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Biomedical subjects

R D Penn

Publications and source records attributed to R D Penn.

At least 73 records · Page 4Linked to original sources
PubMed1989

Distribution of a somatostatin analog after continuous intraventricular administration.

Decreased somatostatin in the brains of patients with Alzheimer's disease has led to an investigation of the efficacy of neurotransmitter replacement therapy. The distribution of a somatostatin analog, octreotide, was determined after 2 to 6 days of continuous intraventricular infusion at 40 micrograms/h in dogs. The tissue concentration was greater than 100 ng/g wet weight in all parts of the brain, which is greater than the normal concentration of native somatostatin. There was no reduction in native somatostatin production because of the infusion of the analog. The cerebrospinal fluid octreotide concentration was 1000 times greater than the plasma concentration. The results demonstrate that neurotransmitter replacement for somatostatin can be achieved by chronic intraventricular infusion of a metabolically stable analog.

Animals↗
PubMed1989

Physostigmine in the treatment of intrathecal baclofen overdose. Report of three cases.

The expanding use of intrathecal baclofen for spasticity has raised a concern about the treatment of overdose in these patients, since no specific baclofen antagonist is available. Since physostigmine has been reported to reverse the respiratory depression and somnolence due to opiates, the drug was tried for the treatment of baclofen overdose. In three cases, intravenous physostigmine (2 mg) completely reversed the respiratory depression and coma caused by boluses of 80 to 800 micrograms of lumbar intrathecal baclofen. Physostigmine, although not a specific antagonist, should provide increased safety for patients receiving intrathecal baclofen.

Adult↗
PubMed1989

Functional outcome after delivery of intrathecal baclofen.

Patients with multiple sclerosis or spinal cord injury often have severe, disabling spasticity. This is frequently treated with oral medications or with destructive neurosurgical procedures. We report on a group of patients with spasticity not relieved by these methods. These patients were subsequently treated with intrathecal baclofen delivered by an implanted programmable drug pump. Twenty-one patients have received this form of treatment, and the functional status of eight has been tracked by the Patient Evaluation Conference System (PECS) for at least six months. In most cases, spasticity, performance of bowel and bladder programs, and performance of ADL improved after delivery of intrathecal baclofen. The improvements appear to be due to the decrease in hypertonicity and the increased ease of movement (passive or active) in affected extremities. Intrathecal baclofen should be considered as a treatment method in patients with severe spasticity of spinal origin.

Activities of Daily Living↗
PubMed1988

An antibody in the CSF of Parkinson's disease patients disappears following adrenal medulla transplantation.

CSF from Parkinson's disease (PD) patients undergoing autologous transplantation of adrenal medulla tissue into their lateral ventricle was examined for the presence of IgG. CSF from 6 of 7 patients incubated with rat brain tissue reacted immunocytochemically to neuronal cell bodies in the substantia nigra and ventral tegmental region. This reactivity gradually disappeared in the months following transplantation. Five of 6 CSF samples from non-transplanted PD patients also produced this immunocytochemical reactivity whereas 26 non-PD samples were immunonegative. Possible implications to the transplant procedure are discussed.

Adrenal Medulla↗
PubMed1988

Intraventricular bethanechol infusion for Alzheimer's disease: results of double-blind and escalating-dose trials.

Ten patients with biopsy-proven Alzheimer's disease (AD) received low-dose (0.35 mg/d) intraventricular bethanechol, a muscarinic agonist, and saline placebo in a 24-week double-blind crossover design. Eight of these ten patients later participated in an open escalating-dose (to 1.75 mg/d) trial of bethanechol. Patients' drug responses were assessed by neuropsychological examination and informant measures of activities of daily living, mood disturbance, and abnormal behavior. Bethanechol appears to have a narrow therapeutic window for positive effects; low doses did not reliably alter patient functioning, moderately increased doses appeared to have a palliative effect on patient mood and behavior, and the highest dose was detrimental to patient functioning. Bethanechol does not appear to ameliorate the dementia of AD, but may exert a mildly positive effect on patient behavior and mood.

Aged↗
PubMed1988

The adrenal medullary transplant operation for Parkinson's disease: clinical observations in five patients.

The recent report by Madrazo and coworkers on the successful treatment of Parkinson's disease using adrenal medullary tissue transplanted to the caudate nucleus has aroused international interest in the procedure. The present article reports our initial experiences with the operation in five patients and discusses the postoperative effects of the procedure, the protocol used to monitor motor performance, and the need for cooperation with the two registries that have been created to follow morbidity, mortality, and efficacy. We intend to alert the neurosurgeon to important side effects, but not to assess the long term efficacy of the procedure. Postoperatively, a number of transient effects were seen in our patients, the most striking being somnolence, delusions, and lack of significant pain in spite of a large abdominal incision. The only complications have been respiratory. After the early postoperative period, gradual improvement of on-off times and Schwab-England disability scores was seen over 20 weeks. Long term cooperative studies are needed to demonstrate the efficacy of this procedure. neurosurgeons doing transplant operations are urged to join the registries so that uniform information can be collected.

Adrenal Medulla↗
PubMed1987

The effect of chronic subarachnoid bupivacaine infusion in dogs.

A functional and histologic examination of the effect of the continuous intrathecal administration of bupivacaine was made in five dogs. After a partial laminectomy at L5, a silicone rubber catheter was inserted into the subarachnoid space and advanced 10 cm cranially. A model 400 Infusaid pump, used for drug delivery, was placed in a subcutaneous pocket between the 13th rib and iliac crest. Drug infusions were individually adjusted and maintained at a concentration such that the animal just exhibited slight gait impairment. Daily bupivacaine doses ranged from 5.7-11.1 mg. Infusions were maintained for a period of 3-16 weeks. Light microscopic examination of spinal cord and roots revealed no abnormalities. A focal mononuclear cell infiltration of the leptomeninges was seen in two drug animals, as well as one catheter control animal. One of the 16-week animals had a residual limp upon drug removal. While we were not able to quantitatively assess the degree of sensory motor dissociation, the results of this study suggest that chronic intrathecal bupivacaine infusion through an implantable pump system may be a short-term alternative to intrathecal morphine in the control of cancer pain.

Anesthesia, Spinal↗
PubMed1987

Stereotactic administration of intratumoral chronic chemotherapy of recurrent malignant gliomas.

There is a continuous search for more efficient treatment of malignant cerebral gliomas. The work of Penn and Croin demonstrates clearly that survival of rats having experimental gliomas is significantly increased by intratumoral chemotherapy. It has been shown that chronic depth electrodes for the investigation of epileptic patients is a reliable and safe method. Using this proven technology originally developed by Talairach, Szikla and co-workers we have developed catheters for intratumoral chemotherapy. Three patients have been treated. It is premature to pretend that this is a treatment which will lengthen the patient's life. Nevertheless, the feasibility of the technique, its precision and safety are assured. Following this course of treatment, we have seen no deteriorations, no side effects, no bone marrow depressions, and no sign of toxicity. Chemical analysis has shown that cisplatin was delivered to the tumor.

Antineoplastic Agents↗
PubMed1987

Cortical biopsy results in Alzheimer's disease: correlation with cognitive deficits.

Neuropsychologic and pathologic data are presented for a group of 11 patients with a clinical diagnosis of probable Alzheimer's disease (AD) according to recently proposed criteria. In all cases, the diagnosis was verified by cortical biopsy. In addition, increased cortical plaque counts were associated with greater deficits in language production and comprehension and poorer performance on an index of global mental status. These results suggest that a clinical diagnosis of AD is very accurate when patient selection is restricted to typical cases and that language deficits may provide a useful indicator of severity of disease in AD patients.

Aged↗
PubMed1987

Direct delivery of medication into a brain tumor through multiple chronically implanted catheters.

A recurrent malignant glioma was treated with cisplatin delivered directly into the tumor. The drug was delivered via 68 small catheters distributed evenly throughout the tumor area. Each catheter was connected to an osmotic minipump that delivered 0.5 microliter of drug solution each hour for 10 days. There were no side effects from the catheter implantation, chemotherapy, or catheter removal. Although the chemotherapy halted progression of the tumor, it recurred, and the patient died 6 months after treatment.

Adult↗
PubMed1987

Long-term intrathecal baclofen infusion for treatment of spasticity.

Seven patients with spasticity of spinal cord origin have been maintained for up to 2 years with continuous spinal intrathecal infusion of baclofen. Prior to treatment, all of the patients had severe rigidity in their lower limbs and most had frequent and extensive spontaneous spasms, all of which greatly interfered with their activities of daily living. Oral antispasmodic medications were ineffective or caused central side effects. The patients underwent implantation of a programmable drug pump connected to a lumbar subarachnoid catheter. Within days of beginning continuous intrathecal baclofen infusion, the muscle tone was reduced to normal levels and spasms were eliminated. Over the ensuing months, muscle tone remained normal, but short-duration spasms could be induced by some activities. The greatest benefits to the patients were improvement in activities of daily living and better sleep due to reduced spasms. The baclofen doses were increased over the first few months but then were stabilized or only increased slightly, with the maximum dose being 650 micrograms/day. The most serious complications were two drug overdoses which took several days to clear up and were due to malfunctions of an earlier pump model. Baclofen clearance from the cerebrospinal fluid occurs with a half-life of 5 hours. The most serious concern in maintaining patients indefinitely on intrathecal baclofen is whether drug tolerance will eventually occur.

Adult↗
PubMed1987

Chronic intrathecal morphine for intractable pain.

Forty-three patients with intractable pain received intrathecal morphine delivered by implanted continuous-infusion (Infusaid) or programmable (Medtronic) devices. In 35 patients the pain was due to cancer, and eight patients had chronic nonmalignant pain. The origin of the nonmalignant pain included lumbar arachnoiditis, multiple sclerosis, severe osteoporosis resulting in a thoracic compression fracture, and intractable pain as a consequence of cancer therapy in individuals cured of their disease. Twenty-eight (80%) of the patients with cancer-related pain experienced excellent or good relief. Side effects were rare. Tolerance occurred infrequently and could be managed effectively. The results of this study support earlier studies on the application of chronic intrathecal morphine for intractable cancer pain. These findings also indicate that, in carefully selected patients, nonmalignant pain may be managed satisfactorily with this technique.

Arachnoiditis↗