Marked hypodiploidy in blast phase chronic myelogenous leukemia: report of a case and review of the literature

The emergence of a near-haploid clone of cells in blast phase chronic myelogenous leukemia is an unusual event. We report such a case and review eight other cases described in the English literature. The significance of the substantial loss of genetic material is discussed as is the phenotypic and genotypic heterogeneity observed in this group of patients.     

Experimental laparoscopic aortobifemoral bypass

The goal of the present study is to develop a technique for laparoscopic aortobifemoral bypass.Piglets weighing between 60 and 78 kg were anesthetized with halothane. The lateral retroperitoneal approach was preferred to the more familiar anterior transperitoneal approach and was successfully completed in 19 piglets. The piglets were placed in the right lateral decubitus position. The first port (2 cm) was inserted halfway between the tip of the 12th rib and the iliac crest. Four other trocars were placed in the retroperitoneum after balloon inflation had allowed creation of a space which permitted visualization of the aorta from the left renal artery down to the aorto-iliac junction. After evacuation of the retropneumoperitoneum, the cavity was maintained using an abdominal lift device and a retractor.Using this approach, we performed four aortobifemoral bypasses (end-to-end aortic anastomosis) after conventional intravenous heparinization (100 IU/kg) in less than 4 h. Blood loss did not exceed 250 ml and the hematocrit remained stable. Postmortem evaluation of the grafts revealed they were positioned as in a conventional bypass, their limbs having followed in the created retroperitoneal tunnels along the path of the native arteries. No mortality occurred before sacrifice of the animals. We believe that this first performed series of totally retroperitoneal laparoscopic aortobifemoral bypasses in the porcine model is useful in preparation for human application due to the anatomical similarities in the periaortic region.     

Hypoplasia of the cerebellar vermis in neurogenetic syndromes

There are conflicting reports on the relationship between cerebellar vermal lobule hypoplasia and autism. Using quantitative magnetic resonance image analysis, we measured the cerebellar vermis in 125 normal individuals with a broad age range and 102 patients with a variety of neurogenetic abnormalities. We conclude that hypoplasia of cerebellar vermal lobules VI and VII is a nonspecific finding that even occurs in several conditions without autistic behavior. This suggests that it is not a specific neuroanatomical marker for autism, nor is cerebellar dys- genesis likely to be solely responsible for clinical autistic behaviors.     

Differential effects of sulindac on renal hemodynamics and function in the rat

Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n=6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n=12). In the 5 mg/kg b.w. sulindac group (n=7), renal blood flow progressively and significantly increased from 7.88±0.36 to 8.98±0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n=7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n=5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P<0.025). Also, Na⁺ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n=15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n=21), it was decreased from 11.5±1.2 to 7.4±0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P<0.05; n=6). In conclusion, differential effects of sulindac on renal hemodynamics, Na⁺ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.     

Diagnostic distance of high grade prostatic intraepithelial neoplasia from normal prostate and adenocarcinoma.

OBJECTIVE: To develop a distance measure based methodology to support the morphological evaluation of high grade prostatic intraepithelial neoplasia (PIN), a direct precursor of prostate cancer. METHODS: Eight morphological and cellular features were analysed in 20 cases of high grade PIN found in radical prostatectomy specimens from patients with adenocarcinoma. The diagnostic distance was evaluated to measure the extent to which the feature outcomes of the individual high grade PIN cases differed from the expected outcome profile of normal prostate, low and high grade PIN, and cribriform and large acinar adenocarcinoma. The belief value for high grade PIN was evaluated with a Bayesian belief network (BBN). RESULTS: Complete separation existed between the cumulative absolute diagnostic distances of these 20 cases from the prototype feature outcomes of high grade PIN and normal prostate the values for which were < or = 3 (range 0 to 3) and > or = 9 (range 9 to 15), respectively. The distances from low grade PIN (range 3 to 9), cribriform adenocarcinoma (range 2 to 8), and large acinar adenocarcinoma (range 5 to 10) were intermediate and showed overlap in their distribution. When taking into consideration whether the severity of feature changes was increasing or decreasing in comparison with the category prototype outcomes, the cumulative directional diagnostic distances from high grade PIN ranged from -3 to +3. Positive distance values were seen relative to low grade PIN (range +3 to +9) and relative to normal prostate (range +9 to +15). Negative values were found relative to cribriform adenocarcinoma (range -8 to +2). The distance values from large acinar adenocarcinoma ranged from -2 to +4 and partly overlapped with those from the high grade PIN category. A bivariate scattergram derived from both diagnostic distance measures showed excellent separation between the groups' distances. BBN analysis confirmed the morphology based diagnosis. The distance evaluation resulted in 18 cases whose belief value for high grade PIN ranged from 0.60 to 0.87. In the remaining two cases the results of the BBN analysis showed a belief value of 0.50 and 0.57 for low grade PIN and of 0.49 and 0.38 for high grade PIN, respectively. CONCLUSIONS: Distance measure based methodology represents a useful diagnostic decision support tool for the accurate evaluation of high grade PIN.     

Choice of coronary heart disease risk factor variables in a cross-sectional study of white South Africans

This report explores the possibility of redefining risk factors so as to improve their observed associations with prevalent coronary heart disease (CHD). A large cross-sectional community study of 5,895 white males and females aged 25-64 years yielded 240 cases of confirmed angina pectoris and 361 of confirmed myocardial infarction. Odds ratios for CHD end-points by level of risk factors when risk factors were expressed in the conventional manner (e.g. total cholesterol, systolic and diastolic blood pressure or current smoking) were often low and not statistically significant. Redefinition of risk factor variables in a manner that improved their specificity or compensated to some extent for the decreased risk factor exposure as a result of a CHD event (e.g. stopping smoking after a myocardial infarct) improved the strength of association. In this study, the most useful cholesterol variable was total cholesterol minus high-density lipoprotein cholesterol; for blood pressure the most useful variable was a blood pressure of 160/95 mmHg or above and/or being on anti-hypertensive treatment; and for smoking the most useful variable was the total duration of smoking (previous and current). Strong associations with CHD end-points were also found for conventionally expressed serum uric acid, diabetes prevalence (females) and family history of CHD. The study suggests that appropriate redefinition of risk factor variables and CHD end-points in cross-sectional studies yields associations similar in strength and direction to those found in prospective studies.     

Recurrent hip dislocation in intermediate spinal atrophy

Recurrent hip dislocation after corrective orthopaedic surgery in children and teenagers with intermediate spinal atrophy has not been reported in the literature. Four cases with long-term follow-up are presented. These represent the only cases surgically treated in 30 years of following spinal atrophy patients. Thus, it seems significant that all hips redislocated after the surgical procedure. In addition, two patients had second operations with subsequent dislocation. Pelvic obliquity should not be the basis for the surgery, as spinal fusion is generally necessary for wheelchair users. The sagacity of performing surgery for hip dislocations is raised.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.     

Clinical Efficacy of New Antiepileptic Drugs in Refractory Partial Epilepsy: Experience in the United States With Three Novel Drugs

Summary: A number of new antiepileptic drugs (AEDs), including topiramate (TPM), felbamate (FBM), and gabapentin (GBP), are approved or believed to be close to approval for marketing in the United States. Key efficacy findings for these AEDs in refractory partial epilepsy were reviewed. Large and significant drug-placebo differences were observed with TPM in two large dose-finding trials conducted in the United States. The minimal effective dose of TPM in the population studied was determined to be approximately 200 mg/day, and doses above 600 mg/day produced good efficacy but little incremental benefit versus the lower dosages for the overall study population. FBM is active in partial epilepsy, although seizure reduction is less marked and drug interactions complicate the findings. GBP is also active in this population, but only the 1,800 mg/day dosage was significantly better than placebo with respect to percent re-sponders. It may be useful to explore higher dosage ranges for both FBM and GBP if they can be well tolerated.