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Biomedical subjects

G Gibbons

Publications and source records attributed to G Gibbons.

32 records · Page 2Linked to original sources
PubMed1988

Intracellular biotransformation of platinum compounds with the 1,2-diaminocyclohexane carrier ligand in the L1210 cell line.

We have previously reported the development of a two-column high performance liquid chromatography system for separation of platinum(II) complexes with the 1,2-diaminocyclohexane (DACH) carrier ligand (Mauldin et al., Anal. Biochem., 157: 129, 1986). Here we report the application of this technique to the study of the intracellular biotransformations of (DL)-trans-1,2-diaminocyclohexanemalonatoplatinum(II) [PtCl2(trans-DACH)] and (DL)-trans-1,2-diaminocyclohexanemalonatoplatinum(II) [Pt(mal)(trans-DACH)] in the L1210 cell line. The two-column high performance liquid chromatography system allowed separation and identification of both parent drugs and intracellular biotransformation products containing glutathione, methionine, cysteine, arginine, lysine, aspartate or glutamate, and serine or threonine. With the exception of the platinum-glutathione complex, the relative abundance of each biotransformation product was independent of drug concentration. The relative abundance of the platinum-glutathione biotransformation product increased with increasing platinum concentration, suggesting that platinum drugs cause an increase in intracellular glutathione levels in a dose-dependent manner. This hypothesis was verified by direct measurement of intracellular glutathione levels. In continuous uptake experiments, the intracellular levels of the parent compounds peaked between 2 and 5 h and declined to negligible levels by 24 h. In pulse-chase experiments, the chemical t1/2 for PtCl2(trans-DACH) and Pt(mal)(trans-DACH) inside the cell at 37 degrees C was determined to be 12-15 and 21-28 min, respectively. This is far shorter than previously determined rates for the displacement of either ligand in vitro. The platinum-amino acid complexes accumulated gradually throughout the 24-h incubation. The free trans-DACH carrier ligand also accumulated to a level approaching 20% of filterable counts during the 24-h incubation, probably due to trans-labilization of the carrier ligand by sulfur-containing nucleophiles. A combination of reverse phase high performance liquid chromatography and a DNA binding assay was used to identify and quantitate the reactive biotransformation products. As expected from previous studies (Mauldin et al., Cancer Res., 46: 2876, 1986), the PtCl2(trans-DACH)-treated cells had approximately 3 times more reactive platinum biotransformation product at early times, but the levels of reactive biotransformation product fell much more rapidly than in Pt(mal)(trans-DACH)-treated cells. In the PtCl2(trans-DACH)-treated cells, the major reactive biotransformation product was the aquachloro species at all time points tested. In Pt(mal)(trans-DACH)-treated

Animals↗
PubMed1988

Lower extremity revascularization with in situ saphenous vein for critical ischemia.

Over a 3 1/2 year period, 55 limbs were revascularized with in situ saphenous vein bypass grafts in 49 patients. Ninety-five percent of grafts were constructed in patients with critical ischemia for limb salvage, and 5 percent were constructed for debilitating claudication. The proximal anastomosis was performed in the groin in all patients. The distal graft was taken to the popliteal artery in 45 percent and to a tibial or isolated popliteal segment in 55 percent, with 55 percent of the grafts having single-vessel runoff. The perioperative mortality rate was 7 percent. The primary immediate patency rate was 91 percent and the secondary immediate patency rate was 98 percent at 1 month. The cumulative patency rate at 42 months was 85.4 percent overall, 86.6 percent for the tibial grafts, and 84 percent for the popliteal grafts. The cumulative limb salvage rate was 100 percent for the popliteal grafts, 90 percent for the tibial grafts, and 94.5 percent overall. All of the patients were followed and 3 required secondary revision. In situ vein bypass is a technically demanding procedure that can be performed successfully in high-risk patients with limbs with minimal runoff and can yield very high long-term patency and limb salvage rates in a community hospital setting.

Aged↗
PubMed1987

Adult esophageal candidiasis: a radiographic spectrum.

With the increasing use of cancer chemotherapy and organ transplantation requiring immunosuppressive therapy, and with the incidence of immunodeficiency states such as AIDS increasing, it is to be expected that candida esophagitis will occur with increasing frequency. Though fiberoptic endoscopy is a more specific and more sensitive approach to the diagnosis of candida esophagitis than barium esophagography, it is also more invasive, and many patients will continue to be examined radiologically, at least initially. The radiologist continues, therefore, to play a significant role in suggesting the diagnosis and it is incumbent on him to familiarize himself with the spectrum of common and unusual radiographic manifestations of this disease.

Adult↗
PubMed1985

Is nasogastric suction necessary after elective colon resection?

It is commonly held that nasogastric suction is necessary after colon resection to prevent small and large bowel distension, wound complications, and anastomotic problems. In this retrospective study of 118 patients undergoing colon resection for malignancy or inflammatory disease, 83 underwent postoperative nasogastric suction and 35 did not. A wide variety of postoperative variables were evaluated in these two groups of patients and few differences were found. However, there were trends toward shorter postoperative hospital stays, and less abdominal distension, nausea, and vomiting could be discerned in the patients who did not undergo nasogastric suction. This retrospective study suggests that routine nasogastric suction may not be necessary or useful after elective colon resection.

Colon↗
PubMed1985

Physiologic assessment of phosphoglycerate mutase deficiency: incremental exercise test.

A third case of phosphoglycerate mutase (PGAM) deficiency, a metabolic myopathy involving terminal glycolysis, was identified in a 24-year-old black man with episodic, exercise-induced myoglobinuria since age 13. To better understand the physiologic consequences of PGAM deficiency, incremental exercise testing was performed. Results were compared with those of two patients having myophosphorylase deficiency and five normals. In contrast to the patients with phosphorylase deficiency, the PGAM-deficient patient achieved near-normal levels of maximal exercise and produced a normal peak lactate after exercise. The mechanisms underlying the asymptomatic performance of such strenuous exercise in this case are uncertain, but the data suggest that unidentified factors are operative in precipitating attacks of myoglobinuria in patients with some metabolic myopathies. Despite similar clinical histories, patients with different glycolytic enzyme deficiencies can have striking differences in exercise tolerance.

Adult↗
PubMed1980

Suspected foodborne carbamate pesticide intoxications associated with ingestion of hydroponic cucumbers.

In the period April 1--15, 1977, nine residents of one Nebraska town experienced violent illnesses with short duration following ingestion of locally grown hydroponic cucumbers. Despite a thorough investigation, the etiologic agent of illness was not determined. From July 16--25, 1978, a second similar outbreak occurred in an adjacent city. Five individuals experienced illness similar to that which occurred in 1977, also following ingestion of hydroponic cucumbers grown at the same greenhouse involved in the 1977 outbreak. The carbamate insecticide, aldicarb, was detected in some cucumbers grown at the hydroponic greenhouse. The source of this chemical in the greenhouse could not be determined.

Acute Disease↗
PubMedDate not supplied

Noninvasive evaluation of the aorto-iliac segment.

Eighty-five patients (169 limbs) were studied in the Noninvasive Vascular Laboratory at the Lahey Clinic as part of a preoperative evaluation for arterial insufficiency. Segmental Doppler systolic pressures and peak velocity waveform analysis using a directional Doppler were performed on all patients. Normal velocity waveforms demonstrated forward flow during systole, reverse flow during the first half of diastole and a return to forward flow again during the latter part of diastole (triphasic flow). Significantly abnormal waveforms did not demonstrate reverse flow during the first half of diastole (monophasic flow). A significantly abnormal angiogram showed a greater than 50% stenosis in the aorto-iliac segment. A comparison of Doppler velocity waveforms with arteriograms showed a 96% correlation. Most errors in our study were technical; related to the assumption that the inguinal skin crease marked the location of the inguinal ligament and the origin of the common femoral artery. In these instances, the superficial femoral artery not the common femoral artery was sampled. Common sources of false positive studies were severe outflow obstruction or recent surgery to the common femoral artery, both showing a loss of laminar flow and a monophasic waveform. Patients who demonstrate reverse flow in the common femoral artery by directional Doppler examination had adequate inflow to support a femoral-popliteal or femoral-femoral by pass graft. Patients with monophasic flow had either inadequate aorto-iliac segments, recent surgery to the common femoral artery or severe outflow obstruction. Supportive data will be presented in detail.

Angiography↗