Reliability testing of the quantitative myasthenia gravis score.
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Biomedical subjects
Publications and source records attributed to D McIntire.
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Allelic loss is a hallmark of tumor suppressor gene (TSG) inactivation. We have allelotyped 29 paired lymphoblastoid and lung cancer cell lines derived from 11 patients with small cell (SCLC) and 18 patients with non-small cell lung carcinomas (NSCLC). Statistical analysis indicated that a threshold of 30% separated non-random allelic loss from the random genetic deletions of malignancy. We have identified non-random allelic loss at 42 of 54 (78%) specific chromosomal regions examined, with 22 regions (52%) common between the two major lung cancer histologic types. There were 3 regions (7%) with allelic loss specific for SCLC and 17 regions (41%) specific for NSCLC. Furthermore, there were significant differences in loss of heterozygosity (LOH) frequencies between NSCLC and SCLC at 13 regions on eight chromosome arms (3p, 5q, 6q, 9p, 10q, 11p, 13q, and 19p). Eight homozygous deletions were present in seven cell lines at four regions, 3p12, 3p14.2, 9p21, and 10q23-25. We have also identified novel sites of chromosomal deletions. In particular, there was frequent loss at 11p13 in SCLC and loss at 6p21.3 and 13q12.3 in NSCLC. In this study, we demonstrate that a) non-random allelic losses in lung cancer involve multiple regions; b) some losses are common to both NSCLC and SCLC subtypes, whereas others are subtype specific; c) there are genetic deletions at novel chromosomal regions; and d) several homozygous deletions have been noted. Our studies demonstrate the usefulness of continuous cell lines for detailed allelotyping, for comparing genetic abnormalities between SCLC and NSCLC, and for identifying homozygous deletions.
OBJECTIVE: To compare compliance, psychiatric disorders, and family support in children with insulin-dependent diabetes mellitus (IDDM) hospitalized with diabetic ketoacidosis (DKA) and clinic controls. METHOD: Twenty-five youths hospitalized with DKA and 25 matched outpatient subjects with IDDM with no history of DKA during the preceding year were assessed cross-sectionally, using the Diagnostic Interview Schedule for Children, measures of general and diabetes-specific family functioning, and measures of self-esteem and social competence. Levels of glycosylated hemoglobin and information about compliance with the treatment regimen were obtained. RESULTS: A significantly higher number of psychiatric disorders was observed in the hospitalized children, with 88% meeting criteria for at least one disorder (versus 28% of controls). Self-esteem and social competence were lower in the hospitalized group, and their families scored lower on problem-solving and diabetes-specific "warmth-caring." CONCLUSIONS: Children with recurrent DKA may be at greater risk of associated psychopathology than diabetic controls with no such history. DKA children's reports of noncompliance may be more sensitive than their parents' reports, and their families may lack warm, caring parent-child relationships.
BACKGROUND: Intra-abdominal complications from transabdominal properitoneal (TAP) laparoscopic herniorrhaphy that would not be expected to occur in an open herniorrhaphy are possible. In a previous study, we reported the incidence of significant intra-abdominal adhesions from TAP herniorrhaphies using polypropylene in pigs. METHODS: To compare this with an open herniorrhaphy technique, we performed open herniorrhaphies on 31 pigs. Additional animals underwent TAP herniorrhaphy with PTFE. Data were collected on operative and trocar-site adhesions. Graft incorporation was recorded. RESULTS: No intra-abdominal adhesions were found in the 31 animals undergoing open herniorrhaphy. Fifteen adhesions were found in the 31 pigs that underwent TAP herniorrhaphy. These adhesions were graded and there were a total of nine significant adhesions with the TAP procedure. A total of 124 trocar sites resulted in two adhesions. Laparoscopically placed polypropylene was better incorporated than PTFE. The laparoscopically placed PTFE grafts commonly were poorly incorporated. CONCLUSIONS: We conclude that there is a risk of intraabdominal adhesions to either the operative site or the trocar sites in TAP herniorrhaphy that is not present in open techniques. One should, therefore, be circumspect in the choice of TAP herniorrhaphy as a primary repair.
Adenoid cystic carcinomas (ACC) constitute approximately 20% of malignant salivary gland tumors. Several histological types of ACC are recognized and may coexist in a single tumor. The authors divided ACC into lower grade (tubular and cribriform subtypes) and higher grade (trabecular and solid) subtypes. A preliminary analysis of 10 ACCs showed a relatively high incidence of loss of heterozygosity (LOH) at the p53 and RB genes and low or absent K-ras mutations and LOH at chromosomal loci 3p, 5q, 8p, and 9p. From 21 tumors, the authors carefully microdissected and analyzed 36 subtype foci. Three interrelated pieces of evidence indicate that the relatively poor prognosis higher grade subtype arises from one or more of the lower grade subtypes via progression events associated with mutations in the p53 or RB genes. First, the number of mutations (both LOH and microsatellite alterations) at either gene is greater in higher grade foci than in lower grade foci; second, multiple mutations (two and occasionally three) are present in only higher grade foci; and third, when lower and higher grade foci are present in the same tumors, identical mutations plus other mutations are present in the corresponding higher grade foci. These findings suggest that molecular analyses of ACCs may provide information of prognostic importance.
Heterogeneity in the quality and task sensitivity of vocal symptoms in the spasmodic dysphonia (SD) population contributes to controversy as to whether this is a single disorder or two disorders with different etiologies (neurogenic versus psychogenic). Perceptual and acoustic assessments of vocal symptoms are inadequate to resolve this controversy. However, myoelectric events are intimately proximal to the source of vocal disruption and may be informative. The present report employs statistical modeling of quantitative amplitude measures of electromyographic activity recorded from thyroarytenoid to examine neuromotor bases of vocal symptoms in SD. Consideration of perceptual ratings of the quality and task sensitivity of vocal symptoms in the context of statistical models provides support for the conclusion that the range of vocal symptoms identified as SD represents a single, neurogenic disorder.
Hypertensive nephrosclerosis is a progressive renal disease and the leading cause of end-stage renal disease (ESRD) in blacks in the United States. It is generally believed that hypertensive renal injury is responsible for progressive renal failure; however, it is not known whether pharmacologic lowering of blood pressure to any level prevents progression of renal disease. Accordingly, we performed a long-term prospective randomized trial to determine whether "strict" [diastolic blood pressure (DBP) 65 to 80 mm Hg] versus "conventional" (DBP 85 to 95 mm Hg) blood pressure control is associated with a slower rate of decline in glomerular filtration rate. Eighty-seven non-diabetic patients (age 25 to 73; 68 black, 58 male) with long-standing hypertension (DBP > or = 95 mm Hg), chronic renal insufficiency (GFR < or = 70 m/min/1.73 m2) and a normal urine sediment were studied. DBP was pharmacologically lowered to < or = 80 mm Hg (3 of 4 consecutive measurements at 1 to 4 weeks intervals) after which patients were randomized. DBP and GFR (renal clearance of 125I-iothalamate) were measured at baseline, at three months and every six months post-randomization. The rate of decline in GFR (GFR slope, in ml/min/1.73 m2/year), estimated by the method of maximum likelihood in a mixed effects model, was the primary outcome variable. In a secondary analysis, 50% reduction in GFR (or a doubling of serum creatinine) from baseline, ESRD and death were combined.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND AND METHODS: The management of episodes of severe pain in patients with sickle cell disease is a difficult clinical problem. We studied 36 children and adolescents with sickle cell disease who had 56 acute episodes of severe pain (44 in 27 patients with sickle cell anemia, 8 in 7 patients with sickle cell-hemoglobin C disease, and 4 in 2 patients with sickle cell-beta (+)-thalassemia). The patients were randomly assigned in double-blind fashion to receive an intravenous infusion of either saline placebo or high-dose methylprednisolone (15 mg per kilogram of body weight, to a maximum of 1000 mg) on their admission to the hospital and again 24 hours later. All the patients received intravenous morphine sulfate until severe pain abated and were then given acetaminophen with codeine. RESULTS: For all episodes of pain, the duration of inpatient analgesic therapy (intravenous and oral) was significantly shorter for the patients who received methylprednisolone than for those given placebo (mean, 41.3 vs 71.3 hours; P = 0.030). The difference was still significant (31.0 vs. 62.5 hours; P = 0.010) when we excluded seven episodes that were complicated by the chest syndrome (three in the methylprednisolone group and four in the placebo group). The patients who received methylprednisolone had recurrent episodes of pain shortly after the discontinuation of therapy more often than did the patients receiving placebo. No adverse effects of methylprednisolone were observed. CONCLUSIONS: A short course of high-dose methylprednisolone decreased the duration of severe pain in children and adolescents with sickle cell disease, but patients who received methylprednisolone had more rebound attacks after therapy was discontinued. On balance, corticosteroids are promising as an adjunct to supportive therapy for painful episodes in children and adolescents with sickle cell disease.
Laparoscopic herniorrhaphy is becoming an increasingly common procedure. The possible creation of intraperitoneal adhesions during laparoscopic herniorrhaphy has not been examined. For the transperitoneal hernia repair to be an acceptable option, the hypothesis that this approach will incite significant adhesions must be rejected. To test this hypothesis, 21 pigs underwent laparoscopic herniorrhaphy using a standard procedure with the implantation of a polypropylene mesh graft on one side while a sham procedure was performed on the other. These animals were later examined laparoscopically for adhesion formation and the condition of the graft. None of the 21 animals developed adhesions to the trocar sites, 12 animals developed adhesions to the area of the polypropylene mesh, and 3 developed adhesions to the side of the sham procedure. There were no adhesions involving the small intestine. It is therefore concluded that the hypothesis should be rejected and that laparoscopic herniorrhaphy does not incite significant adhesions.
We investigated the correlation of p53 abnormalities with survival in 85 patients with non-small cell lung cancer (NSCLC) who had undergone resection with curative intent as part of Lung Cancer Study Group (LCSG) 871. Our previous studies showed that only a subset of p53 mutations in lung cancers result in overexpression. In addition, protein overexpression has been described in the absence of mutation. Therefore, we determined both p53 protein overexpression (by immunostaining) and p53 and ras gene mutations (by single-strand conformation polymorphism and DNA sequencing) in this set of resected tumor specimens. Clinical follow-up data were available for 75 cases. Of the studied patients, 64% showed p53 overexpression and 51% had mutant p53 sequences; however, the concordance rate was only 67%. There was a negative survival correlation with positive p53 immunostaining (p = 0.05), but not with the presence of gene mutations (p = 0.62) in this group of patients. Overexpression of p53 protein determined by immunostaining may contribute to adverse outcome due to the ability of p53 to act as a dominant oncogene, or alternatively, overexpression may reflect ongoing DNA damage in the tumor as a marker for a more aggressive behavior. When adjusted for stage, age, and gender by multivariate analysis, however, there was no independent impact of p53 overexpression on survival.
OBJECTIVE: To determine whether an increase in the oxytocin dosing interval would decrease the incidence of uterine hyperstimulation. METHODS: This study included 1801 consecutive pregnancies receiving high-dose oxytocin. Oxytocin was used for labor augmentation in 1167 and induction in 634 women. Twenty- and 40-minute dosage intervals were compared. The study period was based on an 80% likelihood of detecting 5 and 10% differences in the cesarean and hyperstimulation rates, respectively. Statistics were analyzed with chi 2, Fisher, and Wilcoxon rank-sum tests where appropriate. Multivariate logistic regression and analysis of covariance were used to control for confounding demographic variables. RESULTS: Comparison of the 20- and 40-minute regimens for labor induction yielded no differences in the rates of cesarean delivery for dystocia (16 versus 19%) or fetal distress (5 versus 6%). The 20-minute regimen for augmentation was associated with a significant reduction in cesarean for dystocia (8 versus 12%; P = .05). The incidence of uterine hyperstimulation was greater with the 20-minute than the 40-minute regimen for induction (40 versus 31%; P = .02), but not for augmentation (31 versus 28%). Neonatal outcomes were unaffected by the dosage interval for both augmentation and induction. CONCLUSION: A 40-minute dosing interval for high-dose oxytocin offers no clear advantage over a 20-minute interval. Both regimens were safe and efficient, with no differences in perinatal outcome. The 20-minute interval was associated with fewer cesareans for dystocia when used for labor augmentation, whereas the 40-minute interval resulted in less hyperstimulation when used for labor induction.
BACKGROUND: The frequency and clinical relevance of human antitumor immune responses is not well known, and few target antigens have been identified. PURPOSE: This study was designed to determine the frequency of antibodies reactive against extracts of autologous tumor cell lines and to correlate these data with survival. METHODS: Serum samples were obtained from 40 lung cancer patients treated on National Cancer Institute protocols. These sera were used as probes in immunoblots against protein extracts from tumor cell lines derived from each of these patients. RESULTS: We detected serum antibodies against autologous tumor cell proteins in 21 (58%) of the 36 patients with small-cell lung cancer (SCLC) and three (75%) of the four with non-small-cell lung cancer (NSCLC). Two patients' sera detected the p53 tumor suppressor gene product and two detected the product of the HuD gene (associated with paraneoplastic neurological syndromes) in their autologous tumor cell lysates. SCLC patients with antibodies against autologous tumor cell proteins had improved survivals compared with those in the antibody-negative group (P = .059). All patients who lived longer than 36 weeks were antitumor antibody positive. Sera from six (86%) of seven patients with limited disease were positive for antibodies that reacted against autologous tumor cells, compared with 15 of 29 (52%) of sera from patients with extensive disease. CONCLUSIONS: Our results suggest that the sera from patients with SCLC frequently contain antibodies against tumor cell proteins and that these antibodies are associated with improved survival. IMPLICATIONS: These data suggest that an antitumor immune response may affect tumor growth, and that the anonymous proteins detected by antitumor antibodies in lung cancer patient sera may represent proteins involved in the development of lung cancer or in its clinical manifestations.
A mixture of 80% helium and 20% oxygen has physical properties that increase airflow and decrease resistance in the airway when used as a portion of inspired gas. This study was designed to demonstrate and quantify the effects of a helium-oxygen mixture in a normal airway and when airway resistance is increased. Thirty healthy volunteers were studied breathing room air and the helium-oxygen mixture through a normal airway and an airway that included a resistor. Pulmonary function tests, directed by a registered respiratory therapist, were performed on all subjects using a computerized spirometer. The functional vital capacity, one-second forced expiratory volume, half-second forced expiratory volume, and peak inspiratory flow rate were analyzed. There was a statistically significant increase in 1-second forced expiratory volume using a helium-oxygen mixture in a normal airway. All pulmonary function test scores statistically improved when volunteers inspired helium and oxygen through the restricted airway, demonstrating that helium and oxygen can increase airflow in the presence of an increased airway resistance. This substantiates a role for helium and oxygen in treating conditions associated with decreased airway size and increased airway resistance.
OBJECTIVE: To determine if conventional sperm parameters, specific characteristics of sperm motion determined by computer-aided semen analysis (CASA), sperm penetration assay (SPA), and/or spontaneous acrosome reaction assay could best predict fertility outcome after intrauterine insemination (IUI) from frozen donor sperm. DESIGN: A retrospective analysis of 2,245 cycles of therapeutic donor IUIs were initially studied; 1,147 cycles that met selection criteria were used in this report. SETTING: A university-based assisted reproductive technology center. PATIENTS, PARTICIPANTS: All IUIs were performed on women with documented patency of at least one fallopian tube, ovulatory cycles, and who did not receive human menopausal gonadotropins. Sperm donors had to be used for at least four different recipients (mean of 15) and at least 14 different cycles of insemination (mean of 41). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: Statistical comparisons were made between donors of different relative fertility by using the Mann-Whitney test, Spearman's rank correlation, and multiple regression analysis. These analyses demonstrated that the most significant predictors of the fertility of frozen-thawed donor sperm were curvilinear velocity, straight line velocity, and the total number of motile sperm inseminated. The number of sperm with spontaneous acrosome reactions negatively correlated with fertility outcome, and SPA provided no predictive value. CONCLUSIONS: Our study supports the hypothesis that the study of sperm motion characteristics using CASA after thawing and washing of cryopreserved sperm is a better predictor of fertile outcome after IUI than analysis of fresh semen.
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We are developing a computerized scheduling program that considers the schedule preferences of individual nurses. We want schedules that satisfy the staffing requirements of the unit and the work preferences of the nurses, while being fair. To reach this goal, we must calculate the desirability of every possible schedule for every nurse. The calculated preference scores of the schedules will be used by the computer to assign individual schedules and to keep a running tally of how well nurses' desires have been met. We present here the first model of nurses' scheduling desires. We modeled the schedule preferences as the desire to work the assigned shifts, plus the pattern of day-off, plus the pattern of tour splitting. Using this model, we account for an average of 81% of the variance.
An expert system was developed to schedule nurses according to their preferences for specific schedules. The first step in this project was to determine the reliability and stability of nurses' schedule preferences. If nurses' preferences changed frequently, the proposed expert system would not have been feasible. Our results show that for a 3- to 6-month period most nurses are consistent in their preferences of schedules. While each nurse is unique, cluster analysis indicates that it is possible to group nurses according to desire for tour.