Severe course of community-acquired pneumonia in an adult patient who is heterozygous for Q481P in the perforin gene: are carriers of the mutation free of risk?

Most cases of autosomal recessive hemophagocytic lymphohistiocytosis (HLH) are associated with over 50 mutations in the perforin gene. Some of these mutations have no clear functional association. Only homozygous patients display a full-blown syndrome, whereas no severe disease has been described in heterozygous carriers of these mutations despite the presence of functional and phenotypic alterations in cytotoxic cells. We study the family of a child who died from HLH at 6 months of age due to a Q481P mutation in the perforin gene. The study is particularly interesting because the patient's heterozygous father experienced severe community-acquired pneumonia that could be attributed to deficient in vitro NK cell activity despite normal perforin expression. This case report suggests that impaired NK cell activity in a heterozygote can result in poorer initial control of infections with severe clinical expression.

Splenectomy for poor graft function after allogeneic bone marrow transplantation in patients with chronic myeloid leukemia.

We report four patients with chronic myeloid leukemia (CML) that showed poor graft function after a non-T-depleted bone marrow transplantation (BMT) from an HLA-compatible sibling donor and who were successfully treated with splenectomy. Conditioning was done with cyclophosphamide (CY) and total body irradiation (TBI) without additional splenic irradiation. Three patients had enlarged spleens before BMT. The nucleated cell dose infused ranged from 2.3-3.2 x 10(8)/kg. Bone marrow (BM) examination prior to splenectomy showed BM aplasia (three cases) or hypocellularity (one case). At splenectomy no patient had evidence of cytomegalovirus (CMV) infection or severe acute GVHD; and three patients had moderately enlarged spleens. All patients were transfusion dependent. Complete hematological recovery was obtained in all patients. BM cellularity was normal 1 month after splenectomy. Complete chimerism of donor origin was documented. The four patients are alive (+16 to +58 months after BMT). Thus, in patients with CML, a poor graft function may be successfully corrected by splenectomy.

Degenerative pathologic findings after long-term implantation of bovine pericardial bioprosthetic heart valves.

Degeneration of bioprosthetic heart valves constitutes the most important limitation to their long-term durability and the factor that avoids a wider clinical use of these devices. We studied 26 degenerated bovine pericardial valves that belong to a series of 55 prostheses explanted for various reasons. Age of the patients at implantation of the valve and other factors predisposing to primary tissue failure did not seem to significantly influence the results obtained. Mean implantation time was longer for aortic than for mitral valves (p less than 0.05). Also, the mode of failure was different for mitral and aortic prostheses. Tearing of one or more leaflets without mineralization was more frequent (p less than 0.0025) among mitral than among aortic specimens. Coverage of the valve cusps by a macroscopically visible host sheath was more extensive on the outflow than on the inflow aspect (p less than 0.0015 aortic valves; p less than 0.015 mitral valves). On radiological examination the majority of valves had diffuse and severe mineralized lesions. Collagen degeneration was the most frequent histologic lesion to be found in both mineralized and calcium-free valves. Calcification was also frequent and appeared as mineral deposits that extended between different collagen planes. Scanning electron microscopy revealed the almost complete lack of "endothelium-like" cover on any of the valves and exposure of the underlying fibrous components of the pericardial tissue in areas subjected to abrasion. Transmission electron microscopy confirmed the collagen degeneration and disclosed electron-dense microparticles (probably mineralized) both in the extracellular space and within degenerated host connective tissue cells.

In vivo experimental assessment of polytetrafluoroethylene trileaflet heart valve prosthesis.

This report summarizes the results of a series of experimental implantations of polytetrafluoroethylene valves in sheep. Twelve prostheses were implanted in the tricuspid position in weanling (3- to 4-month-old, 26 +/- 3 kg) sheep. The valve sizes were 23 mm (eight animals) and 25 mm (four animals). There were two early deaths, and the 10 survivors were killed in a stepwise manner to get a mineralization profile of the valve. There was one episode of acute thrombosis but no evidence of pulmonary thromboemboli in any animal. In all cases the leaflets were thin and unretracted, but in half of them one cusp or more were stiffened. One valve displayed a fixed outward eversion of the free margin of two leaflets. Macroscopic calcification was detected in seven specimens and always involved the commissural areas. Radiologic studies confirmed this calcium topography and revealed only one case of severe and diffuse mineralization. In most cases the cusps showed a grossly visible pannus that was thinner and less extensive than usually seen in bioprostheses. Examination with light microscopy disclosed a complete lack of infiltrating cells within the cuspal material (made of compact polytetrafluoroethylene). However, those parts of the prostheses made of expanded polytetrafluoroethylene (the material covering the valve frame and the sutures) did show infiltration by host cells and calcium. Mineralized lesions were of extrinsic type, involving fibrin and fibroelastic host tissue accumulated in the inflow aspect of the commissures. Examination with transmission electron microscopy disclosed electron-dense masses surrounded by an electron-lucent granular homogeneous material in areas of mineralization. The time-course evolution of the tissue calcium content shows a moderate mineralization rate (0.46 +/- 0.31 mg/gm of dry-weight material per week of follow-up) and a marginally significant positive correlation between calcium content and follow-up. Our results suggest that the polytetrafluoroethylene valves have a moderate overall calcification rate and that calcium deposits appear to be always related to the commissural region and to the presence of expanded polytetrafluoroethylene.

Commissural dehiscence of Carpentier-Edwards mitral bioprostheses. Explant analysis and pathogenesis.

Manufacturing factors have seldom been implicated as a direct cause of structural deterioration of valvular bioprostheses; this phenomenon has generally been considered to be of a host-dependent origin. We analyzed the clinical and pathologic data from 12 Carpentier-Edwards mitral bioprostheses removed from 12 patients because of severe dysfunction and showing detachment of the porcine aortic wall from the stent in one commissure or more. These 12 prostheses were part of a group of 92 such valves that were explanted and displayed structural deterioration. They belong to a population of 405 Carpentier-Edwards bioprostheses implanted in the mitral position in our institution between May 1978 and November 1988. The patients included three men and nine women with a mean age of 54 +/- 13 years. One patient had a history of chronic renal failure, and two had systemic hypertension. Prosthesis sizes were 29, 31, and 33 mm (n = 4 for each size). The models of the valves were 6625 (n = 8) and 6650 (n = 4). Mean duration of implantation of the prostheses was 99 +/- 27 months (52 to 136 months) and did not differ depending on the model. There was no significant clustering of commissural detachments depending on valve size, year of implantation, or gender of the patient. No similar phenomenon was observed among 76 explanted aortic Carpentier-Edwards bioprostheses with structural deterioration from a population of 441 valves implanted during the same time frame. Native porcine aortic roots (n = 5) and aortic Carpentier-Edwards bioprostheses explanted because of structural deterioration (n = 4) were used as controls for comparison. Macroscopic examination showed single commissural dehiscence in 10 patients and double in two. Radiology disclosed no or mild mineralization in eight valves and no calcium in the area of aortic wall dehiscence, except for heavily calcified valves. Light microscopy evidenced a significant thinning of the aortic wall at the paracommissural level of mitral bioprostheses (351 +/- 68 microns) compared with either aortic bioprostheses (526 +/- 59 microns; p < 0.01) or control native porcine aortic roots (419 +/- 50 microns; p < 0.01). No difference was found in terms of aortic wall thickness between detached (322 +/- 42 microns) and intact (366 +/- 74 microns) commissures in mitral bioprostheses.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult choroid plexus papilloma of the posterior fossa mimicking a hemangioblastoma. Case report.

The authors report a case of cystic choroid plexus papilloma that originated in the posterior fossa. No connection with the ventricular system was found intraoperatively. Magnetic resonance (MR) and computerized tomography imaging did not furnish a diagnosis, but findings of pathological examinations were consistent with those of choroid plexus papilloma. The authors describe the different appearances of the tumor on MR images and discuss the differential diagnosis with other tumors of the posterior fossa.

[Research on prognostic factors in large-cell lymphomas]. / Investigación de factores pronósticos en linfomas de células grandes.

BACKGROUND: To carry out a study on the prognostic factors in large cell lymphomas (LCL) treated during the last decade and validate the international prognostic index (IPI). METHODS: One hundred twenty-four cases of newly diagnosed LCL, treated from 1978 to 1990, with a mean follow up of 27 months (1-142) were included in the study. The chemotherapy used was: CHOP (65%), ProMACE-CytaBOM (17%) and others (C-MOPP, MACOP-B). RESULTS: Complete remission (CR) was achieved in 71% of the cases and partial in 11%. Logistic analysis allowed the identification of three adverse factors to CR: Ann Arbor stage III, IV (p = 0.004; odds ratio, OR = 0.19), elevated tumoral load (p = 0.006; OR = 0.22) and age > or = 60 years (p = 0.02; OR = 0.31). Recurrence free survival (RFS) at 3 years was 67% (CI 95%; 55-79) with the median not having been achieved. Cox analysis allowed the identification to the ECOG > or = 2 scale as the only independent adverse factor (p = 0.0006; RR = 4.85) while Ann Arbor staging demonstrated marginal influence (p = 0.08). Global survival (GS) at 5 years was 45% (CI 95%; 35-55) with a median of 38 months. Multivariant analysis of independent adverse factors of GS were ECOG scale > or = 2 (p < 0.00001; RR = 6.07), Ann Arbor stage (p = 0.004; RR = 2.64) and hypoalbuminemia (p = 0.01; RR = 2.28). On inclusion of therapeutic response (TR) in the analysis, the factors chosen were absence of CR (p < 0.00001; RR = 9.58) and ECOG > or = 2 (p = 0.0004; RR = 4.24). CONCLUSIONS: Three variables evaluated at diagnosis, general state (ECOG), Ann Arbor stage and albumin, determined the prognosis in this series of large cell lymphoma. A prognostic model was designed from the same with three risk groups. The application of the international prognostic index to this series separated the patients into 4 groups of differentiated prognosis.

[Facial erythema and pancreatic glucagonoma]. / Eritema facial y glucagonoma pancreático.

Glucagonoma is a rare pancreatic tumor, that gives a characteristic clinical syndrome. In this report we describe the case of a 27 year old woman whose only clinical manifestations were a facial erythema and a palpable abdominal mass. Surgical removal of the tumor resulted in elimination of the clinical symptoms. Immunohistochemical findings were consistent with pancreatic glucagonoma.

[Ganglioneuroma of the duodenum]. / Ganglioneuroma del duodeno.

Ganglioneuroma is an exceptional benign tumour of the duodenum and only three cases have been described previously. We report the case of a 71-year-old male in whom this pathology was incidentally discovered, as it usually happens with this type of tumour. Within rare duodenal nonepithelial tumours, gangliocytic paraganglioma is a fairly well defined entity characterized by a proliferation of neurons, Schwann cells, and endocrine-like epithelial cells. Ganglioneuroma lacks this last type of cells and represents and even rarer finding within tumoral pathology of the duodenum. The histopathogenesis of this tumor is discussed and there are theories that defend an hamartomatous origin against a neoplastic nature.

[Nasal angiomyolipoma]. / Angiomiolipoma nasal.

Nasal angiomyolipoma is a anatomoclinical disease that have been described a previous time. It's non epithelial tumour with vascular, muscular and lipomatous elements. It have higher incidence in renal tissue associated with tuberous sclerosis, that hasn't been demonstrated in this case.

Atypical coccidioidomycosis in an AIDS patient successfully treated with fluconazole.

Cervical lymphadenopathy due to Coccidioides immitis occurred as the sole opportunistic infection in a Spanish patient with the acquired immunodeficiency syndrome. Twelve years earlier the patient had lived in the desert regions of the southwestern USA. After an initial course of high doses of fluconazole, the patient recovered without any sequelae. This is the first case of coccidioidomycosis in Spain.

[Morphologic findings in systemic amebiasis. Apropos of 1 case]. / Hallazgos morfológicos en amebiasis sistémica. A propósito de un caso.

Amebiasis is an uncommon infectious disease in our region. We describe the anatomopathologic findings of the autopsy of a patient who died of systemic amebiasis, briefly commenting the anatomo-clinical characteristics of this disease and its diagnosis.

Cerebral toxoplasmosis after autologous peripheral blood stem cell transplantation.

Toxoplasmosis appears to be a rare opportunistic protozoal infection following haematopoietic stem cell transplantation (HSCT). Most cases have been reported in allogeneic HSCT recipients, with only anecdotal reports of infection occurring after autologous transplantation. Reported here is the case of a patient who developed cerebral toxoplasmosis following autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

Hairy-cell leukaemia associated with auto-immune disorders in the form of a 'lupus-type' anticoagulant and a positive direct Coombs' test.

An account is given of a case of hairy-cell leukaemia associated with a 'lupus-type' anticoagulant and a positive direct Coombs' test, both of which were clinically symptom free. This is yet another example of the coexistence of hairy-cell leukaemia and an auto-immune disorder, but the disorder in question has not been described previously.

[Prognostic factors in low-grade lymphoma]. / Investigación de factores pronósticos en linfomas de bajo grado.

PURPOSE: Prognostic factors in low grade non-Hodgkin's lymphoma (LGL) are not well established. The aim of this study is to investigate prognostic factors on LGL treated in our institution during the last decade. PATIENTS AND METHODS: The study was carried out on 70 cases of newly diagnosed LGL, most treated with CVP or clorambucil and prednisone. The median follow-up was 37 months (1-132). Variables reported as prognostic factors in previous series were subjected to bivariate and multivariate analysis. RESULTS: Relevant clinical features were: Ann Arbor III-IV stage 74%, ECOG > or = 2-17%, bone marrow involvement 60% and large tumor burden according to MD Anderson criteria 21%. Complete response (CR) was achieved in 50% and partial response in 29%. In bivariate analysis factors related with poor CR were B symptoms, large tumor burden, high LDH and more than one extranodal site involvement. Logistic regression showed that large tumor burden (p = 0.02; OR = 0.07) and B symptoms (p = 0.07; OR = 0.14) were the best prognostic factors of poor CR. Five year global survival (GS) was 55%, with a median of 76 months. In univariate analysis factors related with GS were ECOG > or = 2, B symptoms, bulky, large tumor burden, retroperitoneo involvement and absence of CR. In multivariate analysis the only factor related with poor GS was large tumor burden (p < 0.00001; RR = 5.93). When therapeutic response was included in the model, absence of CR (p = 0.008; RR = 3.40) and large tumour burden (p = 0.005; RR = 3.86) were the factors selected. CONCLUSIONS: In LGL tumor burden was the most important prognostic variable. Tumor response showed less importance than in high grade lymphomas.