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Biomedical subjects

K H Moore

Publications and source records attributed to K H Moore.

At least 91 records · Page 5Linked to original sources
PubMed1990

Response to treatment of detrusor instability in relation to psychoneurotic status.

A total of 53 females who entered a double-blind crossover trial of oxybutynin and placebo for idiopathic detrusor instability were questioned about life events and associated medical disorders and were given a psychometric test. Their response to treatment was studied in relation to these factors. It was found that 11% of patients had nocturnal enuresis beyond age 8 and 25% had irritable bowel syndrome: their response to treatment was generally poor. Life events were not consistently related to treatment response. The mean psychoneurotic score of "poor responders" (43.7) was similar to that of female psychoneurotic out-patients (47.7), although one-third of poor responders were normal. Patients who responded well to simple anticholinergic treatment had a mean score (30.7), which was similar to that of normal urban females (33.5). Most good responders and one-third of poor responders showed little evidence of psychoneuroticism: a further search for neurophysiological abnormality in idiopathic detrusor instability is needed.

Colonic Diseases, Functional↗
PubMed1990

Domiciliary fetal monitoring in a district maternity unit.

Domiciliary Fetal Monitoring is a new technique which allows fetal heart rate monitoring from within a patient's home. The 30 minute cardiotocograph is transmitted by telephone, to a central labour ward computer, within 45 seconds. Of 522 domiciliary cardiotocographs performed on 100 consecutive patients, 356 (68%) were performed for suspected intrauterine growth retardation or reduced fetal movements. Thirty one (5.9%) recordings were abnormal; a repeat cardiotocograph in hospital was abnormal in 9 cases (1.3%); all such patients were delivered within 7 days. The induction rate for the study group was increased by a factor of 3.2 with respect to all hospital confinements; 49% of infants were small for gestational age (less than 10th percentile). Caesarean section and forceps delivery rates were the same for both groups. No stillbirths occurred in the study group. After the introduction of domiciliary monitoring, the number and duration of hospital admissions for fetal surveillance were reduced by 29% and 52% respectively. Patients were equally as able as midwives to perform domiciliary fetal monitoring. A patient survey revealed widespread satisfaction with the DFM system.

Cardiotocography↗
PubMed1990

The heterogeneity of porcine 32,000 Mr inhibin alpha-subunit: a gel electrophoresis and immunoblot study.

Porcine 32,000 Mr inhibin is a glycoprotein with one asparagine-linked glycosylation site on the alpha-subunit. The presence of carbohydrate on the alpha-subunit was visualized by periodate-Schiff (PAS) staining. This stain for carbohydrate also verified that the beta-subunit of 32,000 Mr porcine inhibin does not contain carbohydrate. When analyzed by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D-PAGE) under reducing conditions, the inhibin alpha-subunit consistently existed as a doublet, and by the PAS stain, both bands of the doublet were glycosylated. Analysis by two-dimensional (2D) PAGE further revealed the presence of charge isoforms of the alpha-subunit. The alpha-subunit of inhibin could be deglycosylated by N-glycanase, but not by endoglycosidase F, endoglycosidase D, or endoglycosidase H. When the N-glycanase-treated inhibin was analyzed by either 1D-PAGE or 2D-PAGE, the molecular size of the alpha-subunit was reduced by 3500 Mr. Each doublet band observed with reducing conditions in 1D-PAGE or 2D-PAGE for the alpha-subunit became a single band (spot) in the deglycosylated alpha-subunit. However, the charge heterogeneity detected by 2D-PAGE was retained, indicating that only a portion of this heterogeneity is attributable to the carbohydrate moiety. The in vitro biological activity of the deglycosylated inhibin was not different from the control sample. The composition of the carbohydrate in inhibin was investigated with the Dionex carbohydrate analyzer. Inhibin contains fucose, glucosamine, galactose, mannose, and glucose. Colorimetric analysis revealed the presence of sialic acid. Taken together, this implies some aspect of the peptide portion of the molecule is involved in charge heterogeneity. Inhibin may have an unusual carbohydrate component, as evidenced by the detection of glucose in inhibin samples. The absence of glucose in the carbohydrate moiety of another glycoprotein fraction that accompanied the inhibin through all the same fractionation procedures argues against the artifactual introduction of glucose in the fractionation medium per se.

Amidohydrolases↗
PubMed1989

Repetitive weekly cycles of interleukin 2: effect of outpatient treatment with a lower dose of interleukin 2 on non-major histocompatibility complex-restricted killer activity.

Fifteen patients with advanced malignancy who had failed conventional therapy were entered into a protocol consisting of 1 inpatient mo of repetitive weekly cycles of interleukin 2 (IL-2) at 3 x 10(6) units/m2/day by constant infusion for the first 4 days of each week. This was followed by IL-2 administered on an outpatient basis at the same schedule but at a dose of 1 x 10(6) units/m2/day for the next 1 to 6 mo. Nine patients had renal carcinoma, four had melanoma, and two had lymphoma. Thirteen patients completed the induction month, and ten patients completed greater than or equal to 1 mo of outpatient therapy. Only one patient had therapy discontinued because of toxicity due to IL-2. No major toxicities occurred during outpatient therapy. After 1 mo of IL-2 at 3 x 10(6) units/m2/day, profound changes similar to those previously documented were seen in peripheral blood lymphocyte (PBL) counts (4.7-fold increase), lymphokine-activated killer activity (16-fold increase), and the percentage of PBL with natural killer-associated markers including a 3.6-fold increase in the percentage of PBL expressing the Leu 19 (NKH-1) marker, a 3.7-fold increase in Leu 11 (FcIgGR), and a 3.0-fold increase in Leu 17 (OKT10). These indicators of IL-2 effect all remained elevated relative to the baseline at the end of 1 and 2 mo of outpatient therapy at the lower dose. However, lymphokine-activated killer activity and Leu 17 percentage were significantly reduced relative to the effect of the higher induction dose. PBL taken from patients while receiving maintenance therapy showed strong and rapid responses to IL-2 in vitro, confirming the in vivo effects of prolonged IL-2 treatment. Nevertheless, there were no complete or partial antitumor responses seen. This study demonstrates that an immunologically active dose of IL-2 can be given long term as outpatient therapy with tolerable toxicity and results in highly IL-2-responsive "primed" lymphokine-activated killer cells.

Adult↗
PubMed1989

Phase 1 clinical trial of recombinant interleukin-2: a comparison of bolus and continuous intravenous infusion.

The toxicologic, biologic, and clinical effects of recombinant interleukin-2 (IL-2) were tested in 25 patients with cancer. Escalating doses from 10(3) to 10(7) U/m2 per day were given by either daily bolus injection (BI) or continuous infusion (CI) for 7 consecutive days. Dose-limiting toxicities included a decline in performance status, systolic hypotension, and fever, which reversed promptly with discontinuation of therapy. The maximum tolerated dose of IL-2 by BI for 7 days was 3 X 10(6) U/m2 per day and for CI was 10(6) U/m2 per day. Significant changes in the number, phenotype, and function of circulating peripheral blood lymphocytes occurred at doses greater than or equal to 10(6) U/m2 per day by both administration schedules. With the initiation of therapy, a decline in the number of circulating peripheral blood lymphocytes (PBL) was seen in patients treated by either BI or CI. Additionally, the in vitro cytotoxic activity of these PBL against K562 was markedly decreased. Within 24 h of completing BI or CI, a rebound increase in the number of circulating PBL was seen. The phenotype of the circulating PBL after completion of treatment showed a significant (p greater than or equal to 0.05) increase in the numbers of OKT-3+, OKT-8+, OKT-10+, OK-Ia+, OKM1+, and OKT-11+ for patients treated by CI. Those patients treated by BI had a significant increase in Ia+ and OKT10+ cells. At IL-2 doses greater than or equal to 10(5) U/m2 per day, the PBL obtained following treatment with rIL-2 demonstrated in vitro cytotoxic capacity against K562 target cells that was significantly enhanced over pretreatment levels. This study demonstrates that IL-2 can be given by CI or BI in a non-ICU setting with acceptable dose-dependent toxicity. Upon completion of treatment an increase in the number of activated cells could be detected. Although no clinical responses occurred, the generation of endogenous activated PBL capable of enhanced cytotoxicity is encouraging. Future studies will explore the use of multiple courses of treatment with IL-2 to determine if therapeutic efficacy can be accomplished.

Antibodies, Monoclonal↗
PubMed1988

Repetitive weekly cycles of interleukin-2. II. Clinical and immunologic effects of dose, schedule, and addition of indomethacin.

Clinical trials with high doses of interleukin 2 (IL-2) have shown antitumor responses, but many of the patients have experienced severe and occasionally life-threatening toxic effects. Preclinical studies indicate that modifications in IL-2 dose, route, and schedule can influence both immune activation and antitumor effects. This study evaluated the clinical tolerance to and immunologic modifications induced by four repetitive weekly cycles of IL-2, with two dose levels (1 X 10(6) and 3 X 10(6) U/m2 per day) of IL-2 and three different daily administration schedules [bolus, continuous, or combined (bolus and continuous)], with and without indomethacin treatment. Patients in all treatment groups experienced acceptable, non-life-threatening toxic effects and immune system stimulation characterized by rebound lymphocytosis with increased numbers of natural killer and lymphokine-activated killer cells and enhanced direct cytolytic function. These immune changes were significantly enhanced by the repetition of IL-2 cycles beyond the first week of therapy. At an IL-2 dose of 3 X 10(6) U/m2 per day, bolus IL-2 was less immunostimulatory than continuous-infusion IL-2. The combined regimen (with half of each daily dose given as a bolus and half as a 24-hr infusion) was as stimulatory as continuous-infusion IL-2 and also induced antitumor effects. Finally, the addition of indomethacin to this regimen did not significantly modify in vitro or in vivo immune response parameters but appeared to worsen the systemic toxic effects of renal dysfunction and capillary leakage. These results suggest that continuous or combined infusion of IL-2 at 3 X 10(6) U/m2 per day on this schedule should be considered for further testing in phase II trials or in combination with other therapeutic modalities.

Adult↗
PubMed1988

Clinical and immunological effects of recombinant interleukin 2 given by repetitive weekly cycles to patients with cancer.

Eleven patients received four consecutive weekly cycles of human recombinant interleukin 2 (IL-2) by continuous infusion for 4 days/week. Two dose levels were tested, 1 and 3 X 10(6) units/m2/day. Toxicities experienced by most patients included fever, rigors, fatigue, anemia, eosinophilia, and liver function abnormalities. All side effects from treatment reversed and no severe or life-threatening problems occurred. A marked lymphocytosis was seen following the 4 weeks of therapy. Fresh lymphocytes obtained during this lymphocytosis mediated enhanced destruction in vitro of a natural killer cell-resistant tumor cell line (Daudi). The increase in the absolute number of circulating lymphocytes and their enhanced ability to mediate direct lysis of Daudi targets resulted in a greater than 100-fold mean increase in cytotoxic potential by the end of IL-2 treatment. One patient, with renal carcinoma, who was treated at 3 X 10(6) units/m2/day experienced a sustained measurable response with greater than 50% regression of pulmonary and hepatic metastases. Five patients were retreated with a second course of IL-2, lasting 4 weeks. This therapy was well tolerated in four of these five patients, with similar immunological changes occurring. No further antitumor responses were seen in these patients. Thus, a relatively well tolerated immunotherapy regimen using IL-2 can induce dramatic increases in lymphocyte number and augment their in vitro antitumor reactivity.

Cytotoxicity, Immunologic↗
PubMed1988

In vivo induction of the lymphokine-activated killer phenomenon: interleukin 2-dependent human non-major histocompatibility complex-restricted cytotoxicity generated in vivo during administration of human recombinant interleukin 2.

The availability of purified human recombinant interleukin 2 (IL-2) has enabled clinical trials to test its in vivo effects. We report here the immunological effects of 7 consecutive days of IL-2 treatment given to 25 patients with cancer in a clinical Phase I study. Peripheral blood lymphocytes obtained from patients following therapy with IL-2 had enhanced proliferative responses to IL-2 and enhanced direct cytotoxic activity on K562 target cells. This lytic activity was further augmented by the addition of IL-2 during the 51Cr release assay. Fresh peripheral blood lymphocytes from some patients who had just completed treatment at the higher IL-2 dose levels were able to kill both the natural killer-resistant Daudi cell line and fresh tumor cells while pretreatment samples and peripheral blood lymphocytes from healthy controls were not. This lytic activity was best detected when IL-2 was present in the in vitro effector assay. These results demonstrate that the administration of IL-2 to patients with cancer induces a population of effector cells able to directly destroy natural killer-resistant target cells, when assayed in the presence of IL-2.

Cells, Cultured↗
PubMed1988

Repetitive weekly cycles of recombinant human interleukin-2: responses of renal carcinoma with acceptable toxicity.

A phase I trial of repetitive weekly cycles of human recombinant interleukin-2 (IL-2) was performed in 23 patients with metastatic carcinoma. Patients received 4 days of IL-2 each week, followed by 3 days of observation, for 4 consecutive weeks. IL-2 was administered iv at 1.0 or 3.0 X 10(6) U/m2/day by one of three schedules involving continuous or bolus infusions. All treatment was carried out in a general hospital ward without intensive care unit monitoring or support. Seventeen patients had metastatic renal cell carcinoma; three of these demonstrated measurable (greater than 50% shrinkage) partial responses. This study demonstrates that IL-2 given alone without lymphokine-activated killer cells in this manner can induce antitumor effects with acceptable toxicity.

Adult↗
PubMed1988

Hepatic hydrolysis of octanoyl-CoA and valproyl-CoA in control and valproate-fed animals.

1. Medium-chain acyl-CoA hydrolase activities were determined in liver from control and valproate-fed rats and rabbits. 2. Octanoyl-CoA was readily hydrolyzed by all control liver preparations. 3. Animals that had been fed diets containing 0.5 or 1.0% (w/w) valproic acid had significantly elevated octanoyl-CoA hydrolase activities. 4. The CoA ester of valproic acid, a branched-chain isomer of octanoic acid, was poorly hydrolyzed by liver preparations from both control and valproate-fed animals. 5. Livers from the valproate-fed animals contained high levels of medium-chain acyl-CoA; total CoA content was also increased. 6. The inefficiency of hepatic valproyl-CoA hydrolysis may play a role in the toxicity of valproic acid.

Acyl Coenzyme A↗
PubMed1988

The in vitro function of lymphocytes from 25 cancer patients receiving four to seven consecutive days of recombinant IL-2.

Twenty-five cancer patients received human recombinant interleukin-2 (IL-2) for 4 to 7 consecutive days in a Phase I trial. IL-2 was administered either as a daily intravenous bolus infusion (lasting 15 min), or as a continuous infusion lasting 24 h each day. Prior studies have demonstrated that in vivo administration of IL-2 at high doses is associated with changes in the phenotype of circulating peripheral blood lymphocytes (PBL) (determined with monoclonal antibodies), and the induction of augmented in vitro natural killer activity (NK) by PBL obtained following in vivo IL-2. We have noted that fresh lymphocytes obtained after 4-7 consecutive days of IL-2 (greater than or equal to 10(6) U/m2/day) show an augmented ability to kill NK-sensitive and -insensitive target cells (K562 and Daudi targets, respectively), especially when tested with IL-2 present during the 4-h 51Cr release assay. We have further analyzed lymphocytes in a battery of in vitro proliferative and cytotoxic assays. We present here the summary of this quantitative analysis of their responses in both antigen-specific and -nonspecific immune responses. Striking in vitro changes were observed in the proliferative response to IL-2 and in cytotoxicity stimulated by (or requiring) in vitro IL-2. Proliferative responses to antigens and to mitogens were not as dramatically altered following in vivo IL-2, nor were allospecific or allo-activated cytotoxic interactions. These studies indicate that the most striking changes in lymphocyte function measured in vitro following in vivo IL-2 are seen in those functions requiring IL-2.

Cytotoxicity, Immunologic↗
PubMed1987

Phase 1 clinical evaluation of recombinant interleukin-2.

The availability of large quantities of pure recombinant IL-2 has permitted clinical studies of its effects in patients with cancer. Based on the rapid half-life (3-5 minutes) and the need for prolonged exposure to IL-2 to maximally stimulate responsive cells we conducted a Phase 1 clinical trial designed to compare the clinical tolerance, immunologic effects and antitumor activity of IL-2 given by CI and daily BI for 7 consecutive days. The MTD of IL-2 based on completion of 7 days of treatment was found to be 3 X 10(6) U/m2/day for BI and 10(6) U/m2/day for CI. These results are approximately equivalent to those reported by others (Lotze, 1985 and Atkins, 1986), provided corrections are made for activity (2.3 Cetus IL-2 units = 1 BRMP IL-2 Unit). Although dose limiting toxicity was observed at the higher doses of IL-2 tested, these doses were tolerated for a shorter period of time (3-4 days) with striking immunologic effects (Sondel et al. 1987). As such, shorter treatment schedules utilizing higher doses of IL-2 warrant further investigation. The toxicity associated with the administration of IL-2 is considerable and clearly dose related. Of particular clinical importance is the fever, hypotension, fluid accumulation and decrease in PS. The etiology of these toxicities appears to be related to the release of endogenous cytokines following activation of the patient's immune system. It is also possible that the in vivo activation by IL-2 of cells mediating NRC may play some role in the toxicity associated with IL-2 (Sondel, 1986). It remains unclear whether immunosuppressive methods such as the use of cyclophosphamide or steroids will enable blockade of the immune mediated toxicity without also diminishing its therapeutic value. Further studies examining methods to control the severe toxicity associated with high doses of IL-2 are needed. The future role that IL-2 may play in treating cancer is unclear. Whether IL-2 alone can have significant antitumor activity may depend on factors such as tumor bulk, the patient's inherent ability to generate cytotoxic cells or the susceptibility of a particular malignancy. As such further studies will need to examine the importance of dose, timing, schedule, method of IL-2 administration as well as tumor burden in a wide variety of cancers.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1986

beta-Hydroxy acyl-CoA inhibition of mitochondrial ATP production.

beta-Hydroxypalmitoyl-CoA and beta-hydroxystearoyl-CoA were synthesized, purified and quantitated. beta-Hydroxypalmitoyl-CoA and beta-hydroxystearoyl-CoA instantly and reversibly inhibited oxidative phosphorylation by rabbit heart mitochondria oxidizing pyruvate. [8-14C]ADP uptake studies showed that the beta-hydroxy acyl-CoA species linearly inhibited the adenine nucleotide translocase system. Free beta-hydroxy fatty acids at comparable concentrations (0.005 mM) did not affect ADP uptake or state III respiration.

Acyl Coenzyme A↗
PubMed1985

Cardiac and hepatic acyl-CoA and acylcarnitine hydrolase activities in clofibrate-fed rabbits.

Catalase activity in the heart of male rabbits was 21% of that found in the liver; clofibrate feeding (0.3% w/w for 10 days) resulted in an 80% increase in both cardiac and hepatic catalase activities. Fatty acyl-CoA oxidase activity in control heart was 11% of that found in control liver; this peroxisomal activity did not increase subsequent to clofibrate feeding. Only acyl-CoA hydrolase activity in the cardiac supernatant was elevated by clofibrate feeding. Acylcarnitine hydrolase activity was increased significantly in the homogenate, extract and supernatant of both heart and liver from the clofibrate-fed rabbit. Clofibrate feeding increased CoASH and carnitine tissue levels in heart and liver.

Animals↗
PubMed1984

Long-chain acyl-CoA and acylcarnitine hydrolase activities in normal and ischemic rabbit heart.

Long-chain acyl-CoA and acylcarnitine hydrolase activities were determined in fresh and perfused rabbit heart and correlated with tissue levels of their respective substrates, long-chain acyl-CoA and acylcarnitine. In fresh heart homogenate acyl-CoA hydrolase activity was 3-fold greater than acylcarnitine hydrolase activity; sonication of homogenate doubled acyl-CoA hydrolase activity but did not significantly change acylcarnitine hydrolase activity. Hearts perfused with 10 mM glucose by the nonrecirculating Langendorff method had depressed levels of acyl-CoA hydrolase activity under both aerobic and ischemic conditions. Extract from buffer-perfused heart showed increased acylcarnitine hydrolase activity and elevated levels of acylcarnitine. Homogenate acyl-CoA hydrolase activity was not sedimented by centrifugal forces up to 50,000 X g; however, less than 25% of homogenate acylcarnitine hydrolase activity remained in the 50,000 X g supernatant. The hypolipidemic drug clofibrate was an effective in vitro inhibitor of acylcarnitine hydrolase activity but not of acyl-CoA hydrolase activity. The fatty acid analog tetradecylglycidic acid inhibited only acyl-CoA hydrolase activity. These results suggest that acyl-CoA hydrolase and acylcarnitine hydrolase activities are differentially affected in the perfused heart by substrate levels and oxygen availability. In addition, the diverse response of these two hydrolase activities to a variety of biochemical parameters implies that the observed hydrolyses of palmitoyl-CoA and palmitoylcarnitine are catalyzed by at least two separate hydrolase enzymes.

Animals↗
PubMed1984

A case report of bilateral double teeth.

A 17-year-old male presented with bilateral double teeth in the 2 2 region and upper arch crowding. These were surgically sectioned and orthodontic treatment carried out to align 321 123. The sectioned teeth remained vital.

Adolescent↗