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Biomedical subjects

S B Johnson

Publications and source records attributed to S B Johnson.

At least 19 recordsLinked to original sources

Simplified derivatization for determining sphingolipid fatty acyl composition by gas chromatography-mass spectrometry.

A simple procedure for simultaneously derivatizing non-hydroxy and hydroxy fatty acids prior to GC analysis [I. Ciucanu and F. Kerek, J. Chromatogr., 284 (1984) 179] has been evaluated for its usefulness in determining sphingolipid acyl composition. The method uses methyl iodide in polar aprotic solvents to generate methyl esters of carboxyl groups and methyl ethers of hydroxyl groups. Methylation efficiency is examined as a function of hydroxyl group presence and location in free fatty acids as well as a function of 2-hydroxy fatty acid chain length. Conditions are also reported for efficient saponification and derivatization of sphingolipid fatty acyl chains as is illustrated using bovine brain galactosylceramide.

Animals

Problem-based learning: an effective educational method for a surgery clerkship.

Problem-based learning (PBL) has been implemented during the clinical years in a few medical schools. The purpose of this study is to determine whether PBL provides a better education than traditional methods. Students in the first and third rotations (n = 42) went through the traditional clerkship, which utilized Socratic teaching (SI), while students in the second and fourth rotations (n = 36) were taught by the PBL method. Two performance measures were used to assess clerkship effectiveness. One was a modified essay examination (MEE) administered as part of the departmental evaluation. The other was the NBME-II exam and its surgery subsection NBME-II-S. The MEE was designed to measure six dimensions of the problem-solving process. The NBME-II was utilized to measure knowledge. Unpaired t tests were used to identify statistically significant group differences. The PBL group performed significantly better on two MEE dimensions: (1) differential diagnosis formation (PBL, 92.5 +/- 0.8; SI, 89.1 +/- 0.5; P < 0.01) and (2) interpretation of clinical data (PBL, 93.3 +/- 0.6; SI, 91.6 +/- 0.4; P < 0.03). A third dimension, ordering appropriate lab and diagnostic studies, approached significance (P = 0.057), and the PBL group performed better. On the NBME-II there was not a significant difference between the two groups. However, the trend (P = 0.059) was for the PBL group to score higher on the NBME-II-S (PBL mean: 502 +/- 15; SI mean: 468 +/- 12). When overall achievement was controlled for, the PBL group performed significantly better than the SI group (P = 0.046) on the NBME-II-S.(ABSTRACT TRUNCATED AT 250 WORDS)

Education, Medical

Psychosocial issues in hemophilia before and after the HIV crisis: a review of current research.

The human immunodeficiency virus (HIV) has had a fundamental impact on quality of life, delivery of care, and directions of research efforts for the hemophilia community. Studies of psychosocial issues in hemophilia before and after the HIV crisis are reviewed. Before this crisis, research addressed personality factors and coping, family functioning, impact of psychological factors on bleeding, effects of home treatment, and school functioning. After HIV problems surfaced, research focused on psychosocial impact of the epidemic, HIV knowledge assessments, and HIV transmission prevention efforts. HIV-positive children with hemophilia have not received sufficient attention. Future directions for research are suggested.

Adaptation, Psychological

Clinical results of decompressive dermotomy-fasciotomy.

Seventy-three dermotomy-fasciotomies (DFs) were performed in 68 patients from 1986 to 1991. A database record was compiled on each patient. Variables included age, mode of injury, method of initial wound closure, and associated injuries. A multivariate stepwise logistic regression analysis was performed to determine which variables were associated with wound complications. Thirty-eight percent of patients who underwent DF developed wound complications. One hundred percent of those patients with postoperative arterial or graft thrombosis developed wound complications (p less than 0.01) as did 78% of those with thromboembolic disease (p less than 0.05). Conversely, only 5% of those who underwent closure of their DF wounds utilizing skin grafts developed wound complications (p less than 0.01) as compared with 51% of those who underwent secondary or primary closure only. Subsequent analysis of the remaining patients, excluding those with severe soft tissue injury, showed an association between location of DF (upper versus lower extremity) and the development of wound complications that approached statistical significance (p less than 0.06). DF is frequently necessary in the treatment of patients with compartment syndrome but is associated with significant morbidity. This study suggests that closure of DF wounds utilizing skin graft allows for continued osteofascial decompression while concomitantly minimizing invasive sepsis.

Adolescent

Behavioral treatment of nocturnal enuresis in children with insulin-dependent diabetes mellitus.

Examined whether a well-established treatment program for functional enuresis, the urine alarm procedure, would be useful for children with both enuresis and diabetes. 5 children between the ages of 7 and 14 whose pretreatment physical examination suggested no neurological impairment were treated. A multiple baseline design across children indicated that the urine alarm procedure was successful in stopping enuretic episodes for all 5 children with treatment gains maintained for the 4 children available for assessment at 2-month follow-up. These results suggest that if no diabetes-related organic impairment is evident, behavioral treatment for enuresis can be beneficial for children with diabetes.

Adolescent

A longitudinal analysis of adherence and health status in childhood diabetes.

Applied structural equation modeling to a longitudinal data set of 193 youngsters with insulin-dependent diabetes mellitus assessed on two occasions, an average of 1.65 years apart. Six adherence constructs, Injection, Exercise, Diet Type, Testing-Eating Frequency, Calories Consumed, and Concentrated Sweets, were quantified from 24-hr recall interviews conducted with mother and child. Glycemic control was indexed by glycosylated hemoglobin (HA1C); lipid metabolism was indexed by fasting triglyceride levels (TRIG). The relationship of each adherence construct to metabolic control was tested separately. Patient age and disease duration served as exogenous variables in all models. Testing-Eating Frequency was associated with HA1C and Injection was associated with TRIG; in both cases better adherence was associated with better metabolic control. However, the standardized regression weights and variance accounted for were small. Patient age was a predictor of both adherence and metabolic control; older youngsters were less adherent and were in worse metabolic control. Inspection of models for younger versus older children suggested that age-homogeneous models improved prediction, but adherence and metabolic control linkages remained weak. Suggestions for refining the model are provided.

Blood Glucose

Early criteria predictive of prolonged mechanical ventilation.

This study was performed to determine if prolonged mechanical ventilation (MV) could be predicted by objective clinical variables present at 48 hours after MV was instituted. During a 3-month period, 49 (54%) of 91 mechanically ventilated surgical intensive care unit patients required MV for 2 or more days. Twelve (24%) of these patients died. Patients requiring 2-13 days of MV had significantly lower alveolar-arterial oxygen gradients (PAO2 - PAO2), PEEP, and FIO2 on MV day 2 compared with patients with MV greater than or equal to 14 days. PAO2 - PAO2 greater than or equal to 175 mm Hg on day 2 in patients without chronic obstructive pulmonary disease (COPD) was 60% sensitive and 91% specific for MV greater than or equal to 14 days. In survivors, a day-2 PAO2 - PAO2 greater than or equal to 175 mm Hg (without COPD) or a GCS score less than or equal to 9 had a 91% positive predictive value and a 96% negative predictive value for MV greater than or equal to 14 days. We conclude that mechanical ventilation for 14 or more days can be accurately predicted at 48 hours after the institution of ventilatory support by these objective criteria.

Female

The death of a child with diabetes from neglect. A case study.

This case report of a child with insulin-dependent diabetes mellitus (IDDM) describes a naturally occurring ABABCA design. The A condition represents poor diabetes management provided in the home setting, and the B and C conditions represent improved diabetes management in residential treatment (condition B) or foster care (condition C). The A condition was consistently associated with episodes of diabetic ketoacidosis, high glycosylated hemoglobin percentage, and school failure. In contrast, the B/C conditions were consistently associated with improved health status and school performance. On two occasions, the child was returned to condition A by the state's protective service agency (HRS) in direct conflict with the recommendations of the child's psychological and medical treatment staff. During her last condition A placement, the youngster died. Chronically ill children who are neglected may not receive the protection they need because of lack of awareness about the psychosomatic aspects of their problem.

Child

Methodological issues in diabetes research. Measuring adherence.

The prevalence of nonadherence in IDDM and NIDDM populations and conceptual and methodological issues relevant to measuring diabetes regimen adherence are reviewed. The prevalence of nonadherence varies across the different components of the diabetes regimen, during the course of the disease, and across the patient's life span. Although prevalence rates might be expected to differ between IDDM and NIDDM populations, this rarely has been evaluated. Conceptual problems in defining and measuring adherence include: the absence of explicit adherence standards against which the patient's behavior can be compared; inadvertent noncompliance attributable to patient-provider miscommunication and patient knowledge/skill deficits; the behavioral complexity of the diabetes regimen; and the confounding of compliance with diabetes control. Methods for measuring adherence include: health status indicators, provider ratings, behavioral observations, permanent products, and patient self-reports, including behavior ratings, diaries, and 24-h recall interviews. A measurement method should be selected on the basis of reliability, validity, nonreactivity, sensitivity to the complexity of diabetes regimen behaviors, and measurement independence from the patient's health status. The timing of measurements should be based on the stability of adherence behaviors and temporal congruity with other measures of interest (e.g., indexes of metabolic control). Directions for future research and suggestions for clinical practice are provided.

Diabetes Mellitus

The MEDLINE Button.

We have developed a computerized method for performing bibliographic searches directly from patient data involving five steps: 1) identifying specific patient data which raises a question in the mind of the user, 2) selection (from a list of generic questions) of a small number of questions which fit the selected patient data, 3) automated translation of the patient data into appropriate terms used for bibliographic indexing, 4) conversion of the question selected by the user into a search strategy, and 5) transfer of the search strategy to a search engine for a bibliographic database. We have modified the Columbia-Presbyterian Clinical Information System to experiment with this method. The first implementation converts patient diagnoses and procedures coded in ICD9-CM into Medical Subject Headings (MeSH) and searches Medline using BRS/Onsite. Challenges include development of a useful set of generic questions and translation from ICD9-CM to MeSH using the Unified Medical Language System (UMLS).

Diagnosis, Computer-Assisted

Haloperidol decanoate pharmacokinetics in red blood cells and plasma.

Red blood cell (RBC) and plasma concentrations of haloperidol (H) and reduced haloperidol (RH) were determined in nine patients (five men, four women) who had been receiving monthly injections of haloperidol decanoate (HD) for at least 3 months. A very sensitive high performance liquid chromatography method was used to measure H and RH, which could be detected at levels as low as 0.1 ng/ml. Blood samples for H and RH were drawn at the end of weeks 1, 2, 3, and 4 of a 4-week cycle. Monthly HD dosages ranged from 50 mg to 200 mg. At each time point RBC H did not differ significantly from plasma H. RBC RH and plasma RH did not change significantly over time and were consistently lower than RBC H and plasma H. However, RBC RH levels were higher than plasma RH levels. Also, the ratios of RBC RH/H were higher than were the ratios of plasma RH/H, which reflect an accumulation of RH intracellularly. HD dosage was highly correlated with both RBC H and plasma H, but RBC RH and plasma RH were not significantly related to dosage at any time point. Significant correlations were observed between HD dosage and prolactin concentration at week 1 and between prolactin concentration and RBC H and plasma H at weeks 1 and 4. Blood concentrations of H and RH and the corresponding standardized areas under the curve were not significantly related to smoking.

Adult

Haloperidol and reduced haloperidol in saliva and blood.

A total of 18 outpatients (17 male, 1 female) ranging in age from 36-66 years old were on a constant dosage of haloperidol in equally divided doses at 9:00 a.m. and 9:00 p.m. for at least 1 month. DSM-III-R diagnoses included schizophrenia (N = 9), schizoaffective disorder (N = 3), bipolar disorder (N = 4), organic mental disorder (N = 1), and delusional disorder (N = 1). Blood samples for steady-state concentrations of plasma and red blood cell haloperidol (H) and reduced haloperidol (RH) were drawn at 9:00 a.m. (12 hr trough). The haloperidol dosage was held at 9:00 a.m. until samples of whole saliva and parotid saliva could be collected for flow rates and concentrations of H and RH. Haloperidol dosages ranged from 1 mg/day to 60 mg/day (mean 11 +/- 15). Correlation coefficients were calculated for saliva concentrations versus blood levels and for saliva secretion rates versus blood levels. The correlations between whole saliva measures and blood concentrations were all higher than the correlations between parotid saliva measures and blood concentrations. In one case the higher correlation reached statistical significance. There was only one case in which substitution of saliva secretion rate improved the correlation between measures with saliva concentration. Our findings suggest that saliva measures of H and RH are useful alternatives to plasma concentrations in monitoring maintenance haloperidol treatment.

Adult

Fatty acid composition of hepatic triglycerides in Reye's syndrome: implications for hepatic desaturase abnormalities.

Serum NEFA profiles in Reye's syndrome are reportedly unique with a disproportionate percent made up of polyunsaturated fatty acids some of which are not ordinarily found in the serum. This pattern is also reflected in the serum triglyceride composition as well. As the liver is probably the sole source of the serum triglyceride in Rye's syndrome because patients are vomiting or in coma, the fatty acid acid composition of the liver triglyceride was examined for insight regarding the lipid abnormalities in this disease. Palmitic acid (16:0) and the sum of all the saturated fatty acids in the liver triglycerides were significantly decreased whereas the sum of the monoenoic fatty acids and the products of delta 9 desaturase activity were increased in Reye's samples. When these data were compared to the fatty acid composition of the serum triglyceride from a separate cohort of Reye's and control subjects, certain inferences regarding hepatic delta 9, delta 6, delta 5, and delta 4 desaturase activities and the elongases can be drawn from the liver and serum triglyceride fatty acid profiles which are unique. Collectively, these data reflect considerable intrahepatic fatty acid desaturation and elongation activity and/or acyl transfer from lipid to lipid of various polyunsaturated fatty acids in Reye's syndrome.

Adolescent

Remodeling of rat hepatocyte phospholipids by selective acyl turnover.

Acyl turnover of rat hepatocyte phospholipids and triacylglycerols was assessed by incubating the cells in media containing 40% H2(18)O and measuring the time-dependent incorporation of 18O into ester carbonyls by gas chromatography-mass spectrometry of hydrogenated methyl esters. Incorporation of 18O into 22-carbon acyl groups was low in phosphatidylcholine, phosphatidylinositol, and phosphatidylserine, whereas in phosphatidylethanolamine, it was about the same as in the other acyl groups. Incorporation of 18O into individual molecular species of phosphatidylcholine and phosphatidylethanolamine was determined after phospholipase C hydrolysis, derivatization to dinitrobenzoates, and separation by high-performance liquid chromatography. In most molecular species, acyl groups at the sn-1 and sn-2 positions became 18O-labeled at drastically different rates, indicating remodeling through deacylation-reacylation. Molecular species expected to arise de novo from acylation of glycerophosphate exhibited similar rates of 18O incorporation at the sn-1 and sn-2 positions. The data suggest that hepatocyte phospholipids are continually synthesized, remodeled by deacylation-reacylation at specific turnover rates up to 10-15%/h, and degraded. This acyl turnover probably does not involve the majority of intracellular unesterified fatty acids whose 18O incorporation was found to be very low. In contrast, the oxygens of extracellular unesterified fatty acids were readily exchanged with the media. This exchange was enzyme-catalyzed, possibly by lipases released into the media from damaged cells. Incorporation of 18O into exogenously added fatty acids was also rapid and resulted in enhanced uptake of 18O-labeled fatty acids into cellular lipids, primarily triacylglycerols and phosphatidylcholine, without drastic change of the intracellular free fatty acid pool.

Animals

Deficiency of essential fatty acids and membrane fluidity during pregnancy and lactation.

In a group of 19 normal pregnant women, plasma lipids were extracted, phospholipids were isolated, and the fatty acid (FA) compositions were measured by capillary gas chromatography. Blood samples were taken at 36 wk, at labor, and at 6 wk postpartum. The FA profiles showed deficiencies of omega 6 and omega 3 FA (omega indicating the length of the terminal saturated chain), the latter more severe, at all three times. Mean melting point (MMP) was calculated for each sample as an index of "fluidity" based upon all FA present. MMP varied linearly with total polyunsaturated FA and with double bond index, current measures of "fluidity" and essential FA status. MMP was elevated 9-11 degrees C in plasma phospholipids of women during pregnancy and labor and postpartum. Lactating mothers showed less recovery from the deficiencies than did the nonlactating mothers, but neither approached normal at 6 wk. The changes seen in phospholipid profiles suggest a significant transfer of omega 3 and omega 6 polyunsaturated FA from the mother to the fetus. These FA are essential for normal fetal growth and development; their relative deficiency in maternal circulation suggests that dietary supplementation may be indicated.

Adult

Assessing daily management of childhood diabetes using 24-hour recall interviews: reliability and stability.

Conducted 24-hr recall interviews concerning daily diabetes management with seventy-eight 6- to 19-year-old patients and their parents. Patients and parents were interviewed independently nine times over 3 months. Data obtained were used to construct 13 adherence measures. All measures yielded statistically significant estimates of parent-child concordance. Parent-child agreement was higher for weekday versus weekend behaviors and when based on nine versus three interviews. For the sample as a whole, parent-child concordance remained stable over the course of the study. Compared to the older patients, the 6- to 9-year-olds exhibited poorer parent-child agreement on measures involving time (e.g., injection and exercise-duration measures). This deficit disappeared, however, as the children became more practiced with the interview procedure. The dietary and glucose-testing measures exhibited moderate stability over the 3-month study. Lower stability estimates were obtained for the exercise and injection measures.

Activities of Daily Living

Obesity and weight loss alter serum polyunsaturated lipids in humans.

Serum omega 6 (n-6) fatty acids were assessed in 12 obese women during an outpatient very-low-calorie diet (VLCD). Ten subjects (S10) achieved a mean weight loss of 17 kg over 3-5 mo (initial weight-for-height 157%). Serum was obtained before (baseline) and monthly during the VLCD and from five of them (S5) after 2-3 mo of weight stability (refed) at 21 kg of loss. At baseline for S10, the serum phospholipid (PL) 20:4 omega 6 was 9.16 wt% and differed from normal (12.81 wt%) by P less than 0.0001, but cholesterol ester (CE) 20:4 omega 6 did not differ from normal. During 3 mo of VLCD, the S10 serum PL and CE 18:2 omega 6 fell (P less than 0.005 and 0.0001, respectively). Serum PL 20:4 omega 6 rose to normal during VLCD months 1-3 (P less than 0.01) while the serum CE 20:4 omega 6 rose above normal (P less than 0.0002). During the VLCD, S5 results paralleled S10. However when refed, S5 PL and CE 18:2 omega 6 and 20:4 omega 6 all reverted to baseline (PL 20:4 omega 6 below normal, P less than 0.001). Serum PL 20:4 omega 6 is low in moderate obesity, corrects to normal during a VLCD, but regresses to the predict abnormality after weight loss.

Adult