Preliminary Studies on the Absorption,Distribution, Metabolism,and Excretion of THIP in Animal and Man using 14C-labelled Compound

Abstract: Distribution of radioactivity in rats, serum levels in human volunteers and rats and elimination of radioactivity in volunteers, rats, and mice following oral administration of ¹⁴C-labelled THIP have been investigated. Peak values of radioactivity in the organs and in serum were seen half an hour after administration, indicating a rapid absorption. Highest concentrations of radioactivity were found in the kidneys, but radioactivity was seen in all investigated tissues including the brain. The radioactivity was mainly excreted with urine (84–93%). Thin-layer chromatography of urine from volunteers, rats, and mice showed that most of the excreted radioactivity corresponds to unchanged THIP. Three metabolites were found in urine from rats each in amounts of 2–7% of the total dose given. Two of these metabolites were also found in urine from the volunteers in amounts of 30–35% and <2%, respectively, and in urine from mice in amounts of 21% and 6% of the total dose, respectively. No radioactivity corresponding to unchanged THIP was found in faeces indicating complete absorption of THIP following oral administration. One of the metabolites, the main one in man and mouse, seemed to be a glucuronic acid conjugate of THIP, but the chemical structure of the metabolites has not yet been established.     

Extended care in nursing homes: a program for a county teaching medical center

A continuity care program for patients in nursing homes using internal medicine residents in training has been developed in a county teaching hospital. Resident physicians on a paid basis assume primary care responsibility for 1000 patients in 29 private community nursing homes. A faculty internist coordinates the activities of the residents and monitors patient care through an extended care office in the county hospital. The program has produced a significant upgrading of the continuity and quality of care of patients in these nursing homes as well as providing medical residents with geriatric and nursing home experience. The increased sensitivity and concern for the needs of nursing home patients developed by the medical residents seems to continue after they complete their training.     

Combination chemotherapy with cyclophosphamide,vincristine, procarbazine,and prednisone (COPP) in children with brain tumors

Summary The chemotherapeutic combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) was used to treat 15 children with recurrent central nervous system tumors and seven children with newly diagnosed brainstem tumors. In patients with recurrent tumors, marginal activity was seen in various histologic types. COPP chemotherapy was clearly ineffective in patients with brainstem tumors. Toxicity consisted of mild to moderate myelosuppression and neurotoxicity.     

Continuous extracorporeal monitoring of animal blood using the glucose electrode.

A continuous extracorporeal monitoring system for blood glucose employing an electrochemical sensor is described. The sensor, about the size of a nickel, is rapid, is specific for glucose, generates its own power, and consists of two galvanic oxygen electrodes. Over one oxygen electrode is affixed a plastic matrix to which glucose oxidase is covalently bound; a blank matrix is over the other, which serves as a reference. Oxygen is consumed in the glucose-oxidase-containing matrix, decreasing the current from the underlying oxygen electrode. The current decrease is nonlinearly proportional to the glucose concentration. The sensor is clamped between small blocks of plastic fitted with inlet and outlet nipples so that blood pumped from the animal passes over the two electrodes and thence to an automated chemical analysis for comparison. Blood is collected and anticoagulant added in a double-lumen catheter. Blood is withdrawn at the rate of 1 cc. per hour. Results obtained by use of the system in rabbits are reported. The capacity of the system to continuously monitor changes in blood glucose produced by repeated glucose tolerances is shown in hypo-, normo-, and hyperglycemic animals. Some properties of the system and its calibration are discussed.     

Operative strategies in patients with symptomatic internal carotid artery occlusion

A 15-year experience with 98 patients who underwent extracranial artery reconstruction for symptomatic internal carotid artery occlusion is reviewed. Thromboendarterectomy of the occluded carotid artery resulted in unacceptably high mortality and morbidity rates, and long-term patency of the internal carotid artery was rarely achieved. Carotid endarterectomy on the side opposite the occlusion proved to be successful in relieving nonlateralizing symptoms of cerebral ischemia, whereas results were less encouraging in patients with focal symptoms in the hemisphere ipsilateral to the occlusion. External carotid artery reconstruction on the side of the occlusion was successful in relieving focal symptoms. Surgical treatment in patients with symptomatic internal carotid artery occlusion should be planned in each patient on the basis of symptoms and anatomic pattern.     

Specific antibodies directed against toxins of Ptychodiscus brevis (Florida's red tide dinoflagellate)

Specific antibodies directed against Ptychodiscus brevis 'brevetoxins' have been produced in a goat. The haptenic toxin T34 was chemically reduced to toxin T17, covalently-linked to succinic acid via anhydride coupling, and coupled to bovine serum albumin using standard carbodiimide condensation procedures. The hapten coupling efficiency ranged from 10.4 to 13.5 moles of toxin bound per mole of protein. Antibody titers were directly related to the frequency of immunization, and weekly intervals appeared optimum for maintaining adequate titers. [3H]Brevetoxin T17 is displaced in a competitive manner from the antibody-antigen complexes by unlabeled toxin, but the antibodies do not distinguish between T17 and T34. The sensitivity achieved, using purified brevetoxins as competitive inhibitors of [3H]T17 binding, was 600 picograms. The assay linearity ranged from 1.5 to 48 ng.