Venous Irritation Related to Intravenous Administration of Phenytoin versus Fosphenytoin

Study Objective . To compare the frequency, severity, and time course of venous irritation after administration of a single intravenous dose of phenytoin with an equimolar dose of fosphenytoin, a water-soluble phenytoin prodrug. Design . Randomized, double-blind, two-period, crossover study. Setting . University hospital clinical research unit. Patients . Twelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medical history, or laboratory assessment. Interventions . Volunteers randomly received a 30-minute infusion of phenytoin sodium 250 mg (250 mg/5 ml) or an equimolar dose of fosphenytoin 375 mg (375 mg/5 ml). Subjects returned for the crossover treatment 14–21 days later. Measurements and Main Results . Subjects assessed venous irritation (pain, burning, itching), and investigators evaluated phlebitis (erythema, swelling, tenderness), induration, exudation, and cording. Phenytoin was associated with a significantly higher degree of pain at the infusion site in all subjects and a significant degree of phlebitis in eight subjects (p<0.05); cording occurred in six subjects. The time course of phenytoin-induced phlebitis was bimodal. Erythema and tenderness were prominent at the end of the infusion and again at 24 hours. Cording was first noted between 24 hours and 1 week after infusion. In contrast, fosphenytoin was associated with mild pain in two subjects, one incident of phlebitis, and no erythema or cording. Conclusions . Fosphenytoin administration resulted in significantly less venous irritation and phlebitis compared with an equimolar dose of phenytoin. The clinical use of this water-soluble phenytoin prodrug should minimize the frequency and severity of infusion-site reactions and should allow convenient, rapid, intravenous administration of drug, undiluted or admixed with intravenous solutions.     

The effect of cigarette smoke on the bovine lens

Smoking has recently been identified from epidemiological studies as a possible cause of cataract but the mechanism involved is not known. Therefore, our laboratory has initiated studies aimed at elucidating these mechanisms. Whole bovine lenses were cultured to examine possible effects of cigarette smoke on amino acid uptake and protein synthesis. Cigarette smoke, filtered to remove nicotine and tar which would not reach the eye in vivo, was bubbled through culture medium. Bovine lenses were incubated in this medium in the presence of [¹⁴C]-leucine for four days. A significant decrease in uptake of [¹⁴C]-leucine and a decrease in protein synthesis were found with smoke treated lenses. This is the first demonstration of an effect of cigarette smoke on the lens. Further work is needed to determine how this metabolic upset is mediated and how it could lead to cataract.     

Ischemic monomelic neuropathy: An under-recognized complication of hemodialysis access

During the past 3 years six episodes of ischemic monomelic neuropathy (IMN) have been identified in five patients as a complication of upper extremity dialysis grafts. All patients had long-standing insulin-dependent diabetes, peripheral neuropathy, and brachial artery graft origins, whereas 60% had peripheral vascular disease. Five episodes occurred immediately after graft placement, whereas one was due to a graft-related thromboembolus. Diagnostic delay was common with initial findings attributed to anesthesia, positioning, or surgical trauma. Electrophysiologic studies showed underlying diabetic neuropathy with severe multifocal neuropathy distal to the grafts. Digital pressure indices were reduced but there was no critical ischemia. In three cases ischemia was completely corrected with improvement in one. One patient had proximal balloon angioplasty with no improvement and of the two untreated patients, one improved slightly. Ischemic monomelic neuropathy is a rare but disabling complication of dialysis access in diabetic uremic patients. Its occurrence is unpredictable and diagnostic delay is common. Correction of ischemia is indicated but usually does not improve the neuropathy. Prevention requires further research to more accurately characterize the patients at risk.Presented at the Twelfth Annual Meeting of the Southern California Vascular Surgical Society, Coronado, Calif., September 17–19, 1993.     

Na+ currents near and away from endplates on human fast and slow twitch muscle fibers

Fast and slow twitch muscle fibers have distinct contractile properties. Here we determined that membrane excitability also varies with fiber type. Na⁺ currents (I_NA) were studied with the loose-patch voltage clamp technique on 29 histochemically classified human intercostal skeletal muscle fibers at the endplate border and <200 μm from the endplate (extrajunctional). Fast and slow twitch fibers showed slow inactivation of endplate border and extrajunctional I_NA and had increased I_NA at the endplate border compared to extrajunctional membrane. The voltage dependencies of I_NA were similar on the endplate border and extrajunctional membrane, which suggests thatboth regions have physiclogically similar channels. Fast twitch fibers had larger I_NA on the endplate border and extrajunctional membrane and manifest fast and slow inactivation of I_NA at more negative potentials than slow twitch fibers. For normal muscle, the differences between I_NA on fast and slow twitch fibers might: (1) enable fast twitch fibers to operate at high firing frequencies for brief periods; and (2) enable slow twitch fibers to operate at low firing frequencies for prolonged times. Disorders of skeletal membrane excitability, such as the periodic paralyses and myotonias, may impact fast and slow twitch fibers differently due to the distinctive Na⁺ channel properties of each fiber type. © 1993 John Wiley & Sons, Inc.     

The natural history of uveitis

Summary Inflammatory diseases of the eye were known to the ancients, but only recently have the underlying mechanisms to this problem become better defined. During the middle portion of this century, most cases of uveitis thought to be caused by infectious agents, such as those responsible for syphilis and tuberculosis. Since then, it has become clear that endogenous mechanisms of immunomodulation play an important role in these disorders, which along with environmental and genetic factors make up an important triad. Animals studies have indicated the pivotal role of the T-cell in many of these disorders. The development of T-cell lines has helped to further delineate cell to cell interactions that occur during an ocular inflammatory event. The presence in the eye of uveitogenic antigens raises the strong possibility of autoimmune driven processes as well, similar to what is seen in the animal models. The better understanding of ocular inflammatory mechanisms has led to improved therapeutic strategies, including Sandimmune, and more recently Cyclosporine G, a related compound that may be less nephrotoxic. Newer therapeutic strategies will focus on even more novel modes of immunomodulation, probably without the use of medications.     

Coping and family functions after closed head injury

Cognitive deficits associated with closed head injury (CHI) have been well studied. Less attention has been directed to the emotional consequences of CHI and subsequent attempts to cope with major life events. CHI typically constitutes a catastrophic injury, yet few studies have examined coping strategies used by individuals after CHI or the effects of CHI on family functioning that may mediate coping. Previous workers have speculated that time since injury is a crucial determinant of coping; however, this has not been investigated with regard to CHI. In this preliminary investigation, 40 patients with CHI were compared with 17 neurologically intact controls. The CHI group was divided into two groups according to time since injury. It was found that patients with CHI used information seeking as their most dominant coping strategy regardless of their time since injury. Patients with CHI had higher family cohesion scores than control subjects. Implications of these findings for psychological response to CHI are discussed.     

Sonographic characteristics of epidermoidcyst of testicle

The ultrasonographic characteristics of an epidermoid cyst of the testicle are presented. Since these, findings are similar to other published case reports, preoperative sonographic diagnosis of this lagon may be possible.