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Biomedical subjects

R H Peters

Publications and source records attributed to R H Peters.

At least 37 records · Page 2Linked to original sources
PubMed1992

Drug abuse history and treatment needs of jail inmates.

The current study evaluates the extent of prior drug use and psychosocial dysfunction related to drug use among 499 jail inmates referred to the Hillsborough County Sheriff's Office Substance Abuse Treatment Program. Results indicate that inmates were involved with drugs for an average of more than 7 years, and with cocaine for almost 5 years. The majority of inmates reported extremely heavy use of drugs in the month prior to the last arrest, including 83% that had used cocaine. Many drug-dependent inmates reported a shift over time from intranasal to freebase cocaine use. Half of all referrals indicated a pattern of regular use within a year of involvement with drugs. The need for lengthy, heavily structured, and intensive treatment approaches for drug-dependent jail inmates is underscored by a history of chronic cocaine and polydrug abuse, a compulsive pattern of drug use, few successful periods of voluntary abstinence, and severe disruption in vocational, social, and psychological functioning. Their history of infrequent and unsuccessful involvement in rehabilitation programs reflects a significant need for compulsory treatment following release from jail, community supervision to ensure compliance with treatment, and development of linkages between jail drug treatment programs, courts, and community treatment providers.

Adult↗
PubMed1991

Determination of the mean normal prothrombin time for assessment of international normalized ratios. Usefulness of lyophilized plasma.

To report a Prothrombin Time (PT) as International Normalized Ratio in controlling oral anticoagulant therapy, the Mean Normal PT (MNPT) is required. To correct for methodological differences in performing the PT test, each laboratory should determine its own MNPT for each batch of reagent using fresh blood samples from a large number of normal individuals. This would be a laborious procedure. Two models for simplified assessment of MNPT were investigated by two laboratories in a collaborative study. According to the models, the MNPT of a new batch of reagent is calculated, using the PT of a lyophilized control plasma measured with the new batch and a reference batch, as well as the MNPT of the reference batch obtained with fresh samples. Experimental results were obtained with 19 batches of bovine thromboplastin, 4 lyophilized normal control plasmas and fresh blood samples of 40 normal individuals. The PTs of the 4 lyophilized normal control plasmas were not identical to the MNPT of the fresh normal samples and also different from each other. Therefore, the uncorrected PTs of these control plasmas cannot be used as MNPT. In general, there was good agreement between measured and calculated MNPT, although some control plasmas gave better results than others. There were no significant differences between the results obtained by both calculation models.

Freeze Drying↗
PubMed1991

Role of glutathione in the in vitro synergism between 4-hydroperoxy-cyclophosphamide and cisplatin in leukemia cell lines.

To explain the sequence-dependent in vitro cytotoxic synergism between 4-hydroperoxycyclophosphamide (4-HC) and cisplatin in the K-562 human leukemia cell line, we have hypothesized that 4-HC decreases cellular glutathione (GSH) levels and that the resulting diminution of the cellular protective effect of GSH leads to the increased cytotoxicity of cisplatin. Exposure of K-562 cells to 4-HC resulted in a concentration- and time-dependent depletion of cellular GSH. To determine the effect of modulation of GSH levels on the toxicity of cisplatin, K-562 cells were exposed to buthionine sulfoximine (BSO) and/or GSH ethyl esters. Depletion of GSH to approximately 10% of control values by BSO potentiated the cytotoxicity of cisplatin, while rapid replenishment of GSH to within normal levels by GSH esters abolished the potentiation of BSO. Doubling cellular GSH by incubation with GSH esters protected against cisplatin cytotoxicity. Of importance, pretreatment of K-562 cells with BSO, in addition to increasing the cytotoxicity of 4-HC and cisplatin, abolished the synergism between the two drugs. The working hypothesis was also tested in two other cell lines in which the cytotoxic synergism between 4-HC and cisplatin was exhibited: the Raji cell line, a human lymphoblastic cell line, and the L1210-CPA cell line, a subclone of the murine L1210 leukemia with resistance to 4-HC. GSH levels in these two cell lines were not altered by incubation with concentrations of 4-HC at which the synergism was observed. In conclusion, the data for the K-562 cell line, indicating that (a) 4-HC depletes cellular GSH levels, (b) the lowering of cellular GSH levels enhances the toxicity of cisplatin, and (c) intact GSH stores are required for the synergism, strongly support the postulate that the cytotoxic synergism between 4-HC and cisplatin is modulated by GSH levels in this cell line. However, the lack of 4-HC-mediated depletion of GSH at concentrations of 4-HC resulting in cytotoxic synergism in the Raji and L1210-CPA cell line indicates that mechanisms other than modulation of GSH levels by 4-HC are responsible for the synergism in these cells.

Animals↗
PubMed1990

Cellular glutathione as a protective agent against 4-hydroperoxycyclophosphamide cytotoxicity in K-562 cells.

Exposure of cells of the K-562 erythroleukemia cell line to 4-hydroperoxycyclophosphamide (4-HC), an analog of activated cyclophosphamide, causes a concentration-dependent inhibition of in vitro colony formation by these cells. For investigation of the role of glutathione (GSH) in the metabolism of 4-HC, GSH levels of K-562 cells were modulated by exposing the cells to buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, and/or to GSH ethyl esters. Both the mono- and diethyl esters of GSH were synthesized in our laboratories and their identities were determined by chromatographic methods and fast-atom-bombardment mass spectrometry. An HPLC method including electrochemical detection used for thiol determination was applied for the measurement of GSH esters. Incubation of the cells with BSO depleted GSH levels to approximately 11% of control values and potentiated the cytotoxicity of 4-HC. By contrast, exposure to GSH esters approximately doubled GSH levels and protected the cells against the toxicity of 4-HC. Moreover, when cellular GSH levels were first depleted by BSO exposure and then replenished by incubation with GSH esters, the BSO-associated potentiation of 4-HC cytotoxicity was abolished. The work described herein extends the application of an HPLC method used for thiol determination to the measurement of GSH ethyl esters. In addition, it established that GSH acts as a competitive protecting agent against the in vitro toxicity of 4-HC in the K-562 cell line.

Antimetabolites↗
PubMed1990

Combinations of 4-hydroperoxycyclophosphamide (4-HC) and cisplatin for bone marrow purging in autologous marrow transplantation: an update.

We are studying the usefulness of combinations of 4-HC and cisplatin as a potential purging regimen for autologous bone marrow transplantation. In all of our studies, in vitro cytotoxicity was determined by clonogenic assay, and drug interaction was quantitated using the multiple drug-effect analysis method. The cells were incubated for one hour (4-HC) and/or 4 hours (cisplatin). We found that the drugs in combination had cytotoxic synergism against human leukemia cell lines (K-562 and Raji). The synergism was sequence-dependent (cells must be exposed to 4-HC first), was present at various molar ratios of the drugs, and most pronounced at high levels of cell kill. We also found that the drugs had cytotoxic synergism against normal human marrow progenitors (CFU-GM). However, the leukemic cells were approximately 55 times more sensitive to the combination than CFU-GM. In a murine system, the drugs were synergistic against L1210 leukemia cells and normal murine CFU-GM, but L1210 cells were at least 130 times more sensitive to the combination than CFU-GM. To determine the ability of L1210 cells to grow in vivo after exposure to the drugs, BDF1 mice were injected with 2 x 10(4) cells which had been incubated with 4-HC and/or cisplatin. The survival time of untreated controls was 13 +/- 2.8 days. For treated groups, the cure rates after 50 days of observation were 33% (4-HC, 40 uM), 0% (cisplatin, 8 uM), and 100% (4-HC + cisplatin). Finally, at concentrations resulting in equivalent toxicity to marrow CFU-GM, cisplatin seemed to be more toxic to murine spleen blast colony forming cells (CFC-BC) than 4-HC. The drugs in combination appeared to have at least additive toxicities against CFC-BC.

Animals↗
PubMed1989

A Multi-centre study to evaluate method dependency of the international sensitivity index of bovine thromboplastin.

In The Netherlands, a particular coagulometer method for prothrombin time (PT) determination with reduced sample and reagent volumes is used by 62% of the laboratories controlling oral anticoagulant therapy. This "micro-method" has been calibrated against the manual tilt-tube technique for PT determination by six Dutch laboratories. Each laboratory tested 20 fresh normal blood samples and 60 fresh patient blood samples using both methods with the same batch of bovine thromboplastin reagent, according to a detailed protocol. Both methods were comparable as to their precision, but PTs measured by the micro-method were significantly prolonged (p less than 0.001, Student's t-test) as compared to the manual method. This effect is stronger for samples of normal subjects than for patients' samples. It was assumed that the International Sensitivity Index (ISI) of the bovine thromboplastin for the manual method was 1.00 in each laboratory. The ISI-values of the bovine thromboplastin for the micro-method determined by the six laboratories ranged from 1.00 to 1.07 (mean 1.03, SD 0.03). Our results indicate that any other laboratory, using this thromboplastin and the micro-method, should obtain accurate assessment of the International Normalized Ratio from their own mean normal PT and an ISI which is 3% higher than the ISI supplied by the thromboplastin manufacturer for the manual tilt-tube method.

Animals↗
PubMed1989

In vitro synergism of 4-hydroperoxycyclophosphamide and cisplatin: relevance for bone marrow purging.

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide (4-HC)-purged bone marrow gives long-term remission in almost half of relapsed acute nonlymphocytic leukemia and non-Hodgkin's lymphoma patients, but relapse of disease is the main cause of failure, suggesting ineffective purging in some cases. Cisplatin (CP) has activity against a variety of human tumors and is not commonly used for initial therapy of leukemia and lymphoma. Using established human leukemia cell lines, combinations of 4-HC and CP were investigated as a potential regimen for improving the ex vivo removal of leukemia cells from bone marrow. The cell lines (K-562 and Raji) were incubated for 1 (4-HC) or 4 h (CP), washed, and assayed for inhibition of colony formation in semisolid media. In both cell lines, CP (4h) was more potent than 4-HC (1 h). Combinations of the drugs in various molar ratios were studied after the cells were sequentially incubated with 4-HC and CP. The effects of the drugs were analyzed using the multiple drug-effect analysis of Chou and Talalay. Analysis of data on in vitro inhibition of colony formation suggested that all combinations studied were synergistic in both cell lines, with the greatest synergism being found in the Raji cell line. In addition, for K-562 cells we could detect at least a 4.6 log reduction in cloning with the CP:4-HC combination (1:10 molar ratio). We conclude that CP is a potential candidate in drug combinations for ex vivo bone marrow purging because of its high potency against human leukemia cell lines, its synergistic activity in combination with 4-HC, and its ability to reduce a high tumor burden when combined with 4-HC.

Bone Marrow↗
PubMed1989

17-Desoxy estrogen analogues.

A series of 17-substituted, 17-desoxyestratrienes have been synthesized and tested as potential postcoital antifertility agents. Estrogen-relative binding affinities were determined, in vivo assays for estrogenic and postcoital antifertility activity were conducted in rats, and selected candidate compounds were further tested for estrogenic activity in monkeys. In the rat, the 17-desoxyestratriene derivatives 8a, 8b, and 30 have shown low estrogenic activity while retaining potent antifertility activity. Structural modifications at the outset included a variety of 17-substituents and an omission of the 17-oxygen functionality, which was previously thought to be necessary for potent activity. The 17 beta-ethyl side chain exhibited the greatest antifertility activity with the largest separation ratio to estrogenicity. Nuclear modification of 17-desoxyethylestrane derivatives at positions 7 and 11 further increased the desired separation of activity, with the 11-hydroxy moiety enhancing separation more than other features.

Animals↗
PubMed1989

11 beta-nitrate estrane analogues: potent estrogens.

Various estrane derivatives 1 reacted with cerium ammonium nitrate (CAN) selectively and efficiently to provide 9 alpha,11 beta-defunctionalized derivatives 2, which were subsequently deoxygenated at C-9 with triethylsilane/boron trifluoride etherate to the desired target 11 beta-nitratoestranes 3a, 3b, and 5. When examined for estrogenic and postcoital antifertility activity, 11 beta-nitrates 2c, 2d, and 3b most notably displayed more potent oral activity than did ethynylestradiol.

Animals↗
PubMed1989

Copulation-illness associations in male rats: lithium chloride dose and delay manipulations.

Male rats that receive an injection of lithium chloride (LiCl) after each pairing with an estrous female gradually decrease their copulatory behaviors. In the present experiments we demonstrated that a 6.0 mEq/kg (0.3 M, 20 ml/kg) dose of LiCl injected after trials spaced twice weekly at 3-4-day intervals induced more rapid acquisition of copulation-illness associations than a 3.0 mEq/kg (0.15 M, 20 ml/kg) dose. Contingent 0.3 M saline or noncontingent 0.3 M LiCl injections did not affect copulatory behaviors. The location of the male rat (home cage or test chamber) during a portion of the aversive state induced by LiCl did not influence rate of acquisition. Copulation-illness associations, once established, were retained over a 60-day interval. Comparable decrements in copulatory behaviors were evident when LiCl was injected at 1-, 5-, or 15-min intervals after pairings with estrous females when the males were detained in the test chambers during the delay intervals; decrements were not observed when the interval was increased to 30 or 60 min. An electric shock analog to the aversive state induced by LiCl did not induce decrements in copulatory behaviors. It was suggested that odor-illness associations may, in part, account for the decrements in copulatory behaviors in this paradigm.

Animals↗
PubMed1989

The biological half-time of radioactive Cs in poikilothermic and homeothermic animals.

Literature data for the half-time of Cs in one-, two-, and three-compartment models have been collated and regressed to yield general descriptions of clearance for homeotherms (warm-blooded animals) and poikilotherms (cold-blooded animals) of different sizes. Cesium half-times increase with body weight and are longer in poikilotherms than in homeotherms. These trends and the values of the associated regression coefficients imply that Cs clearance is a function of metabolic rate. The patterns are especially visible in analyses of the larger compartments, perhaps because the curve splitting required to analyze smaller, more rapidly cleared pools is necessarily subjective. The route by which acutely contaminated animals receive their Cs also influences clearance. Inhaled Cs appears to be retained longer than injected Cs, which is in turn retained longer than ingested Cs. This suggests that Cs is discriminated against in biological transfers, so that Cs dust remains in the lungs whereas Cs in the food is less readily absorbed. These patterns of Cs clearance suggest that large animals, poikilotherms, and animals contaminated by inhalation or injection may receive a greater dose.

Animals↗
PubMed1988

Ultrasonic vocalizations in male rats following acquisition of copulation-illness associations.

Brief 50-kHz ultrasonic vocalizations are emitted by male rats during copulatory encounters with sexually receptive females. These vocalizations also occurred during pairings with estrous females in male rats whose copulatory behaviors had been associatively inhibited by LiCl-induced aversive contingencies. Longer 22-kHz calls, typically emitted during the postejaculatory refractory period, were not observed in these males. These results demonstrate a dissociation of behaviors that were (mounts, intromissions, and ejaculations) and were not (50-kHz vocalizations) associatively inhibited by LiCl.

Animals↗
PubMed1988

Analogues of [(triethylsilyl)ethynyl]estradiol as potential antifertility agents.

Various 17 alpha-ethynylsteroids were prepared and derivatized as the corresponding triethylsilyl compounds 2-35, which were examined for a ratio of antifertility to estrogenic activity that would be more beneficial than that of the presently used agent. Among the triethylsilyl compounds evaluated, only 23 displayed this desired ratio, although two other compounds without the triethylsilyl moiety, 18 and 26, shared similar characteristics.

Animals↗
PubMed1988

Differential effects of yohimbine and naloxone on copulatory behaviors of male rats.

Prior research has demonstrated that both yohimbine, an alpha2-adrenergic antagonist, and naloxone, an opiate antagonist, facilitate components of copulatory behaviors in nonstressed male rats. In the present experiments, we demonstrate that these drugs differentially affect copulatory behaviors when the behavioral testing situation contained an aversive element. Male rats received an injection of lithium chloride (0.3 M, 20 ml/kg, ip) immediately after each encounter with an estrous female. Consequently, male copulatory behaviors gradually declined during successive test sessions. These male rats also received ip injections of either yohimbine (2 mg/kg/ml), naloxone (4 mg/kg/ml), or isotonic saline 20 min prior to each copulation test. Yohimbine-treated rats were more likely to copulate than control rats during both acquisition and extinction of lithium chloride-induced associative inhibition of copulatory behavior. Conversely, naloxone-treated rats were less likely to copulate than control rats during both acquisition and extinction. These data are consistent with the hypothesis that yohimbine increases sexual motivation in the male rat and limit the generality of the excitatory effects of naloxone on copulatory behaviors.

Animals↗
PubMed1988

Effect of trenbolone and testosterone on the plasma elimination rates of sulfamethazine, trimethoprim, and antipyrine in female dwarf goats.

Plasma elimination rates of sulfamethazine (100 mg/kg of body weight, IV), trimethoprim (20 mg/kg, IV), and antipyrine (35 mg/kg, IV) were studied in adult female dwarf goats (n = 5) before and after implantation with trenbolone acetate (5 mg/kg). Pretreatment with trenbolone caused a significant decrease in the elimination rate of the drugs tested: for sulfamethazine, 5 times; for antipyrine, 3 times; and for trimethoprim, 2 times. After treatment with testosterone (1 mg/kg, SC, twice weekly for 2.5 weeks), female goats (n = 5) had a similar decrease in the elimination rate of sulfamethazine. Other induced effects included a change in social behavior, a lower voice, and the development of a typical billy goat-like odor. Plasma creatinine concentrations after androgen administration were significantly higher than those before androgen administration; changes were not observed in plasma urea values. Because of the differences observed, we believe that more attention should be paid to the effects of androgenic agents on drug kinetic properties, with particular reference to studies on clinical efficacy, side effects, and drug residues in food products.

Animals↗