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Biomedical subjects

G Peck

Publications and source records attributed to G Peck.

13 recordsLinked to original sources

The angiotensin IV/AT4 receptor.

The angiotensin AT(4) receptor was originally defined as the specific, high-affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT(4) receptor. Central administration of Ang IV, its analogues or LVV-hemorphin 7 markedly enhance learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The AT(4) receptor has a broad distribution and is found in a range of tissues, including the adrenal gland, kidney, lung and heart. In the kidney Ang IV increases renal cortical blood flow and decreases Na(+) transport in isolated renal proximal tubules. The AT(4) receptor has recently been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). IRAP is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and is predominantly found in GLUT4 vesicles in insulin-responsive cells. Three hypotheses for the memory-potentiating effects of the AT(4) receptor/IRAP ligands, Ang IV and LVV-hemorphin 7, are proposed: (i) acting as potent inhibitors of IRAP, they may prolong the action of endogenous promnestic peptides; (ii) they may modulate glucose uptake by modulating trafficking of GLUT4; (iii) IRAP may act as a receptor, transducing the signal initiated by ligand binding to its C-terminal domain to the intracellular domain that interacts with several cytoplasmic proteins.

Aminopeptidases↗

Isotretinoin-basal cell carcinoma prevention trial. Design, recruitment results, and baseline characteristics of the trial participants. The ISO-BCC Study Group.

The Isotretinoin-Basal Cell Carcinoma Prevention Trial (ISO-BCC Study) is a double-masked, randomized, placebo controlled, multicenter clinical trial. It is the first intramural cancer chemoprevention trial sponsored by the Division of Cancer Prevention and Control of the National Cancer Institute. This trial was designed to evaluate the effectiveness of chronic administration of low dosage levels (10 mg) of a synthetic retinoid, isotretinoin, in reducing the incidence of basal cell carcinoma in a high-risk population and to determine the incidence and severity of side effects associated with this long-term treatment. Between 1984 and 1987, eight clinical centers enrolled 981 participants between the ages of 40 and 75, who had two or more biopsy proven basal cell carcinomas in the 5 years before trial entry. This article describes the trial design, recruitment results, and baseline characteristics of the participant population in the ISO-BCC Study.

Adult↗

Determination of cholinesterase and acetylcholinesterase in amniotic fluid. Uses in prenatal diagnosis and quality control.

The determination of acetylcholinesterase (AChE) has been shown to be as specific as alphafetoprotein (AFP) for the prenatal detection of open neural tube defects although AFP remains the method of choice. This paper describes a semi-automated technique for the analysis of acetylcholinesterase in amniotic fluid that: A) reduces the cost of the procedure; B) allows for a larger number of samples to be run at a time; and C) provides for more accurate and reproducible procedures and results. Six fetuses with neural tube defects (2 with gastroschisis and 3 where one twin was dead) were detected and found to have elevated AChE, TChE and 2 bands by electrophoresis. Quality control procedures using both pure enzyme and amniotic fluid with low and high levels of the enzyme are described. The analysis of 340 amniotic fluids of normal pregnancies indicates that the normal value for AChE is 5.17 +/- 2.63 mU/ml (97% confidence interval for the mean 4.84-5.49 mU/ml. A group of 27 abnormal pregnancies provides evidence that fetal vomiting and regurgitation, fetal demise, multiple cysts syndrome, idiopathic IUGR, arthrogryposis multiplex, hydrocephaly (stenosis of aqueductus), trisomy 21, trisomy 18, hydronephrosis, pyloric stenosis, heart malformation, ectopia cordis and multiple gestation produce elevated levels of pseudocholinesterase (PChE) in amniotic fluid. The use of pseudocholinesterase levels in amniotic fluid for prenatal diagnosis is proposed and discussed in view of its elevated levels in abnormal pregnancies where AChE is normal. The normal values for PChE are 23.86 mU/ml (mean) and 5.83 for standard deviation. Electrophoretic analysis was performed on all samples with values higher than one standard deviation above the mean.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

Phase II trial of 13-cis-retinoic acid in metastatic breast cancer.

Studies have suggested that both natural and synthetic retinoids have extensive chemopreventive activity against a variety of carcinogens in vivo and in vitro. We have previously shown that growth of human breast cancer cells can be inhibited by retinoids, and retinoic acid-binding proteins have been demonstrated in these cell lines and tumor biopsies. We studied the activity of 13-cis-retinoic acid in the treatment of 18 patients with advanced breast cancer refractory to standard cytotoxic and/or endocrine therapy. Patients began on 0.5 mg/kg and escalated to 8 mg/kg over a one-month period unless toxicity (dry skin, dry mucosa, cheilitis, conjunctivitis) forced dose reduction. All these toxicities responded promptly to dose reduction. Four patients exhibited drug related hypercalcemia, 2 complained of severe earache and several had nausea, vomiting and abdominal cramping. There were no objective responses as defined by standard criteria. One patient with thrombocytopenia secondary to documented marrow involvement demonstrated a recovery of platelet count from 9000 to 110,000. 13-cis-Retinoic acid is not of apparent value in women with heavily pretreated breast cancer.

Breast Neoplasms↗

Tinidazole in the prevention of wound infection after elective colorectal surgery.

During the first six months of 1978, 71 patients were the subject of a controlled trial of the use of tinidazole for the prevention of wound infection after elective colonic surgery. The trial design was prospective, randomized and double-blind with tinidazole or placebo given at the last oral intake before operation. The objective endpoint of the trial was the presence or absence of wound infection manifested by pus. All patients underwent a standard preoperative preparation of bowel washouts, and a standardized surgical technique included, in all cases, the use of wound drainage. At the end of the trial there were three wound infections in 40 patients who were given tinidazole, and eleven wound infections in 31 patients who were given placebo. The difference in wound infection rate between these two groups is significant (x2 with Yates correction = 7.3; P less than 0.01).

Clinical Trials as Topic↗

Cutaneous irritation in the topical application of 30 antineoplastic agents to New Zealand white rabbits.

Of 30 antineoplastic agents studied for their primary irritation potential in rabbits, 9 showed some potential for irritation. Five of these 9 agents produced a significant dermal irritation. None of the irritation observed was considered to be irreversible skin damage. The study further showed a strong correlation between irritation observed by the Draize method and acute inflammation evaluated histopathologically. There was a tendency toward increased epidermal thickness of irritated skin sites. None of the agents produced gross or microscopically visible lesions in the internal organs observed.

Administration, Topical↗

Mortality trends in the surgical management of chronic peptic ulceration: 25 years' experience.

This study is of the results of surgical management of bleeding chronic peptic ulceration at Prince Henry's Hospital, retrospective for the periods 1951 to 1960 and 1961 to 1970 and prospective for 1972 to 1977. During the latter five years all patients were admitted from the community to a haematemesis and melaena unit with a defined policy of management and prospective data recording for computer analysis. There was a continuing improvement in mortality over this 25-year period, especially with duodenal ulcer. No clear distinction could be made between conservative surgery and partial gastrectomy in terms of reduced surgical mortality in duodenal ulcer. Bleeding gastric ulcer remains a difficult problem, with a current surgical mortality of 21%.

Adolescent↗

Potential antitumor agents. XVII. physalin B and 25,26-epidihydrophysalin C from Witheringia coccoloboides.

An investigation of Witheringia coccoloboides (Dammer) A. T. Hunziker [Capsicum fuscoviolaceum (Cufodontis) Mort. And Standl.] roots has resulted in the isolation of two cytotoxic compounds: physalin B (1) and a novel physalin, which was characterized by spectral analysis as 25,26-epidihydrophysalin C (2). Both compounds have demonstrated cytotoxic activity in 9KB and 9PS tumor cells (in vitro). Physalin B (1) has demonstrated moderate activity against the 3PS mouse leukemia (in vivo).

Animals↗

Multifactorial analysis of exchanger efficiency and liquid conservation during perfluorochemical liquid-assisted ventilation.

Liquid-assisted ventilation (LAV) of the lung with perfluorochemical (PFC) requires a method of oxygenating and removing CO2 from the liquid. Current PFC LAV techniques consist of total liquid ventilation, PFC lavage, and partial liquid ventilation. Because PFC liquid is volatile, it may be lost from the lung or ventilator circuit in the expired gas. This study evaluated the efficiencies of two types of exchangers (spray bubbler and membrane oxygenator) with respect to CO2 elimination from the PFC liquid and prevention of the loss of PFC liquid. A multifactorial analysis of exchanger efficiency was performed with respect to liquid conservation and CO2 removal. PFC losses and relative efficiencies of two types of exchangers to eliminate CO2 from expired PFC liquid were evaluated, along with two types of PFC liquids. Gas (100% O2 at 4 and 8 L/min) and PFC liquid were circulated countercurrently through the exchangers (oxygenator and bubbler) through a temperature-controlled (25 degrees or 37 degrees C) open circuit. To evaluate effectiveness of CO2 elimination, an exchanger efficiency index (EEI) for CO2 was calculated applying mass-transfer theory to characterize gas transport down a concentration gradient where EEI equals: [PPFCCO2 out--PPFCCO2 in]/PgasCO2 in--PPFCCO2 in]. Rate of PFC loss from the circuit was calculated from mixed expired gas samples using a thermal detector analyzer. EEI and PFC loss rate were analyzed with respect to gas: PFC liquid flow ratios (analogous to the V/Q ratio). The results showed that 1) PFC loss rate and exchanger efficiency to remove CO2 increased with increasing gas: PFC liquid flow rates independent of the type of exchanger or PFC liquid; 2) PFC loss rate at any gas or liquid flow rate was greater for the bubbler than for the oxygenator; 3) the oxygenator was more efficient than the bubbler with respect to CO2 elimination; 4) although PFC loss rate increased with temperature and vapor pressure, there was little difference in the EEIs for the temperatures studied. These results 1) identify exchanger requirements necessary to maintain effective CO2 elimination up to four times normal CO2 loading conditions during LAV; 2) suggest that using a membrane oxygenator as the gas exchanger, in concert with stringent fluid temperature control, improves PFC liquid conservation and CO2 elimination relative to bubbler exchanger configurations; 3) highlight the importance of matching the exchanger type to the physiocochemical properties of the specific PFC liquid to optimize CO2 elimination while reducing PFC liquid loss by minimizing gas relative to PFC liquid flow rates. Because PFC liquid loss occurs with all current means of oxygenating and removing CO2, this study raises the importance of developing alternative, bulk-gas-flow-independent, means to recondition PFC liquids.

Carbon Dioxide↗