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Biomedical subjects

M Mehta

Publications and source records attributed to M Mehta.

At least 73 records · Page 4Linked to original sources

Effect of vehicle on skin penetration and retention of a lipophilic red tide toxin (PbTx-3).

The purpose of this study was to determine the effect of carrier vehicle on the penetration of brevetoxin ([3H]PbTx-3) into skin layers and receptor fluid. Disks of guinea-pig skin were mounted on penetration chambers. Epidermal surfaces were dosed with 0.320 microgram/cm2 of PbTx-3 dissolved in 50 microliters of vehicle [water, methanol, or dimethylsulfoxide (DMSO)]. In vitro skin penetration by PbTx-3 during 24 hr of exposure was 6.2, 2.3 and 26% for water, methanol, and DMSO, respectively (expressed as % of dose applied).

Animals↗

Comparison of the partition coefficient and skin penetration of a marine algal toxin (lyngbyatoxin A).

Lyngbyatoxin A is produced by marine algae, and causes local cutaneous toxicity in swimmers. The purpose of this research was (1) to determine the partition coefficient of lyngbyatoxin A in octanol/water and (2) to use methods in vitro to measure the penetration and distribution of lyngbyatoxin A in guinea pig and human skin. Discs of excised guinea pig and human skin were mounted in diffusion chambers that exposed the epidermal surface to air and bathed the dermis with HEPES-buffered Hanks' balanced salt solution with gentamicin sulphate. The epidermal surfaces were dosed with 26 micrograms lyngbyatoxin A/cm2 dissolved in 13 microliters dimethyl sulphoxide/cm2. The diffusion chambers were incubated at 36 degrees C for varying periods (1.0-24 hr). HPLC was used to quantify lyngbyatoxin A. Skin penetration was calculated by summing the amount of lyngbyatoxin A recovered from the dermis and receptor fluid. The mean partition coefficient for lyngbyatoxin A was 1.53. Penetration of lyngbyatoxin A (expressed as a percentage of dose, n = 3) in guinea pig and human skin was 23 and 6.2 (respectively) after 1 hr of topical exposure. The amount of lyngbyatoxin A in the dermis and receptor fluid did not change significantly over time.

Animals↗

Sequential comparison of low dose rate and hyperfractionated high dose rate endobronchial radiation for malignant airway occlusion.

A pilot trial (S2) was conducted at the University of Wisconsin to determine the feasibility, efficacy, and toxicity of hyperfractionated high dose rate endobronchial radiation. To avoid multiple bronchoscopies, an optimized hyperfractionated schema was derived from the linear-quadratic model. Utilizing a single bronchoscopy, 31 patients with malignant airway occlusion received 4 Gy x 4 fractions over 2 days at 2 cm from source center using a high dose rate remote afterloader. Response and morbidity were compared to a previous trial (S1) in which 66 patients were treated with conventional low dose rate endobronchial radiation. Response was assessed by change in performance status, symptom resolution, percent of lifetime rendered symptom-free or improved, and radiographic reaeration. These parameters were highly comparable between the two groups. The mean ECOG performance status improved from 2.2 to 1.8 for S1 and 2.1 to 1.6 for S2; symptom improvement or resolution was noted in 78% for S1 and 79% for S2; lifetime rendered symptom-free or improved was 54% for S1 and 57% for S2; and the overall radiographic response rate was 78% for S1 and 85% for S2. The overall incidence of fistulae was 7/101. We conclude that endobronchial radiation is an effective and safe modality for palliation, and hyperfractionated high dose rate endobronchial radiation achieves responses similar to low dose rate endobronchial radiation with a similar complication rate.

Airway Obstruction↗

Weight consideration in the use of cerrobend beam blocks.

The technique of using customized field blocking to protect sensitive normal tissue during megavoltage radiation treatment is common practice in modern radiation therapy. The introduction of CT-based treatment planning has revolutionized customized field shaping. We carried out a prospective evaluation of 54 cerrobend blocks during a one-month time period. The goals of this study were to analyze the specific block patterns and correlate these with field size, block weight, and field setup. Factors contributing to excessively large and heavy cerrobend blocks defined as > or = 20 lbs. were identified. Twenty-two percent of blocks were found to be excessively large and one-third of these were a consequence of planning decisions. A review of these situations suggests that alternative methods would have avoided the excessive weight. Concerns have been raised regarding the safety of large and heavy cerrobend blocks. These blocks were therefore analyzed in terms of tray sag and tray break-point. Our data suggest that within this clinical range of block weight, neither tray sag nor tray break-point are of significant concern.

Humans↗

Pharmacokinetic evaluation of drug interactions with anti-human immunotrophic virus (HIV) Drugs. III. 2',3'-Dideoxycytidine (ddC) and zidovudine in monkeys.

A pharmacokinetic evaluation of a potential drug interaction between zidovudine (AZT) and dideoxycytidine (ddC) was conducted in monkeys. Each of six animals received 20 mg/kg of AZT intragastrically in the absence and presence of an intravenous steady-state dosage regimen of ddC. The regimen was designed to produce steady-state ddC plasma concentration of 1.77 micrograms/ml for 30 min. Plasma and urine samples were analyzed for AZT, its major glucuronide metabolite, GAZT, and ddC by HPLC techniques. Pharmacokinetic parameters for AZT and GAZT were calculated by non-compartmental methods. The mean apparent clearance of AZT was 1.40 and 1.78 L/hr/kg in the absence and presence of ddC, respectively. The mean AUC for GAZT was 36.39 micrograms-hr/ml in the absence of ddC and 28.81 micrograms-hr/ml in the presence of ddC. No statistical differences were found in these and other pharmacokinetic parameters in the absence and presence of ddC. The absence of an effect on AZT's pharmacokinetics by ddC is attributed to the primary metabolic and renal elimination pathways for AZT and ddC, respectively. The results of this study provide a rational basis to design combined AZT-ddC treatment regimens in AIDS patients.

Animals↗

Effect of stimulus contrast on simultaneous steady-state pattern reversal electroretinogram and visual evoked response.

We studied the effect of stimulus pattern contrast on the simultaneously recorded pattern reversal electroretinogram (PERG) and pattern reversal visual evoked response (PVER) at 5 check sizes. The stimulus contrast ranged from 24 to 95% in 6 steps of 0.1- or 0.15-log unit increments. PERG amplitude showed a linear increase with an increase in pattern contrast at all check sizes. PVER amplitude showed an increase up to a certain pattern contrast, but was saturated upon further increase in stimulus contrast at all check sizes. The PERG amplitude-check size function curve showed a flattened, inverted-U shape only with the highest contrast and low-pass filter shape or flat shape with lower contrasts. The PVER amplitude-check size function curve showed an inverted-U shape (bandpass filter shape) at all contrasts. These characteristics to the changes in contrast and the spatial frequency tuning suggest that PVER is processed in a different location of visual pathway than PERG.

Adult↗

Methods for in vitro skin absorption studies of a lipophilic toxin produced by red tide.

The penetration and distribution of [3H]PbTx-3 into pig skin was determined using in vivo and in vitro methods. The dose used in each topical study was 0.3-0.4 micrograms/cm2 skin, with dimethylsulfoxide as the vehicle. In the in vivo study, mean cutaneous absorption after 48 h (expressed as percentage of the dose) was 11.5% (n = 3). In the in vitro study, mean cutaneous absorption after 48 h was 1.6% (n = 12), when based on accumulation of radioactivity in receptor fluid, or 9.9% when based on receptor fluid and dermis. [3H]PbTx-3 readily penetrated through the epidermis into the dermis, reaching maximal dermal accumulation at 4 h (9.1% in vivo and 18% in vitro). At 24 h, the amount in the dermis decreased to 2.3% and 15% in vivo and in vitro, respectively and at 48 h the amount in the dermis decreased to 8.2% in vitro. These results demonstrate the important role of the dermis as a reservoir for a lipophilic compound in both in vivo and in vitro percutaneous absorption studies.

Administration, Topical↗

Pharmacokinetic evaluation of drug interactions with zidovudine. I: Probenecid and zidovudine in monkeys.

Pharmacokinetic evaluation of a drug interaction between zidovudine (AZT) and probenecid was conducted in monkeys. Six animals received 20 mg/kg of AZT as single intragastric (ig) and iv doses in the absence and presence of 50 mg/kg of probenecid administered ig. Plasma concentrations of AZT and its 5'-glucuronide metabolite (AZTG) were quantitated for 12 h by HPLC. Amounts of AZT and AZTG in urine were also measured, as were probenecid plasma concentrations. Non-compartmental methods were used to obtain pharmacokinetic parameters for AZT and AZTG. In the presence of probenecid, the total clearance of AZT decreased by 50%, renal clearance decreased, and elimination half-life increased. The volume of distribution at steady-state and systemic bioavailability of AZT were not significantly altered by probenecid. The areas under the plasma concentration-time curves and terminal half-lives of AZTG were increased, and renal clearances of AZTG were decreased. The alterations in AZT and AZTG pharmacokinetic parameters are consistent with inhibition of metabolism and renal tubular secretion by probenecid. Since AZT was administered by both oral and iv routes, clearance, volume of distribution, and bioavailability parameters were independently determined. Based on data reported for humans on the zidovudine-probenecid interaction, monkeys appear to be appropriate animal models for the evaluation of zidovudine drug interactions.

Animals↗

In vitro penetration of tritium-labelled water (THO) and [3H]PbTx-3 (a red tide toxin) through monkey buccal mucosa and skin.

The permeability coefficients (Kp) for tritium-labelled water (THO) were determined in human and monkey skin, and monkey buccal mucosa. Kp of human skin (0.47 x 10(-3) cm/h) correlated favorably with previous reports. Kp of hydrated monkey skin for THO (0.77 x 10(-3) cm/h) was not significantly different (P greater than 0.05) from Kp of hydrated human skin (0.88 x 10(-3) cm/h). Kp of monkey buccal mucosa for THO (6.15 x 10(-3) cm/h) was significantly greater than that for monkey skin. Penetration and disposition of [3H]PbTx-3 into layers of monkey buccal mucosa and skin was determined. [3H]PbTx-3 (5-7 microCi) dissolved in 2 ml of water was applied to epithelial/epidermal surface (2.8 cm2) at zero time. The relative percent dose recovered from the upper layers of buccal mucosa (epithelium) and skin (epidermis) varied, but at each time interval was less than 2.5% of the dose. At most of the time intervals (2-24 h), a larger percent of the dose was recovered from the inner layer of the buccal mucosa (lamina propria) than from the inner layer of skin (dermis). After 24 h, as much as 34 or 13% of the dose was recovered from lamina propria or dermis, respectively. At each time interval studied, less than 2% of dose of [3H]PbTx-3 penetrated into the receptor fluid which bathed the inner surfaces of the lamina propria or dermis. The results of this study demonstrate that monkey buccal mucosa is more permeable than skin to THO and PbTx-3.

Administration, Topical↗

Best's macular dystrophy with a macular hole.

The occurrence of a macular hole with Best's dystrophy is an extremely rare finding with only one reported case in the literature. We wish to report two cases with typical Best's dystrophy in one eye and a macular hole in the contralateral eye. In one case the Pattern Reversal VER (PVER) was also recorded and graphed as an amplitude-check size function curve. The PVER changes in this case were grossly subnormal in both the eyes, suggesting a significant degree of bilateral macular impairment. This implies that a significant amount of functional impairment occurs at the vitelliform stage itself, though how this stage progresses to a macular hole is unclear.

Adult↗

Retinal function in birdshot retinochoroidopathy.

The electroretinograms (ERGs) of 15 patients with birdshot retinochoroidopathy varied from super-normal to non-recordable, depending upon the severity and the stage of the disease. The abnormal ERGs were characterized by a disproportionate decrease of the b-wave amplitude compared with the a-wave amplitude, demonstrating the negative (-) type response. This distinct ERG pattern has not been observed in any other type of uveitis or chorioretinitis, and appears specific to birdshot retinochoroidopathy. ERG findings indicate that in birdshot retinochoroidopathy the neural layers of the retina are more diffusely and severely involved than the receptor-retinal pigment epithelium-choroid complex. In the most advanced stage, the patients becomes night blind with a non-recordable ERG, a situation that is essentially the same as retinitis pigmentosa, except that pigmentation is conspicuously absent in the fundus.

Adult↗

Behavioral training for mothers of mentally handicapped children: teaching of self-help skills.

Deficits in self help skills are an inevitable problem with the mentally handicapped. The acquisition of self-help skills, learned effortlessly by more intelligent children, is a crucial aspect of the overall development of the mentally handicapped child. In the present study, thirty seven mothers of mentally handicapped children aged between 3 1/2 and 8 years, with an IQ of less than 70, were trained in behavioral techniques such as shaping, task analysis, prompting, and modelling, to develop independent self-help functioning in their children. The self-help areas were toileting, feeding, bathing, washing, and dressing. Thirty two per cent of mothers reported complete skill learning. The problems encountered in the course of training and the subsequent evaluation of its efficacy are discussed.

Adult↗

Simultaneous pattern reversal ERG and VER recordings. Effect of stimulus field and central scotoma.

The effects of the sizes of the stimulus field and of an artificially created central scotoma on simultaneously recorded pattern-reversal electroretinogram (P-ERG) and pattern-reversal visual-evoked response (P-VER) were investigated. With an increase in the stimulus field from 4 degrees X 4 degrees to 12 degrees X 12 degrees, the amplitude of the P-ERG increased steadily. The amplitude of the P-VER also showed an increase up to a stimulus field of 6 degrees X 6 degrees or 8 degrees X 8 degrees, but showed no increase with further expansion of the stimulus field. A central scotoma, created by placing a square of black paper at the center of the 12 degrees X 12 degrees stimulus field, was increased from 4 degrees X 4 degrees to 10 degrees X 10 degrees by 2-degree increments. Amplitudes of both the P-ERG and the P-VER decreased with increasing central scotoma size. The P-VER decreased significantly with a 4 degrees X 4 degrees central scotoma. Although both the P-ERG and the P-VER were influenced by the overall stimulus field and the central scotoma, there was a distinct difference in their behavior. The P-VER showed saturation above a certain stimulus field size and, with a central scotoma of 4 degrees X 4 degrees, much more reduction than the P-ERG, suggesting that the P-VER depends more on the macular area than does the P-ERG. The P-ERG also exhibited a substantial macular dependency, which, however, was not as great as that of the P-VER. The greater macular dependency of the P-VER compared to the P-ERG, as observed in our study, reflects the larger anatomic representation of the macula at the higher visual level.

Adult↗

Fracture of the carpal navicular--efficacy of clinical findings and improved diagnosis with six-view radiography.

A prospective study was conducted to determine the usefulness of clinical findings and 25-degree pronation and supination radiologic views to diagnose carpal navicular fractures. All patients presenting to the emergency department during a two-year period who fell on their outstretched hand and had pain and/or swelling in the anatomic snuffbox were evaluated initially and at two weeks. All patients received at least the standard four-view wrist radiography. If a fracture was not detected, two additional views were obtained. Ninety patients were enrolled; 54 fractures of the navicular were evident on initial four-view radiography. Thirty-six patients with a negative initial four-view radiograph had two additional views; 11 of the 36 were found to have a fracture. The other 25 patients failed to show fracture. In this series; no fractures were missed when six-view radiography was used. Anatomic snuffbox tenderness was 100% sensitive and 76% specific and had a 92% positive predictive value for carpal navicular fracture. We conclude that patients clinically suspected of carpal navicular fracture should undergo additional radiologic views if the standard four views of the wrist are negative.

Carpal Bones↗

Transanal and intraperitoneal prolapse in intussusception.

An infant with intussusception who developed an unusual complication of transanal and intraperitoneal prolapse is reported. Complete venous occlusion of the intussusceptum for a prolonged period in a patient with congenital anomalous vascular supply of the colon is suggested as a mechanism responsible for rupture of the intussuscepiens.

Ascites↗

Effect of optical defocus on the steady state pattern reversal visual-evoked response.

The effects of optical defocusing with convex lenses on the amplitudes of pattern reversal visual-evoked response (PVER) were investigated. With the large check size and high-contrast pattern, PVER amplitudes showed a linear decrease in response to initial defocusing up to +5 to +6 dptr. As the degree of defocus increased, the PVER amplitude, though irregular, continued to show reliable, definite responses up to +25 dptr. With the intermediate check size and pattern contrast, PVER amplitudes displayed a linear decrease, but unlike the large-check/high-contrast condition, diminished to noise level after a defocus of greater than +4 to +5 dptr. From these results, we speculate that two phases in this function curve derive from the large-check/high-contrast condition: first, the contrast- or contour-dependent phase, and, second, the luminosity/movement-dependent phase.

Adult↗