The third-year clerkship at one college of medicine was modified to reflect an emphasis on adult learning principles and life-long learning habits. Problem-based learning was selected as the educational method, and the development of a cognitive knowledge base, clinical problem-solving skills, and appropriate clinical skills was stressed. At a yearly faculty education retreat, strengths and weaknesses of the clerkship were discussed. As a result of this meeting, several changes were made in the clerkship, including additional stress on students' usage of the medical library and computerized databases, a tutor development program, the addition of expert resource sessions, and more emphasis on students' development of clinical skills through a preceptor program. A comprehensive evaluation program designed to support the educational goals of the clerkship is in place. The major challenge of the program remains the proper synchronization of curricular, clinical, and student self-study activities essential for an ideal learning experience.
During the 1970s and early 1980s the morbidity and mortality rate from severe head injury significantly decreased. There still are patients who succumb to this severe injury or survive with poor recovery. Currently, about 30% survive with poor recovery, and this rate of poor outcome has not significantly changed during the past decade (1). In an effort to improve the outcome further, investigators have started to study intensively the type of damage inflicted by secondary factors that lead to secondary injury, and those caused by systemic effects of brain injury. Factors that block these negative effects are being developed and studied in an attempt to improve patient outcome. It is our hypothesis that cytokines play an important role in the metabolic response to head injury and that medical intervention that modulates the cytokine response may improve the adverse metabolic effects of head injury. The present chapter focuses on the role of cytokines in the metabolic response to head injury. Specifically, we will present evidence for increased cytokine levels and biologic effects following clinical and experimental brain injury. We will show that cytokine infusion mimics the systemic response to brain injury, and we will discuss potential roles of cytokine modulation following brain injury.
Study Objective . To test the hypothesis that changes in α 1 ‐acid glycoprotein (AAG) concentration alter central nervous system (CNS) drug distribution after subarachnoid hemorrhage. Design . Two‐phase, prospective study. Setting . University‐associated medical center. Patients . Twenty‐one patients with subarachnoid hemorrhage. Intervention . In phase I, serum AAG concentrations of patients with subarachnoid hemorrhage were measured serially and compared with those in 21 controls undergoing elective neurosurgical procedures. In phase II, nimodipine was the pharmacologic probe to determine the relationship between drug distribution into the CNS and changes in AAG concentration. Measurements and Main Results . Serum and cerebrospinal fluid (CSF) samples were collected from patients with subarachnoid hemorrhage treated with nimodipine and used to measure total and unbound drug concentrations. Concentrations of AAG were 39% higher in patients than in controls preoperatively. They decreased significantly by 24 hours after surgery in patients and increased in controls. In both groups the concentrations were higher than reported normal values. During the period of reduced AAG concentration, calculated unbound nimodipine concentrations were 3‐fold higher (p<0.05) than at later periods, with a trend toward higher total concentrations. Overall, mean CSF nimodipine concentration was 6.4% of mean serum total concentration. The CSF concentrations decreased as AAG concentrations increased, independent of serum concentrations (r = −0.52, p<0.02). Conclusion . Concentrations of AAG change after subarachnoid hemorrhage and are transiently influenced by surgery. Unbound drug concentration increases when AAG concentrations decrease, whereas CSF concentrations decrease when AAG concentrations increase. These preliminary findings suggest that changes in AAG concentrations can alter unbound serum nimodipine concentrations and may affect CSF drug distribution.
Phenytoin serum levels were compared in a crossover study of a new 300 mg capsule form and three 100 mg capsules administered once daily. The new 300 mg capsule was equivalent to three 100 mg capsules in efficacy of seizure control and maintenance of phenytoin serum levels. This standard 300 mg dose produced a grand mean drug serum level of 7.63 mcg/ml and was below 10 mcg/ml in 15 to 20 patients. The authors recommend monitoring of phenytoin serum levels and clinical response, to detect needed dosage adjustments for optimum therapeutic benefit from phenytoin and to avoid toxic side effects.
Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population.Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months).Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score.Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.
Head injury is characterized by both the direct injury to the brain and the overall systemic response to the brain injury. The systemic response usually includes an increase in energy expenditure, which can be quantitated by using indirect calorimetry, increased urinary nitrogen excretion, hyperglycemia, hypoalbuminemia, and elevated liver function tests. The mechanism for this hypermetabolism is probably multifactorial and includes the release of mediators in response to the injury (eg, catecholamines, cytokines), steroid therapy, nutrient administration and intercurrent complications, eg, infection. The nutritional management of the patient remains controversial. The issues that have been and that continue to be investigated are the amount and type of nutrients that will optimally allow for nerve regeneration and the optimal route of nutrient administration—enteral versus parenteral. This article reviews the proposed mechanisms for the metabolic response to head injury and the experience with nutritional support in this patient population.
Energy production, substrate oxidation, serum protein levels, and weight change were studied in 16 non-steroid treated patients with severe head injury. Patients were evaluated during an average of 31.3 days from hospital admission to discharge. The mean measured energy expenditure (MEE) was 1.40 ± 0.5 times predicted energy expenditure. Caloric balance [calories received = calories expended[ was achieved by the 2nd week. Despite caloric balance and the administration of at least 1.5 g of protein per kg of body weight per day, the mean nitrogen balance was negative. There was a positive nitrogen balance in only 2 patients. These patients received a mean of 1.43 times the MEE in total kilocalories and 2.3 g of protein per kg of body weight. Fat and protein oxidation exceeded protein and fat administration for 3 weeks postinjury. Albumin levels dropped from a mean of 3.09 ± 0.2 on admission to 1.98 ± 0.4 within 2 weeks. The initial retinol binding protein levels were within the normal range, and the levels increased over time. There was marked weight loss (mean, 15.6 ± 5.9 lb). Head injury induces a profound traumatic response identified by increased energy expenditure, a negative nitrogen balance, weight loss, hypoalbuminemia, and altered substrate oxidation. This response seems to be caused by the head injury alone and is not due to the administration of corticosteroids. (Neurosurgery 17:784-791, 1985)
