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Biomedical subjects

J Brody

Publications and source records attributed to J Brody.

At least 19 recordsLinked to original sources
PubMed2000

Bone markers and bone mineral density during growth hormone treatment in children with growth hormone deficiency.

Growth hormone (GH) has a positive impact on muscle mass, growth and bone formation. It is known to interact with the bone-forming unit, with well-documented increases in markers of bone formation and bone resorption within weeks of the start of GH therapy. These changes relate significantly to short-term growth rate, but it is not evident that they predict long-term response to GH therapy. The consequences of GH deficiency (GHD) and GH replacement therapy on bone mineral density (BMD) have been difficult to interpret in children because of the dependency of areal BMD on height and weight. Some studies have tried to overcome this problem by calculating volumetric BMD, but results are conflicting. The attainment of a normal peak bone mass in an individual is considered important for the future prevention of osteoporosis. From the limited data available, it appears difficult to normalize bone mass totally in GH-deficient individuals, despite GH treatment for long periods. Studies to date examining the interaction between GH and bone have included only small numbers of individuals, making it difficult to interpret the study findings. It is hoped that these issues can be clarified in future research by the direct measurement of bone density (using quantitative computer tomography). Mineralization is only one facet of bone strength, however; other important components (e.g. bone structure and geometry) should be addressed in future paediatric studies. Future studies could also address the importance of the degree of GHD in childhood; how GH dose and insulin-like growth factor-I levels achieved during therapy relate to the final outcome; whether or not the continuation of GH therapy after the attainment of final height may further enhance bone mass; whether the timing and dose of other treatments (e.g. sex hormone replacement therapy) are critical to the outcome; and whether GHD in childhood is associated with an increased risk of fracture.

Biomarkers↗
PubMed1998

Efficacy and safety of an extended-release niacin (Niaspan): a long-term study.

Crystalline nicotinic acid (immediate-release niacin) is effective therapy for lipoprotein regulation and cardiovascular risk reduction. However, inconvenient regimens and unpleasant side effects decrease compliance. Sustained-release formulations designed to circumvent these difficulties increase hepatotoxicity. Niaspan, a new US Food and Drug Administration (FDA)-approved, once-daily, extended-release form, has been found effective and safe in short-term trials. The long-term efficacy and safety of Niaspan lipid monotherapy was studied in 517 patients (aged 21-75 years) for < or =96 weeks in dosages < or =3,000 mg/day. Primary efficacy endpoints were low-density lipoprotein (LDL) cholesterol and apolipoprotein B (apo B) changes from baseline; secondary efficacy endpoints were changes in total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, lipoprotein(a), and total cholesterol/HDL-cholesterol ratio; safety data included adverse events and laboratory values over the 2-year study period. LDL-cholesterol levels decreased significantly: 18% at week 48 and 20% at week 96; apo B reduction was similar (16% decrease at week 48 and 19% at week 96). Large elevations in HDL cholesterol (26%, week 48; 28%, week 96) allowed only modest decreases in total cholesterol (12% and 13%, respectively), whereas total cholesterol/HDL-cholesterol ratio decreased by almost one third. Triglyceride and lipoprotein(a) levels were decreased by 27% and 30%, respectively (week 48), and by 28% and 40%, respectively (week 96). All changes from baseline were significant (p <0.001). Niaspan was generally well tolerated, although flushing was common (75%); however, there was a progressive decrease in flushing with time from 3.3 episodes in the first month to < or = 1 episode by week 48. Aspirin was used by one third of patients before Niaspan dosing to minimize flushing episodes. Although serious adverse events occurred in about 10% of patients, none were considered probably or definitely related to Niaspan. Adverse events in general varied widely, but their true relation to the study drug is difficult to ascertain without a placebo (control) group. No deaths occurred. There were statistically significant changes in hepatic transaminases, alkaline phosphatase, direct bilirubin, phosphorus, glucose, amylase, and uric acid. However, these changes were mostly small and are not likely to be biologically or clinically significant (the decrease in phosphorus is a new finding in niacin therapy). No myopathy was observed. Thus, this long-term study confirms the earlier short-term findings that Niaspan is safe and effective as monotherapy in plasma lipoprotein regulation.

Adult↗
PubMed1998

CD28 receptor endocytosis is targeted by mutations that disrupt phosphatidylinositol 3-kinase binding and costimulation.

Although the lipid kinase phosphatidylinositol 3-kinase (PI-3K) binds at high levels to the cytoplasmic tail of CD28, controversy exists regarding its role in CD28 costimulation. Potentially, the kinase could be linked to a signaling cascade or be needed indirectly in events such as receptor endocytosis. Indeed, little is known regarding both the fate of CD28 following receptor ligation and the events that control the process. In this study, we help to resolve this issue by providing evidence that PI-3K plays a role in regulating CD28 endocytosis. We show that approximately 25 to 35% of wild-type CD28 becomes endocytosed following Ab binding (t1/2 = 10 min), followed by segregation into two pools; one pool is destined for degradation in lysosomal compartments and is blocked by chloroquine, and another pool that is recycled to the cell surface (t1/2 = 2.5 h). Recycling of CD28 could have an important impact on CD80/86-mediated costimulation by replenishing functionally active receptors on the cell surface. Several findings implicate PI-3K in the control of endocytosis. Modulation experiments indicate that CD28-PI-3K complexes are preferentially endocytosed, and mutations that alter PI-3K binding concordantly affect the efficacy of endocytosis. Importantly, mutations that inhibit receptor internalization also block cosignaling. Therefore, previous results documenting a requirement for PI-3K may be explained by a blockage of receptor internalization.

Binding Sites↗
PubMed1998

T-cell lymphoma associated with natural killer-like T-cell reaction.

We report a case of T-cell lymphoma showing in the peripheral blood (PB) exclusively T-lymphocytes with suppresser T-cell preponderance and a high percentage of natural killer (NK) marker positive cells by flow cytometry. A T-cell receptor (TCR) gene analysis of the PB leukocytes demonstrated rearrangements of TCRalpha, TCRbeta, and TCRgamma genes. Therefore, the phenotype and genotype appeared to be consistent with an NK-like T-cell leukemia/lymphoma. However, when the PB lymphocytes were separated by size, it was found that 80% of NK marker positive cells were in the smaller cell population, while the neoplastic cells were in the large cell gate. A diagnosis of T-cell lymphoma with reactive NK-like T-cells was finally confirmed by demonstrating the presence of both large atypical lymphoid cells and large granular lymphocytes (LGL) on PB smears. Although immunoperoxidase stain of bone marrow and colon showed positive T-cell markers in the tumor cell population, cytoplasmic granules could not be identified in tissue sections and, thus, a distinction between T-cell lymphoma and NK-like T-cell lymphoma could not be made by light microscopy until NK markers were studied. CD57 was demonstrated immunohistochemically in small lymphocytes but not in the large tumor cells in the colon. Electron microscopy, however, demonstrated LGL reaction to the lymphoma cells in the colonic biopsy. NK-like T-cell lymphoma usually carries a poorer prognosis than peripheral T-cell lymphoma, thus the distinction of these neoplasms is important. This study emphasizes that T-cell lymphoma may cause an LGL reaction or proliferation. If the lymphoma cells were of the same size as LGL, flow cytometric studies may have misled the diagnosis to NK-like T-cell-lymphoma.

Aged↗
PubMed1998

Development of essential thrombocythemia in a patient treated with interferon alfa and pentostatin for hairy cell leukemia.

A patient is reported who developed essential thrombocythemia after successful treatment for hairy cell leukemia. He was initially treated with interferon alfa and subsequently relapsed within one year of treatment. His diagnosis was reconfirmed and then treated with Pentostatin. Six years after treatment he had a progressive increase in the platelet count and was diagnosed as essential thrombocythemia. Second cancers including various types of hematological malignancy have been reported in patients with hairy cell leukemia treated with chemotherapy or interferon alfa. These malignancies may represent either a new clonal disorder or a complication of drug treatment. This is the first report of a chronic myeloproliferative disorder following successful treatment of hairy cell leukemia.

Aged↗
PubMed1997

Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium.

Estradiol-17beta (E2) acts through the estrogen receptor (ER) to regulate uterine growth and functional differentiation. To determine whether E2 elicits epithelial mitogenesis through epithelial ER versus indirectly via ER-positive stromal cells, uteri from adult ER-deficient ER knockout (ko) mice and neonatal ER-positive wild-type (wt) BALB/c mice were used to produce the following tissue recombinants containing ER in epithelium (E) and/or stroma (S), or lacking ER altogether: wt-S + wt-E, wt-S + ko-E, ko-S + ko-E, and ko-S + wt-E. Tissue recombinants were grown for 4 weeks as subrenal capsule grafts in intact female nude mice, then the hosts were treated with either E2 or oil a week after ovariectomy. Epithelial labeling index and ER expression were determined by [3H]thymidine autoradiography and immunohistochemistry, respectively. In tissue recombinants containing wt-S (wt-S + wt-E, wt-S + ko-E), E2 induced a similar large increase in epithelial labeling index compared with oil-treated controls in both types of tissue recombinants despite the absence of epithelial ER in wt-S + ko-E tissue recombinants. This proliferative effect was blocked by an ER antagonist, indicating it was mediated through ER. In contrast, in tissue recombinants prepared with ko-S (ko-S + ko-E and ko-S + wt-E), epithelial labeling index was low and not stimulated by E2 despite epithelial ER expression in ko-S + wt-E grafts. In conclusion, these data demonstrate that epithelial ER is neither necessary nor sufficient for E2-induced uterine epithelial proliferation. Instead, E2 induction of epithelial proliferation appears to be a paracrine event mediated by ER-positive stroma. These data in the uterus and similar studies in the prostate suggest that epithelial mitogenesis in both estrogen and androgen target organs are stromally mediated events.

Aging↗
PubMed1997

Histiocyte-rich B-cell lymphoma.

This is the second report of histiocyte-rich B-cell lymphoma and the first case analyzed by flow cytometry and cytogenetic study. The immunophenotype determined by flow cytometry was that of a B-cell antigen-positive, surface immunoglobulin-negative B-cell lymphoma with 79% CD11c positive histiocytes. The lymphoid cells were composed of 76% neoplastic B-cells and 24% reactive T-cells. Immunohistochemical staining showed large numbers of histiocytes positive for CD68 and lysozyme in the lymph node and the bone marrow. Neoplastic lymphoid cells were positive for CD20, CD45, CD74 and CDw75. The monoclonality of the tumor cells was established by the evidence of rearrangements of the heavy chain and kappa light chain genes and a complex clonal cytogenetic abnormalities including t(8;14)(q11;q32). The tumor cells were large, pleomorphic lymphoid cells and showed no features resembling those of the L/H cells of Hodgkin's disease as previously reported. The rapidly progressive clinical course in the present case is consistent with the clinical features shown in the original study. The histiocytic component in this tumor is presumably recruited by a lymphokine with the nature of a growth factor from the tumor cells that may also be responsible for the rapid proliferation of the tumor cells and the aggressive clinical course. This entity merits special recognition because it leads to a predictable poor prognosis and because of its potential of being misdiagnosed as true histiocytic lymphoma.

Aged↗
PubMed1996

Relationship between hairy cell leukemia variant and splenic lymphoma with villous lymphocytes: presentation of a new concept.

An unusual case of low-grade B-cell lymphoproliferative disorder with peripheral lymphocytosis and splenomegaly followed for 4 1/2 years is reported. During this period, the phenotype of the tumor cells in the blood changed from that of hairy cell leukemia (HCL)/chronic lymphocyte leukemia (CLL) to HCL/prolymphocytic leukemia (PLL), to PLL. The lymphoid population in the blood showed a mixture of hairy cells, villous lymphocytes, small lymphocytes, and prolymphocytes, corresponding to the phenotypes at various stages. Although relatively specific markers for CLL, HCL, and PLL, such as CD5, CD11c, CD22, CD25, and FMC-7, were positive at various stages, all these markers have also been demonstrated in a large study series of splenic lymphoma with villous lymphocytes (SLVL). In addition, the histologic pattern of the bone marrow biopsy and splenectomy specimen were not typical for HCL. This case can therefore be classified either as HCL variant or as SLVL. As SLVL assumes various cytologic and histologic patterns, which overlap with different lymphoproliferative disorders, especially HCL variants, this entity appears to represent a heterogeneous group of lymphomas/leukemias that may evolve into each other. The absence of activation of c-myc and bc1-2 oncogenes as well as mutation of p53 tumor suppressor gene, together with the presence of only one single rearranged band for both heavy chain and kappa light chain genes in our case suggest that these morphologically different lymphoid tumors may belong to the same family.

Antigens, CD↗
PubMed1996

Hairy cell leukemia in association with thrombotic thrombocytopenic purpura and factor VIII antibodies.

A unique patient is reported with longstanding hairy cell leukemia who manifested two distinct abnormalities of factor VIII; factor VIII antibodies and recurrent thrombotic thrombocytopenic purpura (TTP). The patient presented in 1977 with splenomegaly and pancytopenia and was diagnosed with hairy cell leukemia and was treated with splenectomy. In 1989 he received interferon-alpha because of a relapse which resulted in a hematologic remission. Hospitalization on two occasions for gross hematuria was caused by the development of a factor VIII antibody. He was successfully treated on both occasions with cyclophosphamide, prednisone and active prothrombin complex (FEIBA). In October 1991 he presented with microangiopathic hemolytic anemia and thrombocytopenia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made. Repeat bone marrow biopsy showed hairy cell leukemia. The patient responded to treatment with plasmapheresis, fresh frozen plasma replacement and prednisone. He had two subsequent relapses with the last being refractory and subsequently fatal. During the initial manifestation of TTP and in follow-up evaluation unusually large von Willebrand factor multimers were demonstrated.

Adult↗
PubMed1996

Clinical and morphological features of cases of trisomy 13 in acute non-lymphocytic leukemia.

Trisomy 13 has been infrequently reported as a primary non-random karyotypic change in myeloid leukemias. To elucidate its clinical significance we examined the clinical and hematological data in nine ANLL patients in whom we found this change, in a series of 175 cytogenetically abnormal ANLL patients. Morphologically, six of the patients were FAB-M1, two were FAB-M4 and one was FAB-M5. Bone marrow aspirates contained more than 90% blasts in eight of the patients. By immunophenotype, TdT was present in four of the patients, CD34 was present in four of five patients tested and CD5 was present in one of five patients tested. Blast cells in all patients expressed two or more myeloid surface antigens. These data suggest the proliferation of an immature myeloid cell in these patients. Complete remission was achieved in seven patients; however, remissions were short-lived. Eight patients expired between 1 and 13 months from diagnosis (median survival 5 months). Combining our findings with data in the published literature on trisomy 13 in ANLL, a larger data set consisting of 29 patients was established to determine better the clinical significance of this cytogenetic entity in ANLL. We found that this cytogenetic change has been reported in all subsets of FAB classification excepting M6 and M7. Median age at presentation was 60 years and no association with gender was noted. Median WBC was 29.5 x 10(9)/l, the majority of patients were thrombocytopenic (median platelet count 86 x 10(9)/l) and median survival was 5.2 months. This study associates trisomy 13 with malignant transformation of myeloid progenitor cells. These patients respond well to induction therapy, but relapse occurs quickly and the survival duration is poor.

Adult↗
PubMed1995

Variation in ECT use in the United States.

OBJECTIVE: The authors measured the variation in ECT utilization rates across 317 metropolitan statistical areas of the United States and determined to what degree this variation is associated with health care system characteristics, demographic factors, and the stringency of state regulation of ECT. METHOD: Data from APA's 1988-1989 Professional Activities Survey were used to estimate ECT utilization rates for the metropolitan statistical areas. Multiple regression analysis was used to determine the relative influence of provider, demographic, and regulatory factors on variation in ECT use across areas. RESULTS: Among the psychiatrists surveyed, 17,729 reported treating 4,398 patients with ECT during the study period. No ECT use was reported in 115 metropolitan statistical areas. Among the remaining 202 metropolitan statistical areas, annual ECT use varied from 0.4 to 81.2 patients per 10,000 population. The strongest predictors of variation in ECT use across metropolitan statistical areas were the number of psychiatrists, number of primary care physicians, number of private hospital beds per capita, and stringency of state regulation of ECT. CONCLUSIONS: Rates of ECT use were highly variable, higher than for most medical and surgical procedures. In some urban areas, access to ECT appears limited. Predictors of variation in ECT rates have implications for expanding access to the procedure. The extent of variation suggests psychiatrists continue to lack consensus regarding the use of ECT. Better data on the effectiveness of psychiatric treatments may lead to a broader professional consensus and may narrow variations in clinical practices.

Depressive Disorder↗
PubMed1994

Splenic lymphoma with circulating villous lymphocytes: report of seven cases and review of the literature.

Splenic lymphoma with villous lymphocytes (SLVL) is a relatively new entity with only a few reports published. We report seven cases of SLVL with detailed clinicopathologic and comprehensive immunophenotypic studies to further characterize this lymphoma, which is frequently confused with hairy cell leukemia and other low-grade B-cell lymphoid neoplasms. The diagnostic criteria we used include 1) prominent splenomegaly, 2) insignificant or no lymphadenopathy, 3) lymphocytosis without leukopenia, 4) presence of circulating villous lymphocytes, 5) characteristic cytologic and histologic features, and 6) specific phenotypic and cytochemical findings. Our studies show that SLVL does not represent a pure entity but rather a morphologically heterogeneous group of low-grade lymphomas with various cytologic and histologic features. Although immunophenotyping is helpful in differential diagnosis, multiparameter studies are necessary to confirm the diagnosis. In our series, only two patients died of SLVL, who probably developed transformation to a higher-grade lymphoma.

Aged↗
PubMed1994

Eastern equine encephalitis presenting as focal neuroradiographic abnormalities: case report and review.

We describe a well-documented case of Eastern equine encephalitis (EEE) in a patient who presented with fever and altered mental status and who had focal cranial lesions that were evident on both computed tomography (CT) and magnetic resonance imaging. Only 15 CT scans performed for patients with EEE have been described previously; findings on most were normal or revealed diffuse cerebral edema. It is not widely appreciated that EEE can manifest as discrete lesions on CT. We review the radiographic experience with EEE and interpret it in light of certain clinical and pathological features of the disease.

Brain↗