A loading dose/continuous infusion schedule of fludarabine phosphate in chronic lymphocytic leukemia.

Using a loading dose/continuous infusion schedule, fludarabine phosphate was administered to 51 patients with previously treated chronic lymphocytic leukemia (CLL). All patients had evidence of active disease, and the majority had advanced Rai stages. Of the 42 patients assessable for response, 22 (52%) achieved a partial response, five (12%) had stable disease, and 15 (36%) progressed.

Chemical and elemental analysis of humans in vivo using improved body composition models.

Six chemical compartments [water, protein, mineral (osseus and cellular), glycogen, and fat] consisting of 11 elements (N, C, Ca, Na, Cl, K, H, P, O, S, and Mg) comprise greater than or equal to 99% of body weight in living humans. The combination of three neutron-activation systems, whole body 40K counting, and 3H2O dilution at Brookhaven National Laboratory now potentially makes it possible to quantify greater than or equal to 96% of the chemical and elemental determinants of body weight in vivo. The aims of the present study were 1) to develop 6- and 11-compartment chemical and elemental models, respectively, and 2) to evaluate these models in a group of 20 healthy adults.

Adjuvant therapy of stage II breast cancer treated with CMFVP, radiation therapy and VATH following lumpectomy. A pilot trial.

A pilot study was undertaken to assess the feasibility, toxicity, and efficacy of combined radiation therapy and chemotherapy in the adjuvant treatment of node-positive. Stage II patients with breast carcinoma who had undergone lumpectomy. Therapy consisted of three phases, starting with a six-week CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone) induction, followed by radiation therapy to the breast, and concluding with four cycles of VATH (vinblastine, Adriamycin, thiotepa, Halotesin).

Body composition in elderly people: effect of criterion estimates on predictive equations.

The purposes of this study were to determine whether there are significant differences between two- and four-compartment model estimates of body composition, whether these differences are associated with aqueous and mineral fractions of the fat-free mass (FFM); and whether the differences are retained in equations for predicting body composition from anthropometry and bioelectric resistance. Body composition was estimated in 98 men and women aged 65-94 y by using a four-compartment model based on hydrodensitometry, 3H2O dilution, and dual-photon absorptiometry. These estimates were significantly different from those obtained by using Siri's two-compartment model.

Biliary tract disease in rats with experimental small bowel bacterial overgrowth.

Small bowel bacterial overgrowth, which develops in surgically created jejunal self-filling blind loops, is associated with hepatic injury in susceptible rat strains. The histological findings are portal tract inflammation and bile duct proliferation and destruction. In this study, evidence of injury to the extrahepatic and intrahepatic bile ducts in susceptible and resistant inbred rats with self-filling blind loops was determined by bile flow rates, histological appearance of cross-sections of bile ducts and cholangiography.

A new method to monitor Kupffer cell phagocytosis continuously in perfused rat liver.

A new method was developed to monitor Kupffer cell phagocytosis continuously in perfused liver using a fluorescent probe, rhodamine-gelatin, synthesized from gelatin and rhodamine isothiocyanate. In perfused rat liver, phagocytosis by Kupffer cells was assessed both by uptake of the dye and from fluorescence measured from the liver surface. Uptake of rhodamine-gelatin and surface fluorescence (520----585 nm) increased as perfusate concentrations of rhodamine-gelatin were elevated.

Evidence for peptidoglycan absorption in rats with experimental small bowel bacterial overgrowth.

Surgical creation of jejunal self-filling blind loops (SFBL) causes small bowel bacterial overgrowth which is associated with hepatobiliary inflammation in the susceptible Lewis and Wistar rat strains. Since hepatic injury occurs when small bowel anaerobic bacterial concentrations are increased 4 to 6 log10 units per ml and hepatic bacterial cultures are negative, we postulate that the inflammation is caused by absorption of phlogistic cell wall polymers originating from bacteria within the loop. To demonstrate absorption of bacterial cell wall polymers, we measured plasma and hepatic levels of immunoreactive peptidoglycan-polysaccharide (PG-PS) following intraluminal injection as well as anti-PG antibodies as an indirect measure of absorption and/or accumulation of endogenous PG.

Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline.

Susceptible rat strains develop hepatobiliary injury following the surgical creation of self-filling blind loops that cause small bowel bacterial overgrowth. Luminal bacteria or their cell wall polymers were implicated in the pathogenesis of the lesions because sham-operated rats and rats with self-emptying blind loops, having only slightly increased bacterial counts, did not develop hepatic injury. In this study, antibiotics with different spectra of activities were continuously administered starting 1 day or 22 days after surgery to determine which intestinal flora may be responsible for the development of hepatic injury in rats with small bowel bacterial overgrowth.

Phase II Trial of Fludarabine Phosphate in Multiple Myeloma Using a Loading Dose and Continuous Infusion Schedule.

A phase II trial of fludarabine phosphate using a bolus and continuous infusion regimen in previously treated multiple myeloma was performed. No responses were observed in eleven patients. There was no significant non-hematologic toxicity noted.

Different patterns of chromosome and molecular breakage in classic Ph1 chronic myelogenous leukemia (CML) and variant Ph1 CML.

Variant translocations involving either chromosome 9, chromosome 22, or both with other chromosomes have been reported in about 8% of chronic myelogenous leukemia (CML) patients. In the 22 Ph+ patients studied in our laboratory, two showed variant translocations: t(9;22;11) (q34;q11;q13), and t(9;11) (q34;q11). We compared the pattern of involvement of different chromosomes (and bands) in secondary structural changes in CMLs carrying the t(9;22) (q34;q11) and in the variant translocations.

Extranodal T-cell lymphoma mimicking malignant histiocytosis.

We report a case of extranodal T-cell lymphoma with fever, hepatosplenomegaly, pancytopenia, and diffuse sinusoidal infiltration of the spleen, liver, and bone marrow by the tumor cells, mimicking malignant histiocytosis. This is the second case of T-gamma (T-cell suppressor) lymphoma resembling the case reported by Kadin et al. [N Engl J Med 304:648, 1981].

Stereologic analysis of monocytes and their subcellular organelles in patients with acute monocytic and myelomonocytic leukemia.

The stereologic characteristics of monocytes from patients with acute nonlymphocytic leukemia containing a monocytic component (FAB M4 and M5), and the monocytes from normal individuals were determined by morphometric analysis. The cells studied were monocytic cells beyond the promonocyte stage of development, as defined by ultrastructural criteria. Parameters evaluated included cell and nuclear volumes and surface areas, mitochondrial and myeloperoxidase (MPO)-positive secretory granule volume and numerical density as well as volume and number of the organelles/cell.

Appendicular skeletal muscle mass: measurement by dual-photon absorptiometry.

Dual-photon absorptiometry (DPA) allows separation of body mass into bone mineral, fat, and fat-free soft tissue. This report evaluates the potential of DPA to isolate appendages of human subjects and to quantify extremity skeletal muscle mass (limb fat-free soft tissue). The method was evaluated in 34 healthy adults who underwent DPA study, anthropometry of the limbs, and estimation of whole-body skeletal muscle by models based on total body potassium (TBK) and nitrogen (TBN) and on fat-free body mass (FFM).

Phase I trial of intravenous vinzolidine (LY 104208) given on a biweekly dosing schedule.

Vinzolidine (VZL) is a semisynthetic vinca alkaloid with broad antitumor activity in animal models of malignancy but had unpredictable toxic effects when given orally to humans. To minimize the toxic effects due to potential erratic gastrointestinal absorption, this drug was restudied in man as an intravenous preparation given as a rapid injection every two weeks. The maximum tolerated dose (MTD) on this schedule was 9.

Body composition of humans: comparison of two improved four-compartment models that differ in expense, technical complexity, and radiation exposure.

Multicompartment models are of growing importance in the study of body composition in humans. This study compares two improved four-compartment (water, protein, mineral, and fat) models that differ in expense, technological complexity, and radiation exposure. Primary data (from 31 subjects) for the first model were derived by dual-photon absorptiometry, 3H2O dilution, and hydrodensitometry and for the second model by delayed and prompt gamma neutron-activation analysis and 3H2O dilution.

A successful partnership.

Physicians considering partnership agreements should follow a well-designed plan for recruitment, interviewing, and negotiation. This process can ensure future success of the partnership, and prevent legal difficulties.

New approaches to body composition research: a reexamination of two-compartment model assumptions.

The field of human body composition research by necessity is based upon assumptions related to tissue chemical content. The 2-compartment model, which requires only 1 measurement in addition to body weight, is the cornerstone of current research in this field. Yet the assumptions upon which 2-compartment models are based were developed on a limited scale and their validity under specified conditions is questionable.

Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth.

Hepatobiliary inflammation and other extraintestinal manifestations accompany certain intestinal disorders, perhaps because of proliferation or enhanced transport of luminal bacteria or their phlogistic cell-wall components. Using jejunal self-filling blind loops to create small bowel bacterial overgrowth, we compared biochemical and histological evidence of hepatic inflammation in 3 rat strains chosen for their variable inflammatory responses to bacterial cell wall polymers. Lewis and Wistar rats developed weight loss, hepatomegaly, and hepatic inflammation 4 and 12 wk, respectively, after creation of SFBL.

Acute valproic acid overdose. Clinical course and pharmacokinetic disposition of valproic acid and metabolites.

Acute toxicity in the setting of valproic acid (valproate sodium) overdose is in most cases benign and readily reversible. However, serious toxicity has been reported. We present a case of accidental acute valproic acid overdose in a 26-month-old female, in whom serious neurological, metabolic, haematological and respiratory sequelae occurred.

Chemical determination of human body density in vivo: relevance to hydrodensitometry.

A chemical approach to establishing human body density in vivo was developed by combining recently developed noninvasive methods. Four compartments were measured: protein (P; prompt-gamma neutron activation), water (A; 3H2O dilution), mineral (M; dual-photon absorptiometry and delayed-gamma neutron activation), and fat (F; dual-photon absorptiometry). By this model body weight is equal to P + A + M + F.