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Biomedical subjects

J P Kapp

Publications and source records attributed to J P Kapp.

18 recordsLinked to original sources

Effect of intra-arterial cisplatin and 1,3-bis(2chloroethyl)-1-nitrosourea (BCNU) dosage on radiographic response and regional toxicity in malignant glioma patients: proposal of a new method of intra-arterial dosage calculation.

The frequency of both neurologic toxicity and therapeutic response due to intra-arterial (IA) chemotherapy is decreased by dose reduction. A method to individualize IA drug dosage is needed to provide each patient with the safest, most effective dose. Most trials of IA chemotherapy for malignant glioma have used body surface area (BSA) to calculate dosage; but brain size and arterial distribution do not correlate well with BSA. Fixed doses of cisplatin and BCNU were used in combination to perform 35 IA infusions in 20 malignant gliomas patients. Doses modified by the number of major intracranial vessels supplied by the infused artery were used in 34 infusions in 19 patients. Patients receiving 150 to 200 mg CP and 300 mg BCNU had an incidence of neurologic deficit of 5.6% if greater than or equal to 3 vessels were supplied by the infused artery compared to 42% for those with only 2 vessels. This crude dose modification maintained efficacy while reducing neurologic toxicity. Further refinement is possible using well established intra-arterial pharmacokinetic principles. Intra-arterial dosing based on volume flow at the site of infusion would yield a more reproducible exposure of the infused capillary bed to a drug than methods currently in use. More consistent drug exposure should reduce toxicity due to over dosing and treatment failure due to under dosing.

Adult

Cerebral resuscitation with succinate and fructose-1, 6-diphosphate.

To test the hypotheses that succinate or fructose-1, 6-diphosphate may have a beneficial effect in global cerebral ischemia, we induced complete global cerebral ischemia for 5 minutes in rabbits by occlusion of the ascending aorta and the superior and inferior vena cavae. Fifteen minutes after restoration of cerebral blood flow, animals received an intravenous bolus of either succinate or fructose-1,6-diphosphate followed by continuous infusion. Another group of animals received fructose-1, 6-diphosphate beginning prior to aortic occlusion. Control animals received intravenous glucose by bolus, followed by infusion. Cerebrospinal fluid lactate levels were measured before occlusion and at 2 1/2 hours after occlusion, when the animals were sacrificed. In all animals electrocortical silence was demonstrated for the 5 minutes of global ischemia. The percent change in cerebrospinal fluid lactate levels in all groups was statistically similar. Only two of seven of the control animals recovered electroencephalogram amplitude during the 2 1/2 hour observation period. Time for recovery of amplitude on the electroencephalogram in animals receiving fructose-1, 6-diphosphate either before or after ischemia was statistically similar to controls. In the succinate treated group, all seven animals regained preocclusion levels of electroencephalogram amplitude within 36 minutes of the restoration of cerebral blood flow. Succinate administered after complete global cerebral ischemia resulted in significantly increased recovery of cerebral electrical activity (Fischer's exact test, p less than 0.05).

Animals

Preservation of brain tumor specimens for drug sensitivity testing.

To examine the feasibility of shipment of brain tumor specimens to a central laboratory for drug sensitivity testing, an experimental gliosarcoma (9L) was grown subcutaneously in rats, harvested, stored, and disaggregated. Growth of the disaggregated tumor cells in monolayer culture was evaluated after storage for various times at 2 to 6 degrees C and 37 degrees C in saline and minimum essential medium. Growth potential was maintained for 24 hours when tumor specimens were stored under refrigerated conditions and was best maintained when specimens were stored in saline. Specimens stored at 37 degrees C grew best when stored in minimum essential medium, but growth potential was lost after 12 hours unless the specimens were refrigerated. Shipment of tumor specimens to a central laboratory for drug sensitivity testing appears to be feasible, since under most circumstances, specimens should reach the laboratory for processing within 24 hours of their removal. Storage and transport of specimens in saline on wet ice appears to be optimal.

Antineoplastic Agents

Isovolemic hemodilution in stroke. A study in gerbils.

Isovolemic hemodilution has been reported to increase cerebral perfusion in humans and has been advocated as a treatment for acute cerebral infarction. This study examines the effect of isovolemic hemodilution with low-molecular-weight dextran on mortality and the incidence of neurological deficit in gerbils after internal carotid ligation. Sixty-four Mongolian gerbils were anesthetized with pentobarbital and the left internal carotid artery was ligated in both control and experimental animals. In the experimental group, blood was removed and an equal volume of dextran was injected to reestablish normal blood volume and lower hematocrit to a mean of 30.5. Control animals were not so treated. Animals were observed for neurological deficits for 24 hours after carotid ligation. The incidence of neurological deficit in control animals was 67%; it was 64% in the experimental group. Mortality within the first 24 hours was 28% in the controls and 75% in animals that were treated by hemodilution (p less than 0.001). Isovolemic hemodilution with dextran did not reduce the incidence of neurological deficit after carotid ligation in gerbils and was associated with a significant increase in mortality during the first 24 hours.

Animals

Primary intracranial plasma-cell granuloma. Case report.

The authors report the fourth case of primary intracranial plasma-cell granuloma. The patient was a 16-year-old girl who presented with loss of vision as the major clinical feature. The tumor resembled a meningioma both preoperatively and grossly at surgery. Because the tumor did not respond to steroid treatment following subtotal surgical excision, radiation therapy was administered to the affected area. Major considerations in the differential diagnosis of this neoplasm are discussed.

Adolescent

Supraophthalmic carotid infusion for recurrent glioma: rationale, technique, and preliminary results for cisplatin and BCNU.

The chemotherapeutic agents 1-3 bis(2-chloroethyl)-1-nitrosourea (BCNU) and cis-diamminedichloroplatinum II (cisplatin) have both shown activity against malignant glioma, especially when given by arterial infusion. The combination of these agents given by this method is logical because their individual major toxicities are directed at different organ systems, and because of their differences in restriction by the blood-brain barrier. Both agents are toxic to the eye, and infusion of both agents simultaneously into the internal carotid artery would deliver doses of the drug to the eye which should be associated with an unacceptable level of ocular toxicity. We have developed a technique utilizing a flexible flow-directed catheter with a tip which is manipulated by hydraulic forces for delivery of the drug into the intracranial carotid artery above the origin of the ophthalmic artery, thus sparing the eye from the high concentration of drug during the first pass through the arterial circulation. In 13 patients with recurrent malignant glioma treated by arterial infusion of both agents (cisplatin 150-200 mg, BCNU 300 mg fixed dose), we have had no damage to the ipsilateral eye. Preliminary results of treatment appear to be good, with definite tumor regression following arterial infusion in 10 of 12 radiographically evaluable cases. Median survival to date is 11 months with 3 patients still surviving. The longest survival is 24 months. The supraophthalmic infusion technique protects the eye and the combination of drugs given by arterial infusion produces a high tumor response rate.

Adult

Herpes simplex virus type 1 and neuronal cells--a special cell-virus interaction.

Rat brain glioma cells were semipermissive for herpes simplex virus (HSV) replication, because the growth of HSV was multiplicity-dependent in these cells. By using this property, we successfully isolated 'survivor' glioma cells following HSV infection at low multiplicity and without using any special treatment (such as UV irradiation) either of the cells or of the virus. Under the same conditions there were no survivor BHK or 3T3 cells, which suggests the uniqueness of the glioma cell-HSV interaction. The survivor cells ceased to produce infectious virus after two subcultures, but were highly resistant to superinfection for at least 20 subcultures. Parental cells were significantly more permissive for homologous virus growth than survivor cells. Interferon was apparently not induced in the survivor cells, because they were as susceptible as the parental cells to infection with vesicular stomatitis virus. The survivor cells produced HSV-specific antigens and contained HSV-specific DNA.

Animals

Erythrocyte sedimentation rate following uncomplicated lumbar disc operations.

To determine the normal response of the erythrocyte sedimentation rate following uncomplicated lumbar disc operation, 16 patients were studied with serial erythrocyte sedimentation rates during the first six postoperative weeks. The erythrocyte sedimentation rate should be no higher than 25 mm/hr after the first week following an uncomplicated lumbar disc operation in a patient with a normal preoperative erythrocyte sedimentation rate. In patients with elevated preoperative erythrocyte sedimentation rates, further postoperative elevation may be noted. This value may be incorrectly interpreted unless a preoperative erythrocyte sedimentation rate has been determined for baseline purposes.

Blood Sedimentation

Hyperbaric oxygen as an adjunct to acute revascularization of the brain.

Two recent cases suggest that hyperbaric oxygen may be an important adjunct to the surgical treatment of occlusion of major cerebral arteries within the first few hours after onset of neurological deficit. In both patients, one with an embolus to the right middle cerebral artery and one with a surgical occlusion of the left internal carotid artery, circulation to the ischemic area was restored more than eight hours after occlusion. In the patient with the middle cerebral artery embolus, hemiplegia cleared after a six-minute exposure to hyperbaric oxygen. The patient with occlusion of the internal carotid artery was revascularized by anastomosis of a superficial temporal artery less than 1 mm in diameter to a branch of the middle cerebral artery. Her hemiplegia and aphasia cleared rapidly and concomitantly with intermittent exposure to hyperbaric oxygen during the first nine postoperative days. Postoperative angiograms demonstrated patency in both cases. The implications of these observations are discussed.

Cerebral Angiography

Operative techniques for management of lesions involving the dural venous sinuses.

The basic principles of vascular surgery, adequate exposure, proximal and distal control of hemorrhage, and meticulous approximation of endothelial surfaces should be adhered to in the management of lesions of the dural venous sinuses. Modification of conventional vascular techniques must be made since the major dural venous sinuses are essentially non collapsible and non mobilizable because of the entry of cortical veins at frequent intervals along their course. These problems can be solved by occlusion of the proximal and distal segments of the sinus from within the lumen and by use of a shunt consisting of a siliconized non-collapsible tube with an inflatable balloon cuff at each end. Saphenous vein autografts are used if primary repair is impossible because of loss of tissue. Using these techniques, a patency rate of 91% and a mortality rate of 9% were achieved in eleven cases involving the posterior sagittal and transverse sinuses.

Brain Injuries

Spasmogenic qualities of prostaglandin F2alpha in the cat.

Available data indicate that the concentration of prostaglandin F2alpha required to produce arterial spasm in an experimental model is approximately a thousand-fold higher than the concentration that occurs under physiological conditions. The spasmogenic platelet factor which has been previously described is shown to be a substance other than prostaglandin F2alpha because of differences in susceptibility of the two substances to enzymatic digestion.

Animals