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PubMedDate not supplied

Thank you, Mr Shaw.

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Anecdotes as Topic↗
PubMed1983

Some letters on Jewish Medical Ethics.

Specializing in Jewish Medical Ethics--a term, I believe, first used as the title of my doctor's thesis (1955) subsequently condensed and revised in book form (1959)--I frequently receive inquiries from individuals and organizations seeking guidance on the Jewish attitude to moral issues in medicine. After a review of my voluminous correspondence on many phases of this subject, I have made a small selection on a variety of topics. The correspondence on the last of the four topics, 'Medical Experimentation on Animals', is the longest, because it contains an element of polemics. Since this might make it of special interest to the Journal's readers, and since this subject is infrequently discussed in the literature of Medical Ethics, I decided to include it in this brief selection.

Abortion, Induced↗
PubMed1986

Is there a reciprocal connection between the red nucleus and the interposed cerebellar nuclei? Conclusions based on observations of anterograde and retrograde transport of peroxidase-labelled lectin in the same animal.

The rubrointerposital projection was studied in cats where wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was implanted in various parts of the interposed nuclei. No retrogradely labelled rubral cells were observed following implantations in the posterior interposed nucleus, and only very few such cells were identified in the contralateral red nucleus after implantations restricted to the anterior interposed nucleus with no contamination of cerebellar white matter or cortex. However, when WGA-HRP was delivered by a pressure injection, which in addition to the anterior interposed nucleus included the adjacent white cerebellar matter along the needle track and the overlying cortex, many retrogradely labelled cells were present contralaterally in the magnocellular red nucleus, with some also found in its rostral parvicellular part. The same observation was made when injection of free HRP exceeded the boundaries of the anterior interposed nucleus. These observations indicate that there is a negligible projection from the red nucleus to the contralateral interposed cerebellar nuclei. What has been considered to be rubrointerposital cerebellar fibres probably is the projection to the cerebellar cortex (Exp. Brain Res., 50 (1983) 353-358). Anterogradely labelled fibres could be followed from the implantations in the posterior interposed nucleus to a medial crescent of the entire contralateral red nucleus. Caudal as well as rostral parts of the posterior interposed nucleus project into the same area of the red nucleus. Implantations restricted to the anterior interposed nucleus label a projection to the contralateral magnocellular red nucleus which is topographically organized. The caudal part of the anterior interposed nucleus projects to the dorsomedial portion of the magnocellular red nucleus, the rostral part to its ventrolateral portion. In addition, a mediolateral organization in the anterior interposed nucleus coincides with a caudorostral arrangement in the red nucleus. This topical arrangement corresponds to what has previously been observed in cat and monkey, but due to the small implantation sites used in the present study a more precise mapping of the projection has been obtained. Furthermore, our implantations of WGA-HRP into the red nucleus show especially well the latter topical arrangement in the projection. The observations mentioned above are discussed and related to previous studies of the rubrocerebellar and cerebellorubral projections.

Animals↗
PubMed1979

Percutaneous absorption of clioquinol (Vioform).

The percutaneous absorption of clioquinol from three different preparations for skin treatment (Vioform cream, Locacorten-Vioform cream and Vioform-Hydrocortisone cream) was evaluated. After topical dosages corresponding to 30 mg clioquinol, concentrations in the blood were below the detection limit of the analytical procedure, i.e., smaller than 0.02 micrograms/ml; therefore the percutaneous absorption was evaluated by measuring cumulative urinary excretion of clioquinol and was compared to that found after an equivalent oral dose. The study was carried out in 4 healthy volunteers. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg clioquinol each, the urinary excretion of the drug was between 1.2 and 3.6% of the applied dose. When the same dose of clioquinol was administered orally to two volunteers, 52.4 and 92.9% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations amounted to 1.2-3.6% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of clioquinol was excreted as glucuronide (mean: 96 +/- 3%) and only a small fraction was excreted as sulfate (mean: 3.8 +/- 3%). A small amount of free clioquinol (1.1%) was measured in 1 subject only after the oral dose.

Administration, Oral↗
PubMed1987

Azelaic acid.

This review is an update on the literature accumulated over the past 10 years following the original observation that azelaic acid, a naturally occurring and nontoxic C9 dicarboxylic acid, possesses significant biologic properties and a potential as a therapeutic agent. These studies have shown that azelaic acid is a reversible inhibitor of tyrosinase and other oxidoreductases in vitro and that it inhibits mitochondrial respiration. It can also inhibit anaerobic glycolysis. Both in vitro and in vivo it has an antimicrobial effect on both aerobic and anaerobic (Propionibacterium acnes) microorganisms. In tissue culture it exerts a dose- and time-dependent cytotoxic effect on malignant melanocytes, associated with mitochondrial damage and inhibition of deoxyribonucleic acid (DNA) synthesis. Tumoral cell lines not containing tyrosinase are equally affected. Normal cells in culture exposed to the same concentrations of the diacid that are toxic for tumoral cells are in general not damaged. Radioactive azelaic acid has been shown to penetrate tumoral cells at a higher level than normal cells of the corresponding line. Topically applied (a 20% cream), it has been shown to be of therapeutic value in skin disorders of different etiologies. Its beneficial effect on various forms of acne (comedogenic, papulopustular, nodulocystic) has been clearly demonstrated. Particularly important is its action on abnormal melanocytes, which has led to the possibility of obtaining good results on melasma and highly durable therapeutic responses on lentigo maligna. It is also capable of causing regression of cutaneous malignant melanoma, but its role in melanoma therapy remains to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗
PubMed1994

Chemopreventive action by an extract from Ocimum sanctum on mouse skin papillomagenesis and its enhancement of skin glutathione S-transferase activity and acid soluble sulfydryl level.

We report the chemopreventive property of an ethanolic extract of the leaves of Ocimum sanctum (a traditional medicinal plant) on 7,12-dimethylbenz[a]anthracene induced skin papillomagenesis in male Swiss albino mice. A significant reduction in the values of tumor incidence, average number of tumors per tumor bearing mice and the cumulative number of papillomas was observed in mice treated topically with the leaf extract of O. sanctum at either the peri-initiational, post-initiational stages or continuously at peri- and post-initiational stages of papillomagenesis as compared to the corresponding control group. Topical application of Ocimum leaf extract for 15 days resulted in significant 2-fold elevation of reduced glutathione content in the skin of mice (p < 0.05). Similarly, glutathione S-transferase activity was also observed to be significantly elevated by 25% compared with the control group (p < 0.05) following Ocimum extract treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Microvascular clearance of macromolecules in skeletal muscle of spontaneously diabetic rats.

Microvascular clearance of FITC-Dextran 150 (fluorescein isothiocyanate dextran, MW 150,000) was studied in cremaster muscles of control (BB/W-R) and diabetic (BB/W-DM) rats following daily injections of a full (FD) or a 1/2 (reduced; RD) dose of insulin. The cremaster muscle was placed in an intravital chamber and superfused with bicarbonate buffer (pH 7.4, equilibrated with 95% N2-5% CO2). A 1-hour period of stabilization was followed by the i.v. injection of FITC-dextran 150 and an equilibration period of 45 min. Suffusate samples were collected for 1 h for control measurements. Following this period, bradykinin was applied topically at a concentration of 10(-7) M. Samples were collected for a final hour for the assessment of clearance. The mean +/- SEM FITC-dextran 150 clearance values (microliter/60 min/g) for BB/W-R, BB/W-DM FD, and BB/W-DM RD were 11.5 +/- 1.8, 14.8 +/- 3.4, and 90.5 +/- 12.0, respectively. The corresponding values after topical application of 10(-7) M bradykinin were 23.7 +/- 5.9, 24.2 +/- 4.4, and 98.7 +/- 25.0. Our results indicate that bradykinin evokes a twofold increase in FITC-dextran 150 clearance in the BB/W-R (control) animals and in the BB/W-DM rats receiving full-dose insulin. In contrast, bradykinin does not further enhance the eightfold increase in FITC-Dextran 150 clearance observed in the reduced-insulin dose-treated BB/W-DM group. Thus, our data show that insulin, administered at a full dose, protects the functional integrity of microvascular perm-selectivity in diabetes mellitus.

Administration, Topical↗
PubMed1994

The effects of topical hypothermia and steroids on ATP levels in an in vivo liver ischemia model.

Complex hepatic surgery often requires occlusion of the portal triad in order to decrease parenchymal bleeding. This study was undertaken to evaluate the effects of topical hypothermia and intravenous steroids on liver ischemia by measuring adenosine triphosphate (ATP) levels within the hepatic parenchyma. Forty New Zealand white rabbits were divided into four experimental and four control groups. All experimental animals underwent laparotomy and ligation of the porta hepatis. Serial liver biopsy specimens were obtained at predetermined time intervals. Group I received no further intervention. Group II were topically cooled until intrahepatic temperature reached 30 degrees C. Group III received preligation intravenous methylprednisolone (30 mg/kg). Group IV received both steroids and topical hypothermia. The corresponding control groups underwent laparotomy and isolation of the porta without ligation. Adenosine triphosphate was extracted from the liver parenchyma and quantified by high-performance liquid chromatography (HPLC). The data were analyzed using a three-factor mixed analysis of variance (ANOVA). There was a statistically significant protective effect on ATP levels provided by topical hypothermia at 15 and 30 minutes of ischemia (p < 0.01), but not at 60 minutes (p > 0.05). Steroids were not found to have any protective effect on ATP levels at any time point. The combination of steroids and topical hypothermia provided significant preservation of hepatic parenchymal ATP levels, although less than that of hypothermia alone, at 15 and 30 minutes of ischemia (p < 0.01).

Adenosine Triphosphate↗
PubMed1994

Effects of topical methylene blue on cyclic GMP level, blood flow, and O2 consumption in focal cerebral ischaemia.

We hypothesized that a decrease in cyclic GMP, a second messenger in the glutamate-nitric oxide pathway, would reduce oxygen consumption and improve O2 balance in the ischaemic cerebral cortex. To test this hypothesis, a study was performed in unilateral middle cerebral artery occluded rats which were assigned to either a control or methylene blue (10(-3) M) group. Regional cerebral blood flow was determined using 14C-iodoantipyrine and regional arterial and venous O2 saturations were determined by microspectrophotometry (n = 6). Cyclic GMP level was measured by radioimmunoassay (n = 8). Guanylate cyclase and cyclic GMP-phosphodiesterase activities were determined in an additional set of control rats (n = 10). The cyclic GMP levels were not different between the ischaemic and contralateral areas in the control group. Compared to the cyclic GMP in the control ischaemic cortex, topical methylene blue significantly decreased the cyclic GMP level by 56% in the ischaemic cortex of the methylene blue group. Ischaemia did not alter the activities of guanylate cyclase but mildly decreased cyclic GMP-phosphodiesterase. The regional cerebral blood flow and O2 consumption in the control group were 50% and 32% lower than those in corresponding contralateral cortex. Topical methylene blue did not alter regional cerebral blood flow and O2 consumption in the ischaemic cortex. Our data showed that cyclic GMP is not a major controller on O2 supply or O2 consumption in the ischaemic brain.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1981

Preselecting literature for routine delivery to physicians in a community hospital-based patient care related reading program.

Health sciences librarians have been actively responding to the changing information needs of users by extending services which involve the selection of literature in response to specific requests from health care personnel. A further development is Patient Care Related Reading (PCRR), a hospital-based program of continuing medical education in which the librarian actively participates in the preselection, packaging, and routine delivery of literature for use by physicians caring for patients with certain clinical disorders. Criteria for selection of literature packet topics were developed jointly by librarians and physicians at their own hospitals. Librarians compiled bibliographic material, reviewed articles, and prepared preliminary packets. Physicians reviewed these packets and made suggestions for each article. Librarians then prepared final packets following reviewers' recommendations and distributed them as a routine procedure to all physicians caring for patients with a diagnosis corresponding to prepared topics. Librarians were notified of patients with PCRR clinical problems by admitting office personnel, floor nurses, nursing supervisors, utilization review, and Professional Standards Review Organization personnel as a part of their usual activities. Packets are used by physicians to add to their fund of knowledge, and for review and teaching purposes. PCRR has provided increased visibility of the library and its many services. Recognition of the librarian's role in the program reinforces the concept of the community hospital library as a service-oriented entity, and helps to establish the library as an active partner in the development and implementation of hospital-based continuing education programs.

Hospitals, Community↗
PubMedDate not supplied

Dose-dependent pharmacokinetics of MK-417, a potent carbonic anhydrase inhibitor, in rabbits following single and multiple doses.

MK-417, a potent carbonic anhydrase inhibitor capable of reducing intraocular pressure after topical application, is currently under investigation for the treatment of glaucoma. The purposes of this study were to characterize dose-dependent pharmacokinetics of MK-417 and to determine the accumulating effect of the drug during chronic topical administration in rabbits. Because the drug resided primarily in the erythrocytes, kinetic analyses were performed on whole blood concentration data. Following i.v. administration, both total blood clearance and apparent volume of distribution for MK-417 increased disproportionately between the low and high dose, while the half-life of the drug appeared to be independent of dose. Total blood clearance and apparent volume of distribution increased from 0.993 +/- 0.224 ml/hr/kg (mean +/- SD) and 88.6 +/- 9.4 ml/kg at a dose of 0.05 mg/kg to 2.73 +/- 0.17 ml/hr/kg and 272 +/- 5.5 ml/kg at a dose of 1 mg/kg. The dose-dependent kinetics of MK-417 are probably due to the saturable binding of carbonic anhydrase. Upon instillation of MK-417 into the eyes, the drug was rapidly and well absorbed. At the low dose of 0.05 mg/kg, the bioavailability varied from 58% to 98.5% with a mean value of 76.5 +/- 20.5%. Prediction of concentrations of MK-417 during chronic topical administration were performed based on the corresponding concentrations after a single topical dose using an overlay technique. Good agreement between the experimental data and the predicted blood concentrations of MK-417 during chronic dosing at 0.05 mg/kg, but not at 1 mg/kg, strongly suggests that linear kinetics apply in the case of the low dose but not in the case of the high dose.

Animals↗
PubMedDate not supplied

[Comparative histomorphometry of subchondral bone density and articular cartilage thickness in the tibial head in early human arthritis].

The articular cartilage thickness and subchondral bone density of 50 human tibial heads were histomorphometrically measured by an image analysing system and topographically examined in relation to age, sex and grade of osteoarthrosis (OA). Altogether we evaluated 12,000 items. Independent of OA the lateral tibial plateau shows a significant thicker cartilage layer than the medial. In central joint areas we find a thicker cartilage cover than in marginal. Corresponding to the literature cartilage fibrillation according to OA grade 1 and 2 (Otte 1969, Fassbender 1975) accumulates in the lateral and dorsal tibial head including the meniscus covered area. The cartilage thickness decreases with age independent of OA. Without major alterations of the topographical pattern the cartilage thickness however shows a significant increase in early OA (grade 1). For that reason measurements of the cartilage thickness and joint space narrowing are not appropriate for defining early OA. The subchondral bone density shows high values ventromedially and dorsolaterally independent of sex, age or OA. Beneath central joint areas higher values are found than marginally. Corresponding to the topical literature our results point at the model of the real loaded knee joint, which says that the mean loading forces do not act on the middle of the joint but on the medial plateau. The dorsolateral density centre could be an expression of the functional adaptation of the bended knee joint. In joint areas with cartilage fibrillation (OA grade 1) we find a significant higher subchondral bone density without major alterations of the topographical pattern. It is not possible to define cause and effect, we interpret both as result of higher joint loading.

Adolescent↗
PubMed1990

Two cell kinetic methods studied on the rat corneal epithelium.

A stathmokinetic method (using Colcemid) and the [3H]thymidine technique (pulse labelling with tritiated thymidine, [3H]TdR) have been evaluated in the rat corneal epithelium. The dose is not of critical importance for the Colcemid method, thus indicating an all or nothing effect within the dose range studied. A one point estimate is sufficient to calculate the mitotic rate (MR), and in the rat corneal epithelium a 4 h accumulation period is recommended. After administration of [3H]TdR there is an increasing response with increasing dose, followed by a levelling off at higher doses. It seems reasonable to use the lowest maximal effective dose. The labelling index (LI) can be reliably registered 1 h after administration of the drug. For each of the drugs we found corresponding results after topical application and intraperitoneal injection. Hence, topical application of small doses of both Colcemid and [3H]TdR makes interesting in vivo experiments on larger animals and even on human beings possible. Due to the extreme regularity of the corneal epithelium this part of the eye is an interesting organ for cell kinetic studies and provides an excellent tool for evaluating cell kinetic methods.

Administration, Topical↗