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Biomedical subjects

L M Allen

Publications and source records attributed to L M Allen.

At least 19 recordsLinked to original sources
PubMed1989

Flow cytometric enumeration of colonies for in vitro chemotherapeutic drug evaluation.

The percentage of 50-100 micron colonies formed by LX-T cells in medium containing agarose was determined microscopically, and this value was compared with the percentage determined by a flow cytometric method based on the forward and 90 degree light scatter of the colonies. As assessed by both in vitro methods, LX-T cells exposed to chemotherapeutic agents formed fewer colonies as the drug concentration increased. However, flow cytometric analysis indicated that a change in the number of colonies formed was a consequence of changing chemotherapeutic drug concentration, whereas microscopic colony counting did not always detect the corresponding change in colony number. These experiments demonstrate that measurement of a drug's chemotherapeutic potential by flow cytometric counting of colonies is an alternative to the enumeration of colonies microscopically.

Animals↗
PubMed1984

Slow infusion of vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura.

Vinca alkaloids are useful in the treatment of idiopathic thrombocytopenic purpura, a disorder in which macrophages remove platelets sensitized with antibody. Because vinca alkaloids avidly bind to platelets, drugs can be delivered selectively to macrophages. However, drugs given by bolus injection are cleared too rapidly to bind optimally to autologous platelets, and the use of allogeneic platelets loaded with drug in vitro is cumbersome, expensive, and dangerous. Therefore, slow infusions were devised to prolong the duration of enhanced plasma drug concentrations, thereby providing better conditions for in-vivo drug loading into autologous platelets. Twenty-four patients with refractory idiopathic thrombocytopenic purpura were given slow infusions; 17 had good to excellent responses. Eleven of eighteen patients who had been treated with bolus injections had better results when treated with slow infusions. Patients with improved responses had slower plasma clearance rates than did patients with poor responses. Slow infusion therapy had fewer side effects than bolus injection therapy. Slow infusions are the best method for long-term management.

Adolescent↗
PubMed1984

A double-blind study of prazosin in the treatment of Raynaud's phenomenon in scleroderma.

Nineteen patients with Raynaud's phenomenon in conjunction with progressive systemic sclerosis were given either prazosin hydrochloride (1 mg orally three times a day) or a placebo for eight weeks, after which the treatment procedure was reversed for four weeks. Prazosin was shown to be effective in reducing both the frequency and the severity of vasospasm reported by the patients.

Adult↗
PubMed1983

Neuroendocrine response to cold in Raynaud's syndrome.

Eleven patients with Raynaud's syndrome accompanied by monospecific IgG ANA, nine patients with Raynaud's syndrome in the absence of ANA, and nine normal volunteers were exposed to an ambient cold challenge during which time venous blood was continuously sampled. ANA negative patients were shown to have significantly higher levels of cortisol during a cold challenge than either ANA positive patients or normal controls, and exhibited significantly lower levels of plasma norepinephrine compared with normal controls. ANA positive patients did not differ significantly from normals in their neuroendocrine response to cold. It is suggested that the high plasma cortisol found in Raynaud's syndrome in the absence of ANA may be responsible for the vasospasticity in this group of patients.

Antibodies, Antinuclear↗
PubMed1983

Intra-arterial reserpine for Raynaud's syndrome. Systemic reactions without therapeutic benefit.

Twenty-four patients classified as having Raynaud's disease or Raynaud's phenomenon were given bilateral brachial artery injections of reserpine or saline in a double-blind fashion. In the six weeks following injection, there was no indication that reserpine produced clinical improvement or changed vasomotor reactivity in the treated patients. However, intra-arterial reserpine did produce systemic cardiovascular effects lasting up to six weeks. It is concluded that intra-arterial reserpine as used in this study is an ineffective treatment for Raynaud's disease or Raynaud's phenomenon and may have significant adverse effects.

Adult↗
PubMed1980

The effect of the glutamine analog, AT-125, on the cell cycle of MCF-7 and BT-20 human breast carcinoma cells using DNA flow cytometry.

It was found by DNA flow cytometry that AT-125 preferentially inhibited the cell cycle progression in G1-phase of BT-20 more so than MCF-7 breast carcinoma cells in vitro and that cells washed free of the drug now possessed S-phase DNA content. It was also found that gamma-glutamyl transpeptidase levels were more than 2 times higher in BT-20 than in MCF-7 cells.

Antineoplastic Agents↗
PubMed1980

Immunological modification of adriamycin cardiotoxicity.

Adriamycin-specific antibody has been shown to increase the survival of mice receiving an acute cardiotoxic dose of adriamycin. The concentrations of adriamycin in heart tissue were reduced and those in tumor elevated for more than 2 days in animals that received the antibody. The adriamycin-specific antibody prevented and reversed adriamycin inhibition of cardiac microsomal Na-K ATPase.

Animals↗
PubMed1980

Studies on the pharmacology and cytokinetics of 2,3-dihydro-1H-imadazo[1,2-b]pyrazole (NSC 51143) with P815 mastocytoma cells.

A study has been made of the biochemical, cytokinetic, and pharmacological effects of pyrazole-imidazole (NSC 51143) (IMPY) on P815 mastocytoma ascites cells maintained in mice and of cells maintained in culture. The distribution phase of IMPY equivalents from the peritoneal fluid of the mouse was found to be two hr, with an elimination phase of 69 hr. No consistent alteration in the ribonucleotide pools of the ascites tumor cells in vivo was observed by high-pressure liquid chromatography using i.p. doses of IMPY up to 1000 mg/kg (25% increase in survival). Correspondingly, no significant alteration occurred in the proportion of cells in G0, G1, S, or G2 + M in vivo by flow cytometric analysis. This is in contrast to the in vitro data which showed a signifcant blockage in S phase (50% effective dose, 1.6 x 10(-4) M). Using Dowex 1 chromatography of extracts from ascites tumor cells treated with IMPY in vivo, several intracellular drug metabolites were detected, and their proportion was noted to change with time. No such metabolism was detected in vitro. Some radiolabeled drug was detected in RNA and DNA from the cold, acid-insoluble fraction of ascites tumor cells. Analysis of alkaline sucrose sedimentation indicated that part of the radiolabeled IMPY was in the heavy-sedimenting DNA fraction.

Animals↗
PubMed1979

Hymenolepis diminuta: the role of the tail in determining the position of the worm in the intestine of the rat.

One-worm infections of Hymenolepis diminuta in rats had their strobila severed surgically, in the neck region, on day 14 of an infection. The scolex and remaining strobila survived but were recovered from a more posterior region of the intestine where small worms are attached during development. The movement to the new region was usually not complete in 24 h, but was complete by 72 h, and probably by 48 h. The operation, involving laparotomy and an incision in the duodenal wall which avoided severing the strobila, had no effect on the position of the worm but did depress the growth of the worm during the ensuing 24 h. It is suggested that (1) the preferred site for H. diminuta is 30-50% down the small intestine, (2) the worm monitors information about its position from all over its strobila and (3) as the worm grows, its position is determined by balancing the input of adverse information from its tail and head ends. The slowness with which surgically shortened worms return to the preferred site may be due either to delay in the worm "realising" it has no tail, or to the location stimuli in the intestine being disturbed for 24 h by the operation.

Animals↗
PubMed1979

The effect of early intervention and pre-school stimulus on the development of the Down's syndrome child.

This paper describes the effect on a group of D.S. children of early and continuous parental counselling together with intensive pre-school stimulation in which the parents were fully involved. The stimulated group is compared with a similar group who developed unaided in their own homes, and with a third group who were institutionalised before their second birthday. Developmental Clinics in East Kent providing the stimulus are described. The effects of social class, parental age and family pattern were noted. The tests used were the Griffiths' Developmental and Stanford-Binet Scales, and the school placement at five years was studied. The results show that the stimulated group score higher on the IQ and DQ tests and particularly on Personal Social and Speech Development. School placement acts as an unbiased measurement of progress, and suggests that they are more easily integrated into the normal community.

Child Development↗
PubMed1978

Multicompartment pharmacokinetic model of 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) in humans.

The formation and elimination of the metabolite of 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) (I) were studied in seven patients with advanced cancer who received I intravenously. The plasma concentration-time data best fit a triexponential equation. The volume of the metabolite compartment (27.5 liters) was calculated as a fraction of the extrapolated volume. A larger body clearance (111.7 ml/min) of metabolite as compared to the renal clearance (31.3 ml/min) indicates that the metabolite is lost from the plasma equivalent space by another elimination route. The combination of metabolite data presented here with previously published data for unchanged I leads to a multicompartment model for the distribution, metabolism, and excretion of I and its metabolite. A comparison of algebraically derived model transfer constants with those evaluated by computer fitting the system of differential equations is presented.

Etoposide↗
PubMed1978

Cell population kinetics of fast- and slow-growing transplantable tumors derived from spontaneous mammary tumors of the DBA/2 Ha-DD mouse.

The proliferation kinetics of a fast-growing spontaneous mouse mammary tumor subline (SMT-F) and a slow-growing spontaneous mouse mammary tumor subline (SMT-S) tumor have been determined autoradiographically at 2 different stages of tumor growth. The length of the cell cycle and the growth fraction for SMT-F were 11.2 hr and 0.85, respectively, on Day 14 and 12.1 hr and 0.78 on Day 28. For SMT-S these same parameters were 15.6 hr and 0.50 on Day 14 and 16. 1 hr and 0.45 on Day 28. On Days 14 and 28 the mitotic indices were 1.3 and 1.0%, respectively, for SMT-S, compared to 2.2 and 1.9% for SMT-F. The cell loss rate, cell loss factor, and cell loss were significantly higher for SMT-F than for SMT-S. The difference in the growth rates for these 2 tumor lines was attributable to a slight prolongation of the length of the cell cycle and a reduction in the growth fraction of SMT-S.

Adenocarcinoma↗
PubMed1976

Pharmacokinetics of divided-dose ifosfamide.

The pharmacokinetics of a divided-dose schedule of ifosfamide was investigated in 3 patients given 1, 600 to 2,400 mg/sq m/day for 3 days, with a second course of treatment 21 days later. In contrast to the biexponential decay seen with single-dose ifosfamide (5,000 mg/sq m), data for divided low-dose plasma ifosfamide are best fitted by a monoexponential decay function compatible with a one-compartment open model. Plasma half-life for ifosfamide given in the divided-dose schedule was 6.9 hr, less than half that previously reported for high single-dose ifosfamide. Renal excretion rates and clearances for unchanged drug were similar in both schedules. The proportion of drug metabolized was larger and amount of unchanged drug excreted in the urine was smaller than after single large doses. The elimination constant for unchanged ifosfamide increased from day 1 to day 2 of treatment and remained relatively stable from day 2 to day 3 in the multidose regimen, with all parameters reverting to the pretreatment values 21days later.

Alkylating Agents↗