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Biomedical subjects

B H Thiers

Publications and source records attributed to B H Thiers.

At least 19 recordsLinked to original sources

Acyclovir in the treatment of herpesvirus infections.

The development of the synthetic acyclic purine nucleoside analog acyclovir was a milestone in the field of antiviral chemotherapy. Acyclovir possesses unique biologic properties that make it especially useful for the treatment of herpesvirus infections. This article presents guidelines for the use of acyclovir in both immunocompetent and immunocompromised patients. The problem of acyclovir resistance is also discussed.

Acyclovir

Antiretroviral therapy.

Research into the biology of human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome, has yielded valuable information about the replicative cycle of the virus. The steps involved are (1) attachment of the virus to a receptor protein on the surface of the target cell, (2) entry of the virus into the cell, (3) replication of the viral genome through a DNA intermediary, (4) entry of proviral DNA into the nucleus of the host cell, (5) integration of proviral DNA into the host cell genome, (6) transcription of proviral DNA to viral genomic and messenger RNA, (7) translation of viral messenger RNA to viral proteins, and (8) assembly of viral components into new virions that are released by budding from the host cell membrane. Each step in the HIV-1 replicative cycle offers a potential target for antiviral chemotherapy. Although many drugs have been developed, none appears singularly effective against all stages of HIV-1 infection. Many obstacles remain in the quest for an effective vaccine against HIV-1.

Acquired Immunodeficiency Syndrome

Physician drug dispensing.

We have reviewed the issue of physician drug dispensing by focusing upon quality of care, economic considerations, drug availability, patient compliance, safety, and increased governmental regulation. From a quality of care perspective, the increased use of pharmacist assistants, the tendency toward generic and therapeutic drug substitution, and the less specialized clinical education of pharmacists all pose hazards rather than safety checks upon physician prescribing. There is no evidence that pharmacists charge less than physicians. If they did, there would be no need to protect their incomes legislatively by restricting physician dispensing. Economic motivation per se is less important to a physician than providing a true convenience for his patients and thus encouraging a closer doctor-patient relationship. Physician dispensing adds to the availability of medication and may minimize the number of patients shuttling between pharmacies to obtain complex multi-ingredient preparations. Compliance is enhanced as availability increases. Prepackaged pharmaceuticals prepared under the auspices of pharmacists and dispensed by physicians are at least as safe as those prepared by the ungloved hands of a pharmacist hidden behind store counters. Thus, restricting the physician's right to dispense can negatively affect the quality of medical care, the cost of medications, safety, the availability of pharmaceuticals, and patient compliance. Such limitation is certainly not in the best interest of our patients.

Consumer Product Safety

Dermatologic therapy in the 1980s.

Some of the new therapeutic agents of the 1980s, such as acyclovir and etretinate, will have a long-lasting impact on the treatment of skin diseases. Others have seemingly fallen from grace after an initial period of popularity. This article reviews a number of new agents and provides sources of further information. As with all new treatments, any physician unfamiliar with a product should consult these references and the manufacturer's labeling.

Dermatologic Agents

A new method for the comprehensive automatic morphologic image analysis of Langerhans cells.

Standard techniques used to study Langerhans cell (LC) populations are tedious and time-consuming. We developed a rapid and comprehensive method to evaluate LC using automatic digital image analysis. Human epidermal sheets were stained with OKT6 monoclonal antibody and evaluated on an IBAS 2000 computerized automatic digital image analysis system. The fields were imaged on a Photomicroscope I using a high-resolution monochrome video camera. Each field was digitized, normalized, and filtered. The LC were discriminated by density; each field was interactively edited to separate overlapping cells and to bridge small gaps in the dendrites. The discriminated binary image of the LC was measured for number of cells per field, total area of individual cells per field, and percent of the field occupied by LC. The cell bodies were then separately discriminated and subtracted from the thinned cell image to allow a separate measurement of number and length of dendrites per cell. Finally, the binary cell image in a reference section was dilated to occupy approximately the total field area. This degree of dilation was then applied to all subjects to give the "area of influence." This methodology provides a rapid and comprehensive tool for the evaluation of LC.

Autoanalysis

A randomized double-blind study of inosiplex (isoprinosine) therapy in patients with alopecia totalis.

Twenty-five of 34 patients with alopecia totalis of at least 1 year's duration and associated defects in cell-mediated immunity completed a randomized, double-blind, placebo-controlled crossover trial of the therapeutic effect of inosiplex, a synthetic immunomodulator. Each patient received 20 weeks of treatment with inosiplex and 20 weeks with placebo in randomized order. Eleven patients were identified clinically as responders to inosiplex in terms of hair regrowth. Scalp biopsy results correlated well with drug therapy. Enhanced immune function was found in the majority of responding patients; however, statistical analysis of the results of the entire patient population revealed limited significant differences. No patient experienced adverse side effects attributable to therapy. These results show that inosiplex is a safe and effective therapy for certain patients with alopecia totalis.

Adult

In vitro suppression of human lymphocyte activity by minoxidil.

The in vitro effect of minoxidil on normal human lymphocyte activity was studied. At a concentration of 0.1 mg/ml, minoxidil significantly inhibited phytohemagglutinin-dependent lymphocyte DNA synthesis (p less than 0.05), and at 0.01 mg/ml, 0.05 mg/ml, and 0.1 mg/ml, it suppressed mitogen-dependent production of leukocyte migration inhibition factor (p less than 0.04, p less than 0.01, and p less than 0.01, respectively), without compromising cell viability. Minoxidil thus appears to exert a suppressive effect on normal human T-lymphocytes in vitro. The physiologic relevance of these findings remains uncertain.

Cell Migration Inhibition

An open-label trial of immunomodulation therapy with inosiplex (Isoprinosine) in patients with alopecia totalis and cell-mediated immunodeficiency.

Nine patients with alopecia totalis and associated defects in T lymphocyte function were admitted to an open-label trial of inosiplex therapy. All nine developed enhanced T cell function and seven had clinically significant hair regrowth. The immunologic response to inosiplex was dose-dependent in five patients. These data provide new information on the in vivo effects of inosiplex on the human immune system and support the hypothesis that disturbances of immunologic mechanisms may play a pathogenetic role in alopecia totalis in certain patients.

Adjuvants, Immunologic

The effect of aging and chronic sun exposure on human Langerhans cell populations.

ATPase histochemistry was used to examine Langerhans cell (LC) populations in the skin of young persons with no evidence of solar damage and older adults with chronic actinically damaged skin. The number of LC was significantly decreased in the older age group. Significantly fewer LC were observed in exposed vs covered skin in the older individuals; no such disparity was noted in the younger subjects. Morphologic alterations in ATPase-positive cells were noted in some specimens, most of which were taken from the exposed skin of elderly persons. The results suggest an independent, although possibly additive, quantitative and qualitative influence of aging and chronic sun exposure on the LC population. Decreased numbers of LC in the sun-damaged skin of elderly individuals may play a critical permissive role in the development of cutaneous carcinoma.

Adenosine Triphosphatases

Immunological profiles in alopecia areata.

Cell-mediated immunity and auto-immune phenomena were investigated in sixty patients with active alopecia areata of various degrees of severity. Serum auto-antibodies to thyroid antigens were detected in twenty-three patients. Examination of T-lymphocyte populations, lymphocyte DNA synthesis, and lymphokine production in response to mitogen stimulation revealed no differences between the sixty patients and matched healthy control subjects. However, patients with thyroid auto-immunity and/or the presence of alopecia totalis or universalis showed significant reductions in interactive T lymphocytes (recognized by rosette formation with human B lymphoblastoid cells) and diminished production of leukocyte migration inhibition factor in response to stimulation with phytohaemagglutinin. This suggests that immune mechanisms may be involved in the pathogenesis of alopecia areata which is associated with thyroid auto-immunity or which progresses to total hair loss.

Adolescent

Gm allotype associated resistance and susceptibility to alopecia areata.

IgG heavy chain (Gm) and kappa light chain (Km) allotypes were determined in 42 Caucasian patients with alopecia areata. There was a significant increase in frequency of Gm 1,2,3,17;5,13,21 (P less than 0.001), and a significant decrease in frequency of Gm 1,3,17;5,13,21 (P = 0.009), when results were compared to those of 105 normal healthy Caucasians from the same geographic area. These results can be explained by postulating dominant disease susceptibility and resistance genes in significant linkage disequilibrium with the haplotypes Gm1,2,17;21 and Gm1,17;21, respectively.

Adult

Controversies in mycosis fungoides.

Most clinicians agree that mycosis fungoides is the prototypic cutaneous T cell lymphoma. However, certain clinical characteristics indicate that this disorder may begin as a reactive rather than a neoplastic process. The concept of a nonneoplastic etiopathogenesis of mycosis fungoides is further supported by recent data on the function of Langerhans cells, a population of epidermal cells known to play a critical role in immune surveillance and the development of contact sensitivity. It has been suggested that chronic occupational exposure to environmental allergens results in persistent antigenic stimulation, leading to a breakdown in immune surveillance and eventually, malignancy. Modern laboratory technics have enhanced the clinician's ability to diagnose and stage mycosis fungoides. Data obtained from such studies have indicated that systemic spread may occur much earlier in the course of disease than has previously been appreciated. The therapeutic implications of such knowledge are as yet uncertain.

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