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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↗
PubMed1978

Single and combination antibiotic therapy of Staphylococcus aureus experimental endocarditis: emergence of gentamicin-resistant mutants.

The efficacy of nafcillin and gentamicin used alone and in combination at doses giving serum concentrations comparable to those achieved in patients was studied in rabbits with experimental Staphylococcus aureus endocarditis. The organism used was a penicillinase-producing, methicillin-susceptible, clinical isolate. The addition of gentamicin to nafcillin significantly increased the rate of killing of organisms in valvular vegetations, compared to the effect of nafcillin alone. Gentamicin alone delayed mortality but was not effective in reducing the bacterial populations of the vegetations. Bacteremia persisted in the animals treated with gentamicin alone, in contrast to the groups treated with nafcillin or the combination. Selection of a subpopulation of aminoglycoside-resistant small-colony variants occurred in animals treated with gentamicin alone. This variant was subsequently employed in the rabbit model and produced endocarditis, metastatic infection, and bacteremia comparable to those caused by the parent strain. Animals with infection produced by the variant died later than animals infected by the parent strain. Nafcillin was equally effective in reducing the population of both parent and variant strains in vitro and in therapy of the infected animals. Population studies showed the variant to be a mutant emerging at a rate of 1.9 x 10(-7). It was shown to differ from the parent strain in coagulase and hemolysin production, colonial morphology, and aminoglycoside susceptibility, but was similar by light and electron microscopy and in phage type, pigmentation of colonies, deoxyribonuclease production, mannitol fermentation, and growth rate.

Animals↗
PubMed1978

Recent cases of intracranial tuberculomas.

While intracranial tuberculomas have become uncommon in industrial nations, 12 patients with signs and symptoms of an intracranial mass lesion were recently found to have tuberculomas. Clinical findings suggestive of tuberculosis were frequently subtle or absent. Five patients did not have extracranial tuberculosis. Two patients had intracranial tuberculomas that became superinfected with bacteria and appeared initially as pyogenic brain abscesses. Intracranial tuberculomas in this country almost always occur in adults and represent reactivation of dormant infection. Medical therapy alone is indicated as the initial therapy except in the presence of intolerably increased intracranial pressure. A chemotherapeutic regimen is suggested.

Adult↗
PubMed1978

Septicemia in patients on chronic hemodialysis.

Bacterial sepsis, a major complication of chronic hemodialysis, is due mainly to infections of the vascular access site despite increasing use of internal fistulas. Sixty episodes of septicemia occurred in two chronic dialysis centers, with an incidence of 0.15 episodes of significant bacteremia per patient-dialysis-year in each. Forty-four of the 60 episodes were judged to be due to vascular access site infection by clinical, bacteriologic, and histologic criteria. Seventy percent (31 of 44) of the vascular access site-related episodes were due to staphylococci and 25% (11 of 44) to Gram-negative bacilli; nonvascular access site-related episodes were often due to transplant site infections caused by Gram-negative bacilli or streptococci. Mortality was about 18% in both vascular access site-related and nonrelated septic episodes. Bovine heterograft arteriovenous fistulas more often led to sepsis than did Brescia arteriovenous fistulas. Treatment with appropriate antibiotics was successful in most cases. Routine removal or ligation of the vascular access site was not necessary.

Animals↗
PubMed1978

Ocular penetration of 5-fluorocytosine.

Ocular penetration of 5-fluorocytosine (5FC) was studied in uninfected rabbits after subconjunctival and oral administration. With oral administration, 5FC achieved therapeutic levels in both the vitreous and aqueous humors. The use of a pharmacokinetic model permitted objective comparison of kinetic events within the eye chambers and the serum. The rates of entry and elimination in the vitreous were found to be slower than those in the aqueous, but the mean concentration over 24 hr was the same. The therapeutic levels achieved in the aqueous after subconjunctival administration were of shorter duration, and no detectable levels occurred in the vitreous. Oral administration is clearly therapeutically superior to subconjunctival administration in this model.

Administration, Oral↗
PubMed1977

Angiographic changes of head and neck chemodectomas following radiotherapy.

Angiography is useful in following selected patients with chemodectoma of the head and neck treated by radiotherapy. Comparison of preradiotherapy and post radiotherapy angiograms in three patients revealed a decrease in the following: size of feeding arteries, size of tumor, intensity of tumor opacification, and degree of venous shunting. When chemodectomas are not amenable to physical examination and when the question of radiotherapy complication vs further growth of tumor arises, postradiotheraphy angiography may be of particular value.

Adult↗
PubMed1977

Angiographic observations on chemodectomas of the head and neck.

Angiographic experience with chemodectomas in 21 patients is reviewed. Arterial supply was identified from the vertebral artery, the internal carotid artery, and branches of the external carotid artery. A striated cephalad extension from a cervical chemodectoma (five patients) is believed to represent arterial supply to tumor in vein. In two patients, internal and external carotid arteriograms did not opacify important arteries originating near the carotid bifurcation. Retrograde filling of sigmoid sinus (four patients), tumor mass in jugular vein (two patients), and arteriovenous shunting (nine patients) were observed during the venous phase. Thorough angiogra phy is essential for evaluation of chemodectomas of the head and neck.

Angiography↗