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Biomedical subjects

R W Rand

Publications and source records attributed to R W Rand.

At least 37 records · Page 2Linked to original sources

Ischemic brain rescue by transvenous perfusion in baboons with venous sinus occlusion.

We studied brain retroperfusion in nine adult baboons. Experiments in four baboons determined techniques and the safety of retroperfusion, and experiments in three baboons determined the ability of retroperfusion to reverse cerebral ischemia. Two baboons died before retroperfusion. Arterial blood was continuously circulated by an external pumping system from one femoral artery into the intracranial sinuses through specially designed balloon-tipped catheters placed percutaneously into the sigmoid sinuses bilaterally. The balloons intermittently occluded the sinuses. Ischemia was produced by occluding the left middle cerebral artery. Standard and computed electroencephalography with topographic mapping monitored the onset and reversal of ischemia. Retroperfusion rate exceeded 50 ml/min with a mean intrasinus pressure increase of 27 (0-149) mm Hg in all seven experiments. Venograms demonstrated complete or partial filling of the superior sagittal sinus in each experiment. Four experiments without ischemia established maximal balloon occlusion cycles, retroperfusion rates, and sinus pressure changes. These four baboons were neurologically normal after retroperfusion; two had normal magnetic resonance imaging scans. Ischemic changes, detected by electroencephalography following middle cerebral artery occlusion, were reversed with retroperfusion in all three ischemia experiments. Autopsies in the seven baboons demonstrated no parenchymal hemorrhage or edema. Our results suggest that further investigation of retroperfusion, and possibly retroinfusion of agents for cerebral protection, is warranted.

Animals↗

Leksell stereotactic radiosurgery in the treatment of eye melanoma.

Current experiments indicate that a focussed single radiation treatment with a dose of 6000 to 9000 rads delivered to the 90% zone through a collimator of the Leksell stereotactic radiosurgical unit or 'gamma knife' to the rabbit eye melanoma model is capable of destroying the cancer totally and thus effecting a cure. The beneficial effect in these rabbit eye melanoma experiments appears to be similar to the results obtained by physicians using the Harvard and Berkeley cyclotrons in treating malignant neoplasms in the human eye. Therefore, it is proposed that a properly designed stereotactic radiosurgical unit can be used in patients with eye tumours similar to those selected for the cyclotron systems.

Animals↗

Cryolumpectomy for carcinoma of the breast.

Cryosurgery and surgical en bloc excision in preventing the local recurrence of mammary adenocarcinoma were studied in BALB/cfC3H (supplied by the Cancer Research Institute, University of California Berkeley) syngeneic mice carrying virus induced mammary adenocarcinomas transplanted into the fourth mammary fat pad. Cryosurgical procedures involving multiple freeze-thaw cycles to minus 180 degrees C. followed by tumor excision substantially reduced the local recurrence rate of carcinoma of the mammary gland in the mouse. The use of cryolumpectomy in the treatment of early carcinoma of the breast in humans is presented herein.

Adenocarcinoma↗

Preliminary clinical trial of immunotherapy for malignant glioma.

An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

Adult↗

Effect of localized magnetic-induction hyperthermia on the brain. Temperature versus intracranial pressure.

Normal brain and brain tumor temperatures were studied for their effects on intracranial pressure (ICP) in 13 patients who received 37 localized thermochemotherapy treatments for recurrent primary or metastatic brain tumors. Two transient neurologic complications occurred in patients with an elevated initial ICP value; thus, the authors concluded that an initial ICP value of 30 cm H2O or greater may contraindicate brain hyperthermia. It appears that noninvasive brain hyperthermia by magnetic-loop induction can cause an initial rise in ICP value, although a protective mechanism(s) that tends to lower ICP occurs over time, and also at a normal brain temperature of approximately 42.0 degrees C. Possible mechanisms of ICP reduction include direct heating of the hypothalamus with a reduction in pCO2 and the development of tachypnea and hyperpnea with a reduction in pCO2. Hyperthermia applied to the brain should be undertaken only with adequate monitoring of ICP; in addition, extreme caution should be taken in patients with an elevated initial ICP value and in those patients in whom adaptation to elevated pressure does not occur.

Adult↗

Phase I trial of thermochemotherapy for brain malignancy.

High-grade primary and refractory brain tumors and metastases to the brain from other primary sites are associated with a grave prognosis. Treatment, usually palliative, consists of some combination of surgery, radiation, and chemotherapy. Recently, noninvasive hyperthermia by magnetic-loop induction has been safely used to treat patients with advanced cancer in extracranial sites. Both disease regression and disease stabilization have been observed. This technique was recently applied to brain tumors in an animal model, and its safety was again demonstrated. As a result, a Phase I trial of noninvasive localized hyperthermia in combination with intravenous chemotherapy has been carried out in ten patients whose primary or metastatic brain tumors failed to respond to standard therapy. Ten patients underwent 23 thermochemotherapy sessions using the magnetic-loop induction device. The median, maximum temperature of normal brain after 1 hour of hyperthermia was 41.1 degrees C (range, 38.6 degrees C-43.4 degrees C); the median, maximum temperature of brain tumor was 42.5 degrees C (range, 38.8 degrees C-46.3 degrees C) (P less than 0.01). The temperatures of both the normal brain and brain tumor were obtained during 18 treatments. The tumor temperature was greater than the normal brain temperature in 15 of 18 treatments. In 78% of the treatments, the measured tumor temperature reached at least 42 degrees C, whereas the normal brain reached 42 degrees C in only 13% of the treatments. These data demonstrate the "selective inability" of brain tumor tissue to dissipate heat. Vital signs, intracranial pressure, and neurologic status were monitored throughout the hyperthermia treatments. No mortality or increase in chemotherapeutic toxicity could be attributed to the thermochemotherapy. In addition, there were no local complications or permanent neurologic complications. Two patients with elevated intracranial pressure before therapy had transient neurologic deficits that may have been exacerbated by the hyperthermia. It is concluded that this new, noninvasive modality not only produced effective intracranial tumor heating, but could be performed safely with the proper precautions. Phase II trials are warranted.

Adult↗

Cryolumpectomy for breast cancer: an experimental study.

The effects of cryosurgical procedures and surgical excision in preventing the local recurrence of mammary adenocarcinoma were studied in BALB/cfC3H mice carrying syngeneic, virus-induced mammary adenocarcinomas transplanted into the fourth mammary fat pad. In this report we present evidence demonstrating that cryosurgical procedures involving multiple freeze-thaw cycles followed by tumor excision markedly reduce the local recurrence rate of mouse mammary cancer. Surgical resection without cryotreatment resulted in an 80% local recurrence rate; in contrast, cryotreatment consisting of three freeze-thaw cycles before excision prevented local tumor recurrence in 70% of the animals. The use of cryotherapy and local excision (cryolumpectomy) in the treatment of human breast cancer is discussed.

Adenocarcinoma↗

Combination radiofrequency hyperthermia and chemotherapy (BCNU) for brain malignancy. Animal experience and two case reports.

Patients with high-grade primary and metastatic brain malignancies have a median survival time of 3-8 months, regardless of therapy. Because MagnetrodeTM hyperthermia provides safe, deep internal heating without normal-tissue injury, we studied its effects first on the brain and surrounding tissues of rabbits. The normal rabbit brain (n = 26) could be heated to potentially tumoricidal temperatures (42-43 degrees C) without apparent histopathologic or clinical damage to the brain, skull, external eye, subcutaneous tissue or skin. Intracranial pressure did not rise significantly. Using transplanted VX-2 carcinoma, we showed both the safety and potential efficacy of thermochemotherapy (IV BCNU: 14 mg/kg) in the presence of a solid brain tumor. The average maximum brain temperature achieved was 43.06 degrees C. Mean survival from the time of tumor implantation in the treated group (n = 16) was 18.56 days, compared to 9.3 days for untreated controls (n = 30) (p less than .0001). Two patients have been treated with localized brain hyperthermia combined with intravenous BCNU (80 mg/m2) for a total of eight treatments. Maximum normal brain temperature achieved was 40.0 degrees C in Patient #1 and 41.5 degrees C in Patient #2. A tumor temperature of 42.9 degrees C was achieved in Patient #2. Intracranial pressure remained within the upper limits of normal. Swan-Ganz monitoring in Patient #1 revealed a stable cardiac index and mean pulmonary artery pressure with mild fluctuations in the CVP, PAD, and PCW. No increase in chemotherapy toxicity was observed and no normal tissue injury occurred in either patient. We conclude that non-invasive localized radiofrequency hyperthermia to the brain is feasible and can be performed safely in the presence of a solid brain tumor.

Animals↗

Thermo-magnetic surgery for experimental renal cancer.

Thermo-magnetic surgery is an innovative modality in the treatment of malignancies. This unique combination can produce selectively controlled destruction of deep tumors. Heating of the magnetic metallic compounds of ferrosilicone by hysteresis produces temperatures which are incompatible with cancer cell survival. The intense focal heating causes a coagulation necrosis. Damage to surrounding normal tissue can be avoided by careful temperature monitoring and power control of the magnetic field. Cell destruction in the target tissue has been demonstrated by light and electron microscopy. Reproducible and predictable VX2 renal carcinomas in rabbits have been produced and used as the tumor model in the initial experiments of this research project. A clinical trial with selected cancer patients, performed with this technique of thermo-magnetic surgery, is now a reasonable and feasible procedure.

Animals↗

Thermomagnetic surgery for renal cancer.

Thermomagnetic surgery is a technique that uses hysteresis heating of ferromagnetic materials to produce focally controlled temperatures within solid organs or tumors to cause coagulation necrosis. The degree of heating of a neoplasm is controlled by manipulating the power of the electromagnetic coil system through temperature monitoring. This effectively limits the region of destruction to the disease process and thereby avoids damage to surrounding structures. If the ferromagnetic material is delivered by an arterial route to the tumor or organ additional beneficial effect of ischemic necrosis of tissue may be achieved. This new technique is applicable to selected cases of human cancer. Exposure in the electromagnetic fields or use of the ferromagnetic material in experimental animals has produced no ill effects.

Animals↗

The Gardner neurovascular decompression operation for trigeminal neuralgia.

W. James Gardner developed a unique operation to treat selected cases of trigeminal neuralgia. In 1959 Gardner described the vascular decompression operation of the trigeminal nerve, an operation which has been further refined and popularized by Jannetta and has often been misnamed as the Jannetta operation. Gardner should be given credit for conceiving and developing this neurovascular decompression operation. The value of this operation is illustrated by two cases.

Adult↗

Gardner neurovascular decompression of the trigeminal and facial nerves for tic douloureux and hemifacial spasm.

Neurovascular decompression of the trigeminal and facial nerves for tic douloureux and hemifacial spasm has been performed for the past two decades, starting with W. James Gardner in 1959. Although other neurosurgeons have refined and further perfected the operation, reporting large series of successful results, the credit for the concept and original procedures, including use of the surgical microscope, has generally escaped the attention of present-day neurological surgeons. This paper attempts to correct this inequity.

Facial Muscles↗