Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

Late results of combined mitral valve replacement and coronary bypass surgery

The incremental risk of coronary bypass surgery was analyzed in 718 patients undergoing mitral valve replacement between 1971 and 1983. Ninety-eight patients (14%) had significant coronary artery disease requiring coronary bypass surgery. In 70 of these patients, the origin of the mitral valve disease was nonischemic, whereas 28 patients had ischemic mitral regurgitation unsuitable for conservative valve surgery. There were six operative deaths (9%) and four perioperative myocardial infarctions (6%) after mitral valve replacement and coronary bypass surgery for nonischemic mitral valve disease. Operative mortality was related to low output cardiac failure before operation or perioperative myocardial infarction. Actuarial curves predict survival (+/- standard error) of 55 +/- 7% at 5 years and 43 +/- 8% at 10 years. Preoperative functional class was the only significant predictor of long-term survival in this group (p less than 0.05). The actuarial survival of the 620 patients without coronary artery disease who underwent mitral valve replacement alone was 63 +/- 3% at 10 years. This was significantly better than that of the 70 patients who underwent mitral valve replacement and coronary bypass surgery for nonischemic mitral valve disease (p less than 0.001). Conversely, 5 year survival of the 28 patients with ischemic mitral regurgitation was 43 +/- 10%. This confirms the negative detrimental effect of an ischemic origin of mitral valve disease on survival after mitral valve replacement and coronary bypass surgery (p less than 0.0001).     

Cuffed oropharyngeal airway (COPA) as an adjunct to fibreoptic tracheal intubation

The cuffed oropharyngeal airway (COPA) was evaluated as an adjunct to oral and nasal fibreoptic tracheal intubation in 40 adult patients during general anaesthesia. Time from start to completion of intubation decreased rapidly with experience (median time 138 s). We conclude that the COPA may be a useful adjunct to fibreoptic tracheal intubation, allowing control and support of the airway during the procedure, using various anaesthetic techniques, in an acceptable amount of time. The ability to perform fibreoptic tracheal intubation while effectively supporting the airway using the COPA may be advantageous in managing the difficult airway and in trainee education.      

Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project

The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.     

Microbiology of the urethra and perineum and its relationship to bacteriuria in community-residing men with spinal cord injury

OBJECTIVE: Reasons why some persons with spinal cord injury (SCI) experience recurrent urinary tract infections more than others are poorly understood. We performed a prospective study of bacterial flora of the urethra and perineum in men with and without bacteriuria to understand more completely the relationship between bacterial colonization and invasion of the urinary tract. METHODS: Urine, urethra, and perineum cultures were obtained from 70 men. Microbial flora of these sites was compared for men with and without bacteriuria. RESULTS: Urine colony count was 0 in 16 (22.9%) men. Perinea in 2 men (12.5%) and urethras in 6 men (37.5%) were colonized with various gram-negative bacilli, enterococci, and/or Staphylococcus aureus. Among 54 (77.1%) men with bacteriuria, uropathogens were shown in the perineum in 31 (57.4%) and in the urethra in 46 (85.2%). In 40 (74.1%) of men with bacteriuria, at least one bacterial species present in the urine was also found in the urethra and/or perineum. Differences in the occurrence of uropathogens in men with and without bacteriuria were statistically significant, and organisms were present in higher numbers in men with bacteriuria. CONCLUSION: Men with SCI who have bacteriuria are significantly more likely to be colonized in the distal urethra and perineum with uropathogens that are often present in the urine in comparison with men without bacteriuria.     

Botulinum toxin as an adjunct to serial casting treatment in children with cerebral palsy

BACKGROUND: Although botulinum toxin A is frequently used to augment serial casting in the treatment of soft-tissue contractures in children with cerebral palsy, its effectiveness for this purpose has not been evaluated. The purpose of the present study was to determine whether botulinum toxin A injection increases the efficacy of serial casting. METHODS: A prospective, randomized trial was undertaken to compare serial casting only with serial casting combined with botulinum toxin A (Botox) injection for the treatment of ankle equinus contractures in twenty-three children with cerebral palsy. Range-of-motion testing, spasticity assessment, and computerized gait analysis were performed as long as twelve months after treatment. RESULTS: There was no difference between the groups with regard to the duration of casting required to correct the equinus contracture. Both groups maintained a significant improvement in passive ankle dorsiflexion throughout the follow-up period, although the group managed with casting and Botox had a significant loss of dorsiflexion when the values at six, nine, and twelve months were compared with the value at three months. Peak dorsiflexion during the stance and swing phases was significantly improved in both groups at three months but only in the group managed with casting alone at twelve months. Plantar flexor spasticity was significantly decreased at three months in both groups, but it was significantly decreased at six, nine, and twelve months only in the group managed with casting alone. Spasticity was significantly greater in the group managed with casting and Botox than it was in the group managed with casting only at six, nine, and twelve months. CONCLUSIONS: The present study demonstrates the efficacy of serial casting in the treatment of equinus contractures in children with cerebral palsy who are able to walk. Contrary to our hypothesis, the addition of botulinum toxin A to a serial casting regimen led to earlier recurrence of spasticity, contracture, and equinus during gait. The results of the present study suggest that botulinum toxin combined with serial casting for the treatment of fixed contractures will lead to a recurrence of plantar flexor spasticity and equinus contracture by six months in this patient population. While previous research has indicated that the injection of botulinum toxin A is superior to casting for the treatment of dynamic equinus, the present study suggests that serial casting alone is preferable for the treatment of fixed equinus contractures in children with cerebral palsy.     

Biochemical alterations associated with ALS

Our objective was to identify metabolic pathways affected by ALS using non-targeted metabolomics in plasma, comparing samples from healthy volunteers to those from ALS patients. This discovery could become the basis for the identification of therapeutic targets and diagnostic biomarkers of ALS. Two distinct cross-sectional studies were conducted. Plasma was collected from 62 (Study 1) and 99 (Study 2) participants meeting El Escorial criteria for possible, probable, or definite ALS; 69 (Study 1) and 48 (Study 2) healthy controls samples were collected. Global metabolic profiling was used to detect and evaluate biochemical signatures of ALS. Twenty-three metabolites were significantly altered in plasma from ALS patients in both studies. These metabolites include biochemicals in pathways associated with neuronal change, hypermetabolism, oxidative damage, and mitochondrial dysfunction, all of which are proposed disease mechanisms in ALS. The data also suggest possible hepatic dysfunction associated with ALS. In conclusion, the data presented here provide insight into the pathophysiology of ALS while suggesting promising areas of focus for future studies. The metabolomics approach can generate novel hypotheses regarding ALS disease mechanisms with the potential to identify therapeutic targets and novel diagnostic biomarkers.     

Is it valid to calculate the 3-kilohertz threshold by averaging 2 and 4 kilohertz?

Many guidelines for reporting hearing results use the threshold at 3 kilohertz (kHz), a frequency not measured routinely. This study assessed the validity of estimating the missing 3-kHz threshold by averaging the measured thresholds at 2 and 4 kHz. The estimated threshold was compared to the measured threshold at 3 kHz individually and when used in the pure-tone average (PTA) of 0.5, 1, 2, and 3 kHz in audiometric data from 2170 patients. The difference between the estimated and measured thresholds for 3 kHz was within ± 5 dB in 72% of audiograms, ± 10 dB in 91%, and within ± 20 dB in 99% (correlation coefficient r = 0.965). The difference between the PTA threshold using the estimated threshold compared with using the measured threshold at 3 kHz was within ± 5 dB in 99% of audiograms (r = 0.997). The estimated threshold accurately approximates the measured threshold at 3 kHz, especially when incorporated into the PTA.