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Biomedical subjects

J Halpern

Publications and source records attributed to J Halpern.

At least 73 records · Page 4Linked to original sources
PubMed1990

Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis.

While diffuse large-cell lymphoma (DLCL) is considered to be highly curable with current therapy, treatment failures are observed even with intensive combination chemotherapy regimens. In order to study the prognostic significance of actual dose intensity of chemotherapy in DLCL, we retrospectively analyzed 115 previously untreated patients treated as Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclosphosphamide, vincristine, prednisone, and bleomycin (MACOP-B). The actual relative dose intensity (RDI), the amount of drug actually administered to each patient during the first 12 weeks of therapy, was calculated as standardized to CHOP and analyzed in addition to clinical factors prognostic for survival by univariate analysis. Multivariate recursive partitioning (tree-structured) survival analysis identified the actual RDI of Adriamycin greater than 75% as the single most important predictor of survival. A model incorporating the actual RDI of Adriamycin and performance status, in combination with serum lactate dehydrogenase (LDH) and extranodal disease, defined three overall prognostic groups of patients with respective 3-year survival rates of 89%, 63%, and 18%. The three prognostic groups remained distinct, even when restricted to complete responders. This model was also predictive of survival when dose intensity was analyzed relative to the optimum dose defined for each of the three regimens and when applied to a subgroup of patients aged 50 years or younger. We conclude that actual RDI is an important prognostic factor for survival in DLCL and that analysis of RDI early in the course of treatment may allow modification of the treatment plan.

Aged↗
PubMed1990

Platelet aggregation in septic shock. Effect of pentoxifylline.

In contrast to normal individuals, patients suffering from adult respiratory distress syndrome (ARDS) due to septic shock had increased platelet aggregation and circulatory platelet aggregates in blood. In vitro incubation with pentoxifylline (Trental) decreases platelet aggregates. This suggests that in addition to its platelet aggregation inhibitory effect, it also causes platelet disaggregation. Platelet aggregate patterns were shown to normalize two weeks after clinical recovery.

Adult↗
PubMed1989

Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease.

Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.

Adolescent↗
PubMed1989

Radio-protective effect of sodium meclofenamate. A prospective clinical trial.

Twentyfour patients treated with irradiation to either their pelvis or their chest for neoplastic disease were included in a randomized study of radioprotection with sodium meclofenamate (Meclomen) (SM). Seventeen patients received SM 100 mg, p.os, t.i.d., and seven received placebo. The long-range radiation related chronic gastrointestinal and urinary tract toxicity was diminished by SM. At 12 months post irradiation, SM treated patients experienced less gastrointestinal and urinary symptoms, as well as less measured bladder contraction, than the controls. Acute gastrointestinal signs of radiotoxicity, however, seemed to have been enhanced by SM. The treated patients suffered from nausea, vomiting, and diarrhea. These acute toxic effects were temporary and reversible.

Adult↗
PubMed1988

Radical hysterectomy and pelvic lymphadenectomy versus radiation therapy for small (less than or equal to 3 cm) stage IB cervical carcinoma.

One hundred and three women with FIGO stage IB cervical carcinoma were treated either by radical hysterectomy and bilateral pelvic lymphadenectomy, or external pelvic radiation and intracavitary brachytherapy to deliver greater than or equal to 6000 rads to point A. Surgical therapy was to be limited to stage IB tumors measuring less than or equal to 3 cm in greatest diameter, Patients with lesions greater than 3 cm, medical contraindications to surgery, or advanced age were to be treated by radiation therapy. Of the 55 women treated surgically, 3 (5.6%) were found on final histologic evaluation to have tumors greater than 3 cm. The 5-year estimated disease-free interval was 92.3% for patients treated by surgery and 91.1% for patients treated by radiation therapy. Similar rates were achieved for the 5-year disease-free interval for lesions greater than 1 cm, 1-3 cm, and less than 3 cm in diameter by either surgery or radiation. It is tentatively concluded that radical hysterectomy and pelvic lymphadenectomy or radiation therapy as outlined above provide equally good disease-free intervals for stage IB cervical tumors measuring less than or equal to 3 cm in diameter. Because of a bias against patients treated with radiation, it is possible that radiation could lead to better results than surgery in comparable (younger, healthier, thinner) population. The advantage of surgical treatment in the younger patient is preservation of ovarian function.

Adolescent↗
PubMed1988

Effect of medium chain glycerides on enteral and rectal absorption of beta-lactam and aminoglycoside antibiotics.

The rat enteral and rabbit rectal models were utilized to study the effect of Capmul (medium chain glycerides) on the absorption of a selection of beta-lactam and aminoglycoside antibiotics. All tested non-orally available beta-lactam antibiotics (cefamandole, cefotaxime, moxalactam, cefoxitin, mezlocillin, carumonam, penicillin G and amdinocillin) showed increased absorption enterally in rats and rectally in rabbits when formulated with Capmul. The orally available beta-lactam antibiotics, cephalexin and cephradine, were not enhanced in their enteral or rectal absorption by Capmul in the two model systems. Ampicillin absorption was enhanced rectally and enterally by Capmul. Rectal absorption of the aminoglycoside antibiotics, tobramycin and gentamycin, was enhanced by Capmul while enteral absorption was not.

Aminoglycosides↗
PubMed1988

Mechanism of lipid mobilization by the small intestine after transport blockade.

The nonionic detergent, Pluronic L-81 (L-81) has been shown to block the transport of intestinal mucosal triacylglycerol (TG) in chylomicrons. This results in large lipid masses within the enterocyte that are greater in diameter than chylomicrons. On removal of L-81, mucosal TG is rapidly mobilized and appears in the lymph. We questioned whether the blocked TG requires partial or complete hydrolysis before its transport. Rats were infused intraduodenally with [3H]glyceryl, [14C]oleoyl trioleate (TO) and 0.5 mg L-81/h for 8 h, followed by 120 mumol/h linoleate for 18 h. Mesenteric lymph was collected and analyzed for TG content and radioactivity. An HPLC method was developed to separate TG on the basis of its acyl group species. The assumed acyl group composition was confirmed by gas liquid chromatography analysis. TG lymphatic output was low for the first 8 h but increased to 52 mumol/h at the 11th h of infusion (3 h after stopping L-81). 38% of the infused TO was retained in the mucosa after the 8-h infusion. 95% of mucosal TG was TO, 92% of the radioactivity was in TG, and 2.4% of the 14C disintegrations per minute was in fatty acid. HPLC analysis of lymph at 6, 10, 12, and 14.5 h of infusion showed a progressive rise in TG composed of one linoleate and two oleates, to 39%; and in TG composed of two linoleates and one oleate to 20% at 14.5 h of infusion. On a mass basis, however, 80% of the TG acyl groups were oleate. 3H/14C ratios in the various TG acyl group species reflected the decrease in oleate. We conclude that first, unlike liver, most mucosal TG is not hydrolyzed before transport. The mechanism of how the large lipid masses present in mucosal cells after L-81 infusion are converted to the much smaller chylomicrons is unknown. Second, the concomitant infusion of linoleate did not impair lymph TG delivery after L-81 blockade.

Animals↗
PubMed1988

A morphological analysis of an in vitro model of cytotoxic antitumor activity.

Models of adoptive immunotherapy and cytotoxicity of lymphocytes isolated from tumor tissues were studied. A microcytotoxicity model utilizing serum-free culture conditions was evaluated by light microscopy, scanning electron microscopy, and transmission electron microscopy for antitumor activity. By examining morphologically the relationship between peripheral blood mononuclear cells and tumor-infiltrating lymphocytes, it was demonstrated that the latter and macrophages had morphological features similar to the cytotoxic cells obtained in vitro from peripheral blood. When allowed sufficient time in our culture conditions, the tumor-infiltrating cytotoxic cells seem to kill the tumor cells within a few days to many months. The ultrastructural morphology of the interaction between the cytotoxic cells and the tumor cells was described as well as some proteinaceous secretory granules that seem to be transferred to the tumor cells through these interactions.

Cell Communication↗
PubMed1988

Tumor-infiltrating lymphocytes: in vitro characterization of morphological and phenotypical changes.

Mononuclear cells (tumor-infiltrating lymphocytes [TIL]) that invade tumor tissue in fresh surgical specimens were examined and characterized. Such cells were seen in virtually all 52 tumor specimens analyzed and were found to be physically attached to the tumor cells. The morphology of these cells is described with scanning and transmission electron microscopy. Phenotype analysis of these tumor-infiltrating lymphocytes was also performed. In the fresh surgical specimens, while the tumor cells are viable, TIL cells are mostly null cells (except for weak positivity for Leu-1 antigen). As the culture ages in vitro, the TIL phenotype changes drastically to a wide variety of both T and B cells as well as monocyte-macrophage lineage. While these phenotype changes occur, the tumor cells to which the TIL are attached display progressive signs of necrosis and cell death. Tumor cells without attached TIL cells are not affected by necrotic changes. It is speculated that these described changes in the phenotype and morphology of TIL may be related to acquiring cytotoxic activity against the tumor cells. An attempt to control these changes may possibly be useful for clinical application in cancer immunotherapy.

B-Lymphocytes↗
PubMed1987

Designing clinical trials with arbitrary specification of survival functions and for the log rank or generalized Wilcoxon test.

This article describes a computer program that allows interactive determination of the length of accrual period and follow-up period sufficient to assure desired level of significance and power. The program allows for arbitrary specification of the hypothesized survival curves and the alternative survival curve. It allows use of either the generalized Wilcoxon test or the log rank test. The program can be run on an IBM personal computer.

Clinical Trials as Topic↗
PubMed1987

Methods for analyzing occupational cohort data with application to lung cancer in U.S. uranium miners.

We used two methods to examine how lung cancer death rates vary with cumulative exposures to radiation and tobacco among U.S. uranium miners. We assumed that exposures act proportionately on age-specific death rates among nonsmokers who are unexposed to uranium. The two methods produced similar results when death rate ratios were taken to be the product of radiation and tobacco effects. The estimates were discrepant when death rate ratios were taken to be the sum of radiation and tobacco effects. Both methods indicated better fit for the multiplicative model, as judged by the maximized loglikelihood values. Death rates estimated in this way for white males in the absence of mining and smoking increased only weakly with age. This weak relation suggests that our models of death rates fit poorly. It may be that cumulative exposures are inappropriate measures of the effects of radiation and tobacco on lung cancer death rates.

Adult↗
PubMed1987

Four factors that accurately predict hearing loss in "high risk" neonates.

Two simple overall measures of health--length of stay in the Intensive Care Nursery (ICN) and gestational age--predict hearing loss in ICN graduates. Craniofacial anomalies, congenital perinatal infections, and meconium aspiration are strong predictors of hearing loss, especially in term infants. Findings are based on univariate and multivariate analyses of a number of variables that might be associated with permanent hearing loss. Study variables included all seven High Risk Register items and a number of other features of the ICN history. They were examined in 799 ICN graduates whose hearing had been monitored in their first few years of life. These babies composed 40% of the ICN population and were selected because they had one or more "high risk" factors in their neonatal history. Prevalence of hearing loss in this high risk sample was similar to that found in other ICN samples. Prevalence of hearing loss associated with individual Risk Register items was similar to other published findings for some items and not for others.

Birth Weight↗