Biomedical subjects
M Kincaid
Publications and source records attributed to M Kincaid.
Effects of serotonin reuptake inhibitors on aggressive behavior in psychiatrically hospitalized adolescents: results of an open trial.
Low concentrations of the neurotransmitter serotonin and its 5-hydroxyindoleacetic acid metabolite in the central nervous system have been associated with increased aggressive behavior in animals and humans. Controlled clinical trials of serotonin agonists in depressed adults have suggested that aggressive behavior is less likely during treatment with these medications than with placebo, but there have been no previous studies of selective serotonin reuptake inhibitors (SSRIs) and aggression in children. We prospectively followed the course of aggressive behavior in 19 psychiatrically hospitalized adolescents (not selected for aggressiveness) who received open clinical trials of fluoxetine, paroxetine, or sertraline. The patients received standard doses (equivalent to fluoxetine 10-40 mg daily) for a minimum of 5 weeks. The starting dose was 15 +/- 5 mg, and dosages were raised at a mean rate of 5 mg every 4 days up to a mean dose of 25 +/- 10 mg daily. Results from trials of the three SSRIs were clustered because the sample sizes were not sufficient for separate analyses. Overall, there were no statistically meaningful improvements in the level of aggressive behavior, as measured on a modified version of the Overt Aggression Scale, over the course of these patients' SSRI trials. Symptoms of physical aggression toward others or self were manifest in 12 of the 19 patients while on SSRIs. Of the 19 patients, 13 were assessed both on and off SSRIs: verbal aggression (p = 0.04), physical aggression toward objects (p = 0.05), and physical aggression toward self (p < 0.02) occurred significantly more frequently on SSRIs than off; no increase was observed in physical aggression toward others. Patients with the highest baseline aggressivity scores did not show greater improvement during SSRI treatment. Further research is warranted, particularly to explore whether SSRIs may have therapeutic effects on aggression at higher (or lower) doses than were administered in this open trial.
Symptom stability in geriatric chronic schizophrenic inpatients: a one-year follow-up study.
The results of previous studies of symptom stability in schizophrenia suggest that negative symptoms manifest traitlike characteristics while positive symptoms fluctuate over time. Various prospective studies of chronic schizophrenic patients have found consistent results, regardless of the follow-up period, yet there is little research addressing symptomatology in geriatric schizophrenic patients. Since these patients have a very poor outcome and more severe negative symptoms, their symptoms might differ from younger patients. This study examined the course of symptomatology in 178 geriatric schizophrenic inpatients who were assessed twice at a 1-year interval with the Positive and Negative Syndrome Scale (PANSS). Intraclass correlations revealed that the distribution of negative symptoms was considerably more stable than that of positive symptoms over the interval, and subtypes based on negative symptoms were the only ones that manifested consistent stability over time. There was also a significant increase in negative symptom severity for the sample, with a slight decrease in positive symptom severity. Thus, even in chronic inpatients, with a very extended illness, positive symptom severity is not particularly stable within patients. These data indicate that the characteristics of negative and positive schizophrenic symptoms are similar in younger and geriatric schizophrenic patients, suggesting a continuity of the illness process. Tentative evidence for increasing severity of negative symptoms over a brief follow-up period suggests the possibility of a steady worsening of clinical state in very elderly patients who remained hospitalized.
Aminoglycoside levels in the rabbit vitreous cavity after intravenous administration.
PURPOSE: To determine the penetration of gentamicin and amikacin into the rabbit vitreous cavity after their intravenous administration. METHODS: Gentamicin (1.6 mg/kg every 8 hours) and amikacin (6 mg/kg every 12 hours) were administered intravenously to 25 rabbits that had previously had the lens and vitreous removed from 43 eyes. For each drug, ocular inflammation was induced in one group of eyes by injection of heat-killed Staphylococcus epidermidis, while the other group was maintained as a control. Samples from the vitreous cavity were taken at regular intervals for 72 hours after beginning the intravenous medications and were analyzed for drug concentrations. RESULTS: The maximum intravitreal concentration +/- SD achieved for gentamicin was 1.8 +/- 0.5 microgram/ml. The maximum intravitreal concentration for amikacin was 8.5 +/- 3.2 micrograms/ml. Inflamed eyes demonstrated higher concentrations than did those without inflammation. CONCLUSIONS: In a rabbit model with conditions optimized to enhance penetration of antimicrobials into the vitreous cavity after intravenous administration, neither gentamicin nor amikacin penetrated sufficiently to reach potentially therapeutic concentrations consistently for either Pseudomonas or S epidermidis organisms.
Vancomycin levels in the vitreous cavity after intravenous administration.
PURPOSE: We studied the effects of inflammation, repeated antibiotic doses, and the surgical status of the eye on penetration of vancomycin hydrochloride into the rabbit vitreous cavity after intravenous administration. METHODS: We studied three anatomic states (phakic, aphakic, and aphakic, vitrectomy-treated eyes) subdividing each into inflamed and noninflamed groups. Intravenous vancomycin hydrochloride (15 mg/kg of body weight) was administered every 12 hours for 48 hours. Eyes were harvested for the assay of vitreous cavity antibiotic levels at various intervals from one to 49 hours. We determined concentrations and calculated mean values and S.E.M. RESULTS: Therapeutic levels were not established in the vitreous cavity at any time period in the two phakic groups. At 25 hours, the inflamed aphakic eyes had concentrations of 5.05 +/- 1.9 micrograms/ml and the control noninflamed aphakic eyes 4.5 +/- 1.23 micrograms/ml; slight increases were found by 49 hours. Concentrations tested in the aphakic, vitrectomy-treated eyes at two, 13, 25, and 49 hours demonstrated progressive increases both in the inflamed eyes (5.4 +/- 2.4 micrograms/ml, 9.64 +/- 4.25 micrograms/ml, 9.2 +/- 3.96 micrograms/ml, 10.34 +/- 4.49 micrograms/ml) and noninflamed eyes (3.52 +/- 2.1 micrograms/ml, 5.4 +/- 1.96 micrograms/ml, 6.8 +/- 2.53 micrograms/ml, 8.7 +/- 5.44 micrograms/ml). CONCLUSIONS: Vitreous vancomycin concentrations in aphakic and aphakic, vitrectomy-treated eyes after intravenous administration exceed the minimal inhibitory concentrations for the usual gram-positive pathogens that create endophthalmitis, suggesting a role for intravenous vancomycin in the treatment of bacterial endophthalmitis.
Vitreous cavity penetration of ceftazidime after intravenous administration.
PURPOSE: Penetration of ceftazidime, a third generation cephalosporin, into the vitreous cavity after intravenous administration was investigated. METHODS: Because antimicrobial penetration varies with surgical status of the eye and with inflammation, studies were conducted in phakic, aphakic, and aphakic, vitrectomized eyes in both normal and inflamed conditions. Ceftazidime 50 mg/kg was administered every 8 hours and vitreous cavity concentrations were tested at intervals from 2 to 72 hours after the initial dose. RESULTS: No penetration was found into control phakic and aphakic eyes, but drug concentrations were detected in inflamed eyes at 24 hours. Vitreous concentrations of ceftazidime in aphakic, vitrectomized eyes reached levels well above the minimal inhibitory concentration (MIC) for Pseudomonas organisms within 2 hours of intravenous administration in control eyes (8.5 micrograms/ml) and inflamed eyes (35.4 micrograms/ml). Inflammation and removal of the lens and vitreous significantly enhanced ceftazidime penetration at all time periods tested. CONCLUSION: Ceftazidime penetrates into the vitreous cavity of inflamed eyes after intravenous administration and achieves concentrations above the MIC for Pseudomonas organisms. Penetration is greatest in aphakic, vitrectomized eyes.
Vancomycin levels after intravitreal injection. Effects of inflammation and surgery.
OBJECTIVE: Vancomycin hydrochloride for intraocular injection is the drug of choice for the treatment of suspected gram-positive endophthalmitis. To study its intraocular pharmacokinetics, we injected vancomycin into the vitreous cavity of phakic, aphakic, and aphakic-vitrectomized rabbit eyes and determined its rate of clearance. Inflamed eyes were compared to control eyes in each group. METHODS: Three groups of eyes were prepared. The eyes in Group 1 were phakic, the eyes in Group 2 had the lens removed, and the eyes in Group 3 had both the lens and central vitreous removed. Each group was subdivided into a control group and a group made inflamed by injection of heat-killed Staphylococcus epidermidis. Vancomycin hydrochloride 1 mg in 0.1 cc of diluent was injected into the midvitreous cavity and samples obtained at 2 or 3, 8, 24, and 48 hours after injection. Vancomycin concentrations were measured and clearance rates were calculated for each of the groups. RESULTS: Vancomycin was cleared substantially faster from aphakic-vitrectomized eyes (half-life 9.0 hours) and aphakic eyes (half-life 8.9 hours) than phakic eyes (half-life 25.1 hours). Inflammation increased the rate of elimination of vancomycin only in the aphakic group. CONCLUSIONS: Clearance of vancomycin from the phakic eye is prolonged compared to that of beta-lactam antibiotics, an important pharmacokinetic advantage in treating endophthalmitis. Its clearance from aphakic-vitrectomized eyes is dramatically faster than from phakic eyes and is similar to that of other antimicrobial agents.
Intraocular injection of ceftazidime. Effects of inflammation and surgery.
OBJECTIVE: The clearance of ceftazidime from the rabbit vitreous cavity after injection into phakic, aphakic, and aphakic vitrectomized rabbit eyes was assessed and the duration of concentrations above the minimal inhibitory concentrations for target gram-negative bacteria was determined. To determine the effect of inflammation on the intraocular pharmacokinetics of ceftazidime, each anatomic group was subdivided into inflamed and control eyes. METHODS: Ceftazidime (2.25 mg) was into the vitreous cavity of inflamed and control rabbit eyes and its concentration was assayed 2, 8, 24, and 48 hours later. The half-life for each of the anatomic groups was calculated. RESULTS: The half-life of ceftazidime in control phakic eyes was 13.8 hours. In aphakic eyes the half-life was 11.8 hours and in the aphakic vitrectomized eyes the half-life was 4.7 hours. Inflammation slightly shortened the half-life in phakic (10.1 hours) and aphakic (8.7 hours) eyes. The half-life in aphakic vitrectomized inflamed eyes was 5.1 hours. CONCLUSION: Vitrectomy and lensectomy significantly shorten the half-life of ceftazidime after intravitreal injection. Inflammation increases clearance to a small degree in phakic and aphakic eyes.
The pattern ERG in man following surgical resection of the optic nerve.
Pattern electroretinogram (PERG) results recorded in different laboratories from patients with unilateral traumatic transections of the optic nerve have led investigators to opposite conclusions about the sources of this response. There was no absolute demonstration of complete transection in any of these studies. In the present study, PERGs and flash ERGs were recorded from a patient who, 30 months earlier, had undergone surgical resection of the right optic nerve to remove a glioma. The histological section of the biopsied nerve confirmed complete optic nerve transection. Ophthalmoscopically and angiographically, the right eye was normal except for marked optic atrophy. PERGs were produced by 10 Hz reversal of high contrast checks with check widths from 13 deg 30 min to 12 min arc. Field size was 27 deg X 21 deg and space-averaged screen luminance was 110 cd/m2. Smaller checks (3 deg 23 min to 12 min) produced responses in both eyes, but the responses in the right eye were much smaller than those in the left eye. Large checks and diffuse flashes produced approximately equal responses in the two eyes. The implicit times of the PERGs produced by stimulation of the right eye with smaller checks were shorter than those of the left eye. The authors conclude that, in humans, there is a contribution to the high contrast pattern reversal ERG from cells which are not dependent upon the integrity of the ganglion cell layer. These cells and cells dependent upon ganglion cells may both contribute to the high contrast PERG in the normal human eye.
"We kept our fingers crossed!".
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Presumed ocular histoplasmosis syndrome. A clinicopathologic correlation of a treated case.
A patient with bilateral presumed ocular histoplasmosis had been successfully treated in his symptomatic right eye with laser photocoagulation for subretinal neovascularization in two areas of the macula. The left eye also showed neovascularization clinically and histopathologically but was not treated because there was no detectable leakage and the vision was not affected. There was no change in the left eye over a two-year period. Clinicopathologic correlation of the treated and untreated macular lesions and the peripapillary and peripheral lesions is presented.
Retinal fluorograms using oral fluorescein.
Sodium fluorescein may be safely administered orally. The resulting angiograms serve to document the presence or absence of dye leakage in the same manner as venous injection. The oral route of administration is of particular benefit for use in children, patients with inaccessible veins, and patients participating in studies of late retinal vascular leakage, such as postoperative cystoid macular edema. Serum concentrations of the dye plateau between thirty minutes and one hour, at levels approximating those obtained by intravenous injection.
Health care problems? Typical American view: no serious complaints.
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Retinal fluorography using oral fluorescein.
Fluorescein sodium can be administered safely by mouth. The resulting fluorograms are useful in demonstrating many retinal conditions characterized by bright late leakage, such as cystoid macular edema. Oral administration of fluorescein may be preferred in studies of children, patients with difficult veins, and in some surveys of large patient populations.
Laser scotometry in drusen and pits of the optic nerve head.
Laser scotometry is an accurate means of detecting dense blind spots. A small low-energy spot is guided across the fundus from nonseeing to seeing areas. Patient responses are recorded on fundus photographys, allowing direct correlation with fundus pathology. Accuracy to less than 1 degree is feasible. All typical optic nerve drusen tested with this technique had field defects. In cases of optic nerve pits, dense scotomas correlated with the shape of visible nerve fiber defects rather than with the shape of serous retinal detachments.
The influence of a magnetic field on immunologic and enzymatic reactions carried out at a solid-liquid interface.
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