Search PubMed⌕ Search

Biomedical subjects

E R Cooper

Publications and source records attributed to E R Cooper.

At least 37 records · Page 2Linked to original sources

Limits on optimizing ocular drug delivery.

The problem of optimizing ocular bioavailability of topically applied ophthalmic drugs is discussed. A formula for drug concentration in the tear film is derived using well-known pharmacokinetic relationships and a first-order drug decay model for the tear film. The time integral of the tear film concentration is then related to ocular bioavailability. The results of this analysis show that: (1) high corneal permeability (corresponding to lipophilic compounds) produces the highest bioavailability; (2) the bioavailability of drugs with high corneal permeability is relatively unaffected by drug volume; and (3) by making the dosage volume sufficiently small, a bioavailability improvement factor of approximately 4 can be obtained for drugs with low corneal permeability.

Administration, Topical↗

Malnutrition and carbohydrate malabsorption in children with vertically transmitted human immunodeficiency virus 1 infection.

The nutritional needs of children with human immunodeficiency virus infection are poorly understood. Twenty-eight children with vertically transmitted human immunodeficiency virus infection were evaluated for carbohydrate malabsorption using lactose hydrogen breath tests and d-xylose absorption studies. Lactose malabsorption was a common finding in human immunodeficiency virus-infected children and occurred in 8 of 20 patients who had no identifiable enteric pathogen. Lactose malabsorption occurred at an earlier age in human immunodeficiency virus-infected children than in an age-matched group of 45 symptomatic control children (P = 0.02). However, lactose malabsorption was not associated with higher rates of diarrhea or growth failure. Abnormalities in d-xylose absorption were not significantly associated with either diarrhea or growth failure. However, 39% of d-xylose studies (9 of 23) showed abnormal results and were significantly associated with enteric infections (P = 0.004). Abnormalities in small-bowel morphology were found in 4 of 9 children with growth failure, 3 of whom had an enteric infection and low d-xylose absorption. Lactose hydrogen breath testing and d-xylose testing showed carbohydrate malabsorption in 61% of children (17 of 28). This study demonstrates that human immunodeficiency virus-infected children are at risk for malabsorptive disorders, which are not always related to clinical symptoms. We speculate that human immunodeficiency virus may be directly involved in the development of lactose malabsorption. Carbohydrate malabsorption in human immunodeficiency virus-infected children may not be the only factor responsible for growth failure.

Acquired Immunodeficiency Syndrome↗

Early diagnosis of HIV infection in infants by detection of IgA HIV antibodies.

With the aim of achieving earlier diagnosis of human, immunodeficiency virus (HIV) infection in infants, IgA and IgM HIV antibodies in serum samples from babies born to seropositive mothers were assayed by immunoblot and enzyme-linked immunosorbent assay after removal of IgG with recombinant protein G. 64 samples were from 38 HIV-infected babies with Centers for Disease Control classifications of P1 or P2. Among these infected children IgA HIV antibodies were present in all 23 samples from those older than 12 months, in 12 of 18 samples from babies aged 6-12 months, in 5 of 10 samples from babies aged 3-5 months, and in 2 of 13 from babies under 3 months old. The 6 IgA-negative samples from infants over 6 months were all from infants with severe AIDS and/or hypogammaglobulinaemia. IgA HIV antibodies were present in twice as many samples as IgM HIV antibodies (66% vs 33%). No IgM or IgA HIV antibodies were detected in infants who subsequently seroreverted or in infants born to seronegative mothers. The correlation of the serological results with clinical information on each child suggests that detection of IgA HIV antibodies is an effective method for early diagnosis of HIV-infected infants without signs of infection.

AIDS Serodiagnosis↗

Options for the disposal of unwanted donations.

Donations of biomedical books and journals frequently duplicate the holdings of a receiving library. A decision must then be made concerning the distribution of the material to other libraries that may need it. What options are available to the librarian? Are many volumes of valuable material destroyed each year because libraries lack the necessary staff, space, or money to distribute donated materials? Are libraries restricted in choice of methods for distribution or unaware of available options? A survey questionnaire was mailed to 150 health sciences libraries in the spring of 1988 to determine the various methods used to dispose of unwanted gift materials. A total of 113 responses was received (75% return rate). This paper reports the results and discusses some of the creative methods used by receiving libraries to place unneeded materials. Statistical comparisons are included for the methods used by academic, hospital, and other types of health sciences libraries.

Book Collecting↗

Caring for children with AIDS: new challenges for medicine and society.

Caring for HIV-infected children under 13 years of age poses a serious and steadily increasing challenge to our society. Children with AIDS face devastating medical and psychosocial problems. Because of the unique implications for the entire family when a child is found to be HIV-infected, the health care profession is obliged to confront complex legal and psychosocial issues heretofore unparalleled in modern medicine. Decisions that concern schooling and daycare for the asymptomatic but HIV-seropositive individual are often influenced more by public frenzy than scientific information. Issues regarding reproductive choice and responsible parenthood are all confounded by debilitating and eventually fatal illness in infected parents. Problems of custody and foster care require innovative strategies to avoid further burden to an already stressed system. AIDS has become a disease for which research is standard of care. Access to experimental protocols is complicated by geographic location, public funding, and complexities of informed consent. The responsibility of the physician to an individual patient must be considered, and must be given its proper place within the broader responsibility to science and society.

Acquired Immunodeficiency Syndrome↗

Mechanisms of corneal drug penetration. III: Modeling of molecular transport.

A model relating the parameters of permeability coefficient in the cornea with partition coefficient and molecular weight of the penetrating species is presented. The development of the model is unique in that it includes the availability of a "pore" pathway with the corresponding kinetic data to substantiate this premise. The "pore" pathway is applied to small hydrophilic compounds and assumes that an aqueous diffusional space is available for transport of these compounds. This is in contrast to an alternate "partitioning" mechanism which is the most probable route of transport for larger or more lipophilic entities. The model is consistent with published data from this and other laboratories.

Animals↗

Acquired immunodeficiency syndrome: a new population of children at risk.

Cases of AIDS in children have been described since 1982. Diagnosis is more complex in children than in adults owing to the more varied clinical presentations and the difficulty in interpretation of laboratory tests. Our current understanding of HIV infection in children is reviewed, as well as the controversies regarding medical, psychosocial, and public health issues.

Acquired Immunodeficiency Syndrome↗

Finite dose pharmacokinetics of skin penetration.

A model for estimating in vivo skin permeability coefficients for finite doses is presented. The ratio of the maximum value of the excretion rate to the steady-state flux is a function of the thickness of the applied vehicle and the vehicle-skin partition coefficient. The decay rate of the excretion is a function of skin-vehicle parameters for large doses and, under certain conditions, can even reduce to the total excretory rate constant as the dose is decreased.

Chemistry, Pharmaceutical↗

Application of diffusion theory to the relationship between partition coefficient and biological response.

A diffusion model for transport through multilaminates is studied as a possible way to predict the optimal biological response of a set of congeners with respect to the oil-water partition coefficient, P. The model predicts the bilinear form typical of biological response data and, unlike the earlier kinetic model, also relates the results to physical processes, predicts the structure with the optimal response in terms of diffusion constants, and shows such an optimum prior to steady state for an infinite dose. Diffusion through an oil-water multilaminate causes extraordinary separation of permeating species based on partition coefficient and diffusion constant for times shorter than the lag time.

Diffusion↗

Increased skin permeability for lipophilic molecules.

Treatment of the epidermis with surfactants can markedly increase the transport of polar molecules but only marginally increases the transport of nonpolar (lipophilic) molecules. Thus, other vehicle systems are needed to increase the transport of lipophilic molecules. One method to accomplish this increased transport is to add small quantities of polar lipids to a base vehicle containing propylene glycol. The transport of nonpolar materials such as salicylic acid can be increased by an order of magnitude by the addition of small amounts of fatty acids or alcohols to a formulation. The effect of this mixed system is much greater than the effect of any of the agents alone.

Biological Transport↗

Kinetic analysis of relationship between partition coefficient and biological response.

Both nonequilibrium and equilibrium models were proposed to explain the optimal biological response to a set of congeners with respect to the oil-water partition coefficient (P). A detailed analysis of the kinetic model proposed by Hansch demonstrates the bilinear form of the model, with the initial slope of the logarithm of the concentration for 50% receptor binding versus log P having a slope of greater than one. This result is in contrast to the equilibrium model for an initial slope of less than one. Thus, a criterion is established for deciding whether equilibrium or nonequilibrium processes apply.

Biological Transport↗

Percutaneous transport in relation to stratum corneum structure and lipid composition.

Despite the acknowledged importance of the stratum corneum in limiting water loss and in controlling skin permeability, the basis for these functions remains unknown. To pinpoint those factor(s) of importance for cutaneous barrier function, we correlated the thickness, number of cell layers, and lipid composition of leg vs. abdominal stratum corneum samples with penetration of 3H-water and 14C-salicylic acid across the same tissue sample. Viable upper epidermal sheets were obtained by incubating fresh autopsy or amputation full-thickness skin with staphylococcal exfoliatin. Each sheet was divided into 3 portions. The first piece was mounted in a diffusion cell for penetration studies. The second stratum corneum sample was frozen sectioned, stained with the fluorochrome, ANS, and measured with a micrometer eyepiece. The 3rd piece was pooled with other leg (n = 6) and abdomen (n = 15) specimens for determination of lipid weight percent. In all cases, leg stratum corneum was congruent to 2 times more permeable than abdominal stratum corneum to water and slightly more permeable to salicylic acid, as well. Penetration of both substances correlated inversely with lipid weight % of leg (mean = 3.0%) vs. abdomen (mean = 6.8%), but neither the penetration of water nor of salicylic acid was influenced by the number of cell layers or the thickness of the stratum corneum. We conclude that: differences in the thickness and the number of cell layers in the stratum corneum are insufficient to account for differences in percutaneous transport across leg and abdomen, and that total lipid concentration may be the critical factor governing skin permeability.

Abdomen↗

Pharmacokinetics of skin penetration.

A model for estimating in vivo skin permeability coefficients is presented. Explicit expressions are derived for the permeability coefficient in terms of excretion rates and tissue absorption. The excretion rate has a linear asymptotic limit from which the permeability coefficient can be determined. The usefulness of the model is demonstrated with existing literature data.

Administration, Topical↗