John R. Green

Pharmacokinetics of carbamazepine in normal man

The bioavailability of commercial carbamazepine tablets with and without meals was compared to a propylene glycol solution with respect to extent of absorption in 6 normal humans after a dose of 6 mg/kg. The presence of dose‐dependent kinetics within a clinically significant range was also investigated. Serum and urine samples were assayed by gas‐liquid chromatography (GLC). Carbamazepine is rapidly absorbed from the propylene glycol solution. Eight per cent of the dose was absorbed from the commercial tablet, resulting in therapeutic serum concentrations (3 to 6 mcg/ml). The data were consistent with dissolution rate‐limited absorption. Mean half‐lives ranged from 31 to 35 hr. No dose‐dependent kinetics were observed following administration of doses of 3, 6, or 9 mg/kg. The fraction of dose absorbed, the fraction excreted unchanged in urine, the time of maximum serum concentration, and absorption and elimination half‐lives appear to be independent of dose. The time course of side effects could not be correlated with serum carbamazepine levels, suggesting that metabolites contributed to side effects.

Regional Foot Pressure During Running, Cutting, Jumping, and Landing

Background Evaluating shoes during sport-related movements may provide a better assessment of plantar loads associated with repetitive injury and provide more specific data for comparing shoe cushioning characteristics. Hypothesis Accelerating, cutting, and jumping pressures will be higher than in straight running, differentiating regional shoe cushioning performance in sport-specific movements. Study Design Controlled laboratory study. Materials and Methods Peak pressures on seven anatomic regions of the foot were assessed in 10 male college athletes during running straight ahead, accelerating, cutting left, cutting right, jump take-off, and jump landing wearing Speed TD and Air Pro Turf Low shoes (Nike, Beaverton, Ore). Pedar insoles (Novel, Munich, Germany) were sampled at 99 Hz during the 6 movements. Results Cutting and jumping movements demonstrated more than double the pressure at the heel compared with running straight, regardless of shoe type. The Air Pro Turf showed overall lower pressure for all movement types (P < .0377). Cutting to the left, the Air Pro Turf shoe had lower heel pressures (36.6 ± 12.5 N/cm2) than the Speed TD (50.3 ± 11.2 N/cm2) (P < .0001), and the Air Pro Turf had lower great toe pressures than the Speed TD (44.8 ± 8.1 N/cm2 vs 54.4 ± 8.4 N/cm2; P = .0002). The Air Pro Turf also had significantly lower pressures than the Speed TD at the central forefoot during acceleration (38.2 ± 8.3 N/cm2 vs 50.8 ± 7.4 N/cm2; P <.0001). Conclusion Sport-related movements load the plantar surface of the foot more than running straight. Shoe cushioning characteristics were more robustly assessed during sport-related movements (4 significant results detected) compared with running straight (1 significant result detected). Clinical Relevance There is an interaction between shoe cushioning characteristics and sport-related movements that may influence plantar pressure and repetitive stress injuries.

Pattern‐Sensitive Epilepsy

The authors describe 4 cases of epilepsy triggered by the viewing of line patterns. Two of the patients were brothers.

Quantitative assay for carbamazepine serum levels by gas-liquid chromatography

Abstract A gas-liquid Chromatographic method for determining carbamazepine serum levels from 0.5 to 10.0 μg/ml is presented. Carbamazepine was chromatographed directly; its absorption and decomposition were minimized by masking and neutralization of the column solid support and by use of a solvent of low dielectric constant. Acidic anticonvulsants were separated from carbamazepine by solvent partition, reextracted, and chromatographed separately as their N -methyl derivatives.

Sulthiame: Evaluation as an Anticonvulsant

A double‐blind crossover study showed that sulthiame as sole anticonvulsant was preferable to diphenylhydantoin in only 4 of 21 patients, and other patients had more seizures or unbearable toxicity on sulthiame. When the concentration of diphenylhydantoin in serum was increased and other anticonvulsants withdrawn, seizures were better controlled and side effects often diminished. Although the few patients benefited by sulthiame alone felt more alert, neuropsychologic tests showed that organic communications and intellectual processing deficits were accentuated. Hyperpnea could be troublesome. Previous favorable reports on sulthiame may have been due to the increase it causes in serum diphenylhydantoin when the two drugs are given together.

Carbamazepine as an anticonvulsant A pilot study

In preparation for a major double-blind, crossover study comparing carbamazepine with diphenylhydantoin (DPH), a pilot study was carried out in 12 patients who had a minimum of four focal or major seizures per month. The dose equivalency between carbamazepine and DPH was found to be 3 to 1, and the study demonstrated an effective method for crossover from one agent to the other. It was determined that the half-life of carbamazepine is in the 12-hour range, so that twice-daily doses are effective. At high dosages, acute toxicity could be avoided by giving thrice-daily doses. In 7 of the 12 patients in the pilot study, carbamazepine was the preferable drug. It appears to be an effective independent anticonvulsant of the same order of magnitude as DPH.

Increased Risk of Posterior Glenoid Labrum Tears in Football Players

OBJECTIVE This study was designed to test our hypothesis that football players with shoulder pain, shoulder instability, or both requiring MR arthrography for evaluation are at an increased likelihood relative to non-football players for having a tear of the posterior glenoid labrum. CONCLUSION We conclude that posterior glenoid labrum tears are more prevalent in football players than in non-football players.

Biomechanical analysis of stresses to the fifth metatarsal bone during sports maneuvers: implications for fifth metatarsal fractures.

Abstract Fifth metatarsal stress fractures are an increasing problem in elite and recreational athletic populations. One possible mechanism of injury is the many bending moments applied to the fifth metatarsal during dynamic sports maneuvers involving rapid changes in direction and speed. A potentially important bending moment is loading of the base versus the head of the fifth metatarsal, which tends to cause a bending moment along the bone. To determine which maneuver applies the greatest pressure differential between the base and head of the fifth metatarsal, 10 college-aged male athletes performed running straight, jump take-off, jump landing, cutting right, cutting left, and accelerating while plantar pressures were recorded using a Pedar insole system (Novel Electronics, Inc., St. Paul, MN). Peak pressure at the fifth metatarsal base was subtracted from the peak pressure at the fifth metatarsal head to obtain the fifth metatarsal pressure differential—a corollary to the bending moment. The greatest fifth metatarsal pressure differential was observed during acceleration maneuvers (20 ± 13.1 N/cm2; P < 0.0001) followed by running straight (11.6 ± 8 N/cm2; P < 0.0008). The other maneuvers had low pressure differentials: jump take-off (4.2 ± 10.6 N/cm2), jump landing (3.7 ± 9.2 N/cm2), cutting left (2.3 ± 4.2 N/cm2), and cutting right (–2.1 ± 10 N/cm2). It appears that acceleration maneuvers may apply the largest bending moments to the fifth metatarsal and could lead to stress fractures. Because fifth metatarsal stress fractures are associated with rapid increases in training volume, reducing the number of acceleration events may be effective in altering the balance between bone resorption and bone formation and reducing stress fracture risk. Careful planning of training programs allowing for adequate rest between intense bouts of exercise involving many acceleration maneuvers may be the best preventative measure.

Electroencephalographic Investigations During Evaluation of the Antiepileptic Agent Sulthiame

In a double‐blind crossover trial of sulthiame, a carbonic anhydrase inhibitor, and diphenylhydantoin as sole medication for partial epileptic seizures, EEG changes were related to the drug administered. On sulthiame, the parieto‐occipital rhythms in awake patients were faster and the response to hyperventilation was less pronounced than when the patients were treated with diphenylhydantoin. Epileptiform activity tended to be more frequent on sulthiame and was consistent with change in frequency of seizures more often than not. Epileptiform activity was the less frequent as the serum concentration of diphenylhydantoin was higher.

CARBAMAZEPINE (TEGRETOL) AS AN ANTICONVULSANT A CONTROLLED DOUBLE‐BLIND COMPARISON WITH DIPHENYLHYDANTOIN (DILANTIN)

A large double blind crossover study of carbamazepine (CBZ) in comparison to diphenylhydantoin (DPH) is underway, and the results are presented for the first 20 patients to complete the protocol. The importance of preparatory steps is outlined – beginning with the gathering of preliminary kinetic data about half‐life and peak‐time in epileptic patients. A detailed pilot study was performed with open administration of the agents and hospitalization during the crossover. Detailed blood level monitoring and dose‐equivalence calculations lead to the design of blind crossover protocol from the pilot study.