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Biomedical subjects

R L Humphrey

Publications and source records attributed to R L Humphrey.

At least 37 records · Page 2Linked to original sources
PubMed1984

High-dose cyclophosphamide. An effective treatment for advanced refractory multiple myeloma.

The Eastern Cooperative Oncology Group evaluated cyclophosphamide 600 mg/m2 intravenously daily X 4 (total dose each cycle 2400 mg/m2) as an aggressive approach to the treatment of patients with advanced multiple myeloma. The overall objective response rate is 43%. This includes a 38% response rate for all previously treated patients and a 29% response rate for patients refractory to prior therapy with cyclophosphamide. The objective response duration was 3 months and the survival of responding patients 9 months. A subjective response rate of 63% was observed, characterized by effective pain relief and improved performance. Sixty-nine percent of patients experienced leukocyte cell nadirs less than 500/mm2 with a mean time to marrow recovery of 17 days. Thrombocytopenia was less severe but required platelet transfusion in 43% of patients. Bone marrow toxicity was encountered in all patients, and death in aplasia is a significant risk. Strict adherence to entry criteria, and a systematic plan for hospitalization for antibiotic and blood component support is required for treatment with this regimen.

Alopecia↗
PubMed1984

Serologic evidence for widespread infection with La Crosse and St. Louis encephalitis viruses in the Indiana human population.

The vast under-reporting of La Crosse virus and St. Louis encephalitis virus infections in Indiana residents was evident when numerous inapparent infections were detected retrospectively using serum dilution neutralization analyses of serum obtained in November 1978-April 1979 from 10,208 persons (0.2% of the state's population). An antibody prevalence rate of 3.6% to St. Louis encephalitis virus was detected in the sample population as a whole, with rates as high as 13.2% for residents of individual counties. The estimated average annual rate of infection for the whole population was 0.32%. The antibody prevalence to La Crosse virus in the sample population as a whole was 2.3%, with rates ranging up to 12.5% for residents of individual counties. The estimated average annual rate of infection for the whole population was 0.29%. The epidemiologic behavior of the two viruses was quite different. Age-specific antibody prevalence for St. Louis encephalitis virus indicated a pattern of endemic infection existed in the population as a whole; antibody prevalence rose as the population aged. However, many other infections apparently occurred during the 1975 and earlier epidemics. Age-specific antibody prevalence for La Crosse virus indicated a typical pattern of endemic infection was present. The antibody prevalence to La Crosse virus was best described by the Poisson distribution and that of St. Louis encephalitis virus by the negative binomial distribution. These data support the hypothesis that St. Louis encephalitis virus primarily produces intermittent epidemics in the Midwest while La Crosse virus produces continuous seasonal endemic infections. However, evidence suggestive of a low level of interepidemic St. Louis encephalitis virus infection in the population was also obtained. Computer-drawn synagraphic mapping view "maps" of regional antibody prevalence rates demonstrated the existence of distinct foci of infection for each virus in the human population.

Adolescent↗
PubMed1984

Correlation of proliferative and clonogenic tumor cells in multiple myeloma.

To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [3H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [3H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [3H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity.

Bone Marrow↗
PubMed1983

Direct bone resorbing activity of murine myeloma cells.

The cellular mechanism(s) responsible for tumor-associated bone resorption in multiple myeloma remain uncertain. Both in vivo and in vitro evidence is presented for the direct resorption of bone by mouse plasmacytomas. Morphological examination of autopsy specimens from tumor-bearing mice revealed in vivo erosion of bony surfaces at sites of tumor cell-bone matrix apposition. No osteoclastic bone resorptive activity was evident. Using a 45Ca-labelled, devitalized bone explant assay system, mouse myeloma cells caused the release of isotope at levels from 200-300% above control values. Control cells such as normal spleen lymphocytes and liver cells did not resorb bone. Demonstration of the ability of myeloma cells to independently destroy bone is important to the understanding of the causes of and development of chemotherapeutic approaches to myelomatous bone resorption.

Animals↗
PubMed1983

Ocular and systemic complications of diethylcarbamazine therapy for onchocerciasis: association with circulating immune complexes.

Diethylcarbamazine (DEC) therapy for Onchocerca volvulus infection results in frequent ocular and systemic complications, but the pathogenesis of these complications is unclear. Twenty men with O. volvulus infection were treated over a period of six months with DEC given daily for one week and weekly thereafter. Major systemic and ocular complications included proteinuria, severe pruritus, visual field constriction, optic nerve pallor, chorioretinitis, anterior uveitis, and punctate keratitis. Levels of circulating immune complexes (CICs) were increased (greater than 11% [125I]C1q binding) in 14 of the 20 men prior to treatment. Persons with pretreatment C1q binding activity of greater than 30% were at increased risk to develop constriction of visual fields (P less than 0.05) and proteinuria (P less than 0.015). Linear regression analysis revealed a striking correlation between pretreatment levels of CICs and the total number of both systemic and ocular complications (P less than 0.001) and ocular complications alone (P less than 0.005). These results suggest that CICs may be important in the pathogenesis of the delayed systemic and ocular complications following DEC therapy for O. volvulus infection.

Antigen-Antibody Complex↗
PubMed1983

Modified technique for periodic acid-Schiff staining of glycoproteins on agarose-film electrophoretograms.

We have modified the periodic acid-Schiff staining technique for glycoproteins for use with thin agarose-film electrophoresis membranes. With this procedure, carbohydrate-rich proteins can be detected with negligible background staining and insignificant staining of nonglycoproteins such as albumin and nonglycosylated Bence Jones proteins (free light chains). On the other hand, carbohydrate-rich M components of immunoglobulins M and A in serum and in cerebrospinal fluid from patients with plasma cell dyscrasia are readily detected. The technique is two- to threefold more sensitive than Ponceau S. Glycoproteins in serum and body fluids can be determined as a routine analytical procedure.

Electrophoresis, Agar Gel↗
PubMed1983

Renal transplantation in a patient with multiple myeloma and light chain nephropathy.

A case of multiple myeloma in a 41-year-old white man that resulted in chronic renal failure is discussed. During the period of hemodialysis treatment, remission of the patient's myeloma was induced by chemotherapy. Thereafter a transplanted cadaver kidney functioned well for 3.5 years despite episodes of sepsis, administration of nephrotoxic chemotherapeutic agents, and recurrence of the myeloma with intermittent excretion of Bence Jones protein in the urine. The results of this fully documented case, as well as two other cases we have previously reported, support the strategy of offering cadaver renal transplantation to carefully selected individuals who require long-term dialysis and whose myeloma is in remission after chemotherapy.

Adult↗
PubMed1983

Predictive values of the in vivo diffusion chamber for cyclophosphamide treatment of L1210 murine leukemia.

In vivo culture of tumor cells using the Millipore diffusion chamber implanted i.p. into female C57BL X DBA/2 F1 (hereafter called BD2F1) mice provides a means for direct examination of drug effect on tumor cells. The effect of various doses and schedules of i.p. cyclophosphamide (CY) on murine L1210 leukemia cell count in the chambers was compared to survival of leukemia-bearing animals treated similarly. Tumor cell viability was assessed by transfer of chamber contents to recipient animals who were then observed for survival. Unless perturbed by CY, L1210 cells grew in log phase within chambers to 10(8) cells/cu mm. The effect of CY on chamber cell count was dose related, quantifiable, reproducible, and predictive of survival of leukemia-bearing animals treated similarly. Single doses proved to be more effective than were equally divided doses in decreasing chamber cell number and prolonged leukemic animal survival. Reinjection of L1210 cells rescued from chambers after hosts had been treated with CY revealed that many could not produce tumors. Results suggest that this technique provides reproducible information on drug effects and may be a valuable tool for designing clinically useful dose schedules.

Animals↗
PubMed1982

Angioimmunoblastic lymphadenopathy progressing to immunoblastic lymphoma with prominent gastric involvement.

Two unusual cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), with progression to immunoblastic lymphoma (IL) and prominent gastric involvement are presented, and detailed immunohistologic studies described. In one case, Bence Jones proteinuria of the kappa type was observed during the course of AILD and was identified immunohistochemically in lymph node biopsy specimens and at autopsy. The potential significance of an M component and the importance of recognizing gastric involvement by AILD are discussed.

Bence Jones Protein↗
PubMed1982

Computed tomography of entero-enteric intussusception.

Characteristic computed tomographic findings of entero-enteric intussusception were demonstrated with in vitro studies of surgically created intussusceptions in canine small bowel. The signs were effective in detecting intussusception in two patients, one with metastatic melanoma and a second with a plasmacytoma, both of whom had previously nondiagnostic standard oral contrast medium examinations. The findings consist of a dilated loop of bowel (the intussuscipiens) with a thickened wall, within which is an eccentric soft tissue mass (the intussusceptum) and an adjacent crescentic low density mass on the mesenteric side, representing the invaginated mesentery.

Abdominal Neoplasms↗
PubMed1982

Development and characterization of a cyclophosphamide-resistant mouse plasmacytoma cell line.

Murine LPC-1 plasmacytoma is sensitive to treatment with cyclophosphamide (CY), and animals bearing this tumor in advanced stages can be cured with doses as small as 60 mg/kg. With repeated transfer of LPC-1 cells followed by subcurative CY therapy, we have developed from this CY-sensitive parent line (CY-S) a stable CY-resistant subline (CY-R) that is unaffected by doses as large as 250 mg/kg. Stability of this induced CY resistance in the absence of CY treatment has been demonstrated for greater than 14 transfer generations. The CY-R subline has been compared to the CY-S parent line and shown to be similar with respect to morphology, growth kinetics, survival time, synthesis of IgG 2a kappa M component, and DNA content and distribution. The CY-S parent line responds in vivo to CY analogs (ifosfamide and trofosfamide), as judged by decreased tumor mass and increased survival; the CY-R subline is resistant to the CY analogs. The response to carmustine (BCNU) was tested, and resistance to CY did not predict for response to this alkylating agent since the effect on both CY-S and CY-R lines was equal. The significance of the development of this CY-resistant subline and the implications for future research into the mechanisms of such resistance are discussed.

Animals↗
PubMed1981

Timed sequential chemotherapy of cytoxan-refractory multiple myeloma with cytoxan and adriamycin based on induced tumor proliferation.

Malignant plasma cell proliferation and induced humoral stimulatory activity (HSA) occur in vivo at a predictable time following drug administration. Sequential sera from 11 patients with poor-risk multiple myeloma (MM) undergoing treatment with Cytoxan (CY) 2400 mq/sq m were assayed for their in vitro effects on malignant bone marrow plasma cell tritiated thymidine (3HTdR) incorporation. Peak HSA was detected day 9 following CY. Sequential changes in marrow malignant plasma cell 3HTdR-labeling indices (LI) paralleled changes in serum activity, with peak LI occurring at the time of peak HS. An in vitro model of chemotherapy demonstrated that malignant plasma cell proliferation was enhanced by HSA, as determined by 3HTdR incorporation assay, 3HTdR LI, and tumor cells counts, and that stimulated plasma cells were more sensitive to cytotoxic effects of adriamycin (ADR) than were cells cultured in autologous pretreatment serum. Based on these studies, we designed a clinical trial to treat 12 CY-refractory poor-risk patients with MM in which ADR (60 mg/sq m) was administered at the time of peak HSA and residual tumor cell LI (day 9) following initial CY, 2400 mg/m (CY1ADR9). Eight of 12 (67%) responded to timed sequential chemotherapy with a greater than 50% decrement in monoclonal protein marker and a median survival projected to be greater than 8 mo duration (range 4-21+ mo). These clinical results using timed sequential CY1ADR9 compare favorably with results obtained using ADR in nonsequential chemotherapeutic regimens.

Cell Division↗
PubMed1980

Metabolism of guanido-labeled (C-14)arginine in rats, mice, and man.

[6-14C]arginine, injected intraperitoneally into normal rats, was cleared from the plasma with biphasic decay kinetics. Urinary excretion was efficient (32% of the 25-muCi dose within the first 24 hr) with no preferential tissue retention. In mice, the effective duration of the radiotracer's availability for protein biosynthesis was less than 30 min. When the tracer was administered i.v. to patients with multiple myeloma, it was similarly cleared from the plasma with biphasic kinetics, and was excreted rapidly in the urine (22% of the dose within the first 24 hr). In patients, the guanido-tagged arginine labeled only tumor M component, and the labeling was most intense in patients who had far advanced disease. Estimated radiation dose to humans from a 100-muCi injection was 10 mrads. These studies demonstrate the fesibility of in vivo labeling with [16 -14C]arginine, with minimal radiation hazard, thus providing a simple, sensitive, and specific method for monitoring the synthesis of the plasmacytoma M component in patients with multiple myeloma.

Aged↗
PubMed1979

Studies with murine LPC-1 plasmacytoma using [6-14C]arginine.

[16-14C]Arginine ([6-14C]Arg) was used as an in vivo pulse label to study BALB/c murine LPC-1 plasmacytoma synthesis and secretion of its tumour-associated M component (IgG2a, kappa). With this isotope, an eight- to ten-fold enhancement in the labelling of the gamma globulin region and ten-fold reduction in the albumin labelling were observed. Production and secretion of the M component was detected (within 30 min) after cell transfer. Only mice which received tumour cells showed significant labelling in the gamma globulin region 24 hr after isotope injection. The labelling behaviour of the tumour M component correlated with the administered cell dose. The peak heights of radioactivity in the gamma region increased with increments in cell number. When the percentage radioactivity diverted into M component was plotted as a function of cell dose, a linear relationship was noted. This study demonstrates the feasibility of using [6-14C]Arg as a tool to follow the newly synthesized tumour-associated protein, and provides a means of estimating tumour cell number.

Animals↗