Unusual absorption profile of phenytoin in a massive overdose case

The pharmacokinetics of phenytoin was evaluated in a nonepileptic adult man after the ingestion of an undetermined amount of the drug following an apparent suicide attempt. A serum phenytoin concentration of 45 micrograms/mL was observed on admission 12 hours after ingestion. Phenytoin concentrations steadily increased, reached a maximum of 114 micrograms/mL four days later, then fluctuated at about 100 micrograms/mL for a week, and slowly declined to undetectable levels within the following week. At 96.5 micrograms/mL, the unbound serum concentration was 2.5 times that observed in therapeutic drug concentrations. Computer fitting of the data indicated that the Michaelis-Menten constants, apparent volume of distribution, and renal clearance of phenytoin were consistent with those parameters reported after therapeutic doses. However, phenytoin absorption was best described by parallel first- and zero-order rate processes, with the latter proceeding for as long as two weeks following drug ingestion. This protracted absorption appears to be a result of the presence of a large concretion of phenytoin in the gastrointestinal tract, having a slow disintegration and dissolution attributable to the limited solubility of the drug in the gastrointestinal tract and to the patient's diminished intestinal motility.     

Proteinuria on dipstick urine analysis after sexual intercourse

OBJECTIVE: To examine the role of sexual intercourse as a cause of proteinuria, and establishes its duration, as a knowledge of benign causes of proteinuria is required to avoid unnecessary testing. SUBJECTS AND METHODS: Twenty-four married couples were instructed to produce a urine sample before and after sexual intercourse; their urine was tested for proteinuria by dipstick analysis. RESULTS: Samples were assayed from 22 men and 11 women. Whereas none of the 24 men originally assessed for the study had proteinuria before sexual intercourse, six of the 22 who were eventually enrolled had proteinuria after intercourse (27.3%, 95% confidence interval, 10-50%; P = 0.008). None of the women had proteinuria after sexual intercourse (95% confidence interval, 70-100%). The time to disappearance of proteinuria was <12 h. CONCLUSION: Sexual intercourse is confirmed as a benign cause of proteinuria in men. Whenever possible, it is wise to avoid sexual intercourse at least 12 h before urinary dipstick testing.     

Aural Barotrauma in Submarine Escape: Is Mastoid Pneumatization of Significance?

OBJECTIVE: Submarine escape training is carried out by preselected, healthy young men under strictly controlled conditions regarding exposure to pressure and the rate of pressure change. This provides a unique opportunity to investigate the relations between middle ear characteristics and susceptibility to barotrauma while avoiding possible confounding parameters. We examined a possible association between mastoid pneumatization and middle ear barotrauma (MEB) in submarine escape trainees. STUDY DESIGN: Cross-sectional, parallel-group design. METHODS: Sixty-six subjects aged 19 to 28 participated in the study. The escape simulation included pressurization to 30 or 60 feet followed by a buoyant ascent to the surface. Subjects were evaluated for MEB after each ascent. A Schuller's mastoid radiograph was taken for the evaluation of mastoid pneumatization. RESULTS: Fifteen (23%) of the subjects suffered from MEB, and 6 (40%) of them had bilateral involvement. Repeated impedance audiometry after the completion of a successful ascent revealed a significant increase in middle ear compliance. Schuller's radiographs were obtained from 49 (74%) of the subjects. Of these radiographs, 16 (16%) were of ears that had suffered MEB. Mastoid pneumatization for all ears approached a normal Gaussian distribution, with a mean area of 9.58 cm. The mastoid areas and the proportion of ears with mastoid pneumatization at the extremes of the study population did not differ between barotrauma and no-barotrauma ears. CONCLUSION: In a population with no history of recurrent or chronic otitis media and normal tympanic membrane morphology and compliance, the amount of mastoid pneumatization probably represents merely the normal distribution of variation in organ size and is not related to the ability to equalize pressure in the middle ear.     

Implementation of Lean and Six Sigma principles in ophthalmology for improving quality of care and patient flow

Lean management is a set of principles aimed at improving processes by identifying and eliminating steps that do not add value to the consumer. Such steps lead to wasted time, resources, and expenses and result in customer and employee dissatisfaction. Although initially invented and perfected for factory assembly lines in the automobile industry, it has since disseminated extensively and has repeatedly proven a powerful “engine” for improving quality and quantity in the health-care setting. Lean implementation benefits include improved safety, reduced waiting times, increased patient satisfaction, and cost reduction. Nevertheless, it appears to be less familiar and appreciated in ophthalmology and more specifically as a tool for managing an efficient eye care clinic. In this review, we explain what “Lean” and Six Sigma are and highlight their implementation in settings such as cataract surgery, laser capsulotomy, an ophthalmic emergency room and its role as a powerful tool for improving clinic patient flow. We discuss basic principles of Lean management, review examples of implementing these principles in an ophthalmology practice, and finally, offer physicians practical tools for identifying “wasteful” processes and ways to eliminate them.     

Sensory processing patterns of adults with atopic dermatitis

Background Atopic dermatitis (AD) has been associated with sensory hypersensitivity in children. Objective To examine the sensory profile of adults with AD using a standardized questionnaire that measures sensory processing and related behaviours in daily living. Methods Thirty‐two patients aged 18–53 years with AD and 32 healthy, sex‐ and age‐matched control subjects completed the Adolescent/Adult Sensory Profile (AASP). Severity of AD was assessed by the Severity Scoring of Atopic Dermatitis (SCORAD). Results Patients with AD showed higher sensory sensitivity and avoidance than the controls, mainly in the tactile, vestibular, visual and auditory modalities. Conclusions Adults with AD may suffer from sensory hypersensitivity. Additional studies should examine the influence of the peripheral and the central nervous system on sensory hypersensitivity. Better understanding of the sensory impairment of patients with AD may help improving treatment strategies for the disease.     

Conceived and deceived: the medical interests of donor-conceived individuals

Effective July 22, 2011, a new law in the state of Washington requires any donor of sperm or eggs to provide a medical history and identifying information to fertility clinics. It also allows donor‐conceived individuals to request this information from clinics once they reach the age of eighteen. This is a significant legislative milestone and a promising development in a country that has consistently shied away from regulating the infertility industry in any way. What do we as a society owe donor‐conceived individuals in terms of obtaining access to information about their genetic origins? This essay addresses just one of this set of issues: the regulatory changes required to address the medical interests of donor‐conceived individuals, regardless of whether a human right to know one's genetic origins is acknowledged.     

A mouse model of blast-induced mild traumatic brain injury

Improvised explosive devices (IEDs) are one of the main causes for casualties among civilians and military personnel in the present war against terror. Mild traumatic brain injury from IEDs induces various degrees of cognitive, emotional and behavioral disturbances but knowledge of the exact brain pathophysiology following exposure to blast is poorly understood. The study was aimed at establishing a murine model for a mild BI-TBI that isolates low-level blast pressure effects to the brain without systemic injuries. An open-field explosives detonation was used to replicate, as closely as possible, low-level blast trauma in the battlefield or at a terror-attack site. No alterations in basic neurological assessment or brain gross pathology were found acutely in the blast-exposed mice. At 7 days post blast, cognitive and behavioral tests revealed significantly decreased performance at both 4 and 7 m distance from the blast (5.5 and 2.5 PSI, respectively). At 30 days post-blast, clear differences were found in animals at both distances in the object recognition test, and in the 7 m group in the Y maze test. Using MRI, T1 weighted images showed an increased BBB permeability 1 month post-blast. DTI analysis showed an increase in fractional anisotropy (FA) and a decrease in radial diffusivity. These changes correlated with sites of up-regulation of manganese superoxide dismutase 2 in neurons and CXC-motif chemokine receptor 3 around blood vessels in fiber tracts. These results may represent brain axonal and myelin abnormalities. Cellular and biochemical studies are underway in order to further correlate the blast-induced cognitive and behavioral changes and to identify possible underlying mechanisms that may help develop treatment- and neuroprotective modalities.     

Protein-induced, previously unidentified twin form of calcite

Using single-crystal x-ray diffraction, we found a formerly unknown twin form in calcite crystals grown from solution to which a mollusc shell-derived 17-kDa protein, Caspartin, was added. This intracrystalline protein was extracted from the calcitic prisms of the Pinna nobilis shells. The observed twin form is characterized by the twinning plane of the (108)-type, which is in addition to the known four twin laws of calcite identified during 150 years of investigations. The established twin forms in calcite have twinning planes of the (001)-, (012)-, (104)-, and (018)-types. Our discovery provides additional evidence on the crucial role of biological macromolecules in biomineralization.     

Nanosuspensions of alendronate with gallium or gadolinium attenuate neointimal hyperplasia in rats.

Monocytes/macrophages play a pivotal role in the formation of neointinal hyperplasia following vascular injury. Transient depletion of circulating monocytes by particulate delivery systems containing bisphosphonates, such as alendronate, results in restenosis inhibition. We hypothesized that a self-suspendable nanoparticulate dosage form, with a minimum amount of expients, could be formulated by complexing the negatively charged alendronate with gallium or gadolinium. We further hypothesized that a synergistic biological effect could be obtained by nanosuspensions of alendronate with these counter ions. Nanosuspensions (150-250 nm) of alendronate-gallium and alendronate-gadolinium were successfully formulated with no additives except for the active agents and HCl for pH adjustment. Both nanosuspensions exhibited macrophage cell line growth inhibition in a dose-response relationship in comparison to the various agents in solution and in liposomes. A synergistic effect of the nanosuspensions was observed in the inhibition of raw264 macrophages, and in reducing IL-1beta and TNF-alpha secretion in cell culture. Single IV administration at the time of injury, of alendronate-gallium or alendronate-gadolinium nanosuspensions resulted in inhibition of neointimal hyperplasia and stenosis in the rat model of vascular injury. The results correlated with the significant reduction of circulating monocytes. The nanosuspensions possess the advantages of no additives for minimal provocation of side effects, and the potential of immunomodulating inflammatory disorders.