Potassium inactivation and impedance changes during spike electrogenesis in eel electroplaques.

Various degrees of pharmacological K inactivation were induced by Cs or Ba in isolated single electroplaques of the electric eel. The resulting changes in K conductance give rise to very different steady-state current-voltage characteristics. They also induce differences in ion dynamics during spike electrogenesis. The dynamic changes were studied by AC bridge methods, registering the changes in impedance in synchrony with the neurally or directly evoked spikes. While spike electrogenesis was virtually unaffected by addition of Cs or Ba, the patterns of impedance changes were very different. The various patterns are accounted for by the changes in the respective current-voltage characteristics. The data constitute new evidence for regarding the electrically excitable component of the reactive membrane as a heterogeneous electrochemical system with separate and independently reactive channels that in the electroplaques are permselective for Na and K, respectively.

History repeats itself: pharmacodynamic trends in the treatment of anxiety disorders.

The original treatment indicated for those suffering from neurotic anxiety was to employ psychotherapy to facilitate changes in behavior and coping with stressful events. A spectrum of somatic treatments "from cathartics and emetics to opium and "strengthening tonics", from atropine and digitalis to potassium bromide and chloral hydrate, from barbiturates to benzodiazepines", to serotonergics, came to be used as well [1]. The Food and Drug Administration originally approved many gamma-aminobutyric acid (GABA) facilitating drugs since the 1960s for anxiety treatment. The 1980s evidenced the approval of a few serotonergic treatments that cornered the prescribing market and the front line of most treatment protocols. More recently, GABAergic drugs are making a return in the treatment of anxiety disorders. The following paper details the pharmacodynamic history of treating anxiety and also updates the reader as to the newer GABA-based approaches mentioned above.

Psychiatric medication-induced obesity: a review.

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the aetiology of this weight gain and the potential treatments being used to alleviate this side-effect. We found solid evidence that weight gain is often associated with the mood stabilizers, and antipsychotics and antidepressants. Only few weight neutral or weight loss producing psychotropics are available, and weight gain, outside of an immediate side-effect, may generate secondary side-effects and medical comorbidity. Weight gain may cause hypertension, diabetes, osteoarthritis, sedentary lifestyle, coronary artery disease, etc. Given the likelihood of inducing weight gain with psychotropic medications and the longitudinal impact on physical health, a thorough literature review is warranted to determine the epidemiology, aetiology and treatment options of psychotropic-induced weight gain.

Psychiatric medication induced obesity: an aetiologic review.

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment, but consensus shows that weight gain is prominent. The present review looked at the aetiology and cause of weight gain associated with psychotropic use and presents hypotheses as to why patients gain weight on antipsychotics, mood stabilizers and antidepressants. It is found that most psychotropic medications induce some weight gain, and clinicians are encouraged to utilize active interventions to alleviate the weight gain in order to prevent more serious obesity related comorbidities.

Psychiatric medication-induced obesity: treatment options.

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. The authors undertook a comprehensive literature review in order to provide a better understanding of novel treatment options in regards to alleviating weight gained by use of antidepressants, antipsychotics, and mood stabilizers. There are no agents for management of this weight gain approved by the Food and Drug Administration (FDA), and existing studies on options are mainly uncontrolled, small-scale projects with limited power to produce coherent conclusions. There is a clear need for larger studies on existing options, and future psychotropics without these side-effects are currently in the pipeline.

Adult vernier thresholds do not increase with age; vernier bias does.

Vernier acuity and vernier bias were examined in persons aged 20 to 79 years using a method of adjustments. Vernier bias (mean error) showed a sharp increase between 35 and 45. Vernier acuity (standard deviation or precision of alignment) did not vary significantly with age. These different results indicate the importance of separate evaluation of acuity and bias. Vernier acuity is little affected by minor optical changes that occur with age. Therefore, normal vernier acuity in older persons suggests that the neural substrates which underlie fine-grain discrimination of object location are unaffected by aging over the range investigated.

Retinoblastoma. Cell of origin.

OBJECTIVES: To apply modern techniques of molecular cell biology and to revisit the old question of the cell of origin for retinoblastoma in hopes of gaining a better understanding of the retinoblastoma gene's antioncogenic mechanisms. METHODS: Twenty-two consecutively accessed retinoblastomas were examined with immunocytochemical techniques for numerous retinal proteins. Both single and double labeling were used. Enzyme histochemistry for carbonic anhydrase was used as well. RESULTS: Differentiated areas of the tumors contained abundant Müllerlike cells. Fleurettes stained mostly for red and green cone-specific antibodies while features of blue cones and rods predominated in areas with high cytoplasmic-to-nuclear ratios but no fleurettes. All of the differentiated neoplastic cells were either photoreceptors or Müller's cells. No other retinal cell types were found. CONCLUSIONS: The cells of retinoblastoma are capable only of bipotential differentiation, ie, Müller's cells and photoreceptors. Given this and recent findings concerning retinal embryogenesis, we argue for the rod photoreceptor as the cell of origin. A possible role for the retinoblastoma gene product is discussed.

Ritleng intubation system for treatment of congenital nasolacrimal duct obstruction.

Twenty-eight patients (34 eyes) with congenital nasolacrimal duct obstruction underwent silicone intubation with the Ritleng lacrimal intubation system. The technique involves introduction of a Prolene (Ethicon Inc, Somerville, NJ) monofilament guide thread, securely fastened to the silicone tubing, into a tubular metal probe that opens into the inferior meatus. The outcome was evaluated in terms of ease of intubation and objective success rate. Thirty-two (94%) of the 34 lacrimal systems were successfully intubated with the Ritleng system. Difficulty passing the Prolene thread through the probe and out the tip, necessitating conversion to a Crawford intubation system, was encountered in only 2 eyes (6%). The Prolene spontaneously emerged from the nose in 24 (75%) of 32 eyes, making retrieval simple and uncomplicated. The success rate for relieving signs and symptoms of obstruction was 97% (31/32) for the eyes with the Ritleng system and 100% (2/2) for the eyes with the Crawford system. Bicanalicular silicone intubation with the Ritleng intubation system is an easy and effective technique for treatment of congenital nasolacrimal duct obstruction.

Tyrosinemia type II: nine cases of ocular signs and symptoms.

PURPOSE: To report nine cases of tyrosinemia type II, with ocular signs and symptoms. METHODS: Participants included nine patients (18 eyes) who were followed for a mean follow-up period of 6.5 years (range, 2 to 8 years). Intervention included dietary restriction of tyrosine and phenylalanine, which led to resolution of ocular and cutaneous lesions, improved behavior in one patient, and may have prevented developmental delay in others. The main outcome measures were visual acuity and serum tyrosine levels to determine the response to dietary therapy. Intelligence testing and developmental screening were performed when appropriate. RESULTS: All patients presented with ocular signs and symptoms as the primary manifestation of disease and serve to illustrate the typical ocular findings of this syndrome. Three patients presented with cutaneous manifestations, and one patient had mild mental impairment at the time of diagnosis. CONCLUSIONS: Recalcitrant pseudodendritic keratitis may be the presenting sign in tyrosinemia type II. Awareness of the presenting signs and symptoms may accelerate the diagnosis and dietary intervention. Initiation of a tyrosine-restricted and phenylalanine-restricted diet in infancy is most effective in preventing cognitive impairment.

Congenital intraocular teratoma associated with eyelid coloboma.

PURPOSE: To describe the first case of intraocular teratoma associated with eyelid coloboma and the second reported case of intraocular teratoma. DESIGN: Interventional case report. METHODS: A left intraocular tumor was surgically resected from a 2-day-old female with an associated lower eyelid coloboma. RESULTS: Pathologic evaluation revealed a completely intraocular tumor comprising derivatives of all three germ cell layers giving a diagnosis of intraocular teratoma. The eyelid coloboma was repaired, and a scleral-wrapped hydoxyapatite-integrated orbital implant was placed. CONCLUSION: To our knowledge, this is the second reported instance of teratoma originating within the globe and the only reported case of teratoma associated with eyelid coloboma. Although exceedingly rare, intraocular teratoma should be added to the differential diagnosis of congenital intraocular tumors.

Kinetic perimetry assessment of binocular visual field shape and size in young infants.

Kinetic perimetry was used to measure the extent of the binocular visual field in 8 directions in 77 full-term infants tested as neonates, 4-week-olds, or 8-week-olds. The apparatus consisted of a black, 4-arm arc perimeter, a centrally-located 6-deg stationary white sphere, and an identical sphere that served as the peripheral target. Neonates showed larger visual fields than did 4- and 8-week-olds, perhaps due to the strength of the older infants' fixation of the central target. Infants at all ages showed significantly smaller fields than did adults. However, visual field shape was similar in infants and adults.

Prescribing conventional antipsychotics at two Veterans Administration hospitals: are there geographical differences?

The medical records of 110 patients receiving conventional antipsychotics at two geographically distinct Veterans Administration hospitals (Syracuse, New York, and Omaha, Nebraska) were reviewed. The most common reasons for continuation of conventional antipsychotics were good response and patient or physician choice. Frequently, physicians did not discuss the reasons for continuing conventional antipsychotics or the availability of alternative therapies with their patients. Geographic differences in physicians' prescribing practices of conventional antipsychotics were apparent.

Hypoplastic corpus callosum in ocular albinism: indication of a global disturbance of neuronal migration.

Ocular albinism is distinguished from the more common oculocutaneous albinism by the presence of normal pigmentation of skin and hair in the former condition. Recent studies of ocular albinism have shown that the hypopigmentation of the optic fundus is associated with a number of anomalies of neuronal wiring involving the visual system. We present a patient with ocular albinism who also has a hypoplastic corpus callosum as determined by analysis of midsagittal magnetic resonance imaging scans. Previous studies of the hypoplastic corpus callosum indicate that this anomaly is a defect in neuronal migration as well. The finding of a hypoplastic corpus callosum in a patient with ocular albinism suggests a more generalized defect in neuronal migration not limited to the visual system.

Assaults by patients on psychiatric residents: a survey and training recommendations.

OBJECTIVE: A survey was conducted to determine the frequency and severity of assaults on psychiatric residents and the level of training they receive in the management of violent patients. METHODS: In early 1997 a survey was randomly distributed to 2,553 psychiatric residents, who represented half of all psychiatric residents in the United States. The survey asked about experiences of assaults and training received in management of violent patients. RESULTS: Completed surveys were received from 517 residents, for a 20 percent response rate. Seventy-three percent reported being threatened, and 36 percent had been physically assaulted. A third received no training in managing violent patients, and a third described their training as inadequate. CONCLUSIONS: Two-thirds of psychiatric residents are either undertrained or feel undertrained in dealing with violent patients. The authors propose a training curriculum based on recommendations of an American Psychiatric Association task force report on clinician safety.

Charles Bonnet syndrome in children.

Charles Bonnet syndrome (CBS) is characterized by the presence of complex visual hallucinations in psychologically healthy but visually impaired people. It has been well described in the adult population but has been less well characterized in children. This report describes CBS in 2 children, both of whom had diagnoses of cone-rod dystrophy. After previously normal visual experience, each underwent rapid visual deterioration between 6 and 8 years old. Formed visual hallucinations were noted shortly after loss of vision. The children's symptoms were identical to those described by adults with CBS. Formed visual phenomena included geometric shapes, people, and buildings. Images, which were both stationary and in motion, were described as interesting or entertaining and only rarely as frightening. No other senses were affected (no auditory component). Sixteen additional children with diseases of the eye or optic nerves were questioned about symptoms of CBS, including children with congenitally decreased vision, children with slowly progressive visual loss but current vision better than 20/200, and children with early normal vision who had profound vision loss before 4 years old; all these children denied hallucinations.

The validity of the Ussing flux ratio equation in a three-dimensionally inhomogeneous membrane.

Derivations of the Ussing flux ratio equation have, until now, required the membrane to be both bounded by parallel planes and homogeneous, except in the transmembrane direction. These constraints have been necessary for the theoretical demonstration that the equation is independent of membrane parameters in the absence of carriers, coupling, solvent drag, or "single-file" diffusion. In a new derivation, the flux ratio equation is shown to be valid in this kind of diffusion regime without regard to the three-dimensional structure of the membrane. Thus the constraints on both membrane homogeneity and membrane geometry are shown to be unnecessary. The general use of this equation to differentiate between simple, uncoupled diffusion and other membrane transport phenomena is thus placed on a firmer base. However, as in earlier derivations, it is necessary that isopotential, isobaric, constant concentration surfaces exist sufficiently close to the membrane on both of its sides.

Direct effects on the membrane potential due to "pumps" that transfer no net charge.

The effects of active ionic transport are included in the derivation of a general expression for the zero current membrane potential. It is demonstrated that an active transport system that transfers no net charge (nonrheogenic) may, nevertheless, directly alter the membrane potential. This effect depends upon the exchange of matter within the membrane between the active and passive diffusion regimes. Furthermore, in the presence of such exchange, the transmembrane active fluxes measured by the usual techniques and the local pumped fluxes are not identical. Several common uses of the term "electrogenic pump" are thus shown to be inconsistent with each other. These inconsistencies persist when the derivation is extended to produce a Goldman equation modified to account for active transport; however, that equation is shown to be limited by less narrow constraints on membrane heterogeneity and internal electric field than those previously required. In particular, it is applicable to idealized mosaic membranes limited by these requirements.

Nonsteady-state three compartment tracer kinetics. I. Theory.

A set of differential equations is derived which describes the four unidirectional fluxes of a substance across the boundaries of the central compartment of a serially arranged three compartment system, and the amount of this substance present in the central compartment. An analytic solution is obtained which yields all of these quantities as functions of time. The analysis is associated with a defined set of repetitive experiments from which the necessary data are obtained and during which the two outer compartments must be subject to experimental control. The solution is applicable to both the initial steady state and a transient, time-dependent state created by making a step change in the initial conditions. It describes the fluxes and compartment size without assuming that constant kinetic coefficients relate the fluxes to compartmental quantities but is limited by the requirement that the response of the system be repeatable in time.

Nonsteady-state three compartment tracer kinetics. II. Sodium flux transients in the toad urinary bladder in response to short circuit.

The theoretical approach presented in the previous paper provides an analytical method for determining the unidirectional, nonsteady-state fluxes in a three compartment system. Based on this a study was made of the sodium flux transients in the toad urinary bladder. A transient time-dependent state was generated by suddenly short-circuiting a bladder previously maintained in an open-circuited steady state. The sequence of experiments suggested by the theory provided the data required for the analysis. The results of these tracer experiments were consistent with the complex non-three compartmental structure of this tissue. As a result both of the inadequacy of the three compartment model in representing the tissue and of certain experimental difficulties, attempts at a quantitative solution were not entirely successful. Useful information was nevertheless obtained through a careful use of this model, and a qualitative analysis implied that the sodium influxes into the tissue at both of its surfaces are sensitive to changes in electrical potential while both effluxes are insensitive to this change. This suggests that both of the effluxes result from active processes while both influxes are associated with passive processes. The net transepithelial transport of sodium would then necessarily result from a more complex polarization than that proposed by Koefoed-Johnsen and Ussing.