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D Halperin

Publications and source records attributed to D Halperin.

At least 19 recordsLinked to original sources

Immunomodulatory effects of moxifloxacin in comparison to ciprofloxacin and G-CSF in a murine model of cyclophosphamide-induced leukopenia.

We analyzed the effect of the two quinolones moxifloxacin and ciprofloxacin on the repopulation of hematopoietic organs and on the production of cytokines by various organs of cyclophosphamide (CP)-induced leukopenic mice. The effect was compared to that of G-CSF. Cyclophosphamide injection induced a severe leukopenia, with nadir at day 4 post-injection. All the quinolone and G-CSF-treated animals showed WBC>500/microL at the nadir, compared to 50% of saline-treated mice. Cyclophosphamide induced a marked decrease in the number of myeloid progenitors (CFU-C) in bone marrow (BM) and spleen. Quinolone or G-CSF treatment resulted in a 1.4-4.3-fold increase in CFU-C numbers in the BM; no enhancement was observed in the spleen. Treatment with CP resulted in enhanced colony-stimulating activity (CSA) in bone shaft and spleen and decreased activity in bladder and lung. Treatment of CP-injected mice with quinolones significantly enhanced CSA in the bone shaft, spleen, lung and bladder on different days. In normal mice the highest levels of GM-CSF and IL-6 were observed in lung-conditioned medium (compared to bone shaft, spleen and bladder). Injection of CP resulted in a 22.5- and 93-fold decrease in GM-CSF and IL-6 levels, respectively, in lung-conditioned medium, while treatment with quinolones resulted in 2-4-fold increase in GM-CSF with no effect on IL-6 production. G-CSF treatment had no enhancing effect on GM-CSF nor on IL-6 production. We conclude that moxifloxacin and ciprofloxacin administered to CP-injected mice revert some of the immune suppressive effects of cyclophosphamide.

Animals↗

Gastric atrophy and extent of intestinal metaplasia in a cohort of Helicobacter pylori-infected patients.

Atrophy and intestinal metaplasia (IM) are preneoplastic gastric lesions associated with Helicobacter pylori infection. Atrophy and IM are usually found together; however, the association between increasing degrees of severity of both atrophy and IM has not been evaluated completely. Two pathologists graded atrophy and IM using the visual analog scale of the Sydney classification in gastric biopsies from 368 H pylori-infected patients. Extent of IM also included determining the number of specimens affected. We then correlated the degree of atrophy with the degree and number of specimens affected with IM by calculating relative risks (RR) and 95% confidence intervals (95% CI). The mean number of biopsies examined from each patient was 6.5. Atrophy and IM were found more frequently in the antrum (85% and 75% of biopsies, respectively). One hundred thirty-eight patients had a combination of atrophy and IM, 48 had IM only, and 89 had atrophy only. Fifty-three subjects had mild atrophy and IM (RR = 1.57; 95% CI 1.2-2.1), 69 had moderate atrophy and IM (RR = 1.86; 95% CI 1.9-2.4), and 16 had marked atrophy and IM (RR = 2.47; 95% CI 1.8-3.3). The median number of biopsy specimens with IM increased from 0 in subjects with no atrophy to 3 in subjects with severe atrophy. The degree of IM correlated with the degree of atrophy; the median degree was 0.6 in subjects with no atrophy and increased to 2.32 in those with severe atrophy. Our data suggest that higher degrees of IM in an individual specimen and increasing number of specimens with IM are associated with moderate or severe degrees of atrophy.

Adult↗

Screening markers for chronic atrophic gastritis in Chiapas, Mexico.

Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I <25 microg/l, sensitivity was 6% and specificity was 100%; for pepsinogen I:pepsinogen II ratio <2.5, sensitivity was 14% and specificity was 96%). Combinations of markers did not improve test characteristics. Screening test characteristics from the literature varied widely and did not consistently identify a good screening strategy. In this study, CagA antibodies alone had the best combination of test characteristics for chronic atrophic gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis.

Adult↗

Improved survival in severe acquired aplastic anemia of childhood.

Multi-agent immunosuppressive therapy has produced improved survival for severe acquired aplastic anemia in children. Recently, some investigators have suggested that immunosuppressive therapy may replace bone marrow transplantation as first-line therapy for this disorder. To assess its validity, we compared the outcomes of bone marrow transplantation vs immunosuppressive therapy in one institution from 1987 to 1997. We studied 46 consecutive patients less than 18 years of age who presented between January 1987 and April 1997. Inherited marrow failure syndromes and myelodysplastic syndromes were excluded. Patients received immunosuppressive therapy vs bone marrow transplantation based on availability of HLA-matched donors. The main outcome measures were survival, complete marrow and hematological remission, or partial remission but achieving independence from transfusional support. Twenty patients received multi-agent immunosuppressive therapy (cyclosporine, antithymocyte globulin and methylprednisolone); 11 attained complete remission and three partial remission for a transfusion-independent survival of 70%. Six patients died of infectious and hemorrhagic complications. Twenty-six patients were transplanted and 24 (93%) achieved complete remission; one achieved a PR, 25 remain transfusion independent with a median follow-up of 5.9 years or 70 months. One patient developed AML 34 months after successful transplant and one patient died due to graft failure and complications of transplant. There has been a striking improvement in survival for pediatric patients treated with multi-agent immunosuppression in the last decade. However, transplantation results have also improved and this remains the definitive first-line therapy for severe acquired aplastic anemia in this age group.

Adolescent↗

Alteration of actin organization by jaspamide inhibits ruffling, but not phagocytosis or oxidative burst, in HL-60 cells and human monocytes.

Jaspamide, a naturally occurring cyclic peptide isolated from the marine sponge Hemiastrella minor, has fungicidal and growth-inhibiting activities. Exposure of promyelocytic HL-60 cells and human monocytes to jaspamide induces a dramatic reorganization of actin from a typical fibrous network to focal aggregates. HL-60 cells exposed to 5 x 10(-8) mol/L or 10(-7) mol/L jaspamide exhibited a reduced proliferation rate. In addition, 10(-7) mol/L jaspamide induced maturation of HL-60 cells as indicated by the appearance of a lobulated nucleus in 55% +/- 5% of the cells and immunophenotypic maturation of the leukemia cells (upregulation of CD16 and CD14 B antigens). Further characterization has shown that F-actin is aggregated both in HL-60 cells and in human monocytes exposed to 10(-7) mol/L jaspamide. Well-spread cultured human monocytes contracted and adopted round shapes after treatment with jaspamide. Moreover, a dose-dependent increase in both total actin and de novo synthesized portions of the soluble actin was observed in jaspamide-treated HL-60 cells. Jaspamide treatment inhibits ruffling and intracellular movement in HL-60 cells and monocytes, but does not affect phagocytic activity or respiratory burst activity. The consequential effects of jaspamide-induced actin reorganization on ruffling, versus its negligible effect on phagocytosis and oxidative burst, may shed light on molecular mechanisms of actin involvement in these processes. Jaspamide disrupts the actin cytoskeleton of normal and malignant mammalian cells with no significant effect on phagocytic activity and may, therefore, be considered as a novel therapeutic agent.

Actins↗

Dermoid cyst of the eustachian tube.

We report a case of dermoid cyst of the Eustachian tube in a 2 1/2 -year-old-girl with CT and MRI imaging. This is the 12th described case of such a pathology. Most of the reviewed previous 11 cases affected females on the left side. The surgical approach and the contribution of CT and MRI are discussed.

Child, Preschool↗

Interobserver variability in application of the revised Sydney classification for gastritis.

The Sydney classification for gastritis provides guidelines for histological grading of gastric biopsies. In an ongoing study of gastric preneoplastic lesions in Chiapas, Mexico, 7 biopsies from 150 patients (4 from the antrum and 3 from the body) were obtained during endoscopy and studied histologically. The first 74 endoscopy specimens were read independently by 2 general surgical pathologists. We assessed diagnostic concordance using kappa statistics. The 2 pathologists then jointly reviewed biopsies about which they had disagreed to reach a final diagnosis. A second group of 76 endoscopies was subsequently evaluated independently by the 2 pathologists, and concordance was again assessed. In the first group of biopsies, we found low concordance rates (Heliobacter pylori 0.59, acute inflammation 0.22, intestinal metaplasia 0.60, and atrophy 0.04). In the second group, of independently reviewed cases, there was better concordance (H pylori 0.77, acute inflammation 0.50, intestinal metaplasia 0.70, and atrophy 0.64). We presumed that use of the Sydney classification would result in minimal interpretational differences achieving ideal kappas greater than 0.80. Because pathology results are based on subjective interpretation of this classification, complete diagnostic agreement is practically impossible. Concordance by general surgical pathologists after joint review of cases was similar to that obtained by gastrointestinal pathologists.

Atrophy↗

Ascorbic acid inhibits apoptosis induced by X irradiation in HL60 myeloid leukemia cells.

Exposure of cells to ionizing radiation can cause apoptosis. Since antioxidants have been shown to protect against radiation-induced apoptosis, in this study we have evaluated the putative protective effect of ascorbate against radiation-induced apoptosis as well as the production of peroxides in the cells. HL60 cells transport the oxidized form of ascorbic acid, dehydroascorbic acid (DHA), and accumulate reduced ascorbate. Exposure of the cells to 5-40 Gy X radiation resulted in induction of apoptosis. Preincubation of the cells with DHA reduced the level of apoptosis after exposure to 5-20 Gy. Exposure of the cells to 5 or 20 Gy X radiation did not affect the intracellular concentration of peroxides, while phorbol myristate acetate (PMA), which is known to induce production of H(2)O(2) in cells (and served as a control), resulted in an increase in peroxides and a decrease in intracellular ascorbate. Irradiation of the cells with 1-3 Gy resulted in up-regulation of expression of BCL2 without affecting the level of apoptosis. At higher doses of radiation, enhanced BCL2 expression did not prevent radiation-induced apoptosis. Loading of the cells with ascorbate prior to their exposure to 1-3 Gy X radiation did not affect the enhanced BCL2 expression observed in the irradiated cells. At higher doses of radiation, ascorbate decreased apoptosis and restored the level of BCL2 in the cells. Exposure of the cells to 3-20 Gy X radiation enhanced the cell surface expression of TNFRSF6 (formerly known as Fas/APO-1) antigen and enhanced anti-TNFRSF6 antibody-induced apoptosis of the cells. Ascorbate loading did not affect expression of TNFRSF6 and did not overcome the anti-TNFRSF6 antibody-induced apoptosis. In conclusion, our data demonstrate that exposure of HL60 cells to radiation enhanced BCL2 and TNFRSF6 expression. Ascorbate did not affect BCL2 or TNFRSF6 expression. We therefore conclude that it protects HL60 cells against radiation-induced apoptosis, although the mechanisms of protection must still be elucidated.

Apoptosis↗

The effect of short-term, temporary deferral on future blood donation.

BACKGROUND: Most blood donor deferrals are temporary and short-term. The effect of short-term, temporary deferral (STTD) on blood donor return rates and subsequent blood donations is an important issue. STUDY DESIGN AND METHODS: Donors given STTDs during the first 3 months of 1993 were computer-matched with nondeferred donors on the basis of age, sex, and donation date. Computer records were evaluated during the next 4.25 years (4/93-6/97) to determine donor return rates and subsequent blood donations. RESULTS: The most common reasons STTD were low hemoglobin (46%), colds and/or sore throats (19%), and elevated temperature (10%). Nondeferred donors were 29 percent more likely than donors with STTD to return over the next 4.25 years (80% vs. 62%), and nondeferred donors donated 81 percent more whole blood units (13,798 vs. 7,615) over the same period. CONCLUSION: The study showed that STTD have a very negative impact on blood donor return rates and subsequent blood donations. Actions to alleviate these negative effects are indicated.

Blood Donors↗

Clinical update on type II first branchial cleft cysts.

OBJECTIVE: To describe clinical and radiological signs of type II first branchial cleft cyst in order to facilitate diagnosis. METHOD: Report of three cases of first branchial cleft cyst type II (one of them in association with ipsilateral agenesis of the parotid gland) and review of the literature. RESULTS: Two clinical signs are described: the location of the sinus opening in the neck, which is situated in a triangle limited by the external auditory canal above, the mental region anteriorly, and the hyoid bone inferiorly, and the presence in some cases of a myringeal web that runs from the floor of the external auditory canal to the umbo. In addition, imaging with computed tomography and magnetic resonance of the parotid area may be helpful in confirming the diagnosis.

Branchioma↗

HIV, STDs, anal sex and AIDS prevention policy in a northeastern Brazilian city.

Data on HIV/AIDS, other STDs, and related sexual practices and AIDS prevention measures in São Luís, capital of Maranhão state, were collected in May-July 1995 using participant-observation fieldwork, including a number of face-to-face interviews in addition to archival research, and were updated by correspondence in 1996-1997 and a brief visit in February 1998. In contrast to the continuing severe AIDS epidemic in southern Brazil, public health statistics and public HIV testing recently instituted in São Luís suggest that HIV infection has remained largely concentrated among men who have sex with men, as well as a few, though growing number of cases of women evidently infected by such men. However, other STDs are endemic to the region, and could provide an increasing portal of entry for HIV infection. AIDS prevention education programmes have commenced in public schools and elsewhere in São Luís, but greater emphasis needs to also be placed on the prevention and treatment of other STDs. As in other regions of Brazil and Latin America, the reportedly common practice of anal sex among heterosexuals also represents a significant yet typically underemphasized risk factor for HIV.

Acquired Immunodeficiency Syndrome↗

Rat osteoclast precursors in vivo express a vitronectin receptor and a chloride-bicarbonate exchanger.

In vivo osteoclast precursors, which are mononuclear, were previously found to express TRAP (tartrate-resistant acid phosphatase) and CTR (calcitonin receptor), like multinucleated osteoclasts. In vitro, they were found to express, in addition, VNR (vitronectin receptor) and CBE (chloride-bicarbonate exchanger). In order to ascertain that osteoclast precursors in vivo express VNR and CBE like their in vitro counterparts, we used immunohistochemistry to localize these molecules in developing long bones of neonatal rats. Frozen sections of metatarsals and phalanges of 1-2 day-old rats were stained for TRAP and mineralization using histochemistry or were reacted with polyclonal antibodies specific for either the beta3 chain of the VNR or synthetic sequences of the CBE. Both mature, multinucleated osteoclasts within the forming marrow cavity of metatarsals (as shown previously) and mononuclear osteoclast precursors located outside the bony collar of the phalangeal calcified rudiment (as shown here for the first time) expressed both TRAP, VNR and CBE. These findings suggest that mononuclear osteoclast precursors express many of the phenotypical markers of multinucleated osteoclasts prior to their fusion and multinucleation which may allow them to resorb bone, as suggested by in vitro observations of pit formation by preosteoclasts cultured on resorbable substances.

Animals↗

Prediction of the survival of patients with advanced ovarian cancer according to a risk model based on a scoring system.

PURPOSE OF INVESTIGATION: The aim of the study was to devise a scoring system based on significantly prognostic parameters which might predict the survival time for each individual patient. METHODS: The study group included 40 patients with stage III or IV invasive ovarian cancer, operated on between 1987 and 1994. Different preoperative and intraoperative parameters were examined and their impact on survival was assessed using the Kaplan-Meier method. Survival rates were compared by the log rank test. The parameters, which have been found to be significant prognostic factors, were incorporated into the final risk model, based on a scoring system. The scores were given according to the cut-off point of each prognostic parameter. A correlation coefficient was calculated from the survival curve, representing the combined scores of individual patients versus their survival. RESULTS: From all studied parameters, only gravidity, the stage of ovarian cancer and the preoperative levels of LDH and CA-125 were demonstrated to have a significant impact on survival. On the basis of these four parameters a scoring system was devised. The scores were given considering the cut-off level of each parameter: gravidity < or = 2 versus > 2; stage of the cancer - IIIA, IIIB and stage IIIC versus stage IV; LDH level < or = 240 versus > 240 U/L; CA-125 < or = 100 versus > 100 U/ml. The average of the combined scores representing the four parameters was the final risk factor, which was plotted against the survival of each individual patient. A correlation coefficient of -0.99 was found. CONCLUSIONS: Our data suggest that the survival of each individual patient with advanced ovarian cancer could be predicted quite accurately considering our risk model based on a scoring system which incorporates four preoperative and intraoperative parameters. This scoring system needs to be validated by larger prospective trials.

Adult↗

Pulmonary tuberculosis in the border region of Chiapas, Mexico.

OBJECTIVES: To estimate the prevalence of pulmonary tuberculosis (PTB) in chronic cough patients seeking care at a second level hospital for any complaint, and to identify groups more likely to test TB smear-positive, within the Border Region of Chiapas, Mexico. METHODS: Active case finding of patients with chronic cough (cough of 15 days or more) was carried out among all patients aged over 14 years seeking care for whatever reason in the only hospital in the region for patients not covered by insurance. The coughers identified (n=221) were interviewed and three sputum samples requested for acid-fast smears. In order to identify groups at greater risk a logistic regression model was constructed. RESULTS: A rate of 21 positive PTB smears per hundred patients was found (95% Confidence Interval [CI]=15.5-26.6). The main factors associated with positive PTB were age, occupation and weight loss. The subgroup of chronic cough patients of those aged 35-44 years, agricultural workers and those who had lost weight, had the greatest likelihood of positive PTB smears (68.7%). CONCLUSION: In hospitals that treat rural patients, special efforts should be made to make health personnel more aware of the need to investigate respiratory symptoms in all of their patients, particularly in the subgroups identified with the greatest likelihood of being positive for TB.

Adolescent↗

Ethanol injection to parathyroid tissue: indications and limitations.

Hyperparathyroidism is a potentially life-threatening disease, caused primarily by parathyroid adenoma. Surgical excision of the tumor, with consequent return of calcium levels to the normal range, is considered the treatment of choice. Within the last few years, several reports have described the destruction of parathyroid tissue using ultrasonically guided injection of 96% ethanol into pathologic parathyroid glands, resulting in successful regulation of both primary and secondary hyperparathyroidism. The procedure was reported as an alternative to operative treatment for patients as high surgical risk, such as the elderly and the critically ill. We report the occurrence of transient Horner's syndrome and vocal fold paralysis after successful injections of ethanol into a parathyroid adenoma, and discuss the implications and restrictions of the procedure in view of the medical literature.

Adenoma↗