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Biomedical subjects

M H Miller

Publications and source records attributed to M H Miller.

At least 19 recordsLinked to original sources
PubMed1992

Fleroxacin pharmacokinetics in aqueous and vitreous humors determined by using complete concentration-time data from individual rabbits.

Although composite data from separate subjects can be used to generate single-subject estimates, intersubject variation precludes rigorous ocular pharmacokinetic analysis. Therefore, a rabbit model in which sequential aqueous and vitreous humor samples were obtained following the administration of the quinolone fleroxacin was developed. Mean data from individual animals were used for pharmacokinetic analysis. Following direct intravitreal or systemic drug administration, sequential paracenteses did not alter pharmacokinetic constants or ocular penetration and were not associated with an increase in ocular protein; contamination of vitreous humor with blood was minimal (less than 0.1%). Following direct injection or intravenous administration, vitreous humor concentration-time data were best described by one- and two-compartment models, respectively. The maximum concentration and the penetration into the aqueous and vitreous humors were 1.54 and 0.5 micrograms/ml and 27 and 10%, respectively. Elimination rates from aqueous and vitreous humors and serum were similar following parenteral drug administration. Drug elimination following direct injection was rapid, and the elimination rate from the vitreous humor was not prolonged by the coadministration of probenecid. Our animal model provides a new approach to the rigorous examination of the ocular pharmacokinetics of quinolone antimicrobial agents in the eye.

Animals↗
PubMed1991

Ethnicity and family involvement in the treatment of schizophrenic patients.

In a cross-ethnic study of neuroleptic response, the level of family involvement with the treatment of 26 Asian and 26 Caucasian patients was evaluated. Asian family members were intimately involved, Caucasians much less so. These results quantitatively demonstrated the relatively greater importance of working with family members when treating Asian patients. They also indicate that relatively more effort is needed to increase involvement of Caucasian families in the treatment process.

Asia↗
PubMed1991

Pharmacokinetics of amikacin and chloramphenicol in the aqueous humor of rabbits.

Composite data describing ocular pharmacokinetics are unreliable because of intersubject variation. To address this problem, an animal model was developed in which multiple aqueous samples from single subjects were obtained. Following direct anterior chamber or intravenous administration of amikacin or chloramphenicol, pharmacokinetic analysis of drug concentrations in the serum and anterior chamber was performed by using a nonlinear least-squares regression program. The number of anterior chamber paracenteses performed did not alter the beta elimination rates or percent penetration into the anterior chamber. The aqueous humor and peripheral-compartment terminal slopes were identical. These data indicate that complete ocular concentration-time curves can be obtained without altering antibiotic pharmacokinetics. Following direct injection into the anterior chamber, the elimination rates for both antibiotics followed a one-compartment model, whereas those following intravenous administration best fit an open, first-order, two-compartment model. Following intravenous administration, the anterior chamber elimination rate constants for both drugs were equal to that of the serum and significantly longer than that following direct injection. The elimination rates of both drugs following direct injection were similar. Systemic administration resulted in drug levels in aqueous humor that persisted longer than those following direct injection. Chloramphenicol, a lipophilic compound, gave higher mean concentrations in aqueous humor than did amikacin. Our model provides a new approach which rigorously examines ocular pharmacokinetics and provides data which suggest that for selected compounds the parenteral route of administration is preferable.

Amikacin↗
PubMed1991

Tobramycin uptake in Escherichia coli is driven by either electrical potential or ATP.

Aminoglycoside antibiotics such as streptomycin and tobramycin must traverse the bacterial cytoplasmic membrane prior to initiating lethal effects. Previous data on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis have demonstrated that transport of aminoglycosides is regulated by delta psi, the electrical component of the proton motive force. However, several laboratories have observed that growth of bacterial cells can occur in the apparent absence of delta psi, and we wished to confirm these studies with E. coli and further investigate whether transport of aminoglycosides could occur in the absence of a membrane potential. Treatment of acrA strain CL2 with the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) dissipated delta psi, decreased intracellular ATP levels, and resulted in cessation of growth; after a variable period of time (3 to 7 h), growth resumed, ultimately achieving growth rates comparable to those of untreated cells. Absence of delta psi in these cells was confirmed by absence of [3H]tetraphenyl phosphonium+ uptake as measured by membrane filtration, lack of flagellar motion, and inability of these cells to transport proline (but not methionine). Regrowth was associated with restoration of normal intracellular ATP as measured by luciferin-luciferase bioluminescence assay. Unlike unacclimatized CL2 cells treated with CCCP, these cells transported [3H]tobramycin similarly to untreated cells; aminoglycoside-induced killing was seen in association with transport. These studies suggest that under certain circumstances aminoglycoside transport can be driven by ATP (or other high-energy activated phosphate donors) alone, in the absence of a measurable delta psi. delta uncBC mutants of CL2 incapable of interconverting delta psi and ATP were treated with CCCP, resulting in dissipation of delta psi but no alteration in ATP content. Despite maintenance of normal ATP, there was no transport of [3H] bramycin, confirming that under normal growth conditions ATP has no role in the transport of aminoglycosides.

Adenosine Triphosphate↗
PubMed1991

Trabeculectomy combined with beta irradiation for congenital glaucoma.

Sixty-six eyes with congenital glaucoma were subjected to trabeculectomy between July 1975 and June 1989 are presented. Thirty-one were treated with beta irradiation at the time of surgery with a strontium-90 applicator; 35 were not treated with beta irradiation. The usual dose was 750 rad. Analysis was limited to three years because of the shorter follow-up of the irradiated eyes. Failure in the two groups was compared statistically. When failure was categorised as IOP greater than 21 mm Hg, beta irradiation was found to be significantly protective with an adjusted risk ratio of 0.31 (95% confidence interval 0.11-0.90, p less than 0.05). Failure categorised as the need for additional medical treatment or further surgery showed significant protection with an adjusted risk ratio of 0.33 (confidence interval 0.12-0.94, p less than 0.05). Multiple regression models were used for the analysis of intraocular pressure; beta irradiation was associated with a significantly lower IOP at six months, one year, and three years (p less than 0.05). Other factors identified as being associated with a reduced failure rate or lower IOP were: no previous topical glaucoma medications: age over seven years; lack of previous surgery involving the conjunctiva. The results indicate that beta irradiation may have a beneficial effect on the prognosis of trabeculectomy in children with congenital glaucoma. However, because of the retrospective and observational nature of the study, the results must be regarded as tentative.

Adolescent↗
PubMed1990

CNS side effects of centrally-active antihypertensive agents: a prospective, placebo-controlled study of sleep, mood state, and cognitive and sexual function in hypertensive males.

A prospective, placebo-controlled, comparative evaluation was conducted on two widely prescribed, sympatholytic antihypertensive agents with known CNS effects. In order to separately assess these effects in younger and older male hypertensives, patients were assigned to either of two treatment studies based on age. For study I, 24 males aged 31-59 (mean = 49.8; SD = 7.4) with mild hypertension (mean DBP = 100.2 mm Hg; SD = 8.0) received 3 months of treatment with propranolol (20-80 mg bid), clonidine (0.1-0.3 mg bid), or double-blind placebo in a counterbalanced, crossover design. For study II, 23 elderly hypertensive males (mean DBP = 102.6 mm Hg; SD = 8.2) aged 60-78 years (mean = 65.1; SD = 4.6) were randomized to propranolol (20-40 mg bid) or double-blind placebo therapy. Patients received cognitive testing, mood assessments, and all-night polysomnographic evaluations before and after each treatment period. Multivariate analysis of EEG sleep data was statistically significant for study I, with significant univariate effects on four of the six primary sleep variables: total sleep time was reduced, sleep maintenance decreased, REM latency increased, and percent total REM time was reduced. A similar MANOVA analysis for the effects of treatment on the sleep of older patients (study II) was not significant. However, propranolol administration was found to be associated with a significant decline in cognitive performance in these patients. Significant mood effects were observed with each of the study drugs, and nocturnal penile tumescence (NPT) was significantly decreased in both younger and older patients. Overall, this research suggests that distinct patterns of CNS effects are associated with each of the antihypertensive agents studied.

Adult↗
PubMed1990

Secondary angle closure in association with pseudoexfoliation of the lens capsule.

Two cases of pseudoexfoliation of the lens capsule are presented in which unilateral shallowing of the anterior chamber caused an acute rise in intraocular pressure. Both patients were elderly women. In one case anterior chamber shallowing was precipitated by administration of pilocarpine and the second followed central retinal vein occlusion. We suggest that pseudoexfoliation of the lens capsule weakened the zonule allowing forward shift to the lens and secondary angle closure.

Aged↗
PubMed1990

The effect of topical dexamethasone and preoperative beta irradiation on a model of glaucoma fistulizing surgery in the rabbit.

We studied the effect of topical dexamethasone (1%) and preoperative beta irradiation on a model of glaucoma fistulizing surgery in the rabbit. Intraocular pressure and gross facility of aqueous outflow following surgery were not influenced by either treatment, although blebs persisted longer in the irradiated eyes. Steroids reduced clinically observable inflammation as well as the number of inflammatory cells identifiable by microscopy. Fibroblast production temporarily slowed, and ultra-structural examination demonstrated lipid-filled vacuoles and dilated mitochondria in these eyes. Also, the scar was thinner at 24 days. Beta irradiation delayed wound healing and the scar was thinner in the early postoperative stages, but the light microscopic appearance of the scar was unaltered at 59 days. Inflammation was more pronounced initially, with abundant fibrin in the wound. Recovery of the conjunctival epithelium was delayed. The delay in fibroblast recruitment and wound contraction, the thinner scar tissue, and the increased survival of the bleb are all factors that suggest that beta irradiation may be a useful adjunct to glaucoma surgery.

Analysis of Variance↗
PubMed1989

Acute macular neuroretinopathy.

Acute macular neuroretinopathy is a rare, unilateral, or bilateral condition of abrupt onset causing parafoveal scotomata and occasionally reduced visual acuity. The features are described in five new cases, and the evolution of the lesions described over a period of 9 months to 9 years. One patient was studied by fine matrix perimetry, which indicated a generalized elevation of thresholds at the macula early in the disorder, together with parafoveal scotomata. The thresholds improved over several months, and the scotomata became less dense. In another case, the scotomata were still present at 9 years, although at this time they were less dense. The condition appears to mainly affect young women, and in this group there is a high incidence of a recent immunologic disturbance suggesting an immune-based etiology.

Adult↗
PubMed1989

Cerebellopontine angle epidermoid in a noise-exposed patient.

A cerebellopontine angle epidermoid was identified in a noise-exposed patient as part of an occupational hearing conservation program. The patient is a 24-year-old employee of a major national newspaper who, because of workplace noise levels, was required to be part of a hearing conservation program. A shift in thresholds in 1 year was identified by the audiologic reviewer and referral for audiologic and otologic services was recommended and carried out. The steps leading from the initial air-conduction, pure-tone audiogram to final neurosurgical removal of the epidermoid CPA lesion was described. Such referral is essential if potentially health and life threatening conditions are to be identified and managed, although the primary objectives of the hearing conservation program remains the prevention of sensorineural hearing loss from workplace noise exposure.

Adult↗
PubMed1989

Physiological response patterns to cognitive testing in adults with closed head injuries.

Physiological measures were taken from 7 closed-head-injured patients and 7 control subjects while they took a series of cognitive tests: the finger tapping test from the Halstead Reitan battery, the Digit Symbol test from the WAIS-R, a test of logical memory, and a paced arithmetic test. Physiological reactivity was assessed relative to rest periods, which occurred at the beginning and end of each session. The tests and physiological assessment were administered twice, approximately one month apart. The patient group performed more poorly on the cognitive tests, and showed less physiological reactivity during them than did the control group. This pattern was statistically significant for heart rate, frequency of electrodermal responses, and, during the initial session, respiration rate. The control group also showed greater finger pulse amplitude during the first posttest rest period in the first session, and greater constriction during a logical memory task in the second session. No significant between-groups differences emerged for state or trait anxiety. The patients showed higher frontalis EMG and respiration rate during rest. These results suggest a pattern of poor physiological modulation for task performance in the patients with closed head injuries. The therapeutic implications are discussed.

Adolescent↗
PubMed1989

Some effects of signal bandwidth and spectral density on the acoustic-reflex threshold in the elderly.

The acoustic-reflex thresholds (ART) for multicomponent tonal complexes of varying bandwidth and spectral density were obtained from 20 normal-hearing (air-conduction thresholds less than or equal to 20 dB HL at 250-8000 Hz) young adults ranging in age from 20-30 years and 20 normal-hearing, old subjects ranging in age from 60-71 years. The results revealed that the ART decreased with spectral density, plateauing after seven components in the young group and after five components in the old group; the decrease in the acoustic-reflex threshold as a result of the increase in spectral density was less in the old than in the young group. The bandwidth effect (when bandwidth was plotted in hertz or octaves) on the acoustic-reflex threshold was present in the young adults, but substantially reduced in the elderly, as evidenced by the statistically significant interaction between subject group and signal bandwidth. The spectral density results are discussed in terms of their theoretic implications for the energy summation capacity and frequency resolution of the auditory system. The bandwidth results are discussed in terms of their theoretic implications for the frequency-resolving power of the auditory system.

Acoustic Stimulation↗
PubMed1989

Coaxial needles for repeated biopsy sampling.

A set of coaxial biopsy needles permits repeated tissue samples through an outer, larger needle that remains in place. The tract can be dilated from 23 to 16 gauge with the use of transfer rods, without loss of the initial position. The technique has been used successfully in six patients.

Biopsy, Needle↗
PubMed1989

Brain white-matter lesions and psychosis.

In a prospective study of late-life onset psychosis, five of the first 27 patients studied had extensive white-matter lesions demonstrated by MRI and/or CT. None of 60 age-matched psychiatrically healthy controls demonstrated such lesions. All five patients had a mild dementia and a frontal behavioural syndrome. In addition, every patient performed poorly on neuropsychological tests of frontal function. Dysfunction of the frontal cortex associated with white-matter lesions appears to contribute to the clinical picture of some cases of late-life psychosis.

Aged↗
PubMed1989

The scleroderma neck sign.

The scleroderma neck sign, as described by Barnett, is a visible and palpable tight band over platysma in the hyperextended neck. A recent survey of 76 patients with scleroderma revealed that more than 90% had the scleroderma neck sign. Our study was performed using 15 patients with scleroderma and 30 controls including 3 with primary Raynaud's disease to examine the specificity of the scleroderma neck sign, and to look for a correlation between the presence of the scleroderma neck sign and histological changes of scleroderma in the skin overlying platysma. The scleroderma neck sign was present in 12 of the 15 patients with scleroderma but in none of the 30 controls. It was found both in patients with diffuse (5 out of 5) and limited (7 out of 10) scleroderma. In 10 of the 12 cases where the scleroderma neck sign was positive, there were characteristic histological changes of scleroderma on biopsy of the skin overlying platysma, in 1 there were nondiagnostic abnormalities, and in 1 the biopsy was unsatisfactory. The 3 patients with scleroderma in whom the scleroderma neck sign was absent had either nondiagnostic changes (1) or normal biopsies (2). The 3 patients with Raynaud's disease had normal skin biopsies. The scleroderma neck sign appears to be produced by scleroderma changes in the skin of the neck. In limited or early scleroderma where these changes are otherwise clinically inapparent, the scleroderma neck sign may be diagnostically useful.

Adult↗