Mouse hepatitis virus 3 binding to macrophages correlates with resistance to experimental infection.

Mouse hepatitis virus 3 (MHV3) infection of A/J and BALB/c mice has been used as a model of resistance/susceptibility. A/J mice recover from a mild disease after 4-6 days of infection and the BALB/c mice develop an acute hepatitis and die after 3-4 days of infection. In view of studying the MHV3 binding to cells or cell extracts, we performed an enzyme-linked immunosorbent assay-like virus-binding assay, preparing microplates with L929 cells, A/J or BALB/c mouse macrophages and also with proteins extracted from these cells. Higher MHV3 bindings were observed to proteins of BALB/c macrophages than to the A/J ones. The interferon-gamma (IFN-gamma) activation led to a reduction of MHV3 binding only to proteins of resistant A/J mouse macrophages. Our experiments contribute to the hypothesis that IFN-gamma activation of macrophages plays an important role against MHV3 infection by downregulating the expression of viral receptors.

Down-regulation of Bgp1(a) viral receptor by interferon-gamma is related to the antiviral state and resistance to mouse hepatitis virus 3 infection.

Together with the evidence that the reduced virus growth and the antiviral state induced by interferon (IFN)-gamma, occurring only in macrophages from resistant animals, correlated with the decrease of MHV3 binding to macrophage membrane proteins, we show here the expression of cellular and viral genes in resistant (A/J) and susceptible (BALB/c) mouse macrophages after IFN-gamma activation/infection. The expression of interferon response gene 47 and interferon regulatory factor 1 genes takes place after IFN-gamma activation in both macrophages, indicating their activation. The expression of the biliary glycoprotein 1(a) (Bgp1(a), the main virus receptor) decreased only in IFN-gamma-activated A/J mouse macrophages, in contrast to the expression of the Bgp2 (alternative receptor), which was not influenced by IFN-gamma activation. The synthesis of both viral mRNA and virus particles was delayed only in IFN-gamma-activated A/J mouse macrophages compared with susceptible BALB/c macrophages. Besides the evidence that IFN-gamma may modulate the expression of the Bgp1(a) isoform of carcinoembryonic antigen family, these data show that IFN-gamma, which induces resistance against MHV3 infection, may be involved in the down-regulation of the main viral receptor expression, a key step forward in our understanding of the molecular basis of resistance against virus infection.

Role of drug therapy in the treatment of gastro-oesophageal reflux disorder in children.

Gastro-oesophageal reflux (GOR) is the effortless passage of gastric contents into the distal oesophagus. It can be classified as functional (or symptomatic), in which the infant remains free from disease, or a pathological (GOR disease, GORD), in which gastrointestinal, respiratory or neurobehavioural signs occur with intraoesophageal acidification and the development of oesophagitis. Functional or symptomatic GOR is successfully treated by conservative measures and does not require investigative diagnostic tools; however, both drug administration and an investigative approach are mandatory in patients with GORD. There is currently a great range of proven therapeutic options for GORD that are directed at counteracting the pathogenetic components of the disorder. In this report we discuss the role of different drug classes for treating GORD in children. The choice of therapy for GORD depends upon the severity of signs and the degree of oesophagitis. The presence of oesophagitis, as documented by endoscopy, suggests the use of antisecretory drugs; H2 receptor antagonists are the first-line agents. Nevertheless, individuals with refractory disease or those patients requiring potent inhibition of acid secretion (for example, GORD with respiratory involvement) can be given proton pump inhibitors. Other groups of patients who need potent inhibition of acid secretion are children with neurological dysfunction and those with Barrett's oesophagus. It is still unclear whether patients with frequent relapses are candidates for long term administration of antisecretory drugs or for surgical fundoplication.

Bronchial hyperresponsiveness in children and adolescents with Crohn's disease.

Pulmonary manifestations have been described in Crohn's disease (CD). Bronchial responsiveness to methacholine (MCh) was evaluated in 14 children with CD with no evidence of airway disease, 10 asthmatics, and 10 healthy subjects. In patients with CD total blood eosinophils and serum IgE were 0.20 x 10(9) x L(-1) (95% CI -1.68 to 2.08) and 138.4 kU x L(-)(1) (95% CI 18.84 to 257.96), respectively. Three patients with CD had positive prick tests. Bronchial hyperresponsiveness (BHR) was demonstrated in 10 patients with CD (71%) and in the asthmatics, but not in control subjects. In patients with CD PD(20) appeared significantly greater than in asthmatics (699 microg [95% CI 238 to 1,115] versus 104 microg [95% CI 37.35 to 293]; p < 0.05), and was not related either to baseline FEV(1) or IgE or eosinophils (r = 0.32; r = -0.5; r = -0.15, p = NS, respectively). Neither activity nor treatment or duration of CD affected BHR. Five nonatopic CD patients underwent a second MCh challenge over a 25-mo period: the PD(20) appeared significantly greater than basal PD(20) (1,941 microg versus 575 microg, p < 0.05, respectively), in the absence of significant changes of disease activity. BHR might be the expression of subclinical airway inflammation, a phenomenon which can be responsible for the development of various pulmonary manifestations in CD.

Lansoprazole in the treatment of gastro-oesophageal reflux disease in childhood.

BACKGROUND: Acid suppressive therapy is the mainstay of pharmacologic treatment of gastro-oesophageal reflux disease. Use of proton pump inhibitors in children is still limited and has only included omeprazole in a few controlled studies. AIM: To determine efficacy of lansoprazole, a relatively new proton pump inhibitor, on symptoms and oesophagitis in a group of children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists. The required dose of the drug for inhibiting gastric acidity was also determined. PATIENTS AND METHODS: A series of 35 children (median age: 7.6 years, range: 3-15) with oesophagitis refractory to H2 receptor antagonists received a 12-week therapeutic course with lansoprazole. Prior to the study children underwent symptomatic and endoscopic assessment, oesophageal manometry and 24-hour intragastric and intra-oesophageal pH test. The latter was repeated after one week of therapy while patients were on treatment in order to monitor the degree of acid suppression and adjust the dose of the drug. Symptomatic assessment and endoscopy were repeated at the end of the trial RESULTS AND CONCLUSIONS: In 12 patients (group A), the initial dose of the drug was efficacious (1.3 to 1.5 mg/kg/day), whereas in 23 [group B) the initial dose (0.8 to 1.0 mg/kg/day) was increased by half because of insufficient inhibition of intragastric acidity (i.e., when the intra-gastric pH remained below 4.0 for more than 50% of the recording time). Nine patients in group A (75%) and 8 in group B (53.5%) healed (chi2: 3.6, p<0.05); 1 patient in group A [8.3%) and 7 in group B (30.5%) remained unchanged (chi2: 6.9, p<0.01); 2 patients in group A and 8 in group B improved and underwent a further month of therapy. The two groups did not differ as far as concerns baseline pH, endoscopic and clinical variables. In both groups, those patients failing to respond at the end of the trial showed a more impaired oesophageal motility than improved or healed patients. The drug was well tolerated and no significant laboratory abnormalities occurred. In children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists, a 12-week course of lansoprazole is effective both in healing oesophagitis and improving symptoms. An initial dose of 1.5 mg/kg/day of the drug is suggested. However, if during treatment, patients remain symptomatic the dose should be increased and a prolonged intra-gastric and intra-oesophageal pH test performed to evaluate the acid suppression efficacy of the adjusted dose. A short course of lansoprazole appears to be safe and well tolerated in paediatric age.

Amyotrophic lateral sclerosis. Clinical analysis of 78 cases from Fortaleza (northeastern Brazil).

We report on the clinical characteristics of amyotrophic lateral sclerosis (ALS) in Fortaleza (Northeastern Brazil). For this, we analyzed retrospectively (from 1980 to 1999) 78 cases of ALS from the Service of Neurology of the University Hospital of Fortaleza diagnosed clinically and laboratorially (EMG, muscle biopsy, myelography, blood biochemistry, muscle enzymes and cranio-cervical X-ray). The results showed that they were mostly sporadic ALS (76/78), and they were divided into definite (n = 36), probable (n = 20), possible (n = 15) and suspected (n = 7), according to the level of diagnostic certainty. They were also subdivided into juvenile (n = 17), early-onset adult (n = 18), age-specific (n = 39) and late-onset (n = 4) groups. Clinically, they presented as initials symptoms, principally, asymmetrical (30/78) and symmetrical (24/78) weakness of extremities, besides bulbar signs, fasciculations, and atrophy. Curiously, pain as first symptom occurred in an expressive fashion (17/78). The predominant initial anatomic site, in this series, was the spinal cord, and mainly affecting the arms. As to the symptom accrual from region to region, this occurs more quickly in contiguous areas, and fasciculations are predominant when bulbar region was associated.

Failure of protection induced by a Brazilian vaccine against Brazilian wild rabies viruses.

This report shows that the SMB vaccine currently used in Brazil for human immunisation provides different degrees of protection in mice, depending on the rabies virus strain used as challenge. Using the NIH and Habel potency tests to evaluate the protective activity of rabies vaccine, we observed that vaccinated mice showed a higher resistance to a challenge with a fixed rabies virus (CVS-Challenge Virus Strain). The vaccine potency using the Habel or NIH tests was respectively > 6.4 (log 10) and 1.0 (Relative Potency-RP) when the fixed rabies virus was used for challenge, and from 2.9 to 4.3 (log 10) or 0.13 to 0.8 (RP) when different wild rabies viruses were used for challenge. The presence of virus neutralising antibodies (VNA) could not explain the differences of susceptibility after vaccination, since sera of vaccinated animals had similar VNA levels against both fixed and wild strains before virus challenge (respectively, 5.6 +/- 0.24 and 5.0 +/- 0.25 IU/ml of VNA against the fixed rabies virus and the 566-M strain of wild rabies virus in sera of mice vaccinated with 0.2 units of vaccine). Only cell-mediated immunity parameters correlated with the protection induced by vaccination. The IFN gamma titers found in sera and brain tissues of animals challenged with CVS strain were higher (from 36.7 +/- 5.7 to 293.3 +/- 46.2 IU/ml) than those found in mice challenged with 566-M virus strain (from 16.7 +/- 5.8 to 36.7 +/- 5.8). The proliferation index of spleen cells obtained with CVS stimulation reached a maximal value of 15.1 +/- 0.7 while spleen cells from vaccinated mice stimulated with 566-M virus failed to proliferate. The implications of these data in human protection by vaccination are discussed.

HLA class I and class II allele and haplotype distribution in the Venezuelan population.

Population studies represent an integral part, and a necessary link in a complex chain of host-pathogen interactions, disease pathogenesis, and major histocompatibility complex polymorphism. HLA class I and class II allele and haplotype distributions among Venezuelan mestizos were determined. Genes of Mongoloid, Negroid, and Caucasoid origin have created a distinctive human leukocyte antigen (HLA) genetic profile in this hybrid mestizo population that will influence HLA and disease association studies. The predominant HLA-B DQA1 DQB1 DRB1 haplotype is HLA-B44 DQA1*0201 DQB1*0201 DRB1*0701 (5.3%). It is noteworthy that the HLA-A3 B7 DR2 and the HLA-A1 B8 DR3 linkage groups, which are part of conserved or ancestral haplotypes, the last one associated with a wide range of autoimmune diseases and immune abnormalities in apparently healthy subjects, show low incidence among Venezuelan mestizos. This fact may be useful for future HLA and disease association studies and for localization of genes involved in immune regulation associated with these haplotypes.

Use of a new thickened formula for treatment of symptomatic gastrooesophageal reflux in infants.

BACKGROUND: Paediatricians are familiar with infants complaining of regurgitation and emesis from gastrooesophageal reflux. These subjects, usually growing satisfactorily and healthy, are affected by "functional" or "symptomatic" gastrooesophagel reflux and are treated with posture changes and thickened feedings. AIM: To evaluate in infants with symptomatic gastrooesophageal reflux the effect of a new formula (Nutrilon AR), containing carob flour/locus bean gum as a thickening agent; both clinical features and oesophageal acid exposure were evaluated. PATIENTS: Twenty-four infants (age range: 5-11 months; median age: 8 months; 8 females) presented at our Unit with a history of chronic postprandial regurgitation. METHODS: During a 24-hour intraoesophageal pH test a traditional formula thickened with rice flour at a concentration of 5% was alternated with the formula Nutrilon AR; thereafter infants were randomly allocated to receive, for two weeks, either a traditional thickened formula or the new formula, in addition to posture changes. RESULTS: Intraoesophageal acid exposure was significantly lower in the periods following the new formula than after traditional formula; at the end of the treatment period patients receiving the new formula had a more significant decrease of both symptomatic score and number of episodes of emesis than patients on traditional formula. CONCLUSIONS: The new available formula, with the characteristics of a thickened meal, is better than a formula, traditionally thickened with added rice flour, in the conservative treatment of infants with symptomatic gastrooesophageal reflux.

Common Caucasoid HLA-A1B8DR3 linkage group and immune responsiveness in a hybrid Venezuelan population: preliminary data.

A study performed on Venezuelans reveals a correlation between the common Caucasoid linkage group HLA-A1 B8 (A*0101, B*0801, DR3-) and increased lymphoproliferative activity stimulated by several concentrations of phytohemagglutin and concanavalin A in comparison to the group of persons possessing either the HLA-A1 (A*0101) antigen or the HLA-B8,DR3 (B*0801,DRB1*03012) haplotype. The increased lymphoproliferative activity was simultaneously present with increased CD16 cell counts and decreased CD3 and total mononuclear counts. A further comparison of lymphocyte population and subpopulation counts in peripheral blood and serum Ig G,A,M levels in the HLA-A1+ B8+ versus the HLA-A1-B8-high-responder individuals revealed increased CD16 cell counts and IgM levels in persons with the common Caucasoid haplotype (HLA-A1 B8). The data may suggest that some of the genes responsible for these levels or genes controlling their expression could be localized in or along the length of the common Caucasoid haplotype HLA-A1 B8 between the A and B loci of the MHC.

Predictive value of esophageal manometry and gastroesophageal pH monitoring for responsiveness of reflux disease to medical therapy in children.

OBJECTIVES: The aim of the study was to evaluate, in 42 children with gastroesophageal reflux disease, the predictive value of both esophageal manometry and gastroesophageal intraluminal pH on the responsiveness of the disease to medical therapy. METHODS: Motility of lower esophageal sphincter and esophageal body was carried out through a perfused pediatric sleeve-probe; prolonged recording of the sphincteric profile was evaluated at the occurrence of reflux episodes as detected by an esophageal electrode; intraluminal pH of the esophagus and stomach was also measured for 24-h through portable equipment. Children were treated for 8 wk with cisapride and ranitidine and were classified as healed or refractory after endoscopy and clinical evaluation. RESULTS: Twenty one children healed, and 21 were refractory. Compared with healed patients, refractory patients showed, at basal evaluation, an increased esophageal acid exposure (p < 0.05), a reduced basal sphincteric pressure and peristalsis amplitude (p < 0.01), an increased rate of sphincteric pressure drifts (p < 0.01), and a higher rate of transient lower esophageal sphincter relaxations (p < 0.01). The following parameters contributed significantly (p < 0.01) to a multivariate discriminant analysis: peristalsis amplitude, basal sphincter pressure, rate of transient relaxations of the sphincter, and rate of sphincteric pressure drifts. A correct classification of virtually all cases (97.62%) was reached. CONCLUSIONS: Motor dysfunctions of both lower esophageal sphincter and esophageal body are the major factors predicting refractoriness of reflux disease in children to a standard medical treatment. Of the two main mechanisms of reflux, i.e., transient lower esophageal sphincter relaxation and lower esophageal sphincter pressure drift, the latter had the highest predictive value for the refractoriness of reflux disease.

Simultaneous prolonged recordings of proximal and distal intraesophageal pH in children with gastroesophageal reflux disease and respiratory symptoms.

OBJECTIVES: To characterize both proximal and distal esophageal acid exposure in children with gastroesophageal reflux-related respiratory disease and to investigate the usefulness of dual-channel intraesophageal pH monitoring in these patients. METHODS: Continuous simultaneous recording of distal and proximal esophageal pH was performed in 40 patients with gastroesophageal reflux disease and respiratory symptoms (wheezing, nocturnal cough, obstructive bronchitis) (age range 3-168 months) (group A), in 20 patients with reflux disease alone (age range 7-156 months) (group B), and in 14 controls (age range 5-108 months) (group C). RESULTS: (expressed as median +/- SD) 1) The two groups of patients did not differ with regard to distal and proximal esophageal acid exposure (percentage of reflux) during both the total recording period [distal, A: 9.2 +/- 4, B: 10.7 +/- 7 (NS), C: 1.9 +/- 1.0; and proximal, A: 4.8 +/- 3.3, B: 4.0 +/- 3.3 (NS), C: 1.0 +/- 0.7] and during nighttime [distal, A: 8.0 +/- 6.2, B: 10.4 +/- 6.1 (NS), C: 0.9 +/- 0.65; and proximal, A: 3.72 +/- 3, B: 3.6 +/- 3.0 (NS), C: 0.75 +/- 0.45]. 2) The two groups did not differ with regard to the ratio between proximal and distal esophageal acid exposure during both total and nocturnal periods of analysis. 3) No significant correlation was found between distal and proximal esophageal acid exposure during total and nocturnal recording periods. 4) In patients with reflux-related respiratory disease, the respiratory symptomatic index was significantly higher during distal esophageal acid exposure alone (47.0 +/- 28.6%) than during simultaneous reflux at the two esophageal levels (26.9 +/- 27%) (p < 0.05). Furthermore, reflux episodes associated with respiratory symptoms reached lower pH values than those in patients without symptoms at the two recording sites. CONCLUSIONS: Gastroesophageal reflux into the proximal esophagus does not discriminate between patients with reflux disease alone and those with reflux disease complicated by respiratory symptoms. Symptoms of asthma in reflux patients appear to be elicited more by a reflex mechanism than by aspiration of gastric refluxate into the airways. Intraesophageal acidification seems to be involved in eliciting respiratory symptoms related to reflux disease, and prolonged intraesophageal two-level pH measurement does not seem to be useful in the approach to patients with reflux disease associated with respiratory symptoms.

Strong association between major histocompatibility complex class I antigens and immune aberrations among healthy Venezuelans.

Immune reactivity indicators studied among 55 unrelated Venezuelan mestizo subjects included lymphoproliferative response to polyclonal mitogen (PHA, Con A, PwM) stimulation, NK cell activity, and enumeration of peripheral blood mononuclear cells. HLA-A, -B, -C, -DR, and -DQ antigens were determined by serologic typing. A strong association between impairment of the parameters studied and MHC class I antigens A11 and A3 was found. Subjects with decreased suboptimal (0.5 micrograms/ml) PHA response as well as decreased optimal (0.5 micrograms/ml) Con A response showed high incidence of HLA-A11 antigen (RR = 81, p = 0.001, pc = 0.021 and RR = 54, p = 0.0029, respectively). Subjects with decreased suboptimal (0.5 micrograms/ml) PHA response HLA-A11- with only one exception, were either HLA-A1+ or HLA-A3+. These antigens belong to the same CREG, share public epitopes, and have low incidence in the Venezuelan mestizo population. Six of 10 persons with decreased CD16 subset count (5.17% +/- 0.23% vs 11.69% +/- 0.44%) had HLA-A3 antigen (RR = 17, p = 0.001, pc = 0.021). The data indicate a possible contribution of HLA-A11,A3, molecules through their private and/or public determinants to immune response aberrations which under certain conditions may result in development of diseases.

Antroduodenojejunal manometry in the diagnosis of chronic idiopathic intestinal pseudoobstruction in children.

We analyzed the antroduodenojejunal (ADJ) manometric patterns in a group of 19 consecutive children (mean age, 53 months; range, 5 months to 14 years) referred for suspected chronic idiopathic intestinal pseudoobstruction. Diagnosis was based on typical symptoms, absence of extraintestinal diseases, and structural lesions of the gut at endoscopy and radiology. Surgical full-thickness intestinal biopsies were evaluated in nine patients. Manometry of the stomach and small bowel was performed in the fasting and fed state with a multilumen perfused probe. All patients showed severe abnormalities of ADJ motor activity that were not seen in the eight controls (mean age, 38.2 months; range, 1-9 years). In 12 patients, manometric patterns suggesting neuropathic disease were detected with fasting and/or fed sustained and incoordinated duodenojejunal phasic waves, aberrant propagation and/or configuration of phase III of the inter-digestive motility complex, inability of a meal to convert a fasting into a fed pattern, and prolonged groups of fasting and fed nonpropagated phasic waves. In seven of these patients, histology revealed marked changes of the intrinsic neurons. In four cases, manometry disclosed features suggestive of a myogenic disease, including severe fasting and fed infrequent low-amplitude contractions, sometimes with some degree of propagation; in two of these cases, histology showed morphological abnormalities of smooth muscle cells of the gut wall. In three patients, manometry revealed signs suggestive of mechanical obstruction of the gut, such as repetitive post-feeding clusters and simultaneous repeated broad-based waves; in these patients, more detailed x-ray studies showed organic obstructive causes (ileal lymphoma, Hirschsprung's disease, and intestinal malrotation).(ABSTRACT TRUNCATED AT 250 WORDS)

Omeprazole and high dose ranitidine in the treatment of refractory reflux oesophagitis.

Thirty two consecutive patients (age range 6 months-13.4 years) with severe reflux oesophagitis were randomised to a therapeutic trial for eight weeks during which they received either standard doses of omeprazole (40 mg/day/1.73 m2 surface area) or high doses of ranitidine (20 mg/kg/day). Twenty five patients completed the trial (12 on omeprazole, 13 on ranitidine). At entry and at the end of the trial patients underwent symptomatic score assessment, endoscopic and histological evaluation of the oesophagus, and simultaneous oesophageal and gastric pH measurement; results are given as median (range). Both therapeutic regimens were effective in decreasing clinical score (omeprazole before 24.0 (15-33), after 9.0 (0-18); ranitidine before 19.5 (12-33), after 9.0 (6-12)), in improving the histological degree of oesophagitis (omeprazole before 8.0 (6-10), after 2.0 (0-60); ranitidine before 8.0 (8-10), after 2.0 (2-6), and in reducing oesophageal acid exposure, measured as minutes of reflux at 24 hour pH monitoring (omeprazole before 129.4 (84-217), after 44.6 (0.16-128); ranitidine before 207.3 (66-306), after 58.4 (32-128)) as well as intragastric acidity, measured as median intragastric pH (omeprazole before 2.1 (1.0-3.0), after 5.1 (2.2-7.4); ranitidine before 1.9 (1.6-4), after 3.4 (2.3-5.3)). Serum gastrin concentration was > 150 ng/l in four patients on omeprazole and in three patients on ranitidine. It is concluded that in children with refractory reflux oesophagitis high doses of ranitidine are comparable with omeprazole for the healing of oesophagitis and relief of symptoms; both drugs resulted in efficacious reduction of intragastric acidity and intra-oesophageal acid exposure.

Erythrocyte defects precede the onset of CCl4-induced liver cirrhosis. Protection by silymarin.

The time-course of some alterations produced in erythrocytes during the onset of CCl4-induced liver cirrhosis was studied in rats. Erythrocyte membranes were isolated to measure Na+, K+ and Ca+2-ATPase activities. Membrane lipid composition was determined to calculate the cholesterol/phospholipid ratio and serum samples were used to measure lipoperoxidation. The results demonstrated that as CCl4 treatment progressed, serum lipoperoxidation and membrane cholesterol/phospholipid ratio increased while ATPase activities decreased. ATPase activities in red blood cells of cirrhotic rats were 50% below normal values but those determined in cells of animals treated simultaneously with CCl4 + silymarin were significantly improved. Silymarin co-treatment also preserved the normal cholesterol/phospholipid ratio in the membranes. Our results suggest that the measure of ATPase activities in erythrocytes membranes could be a simple, safe and useful early marker of liver damage and also valuable to test the effectiveness of a given drug therapy.

Histopatologia da medula óssea na síndrome de imunodeficiência adquirida / Histopathology of the marrow in acquired immunodeficiency syndrome

Apresentamos as alteraçöes hematológicas e de histologia de medula óssea em 15 portadores de síndrome de imunodeficiência adquirida em fase considerada final da doença. Treze de 15 pacientes apresentavam-se anêmicos; linfopenia periférica absoluta (linfócitos abaixo de 2.500/mm3) ocorreu em 14/15 casos e plaquetopenia (abaixo 100.000/mm3) em 2/15. A velocidade de hemossedimentaçäo foi superior a 40mm/h em todos os casos. O ferro medular estava aumentado em 6/13 anêmicos, sendo que em 4 deles havia hipoplasia da série vermelha; em 5/13 o ferro medular estava diminuído (três com hiperplasia da série vermelha e dois com normoplasia). A série branca foi hipercelular em seis casos, normocelular em quatro e hipocelular em cinco. A série plaquetária mostrava-se hiperplásica em oito casos (três deles com megacariócitos hiperlobulados, quatro com micromegacariócitos hipolobulados e dois com disposiçöes em grumos e associaçäo com fibrose de medular); hipoplasia megacariocítica ocorreu em cinco casos. Depressäo dos três setores ocorreu em um caso e depressäo de dois setores em três. Em 13/15 o número de linfócitos na medula óssea estava aumentado e, na maioria das vezes, tinham morfologia de linfócitos transformados, sendo que em 11 dos doentes havia aumento de plasmócitos intersticiais ou peritrabeculares. Em dois casos havia formaçäo de nódulos linfóides hiperplásicos peritrabeculares. Em um caso portador de toxoplasmose generalizada observou-se formaçäo granulomatosa, BAAR negativo, e em necrose caseosa. Em 12/15 casos havia eosinofilia medular sem correspondência com o sangue periférico. Fibras reticulínicas aumentadas foram vistas em 11/15 casos e em dois deles o aspecto era de fibrose medular