Proliferative lesions in Castleman's disease.
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Biomedical subjects
Publications and source records attributed to S Desai.
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OBJECTIVE: An intracranial aneurysm is an important acquired cerebrovascular disease that can cause a catastrophic subarachnoid hemorrhage. Despite modern therapy, most patients die or are left disabled as a direct result of a severe initial hemorrhage. The development of more effective treatment strategies depends on understanding the fundamental biology of cerebral aneurysms. The purpose of the present study is to determine whether inflammation or immunological reaction occurs in cerebral aneurysms. METHODS: Aneurysm tissue was collected at the time of microsurgical repair from 23 unruptured and 2 ruptured aneurysms (25 patients) and compared with 11 control basilar arteries harvested at autopsy. Immunohistochemistry was used to localize complement (C3c, C9), immunoglobulins (IgG, IgM), vascular cell adhesion molecule-1, macrophages and monocytes (CD68), T lymphocytes (CD3), and B lymphocytes (CD20). RESULTS: Complement (C3c, P < 0.0001; C9, P = 0.0017), immunoglobulin (IgG, P = 0.0013; IgM, P = 0.031), vascular cell adhesion molecule-1 (P = 0.0022), macrophages (CD68, P = 0.004), and T lymphocytes (CD3, P = 0.0004) were all frequently present in the wall of aneurysm tissue but were rarely identified in control basilar arteries. A few B lymphocytes (CD20, P = 0.41) were found in aneurysm tissue, but none were found in the basilar arteries. CONCLUSION: Extensive inflammatory and immunological reactions are common in unruptured intracranial aneurysms and may be related to aneurysm formation and rupture.
Recent studies have reported and provided nucleotide sequence data from divergent isolates of hepatitis E virus (HEV), including isolates from North America and Africa. Sera were investigated from 29 Chinese patients with a diagnosis of acute hepatitis and who were negative for hepatitis viruses A-E by serology (HEV was excluded by testing for IgG antibody only). To determine whether some patients were infected with HEV but had yet to seroconvert to antibody positivity, RT-PCR was carried out with primers designed within conserved sequences of the HEV open reading frame (ORF) 1 and ORF2 regions. Fifteen patients were found to harbour sequences related to HEV. Analysis of the HEV products revealed that nucleotide sequences from nine of the sera closely matched Burmese-like HEV sequences (more than 92% nucleotide identity across ORF1 and 88% in ORF2). The remaining six HEV isolates were similar to each other but divergent from all other known HEV sequences (74 to 83% nucleotide identity in ORF1 or ORF2). Phylogenetic analysis suggests that the six divergent isolates represent a fourth genotype of HEV, distinct from the previously described Burmese, Mexican and United States variants (genotypes 1, 2 and 3). This novel variant, referred to here as the Chinese genotype (genotype 4), may be responsible for a significant proportion of cases of acute hepatitis in China, as seen by the fact that 40% of the HEV-infected patients in this study were genotype 4 positive.
BACKGROUND AND OBJECTIVES: Giant cell tumor of the tendon sheath (GCTTS) is a lesion of uncertain etiology. To better interpret pathogenesis and aid in the differentiation of GCTTS from other similar pathological processes we reviewed the literature and analyzed the available information. METHODS: We retrospectively studied clinicopathologic findings in 28 cases of GCTTS on the basis of anatomic location and histologic appearance of the lesion. RESULTS: The GCTTS could be divided into those involving the common digits (20 cases) and larger joint group (8 cases) based on anatomic location. Grossly the digit tumors were small, multiple, surrounded by a thin fibrous capsule, and had a variegated appearance, while the large joint tumors were relatively large and covered by one or more layers of synovium. Microscopically both groups consisted of a mixture of round to polygonal histiocytes, foam cells, hemosiderin laden macrophages, and multinucleated giant cells. The giant cells seemed more abundant in the digit tumors, while the pseudoglandular spaces lined by synovial cells were more striking in the large joint group. CONCLUSIONS: Local excision was the treatment of choice in the majority of the patients. Eight patients had local recurrence.
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BACKGROUND: Elevated serum lipoprotein(a) [Lp(a)] levels are associated with the development of native coronary atherosclerosis. The association between increased levels of Lp(a) and the development of accelerated cardiac allograft vasculopathy (ACAV) in patients who have undergone orthotopic heart transplantation has not been firmly established. METHODS AND RESULTS: We studied 74 consecutive heart transplant recipients with at least 1 year survival to determine the relation between Lp(a) and the presence of ACAV. Recipient and donor clinical and laboratory parameters, including mean serum Lp(a) levels, were obtained. ACAV was defined angiographically as > or =30% stenosis in one or more epicardial arteries. ACAV 1 year after heart transplantation was angiographically present in 26 (35%) patients. Mean donor age (36 +/- 13 years [ACAV (+)] vs 28 +/- 10 years, [ACAV (-)]; p = 0.004) and mean serum triglyceride levels 6 months after transplantation (286 +/- 275 mg/dl [ACAV (+)] vs 169 +/- 85 mg/dl [ACAV (-)]; p = 0.025) were univariate predictors of ACAV. No significant difference in mean serum Lp(a) levels was observed (20 +/- 19 mg/dl [ACAV (+)] vs 30 +/- 30 mg/dl [ACAV (-)]; p = NS). Donor age was the single greatest independent predictor of ACAV by multivariate logistic regression (p = 0.02). CONCLUSIONS: Lp(a) does not appear to be a risk factor for the development of ACAV 1 year after heart transplantation. Further studies are needed to define the influence of serum Lp(a) on the development of cardiovascular disease after orthotopic heart transplantation.
PURPOSE: Contemporary chemotherapy has significantly improved the event-free survival (EFS) among patients with T-cell disease. However, myelosuppression has been a significant adverse effect of this approach. In this study, we assessed the impact of r-metHu granulocyte colony-stimulating factor (G-CSF) on the period of neutropenia, number of days of hospitalization, and delays in subsequent administration of chemotherapy in a cohort of patients with T-cell leukemia (T-ALL) or advanced stage lymphoblastic lymphoma (ASLL). PATIENTS AND METHODS: This open-label, randomized trial incorporated r-metHuG-CSF into the induction and two consecutive continuation-therapy cycles of our intensive program for T-cell malignancies. In the induction phase, r-metHuG-CSF was given after two different combinations of chemotherapy, one of which included vincristine, prednisone, cyclophosphamide, and adriamycin and the other a continuous infusion of high-dose ara-C and L-asparaginase. In the two continuation-therapy cycles, r-metHuG-CSF was given following the combination of vincristine, adriamycin, prednisone, and 6-mercaptopurine (MP) and after continuous infusion of high-dose cytarabine (ara-C). RESULTS: Fifty-six patients with T-ALL and 33 with ASLL were enrolled onto study from April 1994 to December 1995. Our data show no significant difference in number of days of absolute neutrophil count (ANC) less than 500/microL, hospitalizations, or delays in therapy in the induction phase. However, in the continuation-therapy phase the number of days of ANC less than 500/microL was significantly shorter (P = .017) on the G-CSF-arm without significantly affecting the number of days of hospitalizations or delays in therapy. CONCLUSION: r-metHuG-CSF did not significantly affect the period of neutropenia, hospitalization, or delays in therapy in the induction phase, whereas in the two cycles of continuation therapy, it significantly shortened the period of neutropenia.
Using data from the first round of Demographic and Health Surveys for 22 developing countries, we examine the effect of maternal education on three markers of child health: infant mortality, children's height-for-age, and immunization status. In contrast to other studies, we argue that although there is a strong correlation between maternal education and markers of child health, a causal relationship is far from established. Education acts as a proxy for the socioeconomic status of the family and geographic area of residence. Introducing controls for husband's education and access to piped water and toilet attenuate the impact of maternal education on infant mortality and children's height-for-age. This effect is further reduced by controlling for area of residence through the use of fixed-effects models. In the final model, maternal education has a statistically significant impact on infant mortality and height-for-age in only a handful of countries. In contrast, maternal education remains statistically significant for children's immunization status in about one-half of the countries even after individual-level and community-level controls are introduced.
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The treatment of ureteroceles in children requires an individualised approach. Antenatal diagnosis is the ideal, so that postnatal urinary antibiotic prophylaxis and appropriate investigations can be organised. Postnatal investigations should assess both upper and lower urinary tract. Renal and bladder ultrasound and radiographic micturating cystourethragraphy under antibiotic cover will both detect vesicoureteric reflux and assess any bladder outlet obstruction due to the ureterocele. Renal function, particularly of the upper moiety, is best evaluated by technetium Tc99m dimercaptosuccinic acid renal scan. Both function and obstruction can be quantitated by the Tc99m-mercaptoacetyltriglycine isotope scan with intravenous volume expansion (10 ml/kg) and furosemide diuresis (1 mg/kg). Intravenous urography provides the best anatomic information when the upper moiety is functional. The surgical management is based on the clinical situation, which is often variable, and therefore needs to be tailored for each patient. The general principles include restoration of anatomy to as near normal as possible and preservation of functional renal tissue.
OBJECTIVE: We determined the sensitivity and specificity of neonatal brain-stem auditory evoked potentials (BAEP) as markers for subsequent hearing impairment and for developmental problems found later in infancy and childhood. METHODS: BAEP studies were performed before discharge in infants treated with extracorporeal membrane oxygenation (ECMO), and two specific abnormalities were analyzed: elevated threshold and delayed central auditory conduction. Behavioral audiometry was repeated during periodic follow-up until reliable responses were obtained for all frequencies, and standardized developmental testing was also conducted. The sensitivity and specificity of an elevated threshold on the neonatal BAEP for detecting subsequent hearing loss, and the relationship of any neonatal BAEP abnormality to language or developmental disorders in infancy, were calculated. RESULTS: Test results for 46 ECMO-treated infants (57.5%) were normal, and those for 34 infants (42.5%) were abnormal, with either elevated wave V threshold, prolonged wave I-V interval, or both on neonatal BAEP recordings. Most significantly, 7 (58%) of the 12 children with subsequent sensorineural hearing loss had left the hospital after showing normal results on threshold tests. There was no significant difference in the frequency of hearing loss between subjects with abnormal (5/21, or 24%) and those with normal BAEP thresholds (7/59, or 12%; Fisher Exact Test, p = 0.28). Therefore the sensitivity of neonatal BAEP testing for predicting subsequent hearing loss was only 42%. Neonatal BAEP specificity for excluding subsequent hearing loss was 76%. In contrast, on language development testing, 19 children demonstrated receptive language delay. Of these children, 12 (63%) had abnormal neonatal BAEP recordings and 7 (37%) had a normal BAEP threshold, normal central auditory conduction test results, or both (p = 0.04). CONCLUSIONS: Neonatal BAEP threshold recordings were of limited value for predicting subsequent hearing loss common in ECMO-treated survivors. However, an abnormal neonatal BAEP significantly increased the probability of finding a receptive language delay during early childhood, even in those with subsequently normal audiometry findings. Because neonatal ECMO is associated with a high risk of hearing and receptive language disorders, parents should be counseled that audiologic and developmental follow-up evaluations in surviving children are essential regardless of the results of neonatal BAEP testing.
Eleven patients with high-risk hematologic malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from partially mismatched family members in whom progenitor cells had been mobilized by G-CSF. Donors were mismatched by up to one antigen in the GVH direction and up to three antigens in the rejection direction. Outcomes were compared with those of 22 patients receiving BCT from fully matched donors. Two mismatched patients died without engraftment on day 21 and 32. One had rejected bone marrow from the same donor, the other was mismatched by two antigens in the rejection direction and received the lowest dose of CD34+ cells. Median time to granulocyte engraftment was 21.5 (range 16-33) days for the mismatched group compared with 16 (11-28) days for the matched group (P = 0.01). No correlation was found between CD34+ cell dose and time to granulocyte or platelet recovery. In the mismatched and matched BCT groups respectively, the risk of grade II-IV acute graft-versus-host disease (GVHD) was 73% vs 28% (P = 0.001) and of chronic GVHD 100% vs 78% at 18 months (P = 0.01). The relationship of T cell dose to acute GVHD could only be evaluated in the matched group and no correlation was found. One of 11 mismatched patients and eight of 22 matched patients had relapse or persistent disease. Disease-free survival at 1 year was similar at 55% for mismatched and 50% for matched BCT. These results indicate that allogeneic BCT from partially mismatched family members is accompanied by a high incidence of GVHD but may result in comparable survival to BCT from fully matched donors.
Myasthenia gravis (MG) is a rare complication of allogeneic bone marrow transplantation (BMT). We present the 11th case in the medical literature, a 23-year-old female 100 months post-allogeneic bone marrow transplantation for acute myelogenous leukemia (AML). After discontinuation of immunosuppression for chronic graft-versus-host disease (GVHD) involving skin, gastrointestinal tract and lacrimal glands, the patient developed severe, progressive dysphagia initially attributed to esophageal candidiasis. With the development of muscle weakness, ptosis, and dysphonia the diagnosis of generalized myasthenia gravis was suspected, and confirmed by elevated anti-acetylcholine receptor antibody titer and a positive edrophonium challenge. Prednisone and pyridostigmine produced improvement, and thymectomy was performed without pathologic evidence of thymoma. Recurrent post-operative respiratory distress required transient mechanical ventilation. Twenty-seven months after diagnosis, the patient requires maintenance prednisone to control symptoms of myasthenia gravis. The clinical features of all reported cases of MG post-allogeneic BMT are reviewed, and universal features include an association with decreasing immunosuppression, the presence of other manifestations of chronic GVHD, anti-acetylcholine receptor antibodies, and the absence of an associated thymoma. HLA Cw1, Cw7 and DR2 were identified at frequencies significantly above that expected from HLA antigen prevalance studies, and may be markers for increased risk of developing MG post-allogeneic BMT. No statistically significant associations with HLA A2, B7, B35 or donor-recipient sex mismatch were present. Reinstitution of immunosuppression and standard therapies for myasthenia gravis were effective in the majority of cases. The role of thymectomy in this population remains unclear.
BACKGROUND: The use of cytomegalovirus (CMV)-"safe" blood has been recommended for CMV seronegative patients with newly diagnosed malignant disease for whom bone marrow transplantation is a future option. STUDY DESIGN AND METHODS: To evaluate this policy, 76 CMV-seronegative children with lymphoreticular malignancies or solid tumors were randomly assigned to receive either blood components that were not screened for CMV antibody or CMV-seronegative red cell (RBC) and platelet units. Subjects were followed for evidence of CMV infection by the use of enzyme-linked immunosorbent assays and virus isolation. Follow-up continued long after the blood transfusions to determine the risk of community-acquired CMV infection. RESULTS: No cases of transfusion-acquired CMV infection were documented. The prevalence of CMV IgG and IgM antibody in blood donors was 40.5 and 0.9 percent, respectively. Patients assigned to receive standard blood components and CMV-negative components were given a median (range) of 7 (1-30) and 9 (1-38) RBC units and 11 (0-123) and 14 (0-71) platelet units, respectively. The risk of transfusion-acquired CMV infection is estimated to be less than 1 in 698 donor exposures. Two patients developed asymptomatic community-acquired CMV infection, for an incidence of 1.7 percent per patient-year of follow-up. CONCLUSION: The risk of transfusion-acquired CMV infection in this population is low, largely because of the patients' low level of exposure to seropositive blood and the use of relatively white cell-reduced components for purposes other than CMV prevention. Such children at this center therefore continue to receive standard blood components. Strategies to prevent CMV seroconversion in these children should include parental education to minimize the risk of community-acquired infection.
Extracorporeal membrane oxygenation is an effective rescue treatment for severe cardiorespiratory failure in term or near term neonates, although cerebral palsy, mental retardation, and sensorineural hearing loss are observed in 10 to 20% of survivors. The objective of the present study was to identify potential risk factors that may explain the neurologic and audiologic sequelae noted in 19% of 181 survivors of neonatal extracorporeal membrane oxygenation from our hospital. Our results suggest the following findings in survivors of severe cardiorespiratory failure treated with neonatal extracorporeal membrane oxygenation: (1) hypotension or the need for cardiopulmonary resuscitation before extracorporeal membrane oxygenation significantly increases the risk of spastic cerebral palsy, (2) profound hypocarbia before extracorporeal membrane oxygenation is associated with a significantly increased risk of hearing loss, (3) mental retardation in the absence of spastic cerebral palsy is unexplained except when due to abnormal fetal brain development, and (4) hypoxemia in the absence of hypotension does not increase the risk of neurologic or audiologic sequelae.
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