Virus-associated hemophagocytic syndrome. Diagnosis and treatment

Virus-associated haemophagocytic syndrome (VAHS) is a rare disease characterized by fever, splenomegaly, cytopenia and histiocytic proliferation with haemophagocytosis in the reticuloendothelial system. The clinical course of VAHS can be dramatic and the prognosis is often poor. The pathogenesis of VAHS is not well understood. Many believe that viral infection provokes an abnormal immune response in predisposed individuals leading to hyperactivation of Th1 helper cells, macrophage proliferation and secretion of large amounts of cytokines. The resultant hypercytokinaemia may be responsible for the clinical and biochemical manifestations of VAHS. In this article the clinical features, presumed pathogenesis, diagnostic criteria and treatment of VAHS are discussed.     

Rearrangement status of the malignant cell determines type of secondary IgH rearrangement (V-replacement or V to DJ joining) in childhood B precursor acute lymphoblastic leukemia

Immunoglobulin heavy chain (IgH) oligoclonality in childhood B precursor acute lymphoblastic leukemia (ALL) as determined by Southern analysis is found in 30-50% of patients and has been shown to be the result of ongoing IgH rearrangement (mostly V(H)-replacement and V(H) to D-J(H) joining) after malignant transformation. It is unknown however, what determines the type of secondary rearrangement. Also the biological basis of the variable degree of oligoclonality observed in childhood ALL is poorly understood. We analyzed in detail the IgH rearrangement status of the leukemic cells for a random panel of 18 childhood B precursor ALL patients by polymerase chain reaction (PCR)/sequencing analysis and by Southern analysis. By Southern analysis 10/18 (55.6%) patients were considered oligoclonal and 8/18 (44.4%) monoclonal. In contrast, by PCR minor clonal rearrangements were detected in 14/18 (77.8%) patients. V(H)-replacement was found in 7/14 patients, V(H) to D-J(H) joining in 6/14 patients and an unusual type of secondary rearrangement, V(H)-D to J(H) joining, in one patient. Only a single type of secondary rearrangement was detected in each patient. The type of secondary rearrangement (V(H)-replacement or V(H) to D-J(H) joining) depended on the rearrangement status (VDJ/VDJ or VDJ/DJ, respectively) of the dominant leukemic clone as determined by Southern analysis. We found that in addition to a more 'advanced' IgH rearrangement status patients with V(H)-replacements also have a more 'advanced' TCRdelta rearrangement status, which possibly reflects exposure of both the IgH locus and the TCRdelta locus to recombinase activity in a preleukemic clone. Finally, we investigated a putative relationship between oligoclonality by Southern analysis and S-phase fraction of the leukemic cell population. We found a significantly lower percentage cells in S-phase for oligoclonal patients as compared to monoclonal patients. Our data add to the understanding of ongoing rearrangement of antigen receptor loci in childhood ALL and have implications for the monitoring of minimal residual disease by PCR.     

Sibling Adaptation to Childhood Cancer Collaborative Study: the association of sibling adaptation with maternal well-being, physical health, and resource use

OBJECTIVE: To assess the role of heredity in the development of keratoconus. DESIGN: Prospective study. SETTING: Eye clinic providing secondary and tertiary ophthalmic care in Toronto. PATIENTS: Thirty-nine patients with keratoconus (57 eyes) and 48 relatives of 11 patients with keratoconus. The corneal topography of the family members was compared with that of a group of 68 volunteer control subjects (136 eyes) without clinical evidence or a family history of keratoconus. OUTCOME MEASURES: Three quantitative measures derived from computerized videokeratography: the relative steepness of the inferior cornea versus the superior cornea, central corneal power and the difference in central corneal power between the two eyes. All the data were statistically analysed with the use of nonparametric discriminant analysis. RESULTS: Fifteen family members who were believed to be clinically normal on the basis of refraction, keratometry and slit-lamp examination has statistically significant topographic abnormalities suggestive of early or mild keratoconus. CONCLUSIONS: The presence of these findings in family members of patients with keratoconus may represent the incomplete expression of a gene contributing to the development of the condition. Pedigree analysis suggested an autosomal dominant inheritance pattern in 9 of the 11 families. Our results underline the value of videokeratography for accurate family pedigree analysis and the diagnosis of keratoconus.     

Etiological factors of epilepsy

INTRODUCTION: The epilepsies are one of the main reasons for consultation and hospital admission in neurology. They may be caused by multiple factors. OBJECTIVES: To determine the types of epilepsy, their aetiology and the value of a clinical history in diagnosis of their cause. PATIENTS AND METHODS: We studied 96 epileptic patients aged over 15 years in the epilepsy clinic of the Hospital Dr. Carlos J. Finlay in La Habana, Cuba. On a questionnaire we recorded: family history, pre-, peri- and postnatal histories, clinical features of the crises and physical exploration. All had inter-ictal electroencephalograms, 62 had cranial CTs, 36 had MR studies and 8 had both types of imaging studies. We excluded acute metabolic disorders and cerebral tumours. RESULTS: There was a predominance of persons aged between 26 and 35 (78%) and 59.37% were men. Symptomatic epilepsy was seen in 51.4%, in 38.54% this was cryptogenic and in 10.41% idiopathic. Perinatal damage was present in 20.8%, head injury in 11.4%, febrile convulsion in 10.4%, meningoencephalitis in 8.3% and cardiovascular disease in 4.1%. CONCLUSIONS: The international classification of epilepsy permits our patients to be divided into groups. In most of them aetiological factors were detected after an interview and medical exploration.     

Management of renal angiomyolipoma: analysis of 15 cases

OBJECTIVE: We present our experience with 15 patients with renal angiomyolipoma warranting intervention. METHODS: The medical records and radiological studies were reviewed for patient age and sex, tumor location and size, association with tuberous sclerosis, and treatment approach. All patients were regularly followed by ultrasound and computed tomography scan. RESULTS: Presenting symptoms were retroperitoneal bleeding in 9 patients and flank pain in 6. Excluding cases of tuberous sclerosis (mean tumor diameter 11 cm), the mean diameter of the two tumors that bled was 5.4 cm, similar to those in the patients presenting with flank pain. Two patients with retroperitoneal bleeding had tumors < 3 cm. Angioinfarction was performed in 7 patients, partial nephrectomy in 3, and total nephrectomy in 4. One patient with tuberous sclerosis, who was observed only, died of bleeding and sepsis. The mean follow-up period of 4.3 years revealed stable creatinine levels and no recurrent hemorrhage. CONCLUSIONS: The management approach of angiomyolipoma should be aimed at parenchymal preservation which can be effectively accomplished by limited surgery or preferably by selective embolization. Preventive embolization may be feasible even for small tumors. However, any doubt about the diagnosis of angiomyolipoma should be clarified by surgery.     

Clinical use of low output settings in 1.2-mm2 steroid eluting electrodes: three years of experience

A new generation of tined steroid-eluting leads featuring 1.2-mm2 distal electrodes (CapSure Z, Medtronic Inc., Minneapolis MN, USA) has the potential to reduce battery current drain and enhance pulse generator longevity by means of high pacing impedance and low pacing threshold. Forty patients aged 50-87 years (mean 72.4 years) were implanted with 33 ventricular (models 4033 and 5034) and 30 atrial-J (models 4533 and 5534) leads with 1.2-mm2 electrodes. Low pacing outputs, mainly in the range from 1 V/0.20 ms to 1.6 V/0.36 ms with > or = 3:1 pulse width safety margins (PWSM) applied, were instituted at 3-6 months of implantation and adjusted at subsequent follow-up controls according to changes in thresholds. Cumulative follow-up period of low outputs was 1,512 months (24 months per lead, range 9-36 months), which involved 3.43 follow-up controls per lead (range 2-5). During follow-up, pulse width thresholds (PWTs) at the used amplitudes did not change in 55.5% of the leads; PWTs increased by < or = 100% in 36.5%, by 101%-200% in 1.6%, and by > 200% in 6.3% of the leads. Changes in PWT that would apparently exceed 3:1 PWSM over a 1-year period occurred in one atrial lead where even the nominal 3.5 V/0.4-ms output would not be effective and in one ventricular lead in the aftermath of an acute myocardial infarction (300% PWT rise at 1.6 V). Based on the present observations, pacemaker dependent patients require > or = 4:1 PWSM and other patients > or = 3:1 PWSM with output pulse widths < or = 0.60 ms and annual pacemaker clinic visits. Calculated battery current drain and anticipated longevity associated with a variety of pacing outputs and impedances are provided, compared, and discussed. Correlation between acute and chronic pacing impedances and pacing thresholds was weak, implying that a systematic intraoperative pacing site optimization cannot contribute significantly to the extension of average battery longevity.     

An algorithm for automatic measurement of stimulation thresholds: clinical performance and preliminary results

We have developed an algorithmic method for automatic determination of stimulation thresholds in both cardiac chambers in patients with intact atrioventricular (AV) conduction. The algorithm utilizes ventricular sensing, may be used with any type of pacing leads, and may be downloaded via telemetry links into already implanted dual-chamber Thera pacemakers. Thresholds are determined with 0.5 V amplitude and 0.06 ms pulse-width resolution in unipolar, bipolar, or both lead configurations, with a programmable sampling interval from 2 minutes to 48 hours. Measured values are stored in the pacemaker memory for later retrieval and do not influence permanent output settings. The algorithm was intended to gather information on continuous behavior of stimulation thresholds, which is important in the formation of strategies for programming pacemaker outputs. Clinical performance of the algorithm was evaluated in eight patients who received bipolar tined steroid-eluting leads and were observed for a mean of 5.1 months. Patient safety was not compromised by the algorithm, except for the possibility of pacing during the physiologic refractory period. Methods for discrimination of incorrect data points were developed and incorrect values were discarded. Fine resolution threshold measurements collected during this study indicated that: (1) there were great differences in magnitude of threshold peaking in different patients; (2) the initial intensive threshold peaking was usually followed by another less intensive but longer-lasting wave of threshold peaking; (3) the pattern of tissue reaction in the atrium appeared different from that in the ventricle; and (4) threshold peaking in the bipolar lead configuration was greater than in the unipolar configuration. The algorithm proved to be useful in studying ambulatory thresholds.     

Role of chronic inflammation in the promotion of prostatic hyperplasia in rats

PURPOSE: Chronic prostatitis is a common histopathological finding in prostatectomized patients. A possible interrelationship between the presence of leukocyte exudate and the extent of the hyperplastic lesions has been suggested. The aim of the present study was to analyze the effect of the immunomodulator compounds, Complete Freund Adjuvant (CFA) and cyclosporin A (CsA), administered alone or together with citral on the induction and extent of rat prostatic hyperplasia. MATERIALS AND METHODS: Adolescent Wistar rats (42 days old) were given citral alone or combined with CFA or CsA for one month. Semiquantitative analysis of the extent of the hyperplastic lesions was made with the histoscore protocol. RESULTS: CsA did not induce hyperplastic changes or abolish the ability of citral to promote hyperplastic changes or to affect the extent of the lymphocytic exudate in the stroma. CFA itself, however, had a proliferative action on the prostatic epithelium, and it augmented the hyperplastic changes induced by citral and even induced atypical transformations of the acinar epithelium. CONCLUSIONS: Immunoinflammatory stimulators might play a role in the prostatic epithelial cell growth and proliferation processes, most probably by modulation of the cytokine system.