Agnogenic myeloid metaplasia (AMM)--correlation of bone marrow lesions with laboratory data: a longitudinal clinicopathological study on 114 patients

A clinicopathological study was performed on 114 patients (46 male/68 female, median age 67 years) with the diagnosis of agnogenic myeloid metaplasia (AMM) respectively primary osteo-myelofibrosis which was not preceded by any other or allied subtype of chronic myeloproliferative disorders. On admission patients revealed a striking variability of laboratory data as well as different histopathological features of initial bone marrow biopsies. For this reason discrimination was done into two groups based on bone marrow findings: group I patients (n = 46, 19 male/27 female) showed a hypercellular marrow without or only borderline (n = 24) to slight (n = 22) reticulin fibrosis and group II cases (n = 68, 27 male/41 female) displayed coarse bundles of collagen fibres (n = 18) frequently accompanied by osteosclerosis (n = 50). Statistical analysis of the corresponding initial hematological findings resulted in significant differences. These differences concerned also the complications occurring during the lengthy course of disease, which included a higher incidence of pancytopenia and severe marrow failure with hemorrhage and blast crisis in group II patients. However, overall survival time was not different in both groups. This may be related to the similarity of age distribution (64 resp. 65 years) and its significant association with arteriosclerotic vascular lesions. Consequently acute myocardial infarction and congestive heart failure were frequent causes of death in addition to infections due to marrow failure and blast crisis. Repeated bone marrow biopsies in 24 patients revealed an insidious transition from hypercellular lesions (group I) into advanced fibro-osteosclerotic changes (group II) concurring with laboratory data. Therefore our discrimination into two groups of patients represents variable stages or static histological and corresponding hematologic features in the evolution of a dynamic disease process in AMM.     

Changes in the bidirectional sodium flux across the intestinal mucosa in Crohn's disease.

Bidirectional sodium flux across the intestinal mucosa was measured in a group of 10 patients with Crohn's disease treated in the past by panproctocolectomy with ileostomy and compared with a similarly treated group of 11 patients with ulcerative colitis. All of them were in good health at the time of the study and a recent radiological examination of the small intestine was normal. A significant reduction in bidirectional sodium flux was found in those patients with Crohn's disease and suggests that the intestinal mucosa is involved to a greater extent than can be judged by radiological appearances alone. This adds weight to the concept that Crohn's diseases is a diffuse rather than a focal lesion of the gastrointestinal tract.     

Protective effect of N-methyl-D-aspartate antagonists after focal cerebral ischemia in rabbits

We studied the efficacy of postischemic, systemic treatment with the N-methyl-D-aspartate (NMDA) receptor antagonists dextromethorphan and dextrorphan in a rabbit model of transient focal cerebral ischemia. Twenty-two rabbits underwent 1-hour occlusion of the left internal carotid and anterior cerebral arteries followed by 4.5 hours of reperfusion before sacrifice. One hour after the onset of ischemia, immediately after removing the arterial clips, the rabbits were blindly assigned to treatment with dextromethorphan (20 mg/kg i.v. loading dose followed by 10 mg/kg/hr maintenance infusion, n = 7), dextrorphan (15 mg/kg i.v. loading dose followed by 15 mg/kg/hr maintenance infusion, n = 7), or an equivalent volume of normal saline alone (n = 8). The maintenance infusion of drugs or saline was continued for the duration of the experiment. The formalin-fixed brains were analyzed with magnetic resonance imaging using coronal T2-weighted images, and ischemic neuronal damage was assessed on standard coronal hematoxylin-and- eosin-stained sections. The area of neocortical ischemic neuronal damage was significantly reduced in the groups treated with dextromethorphan (4.2%, p less than 0.01) and dextrorphan (6.1%, p less than 0.01) compared with the controls (36.2%). Magnetic resonance imaging demonstrated significantly smaller areas of cortical edema in the groups treated with dextromethorphan (14.6%, p less than 0.01) and dextrorphan (8.0%, p less than 0.01) compared with the controls (32.9%). These clinically tested antitussives with NMDA-antagonist properties may have therapeutic value in the treatment of human cerebrovascular disease.     

Tendon echogenicity: ex vivo study

Recent publications discussing the echogenicity of normal tendon have described it variously as hyperechoic or hypoechoic. Since the echogenicity of tendon has been used to define normality and abnormality, certain knowledge of the normal echogenicity of tendon is crucial. Fresh tendon and muscle from beef hock was scanned with sector- and linear-array-transducer imaging at multiple angles and distances. The echogenicity of tendon was found to be very angle-dependent, a characteristic known as anisotropy. Scanned perpendicular to its long axis with a linear-array transducer, tendon was significantly more echogenic than muscle. With a change in angle, echogenicity of tendon decreased relative to that of muscle (the echogenicity of muscle remained the same), becoming isoechoic at angles of 2 degrees -7 degrees and hypoechoic at greater angles. Tendon studied with a sector transducer exhibited varying echogenicity. If echogenicity is used as a diagnostic criterion, the angle of the interrogating ultrasound beam must be very specifically defined.     

Naturally Occurring Polymers of IgA Lacking J Chain

Two of twenty IgA myeloma proteins studied were found to lack J chain. Both IgA proteins contained dimers and higher polymers (trimers, tetramers, pentamers) in proportions similar to those found in most classical 'J-positive' proteins. Both the 'J-negative' proteins contained bound albumin and alpha-1 anti-trypsin (α1AT), and reduction with mercaptoethylamine caused a release of albumin and α1AT concomitant with depolymerization of the higher polymers of IgA. These proteins formed complexes with secretory component (SC) in vitro, indicating that the presence of J chain is not a requirement for SC binding.     

AIDS risk behaviors and knowledge among heterosexual alcoholics and non-injecting drug users

The disinhibitory effects of abusable substances on sexual behavior and the increasing HIV prevalence among heterosexuals suggest that alcoholics and non-injection drug users may be at risk for HIV infection. We examined alcohol and non-injection drug use as AIDS risk factors, AIDS risk knowledge, and the effect of AIDS education upon voluntary HIV testing among 91 heterosexual male inpatients in a VA alcohol rehabilitation program. Questionnaire data revealed relationships between age, the use of alcohol, marijuana and intranasal cocaine just prior to sex and an increase in the number of female sexual partners. Use of alcohol just prior to sex was also associated with an increased number of unprotected sexual behaviors. AIDS risk knowledge in our sample was comparable to norms from previous studies. Inpatients received education concerning alcohol and sexuality either with or without an AIDS component. AIDS education and offer of HIV testing were associated with increased requests for HIV testing.     

Postnatal Toxicity following Prenatal Reserpine Exposure in Rats: Effects of Dose and Dosing Schedule

Postnatal Toxicity following Prenatal Reserpine Exposure inRats: Effects of Dose and Dosing Schedule. BUELKE-SAM, J., KIMMEL,G. L., WEBB, P. J., SUKKER, W., JR., NEWPORT, G. D., NELSON,C. J., AND KIMMEL, C. A. (1984). Fundam. Appl. Toxicol. 4, 983–991.Pregnant CD rats were treated subcutaneously with 0, 0.1, 0.33,or 1.0 mg reserpine/kg/day either on Days 12–15 or onDays 16–19 of gestation. Dams were allowed to deliverand litters (4 ± 1 of each sex) were weighed weekly andheld to 21 days of age. Basal ornithine decarboxylase (ODC)activity and neurocheraical determinations were made on heartsand brains, respectively, from pups culled from litters on postnatalDay 1, and from two males and two females/litter at 21 daysof age. Following both treatment schedules, the high dose ofreserpine resulted in maternal weight loss during dosing, increasedstillborn pups, reduced pup weight at birth, retarded postnatalgrowth, and decreased survival to 21 days of age. Basal cardiacODC activity was reduced to 33% of control levels only on PostnatalDay 1 in both high-dose groups, while absolute heart weightdecreased and relative heart weight increased in these pups.Whole-brain concentrations of two neurotransmitter metabolites,3–4-dihydroxy-phenylacctic acid (DOPAC) and 5-hydroxyindoleaceticacid (5-HIAA), were increased only at Postnatal Day 1 in thehigh dose group treated on Days 12–15 of gestation. Noother changes were found in concentrations of these metabolitesor in the transmitters dopamine and serotonin. The only effectfound following administration of 0.33 mg/kg reserpine was areduction in maternal weight gained during both dosing periods.No signs of toxicity were observed following low-dose exposureon either schedule. Most previously reported postnatal functionalstudies following reserpine exposure have used mid- to late-gestationaltreatment with 1.0 mg/kg, a dose shown here to result in markedovert maternal and fetal toxicity. Such overt toxicity raisesthe question of whetheT the functional effects of reserpineare primary or may be secondary to general toxic effects. Suchquestions must be considered when interpreting postnatal functionaldata and in the design of further studies.