme methylenetetrahydrofolate reductase (MTHFR) involved in Hcy metabolism has been associated with increased levels of Hcy. To determine the role of hyperhomocysteinemia in the pathogenesis of stroke in children with sickle cell disease (SCD), Hcy levels and C677T MTHFR genotype were determined in 40 patients homozygous for hemoglobin SS and compared with 197 healthy children. Eleven of 40 patients with SCD had a history of stroke. The prevalence of homozygosity for the C677T MTHFR variant was 5% in the patients with SCD. The median Hcy level was 5.8 micromol/L in the patients versus 5.4 micromol/L in the controls (Fisher's, P > 0.05). There was no correlation of Hcy levels with the MTHFR genotype in patients with SCD. In patients with SCD and stroke, the median Hcy level was 4.8 micromol/L versus 6.0 micromol/L in those without stroke (P = 0.44, Mann-Whitney rank sum test). There was no difference in the proportion of patients with SCD with or without stroke who were homozygous for the C677T MTHFR mutation (0/11 versus 2/29; Fisher's, P = 1.000). In conclusion, this study failed to demonstrate an elevation in plasma Hcy levels in children with SCD compared with normal controls. Furthermore, hyperhomocysteinemia did not seem to be a significant factor in the pathogenesis of stroke in children with SCD.

Efficacy and mortality in treatment of refractory generalized convulsive status epilepticus in children: a meta-analysis.

There is no consensus on the choice of drug treatment for refractory generalized convulsive status epilepticus in children. The objective of this meta-analysis of the published literature was to determine the effects of drug treatments on efficacy (seizure cessation) and mortality in children with this condition, controlling for potential confounding factors. One hundred eleven children, treated with diazepam, midazolam, thiopental, pentobarbital, or isoflurane, met strict inclusion criteria. Diazepam was significantly less efficacious than other treatments (P = .006) stratifying for etiology. Overall mortality was 20% in symptomatic cases and 4% in idiopathic cases (P = .038). Mortality was less frequent in midazolam-treated patients (P = .021) stratifying for etiology. Midazolam appears to be a good choice for initial treatment of refractory generalized convulsive status epilepticus in children, but the attribution of differences in efficacy and mortality solely to drug effect is not possible based on the published literature.

Transforming growth factor beta1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis.

The transforming growth factor beta (TGF-beta) pathway is known to play an important role in both human and urine colon cancer. However, the staging, ligand specificity, and mechanism underlying the tumor suppressive activity of this pathway are unknown. We developed a mouse model for colon cancer that identifies an early role for TGF-beta1 in tumor suppression and implicates TGF-beta2 or TGF-beta3 in the prevention of metastasis. Analysis of the development of colon cancer in TGF-beta1 knockout mice pinpoints the defect to the hyperplasty/adenoma transition and reveals that the mechanism involves an inability to maintain epithelial tissue organization and not a loss of growth control, increased inflammatory activity, or increased genetic instability. These mice provide a unique opportunity to investigate the specific role of TGF-beta1 at this critical transition in the development of colon cancer.

Prospective assessment of coronary heart disease risk factors: the NHANES I epidemiologic follow-up study (NHEFS) 16-year follow-up.

OBJECTIVE: Our specific aim in the 16 year prospective NHANES I epidemiologic follow-up study (NHEFS) was to assess the important roles of modifiable dietary and behavioral factors in causation and prevention of deaths and hospitalizations for coronary heart disease (CHD). METHODS: Using NHEFS 16 year follow-up data (1971 to 1987), we studied 5811 subjects, 1958 with and 3853 without CHD events, using logistic regression. RESULTS: In age groups 40 to 49, 50 to 59, 60 to 69, and 70 to 74 years (at study entry in 1971-4), the numbers of men and women were respectively 597 and 1019, 570 and 619, 932 and 1042, and 486 and 546. The following factors were independently positively associated (p < .05) with CHD: age, serum cholesterol, body mass index, cigarette use, and region (Midwest, Northeast). The following factors were independently negatively associated (p < .05) with CHD: gender (female), race (black), fish intake, alcohol, high school education, moderate exercise, and moderate and heavy habitual physical activity. Subjects with serum cholesterol > 249 mg/dl benefitted less (p = .04) from fish intake than those with 209 to 249 or < 209, and benefitted less (p = .03) from alcohol intake (CHD incidence [%]): [see text] CONCLUSIONS: These associations emphasize the important role of modifiable dietary and behavioral factors in the causation and prevention of CHD.

Attention-deficit hyperactivity disorder among homeless veterans.

Among 100 participants in a Department of Veterans Affairs domiciliary program for chronic mentally ill homeless veterans who were consecutively referred for psychiatric consultation, 81 who were not psychotic and did not have central nervous system damage were screened for attention-deficit hyperactivity disorder (ADHD). The screening instrument was a four-item questionnaire. Fifty of the 81 participants screened positive, yet none of the patients or their clinicians had considered ADHD a possible influence on their lives. The study results suggest that clinical staff working with homeless veterans should receive better training in recognizing the various presentations of ADHD among adults.

A comparison of exposures to refractory ceramic fibres over multiple work shifts.

As part of an ongoing, industry-wide study in the manufacture of refractory ceramic fibres (RCF), time weighted average (TWA) exposures have been collected at five facilities according to a standardised protocol. Work activities were grouped into dust zones (DZs). Persons to be sampled were randomly selected according to a protocol designed to assure that at least one sample was collected annually from each DZ; each work shift is also sampled at least annually. TWA exposures calculated over a sampling period of at least 360 min were included in the data set. DZs were combined into one of three groups (DZGs): fibre production; vacuum processes; other. The data were analysed to identify any differences by DZG between airborne fibre exposures, by the shift worked at each facility, and across all facilities. There were no statistically significant shift-related differences detected between airborne fibre exposures across the five RCF facilities when analysed as a group. Within four of the facilities, no shift-related differences were detected between airborne fibre exposures; however, at one facility, first and third shift exposures were statistically different. No documentation related to job activities was found to account for the observation. The data generally support the use of a single exposure estimate for each DZG in each of these facilities, regardless of shift worked. Researchers reconstructing exposure and not able to determine the shift worked by study subjects may find these results useful, but are cautioned that substantial differences in exposure across shifts may exist in other types of manufacturing.

Effect of food palatability on early (cephalic) phase of diet-induced thermogenesis in nonobese and obese man.

OBJECTIVE: To study the effect on the early (cephalic) phase of diet-induced thermogenesis (EDT) of palatable vs unpalatable food, in nonobese and obese man. SUBJECTS: Twenty-four nonobese volunteers and 19 obese clinic patients. DESIGN AND MEASUREMENTS: A palatable, liquid formula meal of Ensure (1048 KJ, 450 ml), and of Ensure made unpalatable by addition of aqueous KCl, were sipped on nonconsecutive mornings. O2 consumption (ml/min) was measured before, and starting 30, 60 and 90 min after beginning the test meal, from which EDT was calculated as KJ/min. RESULTS: Palatability of the test meal significantly increased EDT (palatability effect, P = 0.004) but obesity status per se, did not affect EDT. Nevertheless, the effect of palatability on EDT was dependent on obesity status, being seen only in the nonobese. EDT was significantly greater in the nonobese after the palatable than the unpalatable meal: (mean +/- s.e.m.) 2.45 +/- 0.14 vs 1.83 +/- 0.14; P < 0.0001, but not in the obese: 1.93 +/- 0.28 vs 1.73 +/- 0.20; P < 0.21. Therefore only after the palatable meal was EDT less in the obese compared with the nonobese: P < 0.05. The threshold for the unpleasant taste of added KCI was 31% higher in the obese than the nonobese: 4.2 +/- 0.4 vs 3.2 +/- 0.2 [g KCI]; P < 0.025. CONCLUSIONS: The early (cephalic) phase of dietary thermogenesis (EDT) is significantly increased in the nonobese by palatability, but not in the obese, so that only after a palatable meal is EDT less, or 'deficient,' in the obese compared with the nonobese. Also, the obese have a higher threshold for the unpleasant taste of KCI (in Ensure) than the nonobese.

Prospective 10-year evaluation of hypobetalipoproteinemia in a cohort of 772 firefighters and cross-sectional evaluation of hypocholesterolemia in 1,479 men in the National Health and Nutrition Examination Survey I.

Our specific aim in a 10-year prospective study of 772 Cincinnati firemen (predominantly aged 26 to 46 years) was to determine the prevalence, attributes, and etiology of persistent hypobetalipoproteinemia, defined by entry low-density lipoprotein cholesterol (LDLC) less than 75 mg/dL. A second specific aim was to cross-sectionally assess hypocholesterolemia (defined by total serum cholesterol [TC] < 130 mg/dL) in 1,314 white and 165 black men aged 26 to 46 years in the National Health and Nutrition Examination Survey (NHANES I). The 141 black and 631 white firemen had 4,973 person-years of follow-up time (median, 7.1 yr/man). Of 772 men, 44 (5.7%) had entry LDL levels less than 75 mg/dL; they had a mean follow-up time of 7.3 yr/man. Of these 44 men, there were 12 (1.8% of the cohort) with entry LDLC less than 75 mg/dL, and at least 67% of their follow-up LDLC levels were less than 75. Their mean entry TC and LDLC levels were low (130 and 58 mg/dL), mean triglyceride (TG) was low (63 mg/dL), and mean high-density lipoprotein cholesterol (HDLC) was high (60 mg/dL), LDLC remained at less than 75 mg/dL in 81% of their follow-up samples. Their mean entry and follow-up cholesterol and LDLC did not differ (P > .1, 130 v 133 mg/dL and 58 v 63 mg/dL). Compared with 32 men with entry LDLC less than 75 mg/dL but with less than 87% of follow-up LDLC less than 75 mg/dL, the 12 men with persistently low LDLC had lower mean Quetelet indices and diastolic blood pressure at entry (2.36 v 2.58, P = .056; 73 v 80 mm Hg, P = .03) and on follow-up study (2.45 v 2.69, P = .04; 72 v 79 mm Hg, P = .05). Of 12 men with persistently low LDLC, two had truncated apolipoprotein (apo) B (familial hypobetalipoproteinemia, two had the apo E genotype 2/3, and two had acquired hypobetalipoproteinemia that antedated mortality from melanoma by 9 years and from alcoholism by 2 years. Comparable to white and black firemen aged 26 to 46 years, 2.9% and 3.6% of whom had entry serum TC less than 130 mg/dL, of 1,314 white and 165 black men in the NHANES I study (aged 26 to 46), 1.8% and 3.6% had hypocholesterolemia (entry TC < 130 mg/dL). Daily mean calorie, fat, and protein intake (grams per day) did not differ (P > .05) in men with entry TC less than 130 mg/dL compared with those with TC 130 to 230 or greater than 230 mg/dL. Hypocholesterolemia in white and black men in NHANES I could not be attributed to hypocaloric intake or to protein, fat, or carbohydrate undernutrition. There appear to be racial differences in the prevalence of hypocholesterolemia. Blacks comprised 18% of the firemen's cohort but 42% of those with persistent hypobetalipoproteinemia; among NHANES I subjects, 3.6% of blacks were hypocholesterolemic versus 1.8% of whites. Unless persistent hypobetalipoproteinemia reflects an underlying disease, alcoholism, etc., it is often heritable, and may be associated with a reduced likelihood of coronary heart disease (CHD) and with increased longevity.

Overexpression and amplification of glutathione S-transferase pi gene in head and neck squamous cell carcinomas.

Human glutathione S-transferase pi (GST-pi) may serve as a useful tumor marker because of the high frequency with which it is found in elevated levels in several tumor types. To determine whether GST-pi is useful as an indicator for cancers of the head and neck, expression of GST-pi mRNA was investigated by Northern analysis in this tumor type. Overexpression of GST-pi mRNA was detected in 9 of 36 (25%) primary head and neck squamous cell carcinomas (HNSCCs). When Southern blot analysis was used to examine the relationship between overexpression and amplification of the GST-pi gene, only 3 of 36 tumors (8%) showed GST-pi gene amplification. Thus, gene amplification is not critical to GST-pi mRNA overexpression in HNSCCs. Moderately and poorly differentiated HNSCCs tended to manifest elevated GST-pi mRNA compared with well differentiated tumors (30% for moderately and poorly differentiated tumors versus none of the well differentiated tumors examined). However, there was no significant correlation between GST-% mRNA overexpression and clinical stage, T stage (tumor size), N stage (neck nodal status), pathological nodes, or patient survival.

Pulmonary function in obese subjects with a normal FEV1/FVC ratio.

STUDY OBJECTIVE: To determine pulmonary function test (PFT) profile and respiratory muscle strength (RMS) of a group of obese individuals who did not have evidence of obstructive airway disease or other underlying diseases affecting their respiratory system. DESIGN: Prospective, open. SETTING: PFT laboratory, VA Medical Center. PARTICIPANTS: Sixty-three consecutive obese (body mass index greater than 27.8 kg/m2) male subjects without overt obstructive airway disease (FEV1/FVC ratio greater than 80%). MEASUREMENTS AND RESULTS: Standard PFTs and maximum static inspiratory (PImax) and expiratory (PEmax) mouth pressures were determined. RMS was calculated from the following formula: (PImax+PEmax):2. Two distinct groups were identified, those with normal maximum voluntary ventilation (MVV) (> 80% predicted) and those with low MVV. Both inspiratory and expiratory flow rates (FVC, FEV1, forced expiratory flow at 50% vital capacity [V50], maximum inspiratory flow rate [MIFR]), lung volumes (vital capacity [VC], inspiratory capacity [IC], expiratory reserve volume), PImax, and RMS were significantly lower, and residual volume/total lung capacity (RV/TLC) ratio was significantly higher in obese subjects with low MVV compared with those in whom MVV was normal. MVV correlated significantly with FVC, FEV1, V50, MIFR, TLC, VC, IC, RV/TLC, and RMS; the strongest correlation was with MIFR (r = 0.76, p < 0.0001). CONCLUSIONS: Standard PFTs allow recognition of a subgroup of obese subjects without overt obstructive airway disease who have more severe lung dysfunction, the marker of which is a low MVV. Peripheral airway abnormalities may be responsible for these observations.

The loss of heterozygosity in retinoblastoma and p53 suppressor genes as a prognostic indicator for head and neck cancer.

Inactivation of tumor suppressor genes, including p53 and retinoblastoma (Rb), are commonly found in all cancers, including head and neck squamous cell carcinoma. Alterations at either p53 or Rb, however, are only weakly associated with tumor aggressiveness. In many cancers loss of heterozygosity (LOH) at multiple loci is associated with decreased survival. The polymerase chain reaction and highly informative microsatellite markers were used to compare DNA from matched sets of 63 head and neck squamous cell cancers and normal tissue for LOH at the p53 and Rb loci. At p53, 50 were informative, with LOH occurring in 19 (38%). Of the 57 that were informative at Rb, LOH occurred in 21 (37%). Of the 46 that were informative at both p53 and Rb, LOH occurred in 10 (22%) at both loci. When LOH for p53 and Rb individually was compared to stage, differentiation, and survival, there was no correlation. However, the patients with LOH at both loci had a significantly poorer survival (P = .009). This strongly supports the contention that simultaneous alterations of these two tumor suppressor genes favor tumor aggressiveness and can be used as a prognostic indicator.

Risk factors for coronary heart disease among firefighters in Cincinnati.

Since 1984, coronary heart disease (CHD) risk factors have been prospectively assessed among Cincinnati firefighters free of CHD at study entry. In total, 806 firemen with a mean age of 37 years at entry have been followed for 6.4 years on average, contributing 5,173 person-years. CHD risk factors were measured every 1-4 years and included weight, blood pressure, cigarette use, fasting glucose, and lipid profile. When, in aggregate, these CHD risk factors were found to be in a high risk range, suggestions were made serially to reduce CHD risk. A composite high CHD risk factor score led to an exercise electrocardiogram (ECG) with thallium scan, which was repeated every 1-4 years. Myocardial infarction (MI) occurred in 7 men, with 1.35 MIs/1,000 man-years; 15 others developed CHD, with 4.25 MI + CHD/1,000 man-years. The firefighters' MI event rate (1.35 MIs/1,000 man-years) was lower (but not significantly, p > 0.1) than that for employed 30- to 39-year-old men free of CHD at entry (2.07/1,000 man years), who had an average follow-up of 5.4 years in the NHANES I study. At study entry, the 22 men who later developed CHD (vs. the 784 who did not develop CHD) were older (p = .0001), smoked more (p = .0001), and were more likely to have first degree relatives with CHD before age 60 (p = .017). After covariance adjusting for age, race, and Quetelet index, men with CHD (vs. those CHD free) had higher systolic and diastolic blood pressures (p = .0001, .0001), higher LDL cholesterol (p = .04), higher total cholesterol (p = .014), and higher triglycerides (p = .03). By Poisson regression, significant independent predictors of CHD events were age (p = .0007), cigarette smoking (p = .001), diastolic blood pressure (p = .056), and family history of CHD at age < or = 60 (p = .048). Men who later developed CHD and those without CHD did not differ by history of smoke inhalation (p > 0.3). The calculated ratio of savings to cost attributable to the program per year was 5.9/1 ($258,500/$43,600). In the current study, firefighting as an occupation was not associated with increased CHD event rates. CHD events that did develop were, for the most part, associated with modifiable CHD risk factors.

The important role of modifiable dietary and behavioral characteristics in the causation and prevention of coronary heart disease hospitalization and mortality: the prospective NHANES I follow-up study.

OBJECTIVE: Our specific aim in the prospective, longitudinal assessment of 8,251 subjects in the National Health and Nutrition Examination Survey, NHANES I, followup study was to assess the important roles of modifiable dietary and behavioral characteristics in the causation and prevention of coronary heart disease (CHD). METHODS: Using NHANES I prospective 10 year followup data, we studied 8,251 subjects; 492 with cardiovascular events and 7,759 without events during the followup period (1971-75 to 1982-84). Using general linear models and logistic regression, we assessed the relationships of CHD risk factors to CHD morbidity and mortality. RESULTS: By logistic regression, the following factors were independently, significantly, and inversely associated with coronary heart and vascular disease deaths and hospitalizations: alcohol intake, dietary riboflavin, dietary iron, serum magnesium, leisure time exercise, habitual physical activity, and female gender. Positive significant independent determinants of CHD events included cigarette smoking, sedimentation rate, Quetelet index, maximum body weight, and age. CONCLUSIONS: These associations emphasize the important role of modifiable dietary and behavioral characteristics in the causation and prevention of CHD.

Chronic hypercapnia in obstructive sleep apnea-hypopnea syndrome.

In order to determine the relationship between chronic hypercapnia and anthropomorphic data, pulmonary function tests and slopes of ventilatory responses to hypercapnia (HVCR) and hypoxia (HVR), we studied 55 patients with sleep apnea-hypopna syndrome (SAHS). Patients were divided into hypercapnic, PaCO2 > or = 45 mm Hg (Group I, n = 23, PaO2 = 61 +/- 10 and PaCO2 = 50 +/- 5 mm Hg, and [HCO3-] = 30 +/- 4 mEq/l [means +/- SD]) and normocapnic (or eucapnic), PaCO2 < 45 mm Hg (Group II, n = 32, PaO2 = 76 +/- 10 and PaCO2 = 39 +/- 4 mm Hg and [HCO3-] = 25 +/- 3 mEq/l [means +/- SD]) groups. When compared to the normocapnic group, hypercapnic patients were significantly heavier (with greater body surface area) and had significantly more severe restrictive and obstructive defects and impaired HVR and HCVR. The means (+/- SD) of some of the data follow (* indicates p < 0.05 when Group I is compared to Group II): [table: see text] When subgroups of hypercapnic and eucapnic patients with similar lung functions were compared, the subgroups differed significantly in their weights; conversely, in subgroups with comparable weights, lung function tests differed significantly. These data suggest that the mechanisms of chronic hypercapnia are multifactorial, and we hypothesize that, in the face of repetitive apneas and hypopneas, increased weight and abnormal lung function tests interact and contribute to the generation and maintenance of hypercapnia.

Acute respiratory acidosis: large-dose furosemide and cerebrospinal fluid ions.

NaCl cotransport carrier is known to be involved in transepithelial fluid absorption and secretion in various tissues. Recent studies indicate that Na-K-2Cl cotransport carrier also exists in the choroid plexus cells and that inhibition of the carrier decreases cerebrospinal fluid (CSF) production. In this study, we used large-dose intravenous furosemide, an inhibitor of Na-K-2Cl carrier, to determine the effects on cisternal CSF ionic composition in acute respiratory acidosis. In pentobarbital-anesthetized mechanically ventilated dogs, renal pedicles were ligated to prevent furosemide-induced diuresis. The experimental group (group II, n = 7) received 400 mg/kg of furosemide intravenously, and group I (control group, n = 7) received the vehicle. In group II, serial serum and CSF furosemide concentrations were approximately 10(-3) and 10(-5) mol/l, respectively. During 5 h of acute respiratory acidosis in both groups, the mean arterial PCO2 increased approximately 25 Torr, with comparable changes in CSF PCO2. In both groups, CSF [HCO3-] and [H+] rose approximately 3 meq/l and 20 neq/l, respectively. Changes in CSF [Na+], [K+], [Cl-], and [Na(+)-Cl-] were also similar and were not significantly different from each other when the two groups were compared. These data show that furosemide at the dose that inhibits NaCl cotransport carrier does not significantly alter ionic composition of cisternal CSF.