Further characterization of morphologically defined typical and atypical CLL: a clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases

We analysed a group of 390 patients, diagnosed with chronic lymphocytic leukaemia (CLL). Cases were subclassified as morphologically typical and atypical CLL according to the criteria of the FAB proposal. Typical CLL cases were mostly diagnosed at a low-risk stage (Binet A/Rai 0), required no immediate treatment and expected a long survival; atypical CLL cases mostly presented at a more advanced risk stage (Binet B/Rai I–II), usually required immediate treatment and their survival was shorter. Moreover, clinical staging was of prognostic significance in typical but not in atypical cases.   In typical CLL, del(11q) was the most common chromosomal abnormality (21%) whereas in atypical CLL trisomy 12 was found in about 65% of the cases documented with an abnormal karyotype. Although chromosomal abnormalities were associated with a poor survival in typical CLL, they are of no prognostic significance in atypical CLL.   Based on these data, we conclude that subtyping CLL by morphology enables the identification of two groups of cases, each characterized by a specific clinical presentation, different cytogenetic abnormalities and prognostic parameters. We speculate that these two groups may represent two related, but different, diseases with different prognostic parameters and a different survival.     

Total cortisol,free cortisol,and growth hormone associated with brief social separation experiences in young macaques

Many behavioral, immunological, and physiological consequences of brief maternal separation in bonnet (Macaca radiata) and pigtail monkeys (Macaca nemistrina) have been documented. However, the impact of social separation on plasma cortisol and growth hormone is unknown for these particular species. In the present study, the behavioral and endocrinological consequences of a 2-week maternal separation in socially housed infant bonnet and pigtail monkeys were followed. In seven pairs (separated and matched control) of bonnet and six pairs of pigtail infants, plasma was obtained under baseline, separated, and reunion conditions twice weekly for the duration of the study. Blood samples were obtained from both infants of the pair in approximately 10 min. Plasma total cortisol, free cortisol, and growth hormone were measured in these samples. Focal animal behavioral observations were made on all subjects twice daily throughout the study period. In both species, total cortisol and free cortisol rose immediately following maternal separation in comparison to the matched nonseparated controls and returned to basal levels (e.g., that of matched non-separted controls) following reunion with the mother. In contrast, plasma growth hormone rose only in the pigtail infants over a time course that peaked around the time of reunion. Multiple regression techniques indicated for the first week of separation, in the separated but not control subjects, that mean plasma free and total cortisol was positively related to distress behaviors (vocalization and postural slouch) observed during this week and negatively related to social behaviors (play and proximity to others) noted during the same period. In contrast, plasma growth hormone was related to both species and sex of the subjects but unrelated to behavioral variables. © 1995 John Wiley & Sons, Inc.     

Evidence of an abnormal intramuscular component of fatigue in multiple sclerosis

The goals of this study were to investigate muscle fatigue in patients with multiple sclerosis (MS), and to determine the relationships between muscle fatigue, clinical status, and perceived fatigue. The fatigability of the anterior tibial muscle was quantitated in patients and controls during 9 min of intermittent stimulation (used to eliminate central sources of muscle fatigue). During exercise, the decline in tetanic force, phosphocreatine, and intracellular pH was greater in patients than in controls. The compound muscle action potential amplitude did not decrease during exercise, indicating that there was no failure of neuromuscular transmission during fatigue. Thus, the excessive fatigue in MS developed from sources beyond the muscle membrane. Following exercise, the recovery of tetanic force was delayed in patients (a pattern that suggests abnormal excitation–contraction coupling), whereas the recovery of metabolites was complete in both groups. Muscular fatigue was correlated with clinical disability but not with perceived fatigue. These results suggests that fatigue in MS has both central (perception, upper motor neuron dysfunction) and peripheral (impaired metabolism and excitation–contraction coupling) components.© 1995 John Wiley &Sons, Inc.     

Influences on Food Selection of Women on High- and Low-Fat Diets

There is evidence that long-term maintenance of a low-fat diet reduces preference for high-fat foods. Sensory evaluation of the taste of fat, and preference for high and low-fat foods were studied in a group of former participants in a randomized dietary intervention trial aimed at lowering fat consumption. Intervention subjects consuming less than 25% of daily calories as fat and control subjects consuming more than 35% of daily calories as fat agreed to be in a "taste perception" study. In Study 1, subjects tasted 20 dairy solutions containing different levels of fat and sugar. Subjects rated the perceived intensity of fat taste, and of liking, for each of the solutions. In Study 2, subjects were asked to taste and rate 4 high-fat and 4 low-fat snack foods, and were then allowed to freely consume these foods in a preference test. Intervention and control subjects were similar in their sensory evaluation of the taste of fat in Study 1. In Study 2, intervention subjects reported a reduced hedonic rating of the taste of high-fat snack foods compared to control subjects, yet intervention subjects consumed the same amount of high-fat snack foods as control subjects. We conclude that a successful outcome in a dietary intervention may be due to social and cognitive factors, in addition to potential changes in hedonic response to fat.     

Biocompatibility of Hemoglobin Solutions. II. The Inflammatory Reaction of Human Monocytes and Mouse Peritoneal Macrophages

This study explored the inflammatory mechanism of toxicity of hemoglobin solutions (Hb-S). Human monocytes and mouse activated peritoneal macrophages were incubated with seven different solutions. The first four consisted of non-cross-linked bovine Hb. Of these, Hb-SI was incompletely purified of stromal phospholipids, Hb-SII was contaminated with environmental bacterial endotoxins, Hb-SIII was pure hemoglobin, and Hb-SIV was pure Hb with the addition of superoxide dismutase (SOD), catalase (CAT), and mannitol (M). The other three solutions were made of pure bovine Hb cross-linked with different agents: Hb-SV, reacted with glutaraldehyde; Hb-SVI reacted with bis-3,5-dibromosalicyl fumarate (DBSF); and Hb-SVII reacted with a ring-opened dialdehyde derivative of 5'(pyro)-phosphate of adenosine (ATP) (o-ATP). The reaction of monocytes and macrophages was studied in terms of (a) O2-derived radicals, as determined by the measurement of H2O2 and lipid peroxides; (b) complement factor C3a desArg; (c) 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin); and (d) TxB2 (stable metabolite of thromboxane) released into the culture supernatants. The most significant reactions were obtained with the solutions contaminated with stromal phospholipids or bacterial endotoxins. Pure Hb was less reactive. Further reduction in proinflammatory activity was achieved by the addition of oxygen radical-scavengers (SOD, CAT, and M), or by the cross-linking of Hb with DBSF or o-ATP.     

Clonidine Use and Abuse Among Methadone Program Applicants and Patients

Forty-eight consecutive applicants and 30 known clonidine-abusing methadone patients at three methadone treatment programs were surveyed regarding their use of clonidine. Two distinct patterns of clonidine use emerged. Of 22 applicants who took clonidine illicitly, 15 used it primarily to decrease opioid withdrawal, as well as for its sedating effect. Applicants mostly obtained it from physicians, used an average dose of 0.37 mg at a time, and about one third believed clonidine to be addictive. In contrast, clonidine-using patients took clonidine primarily for its psychoactive effects, including the interaction with methadone, in addition to decreasing opioid withdrawal. Patients obtained clonidine frequently on the street and from family or friends, but less from physicians. The average reported dose for patients was 0.6 mg. The vast majority of these patients felt clonidine was addictive. Our findings, when coupled with the risk inherent in clonidine overdose, suggest that further research into the identification and treatment of clonidine abuse among methadone patients is warranted.     

Desmoplastic malignant melanoma presenting with orbital involvement

Desmoplastic malignant melanoma (DMM) is a rare variant of spindle cell melanoma. We report a case of DMM of the forehead secondarily involving the orbit. The diagnosis was based on light microscopic features, including prominent peripheral cell nest formation and spindle cell fascicles in densely collagenous stroma. Immunohistochemical studies showed strong uniform staining for S100 antigen throughout the tumour. It was negative for HMB 45, smooth muscle actin, desmin, cytokeratins and Type IV collagen. Electron microscopy showed neither melanosomes nor myelin figures. The clinical and histological characteristics of desmoplastic malignant melanoma, and its differential diagnosis of malignant schwannoma, are discussed. DMM has a poor prognosis, since it tends to invade deeply, recur locally and metastasise readily.     

Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.

The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases.