Neurocognitive functioning in adults with phenylketonuria: Report of a 10-year follow-up.

BACKGROUND: The long-term prognosis of early treated phenylketonuria (PKU) is still under discussion. Aim of this controlled long-term study was to assess the neurological and neuropsychological outcome in adult patients with early-treated PKU. METHODS: We investigated 35 patients with early-treated classical PKU aged 29 to 51 years (mean age 41 years) and 18 healthy controls matched for age and socioeconomic status. Patients and controls were assessed for their intelligence quotient (IQ), attention and information-processing abilities. Magnetic resonance imaging (MRI) of the brain was performed in all patients. Neuropsychological assessments and MRI were repeated at a five-year and a ten-year follow-up. RESULTS: In the entire interval IQ, information processing and attention of patients and controls remained constant. At both follow-up assessment times the IQ scores were significantly lower in patients compared to controls. Older adult patients (> 42 years) showed poorer information processing and attention at both assessment times compared to young adult patients (< 42 years) and controls. IQ, information processing and attention showed no correlation to imaging results. IQ, however, was significantly correlated to blood phenylalanine (Phe) levels in patients´ childhood and adolescence, and Phe levels had been higher in the adolescent years of older adult patients. CONCLUSIONS: Cognitive performance in adult patients with early-treated PKU does not seem to deteriorate in a ten-year interval. Neuropsychological assessment in adults with PKU revealed neurocognitive impairment particularly in older adult patients. This seems to refer to an early relaxation of diet that was recommended when the older patients were adolescents. Results indicate a benefit of dietary control during adolescence in PKU.

Physiologically based pharmacokinetic (PBPK) tool kit for environmental pollutants--metals.

The Agency for Toxic Substances and Disease Registry (ATSDR) is mandated by the US Congress to identify significant human exposure levels, develop methods to determine such exposures, and design strategies to mitigate them. Physiologically based pharmacokinetic (PBPK) models are increasingly being used to evaluate toxicity of environmental pollutants through multiple exposure pathways. As part of its translational research project, ATSDR is developing a human 'PBPK model tool kit' that consists of a series of published models re-coded in a common simulation language. The tool kit currently consists of models, at various stages of development, for priority environmental contaminants including solvents and persistent organic pollutants. Presented here are results of translational activities of re-coding models for cadmium, mercury, and arsenic. As part of this work, following re-coding each new model was evaluated for fidelity followed by sensitivity analysis. Good agreement was generally obtained for all three models when predictions of original and re-coded model simulations were compared. Also presented is an application of the cadmium toxicokinetic model to interpret biomonitoring data from the National Health and Nutrition Examination Survey (NHANES). The PBPK tool kit will enable ATSDR scientists to perform simulations of exposures from contaminated environmental media at sites of concern and to better interpret site-specific biomonitoring data.

Levamisole: a dangerous new cocaine adulterant.

Levamisole has increasingly been discovered in street cocaine as an adulterant. Recent reports have linked levamisole in street cocaine to agranulocytosis in cocaine users. It is well known that agranulocytosis is associated with therapeutic use of levamisole, and this may have led to the withdrawal of the drug from the US market. Levamisole was a US Food and Drug Administration-approved drug that has been used as an immunomodulator, a chemotherapy adjuvant, and anthelmintic medication. The purpose of adulterating street cocaine with levamisole is not known, but it has been speculated that it is added intentionally in order to potentiate the effects of cocaine. This may be supported by the recent report of metabolism of levamisole to aminorex in racehorses. Aminorex and related compounds, specifically 4-methylaminorex, or "ice," have high abuse potential because of their amphetamine-like pharmacological activity. This metabolism has not been reported in humans, and therefore the intended role of levamisole in street cocaine remains an enigma.

Factors influencing the difference between maternal and cord blood lead.

AIMS: To determine the factors that affect why some infants receive higher exposures relative to the mother's body burden than do others. METHODS: A total of 159 mother-infant pairs from a cohort of women receiving prenatal care at Magee-Womens Hospital in Pittsburgh, PA from 1992 to 1995 provided blood samples at delivery for lead determination. The difference between cord and maternal blood lead concentration (PbB) and a dichotomous variable indicator of higher cord than maternal PbB, were examined as indicators of relative transfer. Women were interviewed twice during the pregnancy about lifestyle, medical history, calcium nutrition, and physical activity. RESULTS: Higher blood pressure was associated with relatively greater cord compared with maternal PbB, as was maternal alcohol use. Sickle cell trait and higher haemoglobin were associated with a lower cord relative to maternal blood lead PbB. No association was seen with smoking, physical exertion, or calcium consumption. CONCLUSION: While reduction in maternal exposure will reduce fetal exposure, it may also be possible to mitigate infant lead exposure by reducing transfer from the pregnant woman. Interventions aimed at reducing blood pressure and alcohol consumption during pregnancy may be useful in this regard.

Synthesis, dark toxicity and induction of in vitro DNA photodamage by a tetra(4-nido-carboranylphenyl)porphyrin.

The total synthesis of tetra(4-carboranylphenyl)porphyrins 4 and 6 and their zinc(II) complexes 5 and 7 are described. These compounds were characterized by analytical and spectroscopic methods and, in the case of 5, by X-ray crystallography. The water-soluble nido-carboranylporphyrins 6 and 7 were found to have low dark toxicity towards V79 hamster lung fibroblast cells, using a clonogenic assay (50% colony survival, CS(50)>300 microM). Upon light activation nido-carboranylporphyrin 6 effectively induced DNA damage in vitro. Two different methods were used to assess the extent of DNA damage: the super-coiled to nicked DNA and the alkaline Comet assay using human leukemia K562 cells. Significant PDT-induced DNA damage was observed for porphyrin 6 using both assays, compared to light-only and porphyrin-only experiments. It is concluded that this type of nido-carboranylporphyrin is a promising sensitizer for both the boron neutron capture therapy and the photodynamic therapy of tumors.

Patterns and determinants of blood lead during pregnancy.

The pattern of blood lead during pregnancy was investigated in a cohort of 195 women who, between October 1992 and February 1995, entered prenatal care at Magee-Womens Hospital in Pittsburgh, Pennsylvania, by week 13 of pregnancy. Blood was drawn as many as five times, once in each of the first two trimesters and a maximum of three times in the third trimester. Blood lead determinations were made by atomic absorption spectrophotometry. Potential sources or modifiers of lead exposure were collected by interviews, including sociodemographic, pregnancy history, occupational, and lifestyle data. Results confirmed a previously reported U-shaped curve in blood lead concentration during pregnancy as well as findings that blood lead levels increase with age, smoking, lower educational level, and African-American race and decrease with history of breastfeeding and higher intake of calcium. Additionally, interactions were found between time since last menstrual period and both maternal age and calcium. Specifically, older mothers showed steeper increases in blood lead concentrations during the latter half of pregnancy than did younger mothers, and intake of calcium had a protective effect only in the latter half of pregnancy, an effect that became stronger as pregnancy progressed. These findings provide further evidence that lead is mobilized from bone during the latter half of pregnancy and that calcium intake may prevent bone demineralization.

Risk analysis for thoracoscopic lung volume reduction: a multi-institutional experience.

OBJECTIVE: Most reports of thoracoscopic lung volume reduction (TLVR) are relatively small and early experiences from a single institution, factors which limit both the statistical validity and the applicability to the population at large. In order to address these shortcomings we undertook an analysis of the TLVR experience at five separate institutions to assess operative morbidity and identify predictors of mortality. METHODS: Questionnaires were sent to four groups of surgical investigators at five institutions actively performing TLVR. Data was requested regarding preoperative, operative and postoperative parameters. Twenty-five potential predictors of mortality were analyzed and seven proved to be at least marginally significant (P<0.10). These parameters were entered into a stepwise logistic regression analysis to identify independent predictors. RESULTS: The 682 patients (415 males, 267 females, mean age 64.0 years) underwent unilateral (410) or bilateral (272) TLVRs. Overall, operative mortality was 6% with half of the deaths resulting from respiratory causes. The remaining patients were discharged to home (88%), a rehabilitation facility (4%) or a ventilator facility (2%). There were 25 perioperative factors chosen representing clinically important indices such as spirometry, oxygenation, functional status, clinical and demographic variables. Univariate analysis identified seven variables as predictors of mortality (P<0.10) and these were entered into a stepwise logistic regression analysis. Only age, 6-min walk, gender (male 8%, female 3% mortality) and the procedure performed (unilateral 4.6%, bilateral 8%) were independent predictors while preoperative steroid therapy, preoperative oxygen administration, and time since smoking cessation dropped out of the model. The specific institution, learning curve (early vs. late experience), type of lung disease, spirometric indices and predicted maximum VO(2) were not significant predictors. CONCLUSION: This experience suggests that unilateral and bilateral lung volume reduction procedure can be performed with acceptable morbidity and mortality. Although age, gender, exercise capacity and the procedure performed are all independent predictors of mortality, the risk of operative death did not appear excessive in this fragile patient subset.

Study of the effect of lactational bone loss on blood lead concentrations in humans.

Lactation and other clinical states of high bone turnover have been suggested to release lead (Pb) stored in bone into blood and tissues. Previous observations on the influences of lactation have been anecdotal, or at high blood Pb concentrations with varying past exposures, or complicated by postpartum fluid changes. A prospective observational study was performed to investigate possible changes in blood lead concentrations at multiple intervals during lactation for 6 months postpartum and to relate changes in blood lead concentrations to changes in bone density and other variables. Volunteer pregnant subjects (n = 58) were enrolled from a midwifery service at an academic public health hospital. Subjects were mostly Hispanic, recently immigrated, of low economic status, not receiving supplemental calcium, and had low blood Pb concentrations (2.35 +/- 2.05 microg/dl at enrollment). Bone density losses over 6 months for the group averaged -2.46 +/- 6.33% at the vertebral spine and -0.67 +/- 5.21% at the femoral neck. In predicting final bone density, apart from initial bone density only the total number of breast-feedings was a significant independent variable of the variables tested, accounting for an additional 12% of the variability. No changes in blood Pb concentrations were seen over the interval beyond 2 weeks postpartum (minimum detectable change was 0.4 microg/dl). There was no relation between the changes in bone density and changes in blood Pb or the integrated blood Pb over the 2-week to 6-month period. Normal (nonlactating) bone resorption rates contribute a large fraction of the Pb in blood during low-exposure circumstances. However, during lactation the increase in bone resorptive processes is probably relatively small with a larger decrease in deposition accounting for net bone loss, as suggested by other investigations. Thus, concomitant release of Pb from bones of lactating subjects with low blood lead concentrations on this background of high normal resorption was not large enough for detection.

Long-term survival after thoracoscopic lung volume reduction: a multiinstitutional review.

BACKGROUND: It has been suggested that bilateral thoracoscopic lung volume reduction (BTLVR) yields significantly better long-term survival than unilateral thoracoscopic lung volume reduction (UTLVR). METHODS: All perioperative data were collected at the time of the procedure. Follow-up data were obtained during office visits or by telephone. RESULTS: A total of 673 patients underwent thoracoscopic LVR: 343 had either simultaneous or staged BTLVR and 330, UTLVR. As of July 1998, follow-up was available on 667 (99%) of the 673 patients with a mean follow-up of 24.3 months. The patients in the BTLVR group were significantly younger (62.6+/-8.0 years versus 65.4+/-8.1 years; p < 0.0001), had a higher preoperative arterial oxygen tension (69.7+/-12 mm Hg versus 65.3+/-11 mm Hg; p < 0.0001), and had a superior preoperative 6-minute walk performance (279.9+/-93.6 m [933+/-312 feet] versus 244.5+/-101.4 m [815+/-338 feet] p < 0.0001). There was no difference in the operative mortality rate between the two groups (UTLVR, 5.1%, and BTLVR, 7%). Actuarial survival rates for the UTLVR group at 1 year, 2 years, and 3 years were 86%, 75%, and 69%, respectively versus 90%, 81%, and 74%, respectively, for the BTLVR group (p = not significant). CONCLUSIONS: Contrary to previous reports, survival after BTLVR was not superior to that after UTLVR even though the former group appeared to have a lower risk preoperatively because of younger age, higher arterial oxygen tension, more advantageous anatomy, and better functional status. Despite thoracoscopic LVR, the actuarial mortality rate approached 30% at 3 years, and this calls into question whether this procedure offers any survival advantage to patients with end-stage emphysema.

Methodological considerations for the accurate determination of lead in human plasma and serum.

Studies which accurately measure plasma or serum lead (Pb) are needed to evaluate the 'biologically active' fraction of Pb in the circulation, and to clarify the role of plasma in the transportation of Pb between different compartments of the body. We evaluated several methodological aspects which influence the determination of Pb in plasma and serum. Generally, venous blood was obtained by different sampling methods (routine and ultraclean) from 3 subjects without history of Pb exposure. After centrifugation (800 g) for 10 min, the plasma or serum was analyzed by inductively coupled plasma-high-resolution mass spectrometry (ICP-MS). Several evaluations were conducted, including 1) comparison of an ultraclean serum collection method with a plasma collection method that used a commercial Vacutainer-type tube for trace metals (EDTA anticoagulant); 2) the effect of whole blood standing time prior to centrifugation on plasma or serum Pb concentration; and 3) comparison of a method using commercial heparinized Vacutainer tubes to an ultraclean plasma sampling method that utilized a low-Pb heparin anticoagulant. Plasma or serum iron (Fe) levels were also measured to evaluate hemolysis. The 3 subjects had whole blood Pb (blood-Pb) levels of 1.8, 2.0, and 2.7 micrograms/dl. Their corresponding ultraclean serum-Pb levels were 0.40%, 0.30%, and 0.48% of their whole blood-Pb levels, respectively. By comparison, the EDTA Vacutainer method plasma-Pb values were 1.7%, 1.5%, and 2.4% of whole blood-Pb, respectively. Whole blood standing (clotting) times of 15, 40, and 70 min before centrifugation resulted in increasing ultraclean serum-Pb levels of 0.21%, 0.81%, and 1.2% of whole blood-Pb (1.8 micrograms/dl), respectively. Whole blood standing time had no effect on plasma-Pb levels when heparin Vacutainers were used, or when a low-Pb heparin was used to obtain ultraclean plasma. However, plasma collected using the commercial heparin Vacutainer method contained consistently higher and more variable Pb levels than samples collected using the ultraclean plasma-Pb method. Hemolysis, when present, contributed significantly to both plasma-Pb and serum-Pb levels. In conclusion, plasma-Pb and serum-Pb levels are dependent upon methodologic processing techniques, including Pb contamination control, redistribution due to EDTA anticoagulant, hemolysis, and time dependency in sample processing. While true plasma-Pb and serum-Pb levels by any method have yet to be defined, these data provide a methodological basis from which to investigate variation in Pb partitioning between whole blood and plasma within individuals.

Indium as internal standard in square wave anodic stripping analysis of lead in blood with microelectrode arrays.

The toxic effects of lead on humans, especially children have been well documented. ASV has been an important technique in the analysis of lead in blood of humans. This research has demonstrated that indium(III) can be used as an internal standard in the analysis of lead in blood samples with mercury film microelectrode arrays. Indium is a good choice because of a low endogenous blood concentration and because baseline separation of anodic stripping peaks among Cd, In, and Pb can be achieved under appropriate conditions. The concentration of sodium bromide strongly influences the resolution of these metals and the sensitivity of ASV to In(III) in solution. Square wave anodic stripping voltammetry together with screen-printed microelectrode arrays showed that the ratio of the anodic stripping peak currents of Pb and In varies linearly with the concentration of Pb in blood samples ranging from 1.2 to 30.0 micrograms/dL. The average intraassay precision (rsd) was 6.7%.

Cisapride poisoning.

A MEDLINE search from 1966-1996 revealed no reports of cisapride poisoning. An 8-mo-old, 8.9 kg girl received 8 mL of cisapride (Propulsid Suspension, 1 mg/mL, Janssen Pharmaceutica, Titusville, NJ) rather than the usual dose of 0.8 mL, resulting in an inadvertent, 10-fold, iatrogenic, dosing error. She developed emesis, hyperactive bowel sounds, abnormal behavior, mild hyperthermia, tachycardia, hypertension, and thrombocytosis. This is the first published report of poisoning with cisapride.

Thoracoscopic lung volume reduction surgery reduces dyspnea and improves exercise capacity in patients with emphysema.

Improved ventilation and exercise capacity follows thoracoscopic lung volume reduction surgery (TLVRS) in patients with severe emphysema. This improvement could be related to changes in inspiratory and expiratory flows following surgery, with consequent improvement in dyspnea indices. Changes in inspiratory/expiratory flows at rest and exercise and their relation to subjective improvement in dyspnea after TLVRS are not well known. We studied 25 patients with severe emphysema who underwent unilateral TLVRS performed in well-defined zones with decreased perfusion in nuclear medicine lung scans. Early follow-up after surgery (4.2 +/- 0.8 mo) showed significant improvements in exercise tolerance: The distance covered over a 6 min walk test increased from 934 +/- 297 to 1,071 +/- 241 ft (p = 0.01). Exercise tolerance using a bicycle ergometer showed increased exercise endurance from 4.43 +/- 1.7 to 5.71 +/- 1.8 min (p < 0.001). The maximum workload tolerated increased from 37 +/- 19 to 52 +/- 21 W (p < 0.01) and VO2 max changed from 9.7 +/- 2 to 11.8 +/- 3 (ml.kg)/min (p < 0.01). This increment was achieved by generating significantly larger minute ventilation (VE), from 24 +/- 11 to 29 +/- 10 L/min, reached through larger tidal volumes (increasing from 951 +/- 330 to 1,145 +/- 367 ml), while maintaining the same maximum respiratory rates. Increased VE was also accompanied by significant increases in both average inspiratory and expiratory flows measured during exercise: from 0.89 +/- 0.41 L/s to 1.06 +/- 0.08 L/s, and from 0.77 +/- 0.37 to 0.90 +/- 0.32 L/s respectively (p < 0.01). The parallel increment in flows resulted in constant T1/Ttot relationship. These functional changes correlated with increased inspiratory flows at rest measured with pulmonary function tests (forced inspiratory volume in one s [FIV1], expiratory flows [FVC, FEV1], and increased maximum voluntary ventilation [MVV]) following the surgically induced reduction in residual volume (RV). These objective changes occurred parallel to improved dyspnea indices. The Baseline Focal Score was 3.36 +/- 1.47 and the Transition Focal Score was 6.12 +/- 0.7. The objectively measured variables at rest that best correlated with subjective improvement in dyspnea were the change in MVV, change in resting arterial PaO2, and change in FEV1 following TLVRS. Exercise variables did not have significant correlation with subjective markers indicating improvement in dyspnea, with the exception of the change in Dyspneic Index [(VE/MVV)100] at maximum exercise.

Histopathologic diagnosis made in lung tissue resected from patients with severe emphysema undergoing lung volume reduction surgery.

STUDY OBJECTIVES: This study reports histopathologic findings in a group of emphysema patients who underwent thoracoscopic lung volume reduction surgery (75) or sternotomy (five) with the purpose to induce functional improvement and relief of dyspnea. Immediate outcome and complications were correlated to histologic patterns. DESIGN: Histopathologic material obtained in lung volume reduction surgery in 80 consecutive patients was analyzed. Thirty patients who had other histopathologic diagnoses in addition to emphysema were grouped and compared with 50 patients found to have emphysema exclusively. Postoperative outcome and preoperative lung function variables were compared. MEASUREMENTS AND RESULTS: All patients had severe obstructive lung disease and significant air trapping preoperatively documented by pulmonary function testing. All had severe exertional dyspnea. All had chest radiographs, CT, and nuclear medicine lung scans consistent only with emphysema. All portions of resected lung tissue were weighed, lung volume was estimated, and routine histopathologic studies were made. Thirty patients (37.5%) had unsuspected findings such as interstitial fibrosis, noncaseating granulomatosis, chronic inflammation, and unsuspected neoplasia (three carcinomas, one carcinoid). Retrospective review of imaging studies in these patients failed to show infiltrative processes. The average lung weight resected in this group was significantly heavier (65+/-18 g) compared with the other group (56+/-13 g), although both had the same estimated lung volume. Average number of days requiring chest tubes and length of hospitalization was also significantly higher (12.8+/-19 vs 6.4+/-5 days with chest tubes and 17.4+/-22 vs 8.5+/-6 days of hospitalization, respectively). None of the preoperative pulmonary function tests variables were different between the two groups. Serious postoperative complications were more frequent in these patients compared with those who showed only emphysema. CONCLUSIONS: A significant portion of patients diagnosed as having severe emphysema will have other unsuspected histologic findings. When subjected to lung volume reduction surgery, this subgroup will have more serious complications and longer periods of air leaks, requiring longer hospitalization time. Retrospective review of imaging studies and preoperative pulmonary function tests used to select patients for lung volume reduction failed to identify this subgroup.

Hemodynamics and gas exchange after single lung transplantation and unilateral thoracoscopic lung reduction.

BACKGROUND: Single lung transplantation and recently thoracoscopic lung reduction (TLR) have become surgical alternatives to manage emphysema. We report here early outcomes of 10 single lung transplant (SLT) recipients with severe emphysema compared with 10 patients treated with unilateral TLR. METHODS: Ten consecutive recipients of (SLT) and 10 patients undergoing unilateral TLR were studied. Both groups had measurements of preoperative pulmonary function and arterial blood gases. Hemodynamic measurements were made by use of a right ventricular ejection fraction/volumetric pulmonary artery catheter during and immediately after surgery in both groups to compare hemodynamic and gas exchange response in each procedure. Pulmonary function tests were repeated 3 months and 1 year after surgery. Complications and functional outcome are reported. RESULTS: Both groups had the same severity of obstructive disease (mean forced expiratory volume in 1 second = 20% +/- 5% for the SLT group and 23% +/- 9% for the TLR group) and similar patterns of right ventricular dysfunction. During operation, SLT recipients showed worse hypercapnia and pulmonary hypertension than TLR subjects when ventilation and perfusion to the operative lung were interrupted. Patients undergoing TLR only had interrupted ventilation, which was transiently reversed when severe hypoventilation or hypoxemia occurred. All patients undergoing TLR were extubated immediately after surgery. SLT recipients were extubated an average of 42 hours later. Pulmonary function testing performed 3 months after surgery showed improvement in both groups. SLT recipients showed larger improvements in airflow but comparable improvements in forced vital capacity. Both groups achieved similar improvements in gas exchange. This trend continued a year after surgery. Patients undergoing TLR were not subjected to complications of immunosuppressive therapy or exposed to opportunistic infections. CONCLUSIONS: Early results show TLR as an acceptable alternative to SLT in carefully selected patients with the same severity of obstructive lung disease. Long-term follow-up studies are needed to establish long-term differences in functional outcome and development of complications. TLR may be an option for patients with severe dyspnea related to emphysema who do not meet criteria for transplantation.

Nursing care of the thoracoscopic lung volume reduction patient.

BACKGROUND: Several methods to surgically enhance pulmonary function and improve the quality of life in patients with bullous emphysema are currently being evaluated. One of these methods, lung volume reduction, is performed in patients with bullous emphysema that can no longer be well managed with medical therapy. OBJECTIVES: The focus of this article is to review bullectomy via unilateral thoracoscopy with an endoscopic stapler in the management of end-stage pulmonary emphysema, and to discuss nursing care of these patients. METHODS: An experimental study was used, including review of the literature and analysis of clinical experience using chi-square and t test analyses of pre- and postoperative variables. RESULTS: At 3-month follow-up there were significant improvements in forced expiratory volume in 1 second, forced vital capacity, minute volume ventilation, partial pressure of oxygen, residual volume, and 6-minute walk when pre- and postoperative parameters were compared. Operative mortality was 4%, with the most common complication being prolonged air leak, occurring in 30% of patients studied. CONCLUSIONS: There is now consistent preliminary information to support the concept that lung volume reduction improves pulmonary function and quality of life in a significant percentage of patients.

Discrepancies in osmolal gaps and calculated alcohol concentrations.

OBJECTIVES: To estimate unexplained osmolal gaps (UEOG) during ethanol ingestions after accounting for measured ethanol concentrations and to explore the causes of observed discrepancies. DESIGN AND SPECIMENS: A random convenience sample of serum specimens with a request to perform osmometry for the detection of alcohols was studied. MAIN OUTCOME MEASURES: Serum concentrations of sodium, glucose, urea nitrogen, ethanol, osmolality, and ethanol were measured by two analytic methods to determine calculated osmolalities and osmolal gaps using two commonly used formulas. RESULTS: In 79 serum specimens submitted for osmometry, mean ethanol concentrations were 199 +/- 154 (SD) mg/dL; 15 specimens had no detectable ethanol. After regression of the calculated ethanol concentrations and the measured ethanol concentrations, the Dorwart and Chalmers formula showed a large constant bias of 45.217 +/- 6.414 (SE) mOsm/kg in predicting measured ethanol concentrations. The Smithline and Gardner formula was similarly as precise (r = .9786), but had a much smaller bias of -3.929 +/- 6.623 (SE) mOsm/kg. Actual mean differences between measured and calculated osmolalities (including ethanol osmols) gave an estimate of UEOG seen during ethanol ingestions. Using the less biased formula, the mean UEOG was 1.4 +/- 8.5 mOsm/kg, giving a 95% upper limit of the reference range of 18 mOsm/kg in this population with ethanol ingestions. Three significant outliers were identified and their UEOG could be explained by the presence of mannitol, isopropanol, or possibly a change in the assumed value for fractional water, normally a constant in these formulas for calculated osmolality. Other specific causes of osmolal gap and UEOG are discussed. CONCLUSION: The potential range of osmolal gaps seen during ethanol ingestions after accounting for ethanol is demonstrated to be greater than in previous studies, which have included a lower proportion of ethanol-intoxicated subjects in their study sample.

Serum concentrations of methanol after inhalation at 200 ppm.

Methanol has been proposed as an alternative automotive fuel to reduce pollution in the urban environment. Utilization of methanol will increase exposure to low levels of methanol vapors for the general public and in occupational settings. Information on absorption by inhalation and serum concentrations after low-level exposure would be important in evaluating the health impact of generalized methanol exposure. During a randomized double-blind study of the potential neurobehavioral effects of inhaled methanol at 200 ppm for 4 hours, 15 timed specimens from 22 subjects were obtained for methanol analysis by head-space gas chromatography. Methanol was rapidly absorbed by inhalation (absorption rate constant = 0.87 +/- 0.60 hours-1). Serum methanol concentrations were increased by more than fourfold at the end of the exposure period (6.5 +/- 2.7 vs 0.9 +/- 0.6 mg/L), as were urinary methanol excretion rates, although formate concentrations were not increased over background concentrations. The overall (n = 22) elimination half-life was 3.2 +/- 2.3 hours. Elimination from plasma fit a monoexponential model for only half of the subjects during the 4-hour postexposure follow-up period (mean half-life = 2.2 hours). Subjects with poor fits either showed greater variability or apparent slow (nonsignificant) declines in serum methanol concentrations, possibly because of the offsetting contributions of dietary intake or endogenous production, but more likely as a result of the limited number of sampling times and limited follow-up period.

Unilateral video-assisted thoracic surgical lung reduction.

BACKGROUND: Lung reduction has been demonstrated to be a promising treatment for end-stage emphysema when performed on both lungs via sternotomy. The role for a thoracoscopic approach has not yet been determined. METHODS: Unilateral video-assisted thoracic surgical lung reduction was performed on 50 patients for the treatment of end-stage emphysema. There were 34 men and 16 women with a mean age of 61.5 years (range, 31 to 78 years). Emphysema was secondary to smoking in 45 patients (90%), and alpha 1-antitrypsin deficiency in 5 patients (10%), 4 of whom had smoked in the past. Lung reduction was performed unilaterally using a thoracoscope and a stapled resection without the routine use of bovine pericardium. The side to be operated on and site of resection were determined preoperatively by examination of the perfusion and computed tomographic scans of the lungs. The average amount of lung removed was 59 +/- 15 g (range, 29 to 111 g). RESULTS: Morbidity included prolonged air leak in 15 patients (30%), bleeding in 3 (6%), pneumonia requiring reintubation in 3 (6%), myocardial infarction in 1 (2%), and perforated ulcer in 1 (2%). Seven patients (14%) required a second thoracic procedure for management of these complications. Two patients died, for an operative mortality of 4%. Follow-up obtained between 1 and 3 months in 25 patients revealed significant improvement in forced expiratory volume in 1 second (0.71 to 0.95 L; p < 0.001), forced vital capacity (2.24 to 2.58 L; p < 0.01), and oxygen tension (59 to 67 mm Hg; p < 0.01). The improvement in functional capacity as measured by 6-minute walk approached statistical significance (771 to 923 ft; p = 0.06). CONCLUSIONS: Significant subjective improvement in dyspnea has been noted in 41 of 48 hospital survivors (85%). For patients with end-stage emphysema, unilateral video-assisted thoracic surgical lung reduction appears to be a preferable alternative to standard medical management.

Critical pathways as an effective tool to reduce cardiac transplantation hospitalization and charges.

A critical pathway is a component of managed care focusing on outcome-oriented, cost-effective care. This retrospective review of 74 cardiac transplants in 72 patients evaluated the influence of critical pathways on clinical management, length of hospitalization, and hospital charges. Transplant patients were divided into group 1 (n = 51), which received standard primary nursing care, and group 2 (n = 23), which received nursing case management using a critical pathway. The number of intensive care unit days for group 2 was significantly smaller than for group 1, as were duration of hospitalization and hospital charges. The critical pathway provided for systematic delivery of care and decreased length of hospitalization and charges without compromising safety or quality.