Biomedical subjects

D J McCarthy

Publications and source records attributed to D J McCarthy.

At least 19 recordsLinked to original sources

PubMed1991

Toxicity and antitumor activity of liposome-entrapped retinoid Ro13-7410.

We compared the toxicity of free and liposome-entrapped retinoid, Ro13-7410 in C2DF1 mice. Mice received 7 daily i.p. injections of liposome-entrapped Ro13-7410 at doses of 5, 10, 100, 500, or 1000 micrograms/kg bw/day. For comparison, two groups of mice were used as controls, one group received Ro13-7410 in corn oil and a second group received liposome-entrapped Ro13-7410 that had been solubilized with detergent. The liposomes were then tested for chemotherapeutic activity against human myelocytic leukemia (HL-60/MRI) implanted in athymic NCr-nu mice. The doses used in the chemotherapy experiment (20, 50, and 100 micrograms/kg bw/day) were selected based on the results of the toxicity experiment in CD2F1 mice. CD2F1 mice were marginally protected from toxicity after receiving retinoid in liposomes relative to controls. There were 2/5 survivors in the 1000 micrograms/kg bw/day Ro13-7410-liposome group after 7 daily i.p. doses compared to 0/5 for both the corn oil and solubilized liposome groups, and 4/5 survivors in the 500 micrograms/kg bw/day Ro13-7410-liposome group after 7 daily i.p. doses compared to 2/5 for both the corn oil and solubilized liposome groups. We observed no dramatic differences in toxicity among the treatment groups over the range of doses administered. There were 2/6 long-term tumor-free survivors in athymic mice receiving liposome-entrapped retinoid, at 50 micrograms/kg bw/day for 7 days, compared with 0/6 and 0/9 survivors in groups receiving empty liposomes or no treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Diagnosis and treatment of tinea pedis. A review and update.

Fungal foot infections are becoming an increasingly common public health problem as the population ages. New studies have shown that some of the traditional therapeutic antifungal agents have multiple actions that enable them to be more efficacious than previously thought, and more efficacious than other agents without multiple actions. In this review article, the pedal infections commonly referred to as tinea pedis, or athlete's foot, are described. The etiologic agents involved in the pathogenesis, the methodologies for proper diagnosis, and the therapeutic agents commercially available for treatment are reviewed.

Antifungal Agents↗

PubMed1990

Pharmacological and toxicological properties of arotinoids SMR-2 and SMR-6 in mice.

Studies were conducted to define primary pharmacological and toxicological properties of two arotinoids, SMR-2 and SMR-6, in male B6D2F1 mice. Mice were gavaged daily for up to 22 days with retinoids in corn oil (0.1, 0.2, or 0.4 mg/kg day SMR-2 or SMR-6 or 2.5, 10, or 30 mg/kg all-trans-retinoic acid as a reference control). Toxicological and biochemical endpoints were assayed after 8, 15, and 22 days. At toxic doses, i.e., those inducing weight loss, morphological changes were observed in skin, lymph nodes, spleen, bone marrow, liver, thymus, forestomach, adrenal, bone, and testes. Biochemical alterations included elevated serum alkaline phosphatase, corticosterone, and interleukins-1, -2, and -3. Additional immune alterations included increased responsiveness of spleen cells to both thymus-dependent and thymus-independent mitogens and increases in the total number of B cells in the spleen. At doses not inducing weight loss, target organ effects included the appearance of plasma cells and infiltration of polymorphonuclear cells in lymph nodes; myeloid cell hypercellularity in bone marrow; hematopoiesis in spleen; subacute inflammation in forestomach; and periportal cytoplasmic vacuolization in liver. At the low doses, SMR-2 resulted in decreased responsiveness of spleen cells to mitogens and SMR-6 caused increased responsiveness. SMR-6 also increased interleukin-1 and-2 production at low doses. Biochemical effects included reduced activities of liver aryl hydrocarbon hydroxylase (AHH) and soluble brain protein kinase C. Overall, the results suggest that leukopoiesis and reduced liver AHH and reduced soluble protein kinase C activities are the primary and initial pharmacological and toxicological effects of retinoids.

Animals↗

PubMed1990

Periungual fibroma.

Periungual fibromas are rare benign dermatologic lesions that may be acquired or associated with tuberous sclerosis or von Recklinghausen's disease. Periungual fibromas may place excessive pressure on the nail matrix, resulting in the potential for extensive nail pathologic conditions and pain. Radical surgical excision of the lesion is the preferred treatment in symptomatic cases. The case of such a foot lesion occurring in an elderly man, including histopathologic analysis of the excised lesion, is detailed here.

Aged↗

PubMed1989

Retinoid-induced hemorrhaging and bone toxicity in rats fed diets deficient in vitamin K.

The recent increase in the clinical use of synthetic vitamin A compounds has led to concern of possible side effects. Some of these effects are known to be influenced by dietary levels of vitamin K. We therefore compared the toxic effects of 13-cis-retinoic acid (13cisRA), retinyl acetate (ROAc), and N-(4-hydroxyphenyl)retinamide (4HPR) in male Sprague-Dawley rats maintained on diets containing different levels of vitamin K. Animals were fed either an NIH-07 diet supplemented with menadione (3.1 ppm vitamin K3), an NIH-07 diet not supplemented with menadione, or an AIN-076 purified diet devoid of vitamin K. The retinoids had no effect on prothrombin times of animals fed the supplemented diet. When menadione was omitted from the diet, however, 4HPR-dosed animals had elevated prothrombin times. This effect was observed as early as Day 7 and was accompanied by one confirmed hemorrhagic death. 13cisRA-dosed animals showed no change in prothrombin times. In the high-dose ROAc group, there was a twofold increase in prothrombin times but only after prolonged dosing. In animals fed the NIH-07 diets, 13cisRA and ROAc induced multiple bone fractures at all dose levels. In contrast, 4HPR administered at the highest dose induced only one fracture in one animal. Animals fed the purified diet lost weight faster and diet sooner than those maintained on the other diets. Bone fractures were not observed in these animals because of early deaths resulting from hemorrhaging. For all retinoid-dosed groups maintained on the purified diet, changes in prothrombin times occured as early as 1 week. The order of effect was 4HPR greater than ROAc greater than 13cisRA, with increases in prothrombin times correlating with increases in hemorrhagic deaths. Hence, the degree of retinoid-induced hemorrhage, but not the incidence of bone fractures, was inversely related to vitamin K levels in the diet. 13cisRA and ROAc, but not 4HPR, caused a dose-dependent reduction in plasma osteocalcin, an effect that correlated with retinoid-induced bone effects. In contrast, serum alkaline phosphatase was elevated in animals dosed with 13cisRA or 4HPR but not in those dose with ROAc. For this enzyme, the electrophoretic pattern on agarose gel showed a decrease, compared to controls, in the major isozyme in serum of ROAc-dosed animals. Hence, plasma osteocalcin is a better predictor of retinoid-induced bone effects than serum alkaline phosphatase.

Alkaline Phosphatase↗

PubMed1989

Modification of retinyl acetate toxicity in rats by coadministration of menhaden oil.

Menhaden oil, which has hypolipidemic and anticarcinogenic activity, reduces the hypertriglyceridemia caused by retinyl acetate. Male Sprague-Dawley rats were dosed daily for 30 days by gavage with either corn oil (CO); menhaden oil (MO); 20, 80, and 250 mg/kg retinyl acetate (ROAc) in CO; or 20, 80, or 250 mg/kg ROAc in MO. Hypertriglyceridemia by ROAc was reduced by coadministration of MO, and serum cholesterol values were reduced to levels similar to those for rats receiving MO alone. Coadministration of MO reduced the ROAc-induced fracture incidence at 80 mg/kg but not at 250 mg/kg. For groups dosed with ROAc and CO or MO, there were no differences in weight-gain depression, elevation of serum alkaline phosphatase, or reduction of food consumption, suggesting that reduced absorption of ROAc was not the basis for the activity of MO. The reduction in retinoid toxicity by MO suggests a need for further study of the toxicity and anticarcinogenicity of retinoid/menhaden oil combinations.

Alkaline Phosphatase↗

PubMed1989

Lower extremity peripheral vascular disease. Part 1: Scanning electron microscopy.

The surgical loss of the foot or leg is vigorously resisted by podiatrists who are committed to the conservation of limbs at risk because of peripheral vascular disease. Pathologic changes in blood vessels may, however, progress to a point where no other option is available to the patient. This study assesses amputation of the extremities and investigates tissue alterations that can be identified in diseased blood vessels implicated in these circumstances. Gross pathology and scanning electron microscopy are examined in this, the first of a two-part study.

Amputation, Surgical↗

PubMed1989

Lower extremity peripheral vascular disease. Part 2: Light and transmission electron microscopy.

In spite of the most vigorous efforts to intervene medically and surgically when peripheral vascular disease threatens a patient, amputation of the extremity may be the only option left to arrest the progression of the disease. In a previous study, the authors assessed amputations, examined gross pathology, and identified scanning electron microscopic features associated with atherosclerotic disease. In the present study, the authors discuss this disease in terms of conventional light microscopy and transmission electron microscopy.

Arteriosclerosis↗

PubMed1989

Modified V-Y capsulorrhaphy in hallux abducto valgus surgery.

The two-stage capsular closure modification of the V-Y capsulorrhaphy in hallux abducto valgus surgery is a technique for restoring the soft tissue anatomical relationships of the first metatarsophalangeal joint in a bunion deformity. The first stage of the V-Y capsulorrhaphy corrects the plantar and lateral deviation of the abductor hallucis tendon. The second stage of the V-Y capsulorrhaphy closure allows for the correction of abductus and valgus rotation of the hallux. Inasmuch as each element of the soft tissue deformity in hallux abducto valgus deformity is corrected individually, greater precision can be applied to each constituent of the hallux abducto valgus deformity.

Cartilage, Articular↗

PubMed1989

Homologous and heterogenous bone grafting in podiatric surgery.

Homologous and heterogenous bone grafting as it might be used in podiatric surgery is reviewed with emphasis on histologic events observed. New bone proliferation, resorption, revascularization, and remodeling are contrasted with autogenous bone grafts, which are generally thought to be the preferred surgical option.

Bone Transplantation↗

PubMed1989

Podiatric pathology of lupus erythematosus.

Lupus erythematosus is an enigmatic disease. Its podiatric manifestations are largely cutaneous, but vasculitic involvements may produce complications. The authors review much of the histopathology of lupus erythematosus that is relevant to the podiatric physician and surgeon. Awareness of the serious systemic implications of lupus erythematosus and the internal medications used in treatment is part of the physician's responsibility in understanding the whole patient.

Foot↗

PubMed1989

The developmental anatomy of pes valgo planus.

Pes planus or flatfoot becomes a medical problem only when symptoms develop. The mere absence of a well-formed medial longitudinal arch does not necessarily imply pathology. Many apparently "flat feet" demonstrate congruent joints, and the extremities function normally. The size and shape, as well as the angles of declination for the talus or astragulers and the calcaneus or os calcis, are most often determined at the moment of fertilization by the genes of the patients. The zygote or fertilized ovum is a first totipotent. Cell division normally occurs as development proceeds, but the embryo is vulnerable to alterations of the cell cycle. Teratogenic substances can induce death or substantial structural modifications to the developing fetus. The post-World War II tragedy of the medical use of the drug thalidomide in pregnant mothers resulting in amelia is testimony as to how the lower extremity can be adversely affected. Early chromosomal aberrations including duplication, deletion, breakage, inversion, translocation, and mosaicism have been shown to be involved in faulty development of the foot, and there is no reason not to implicate pes valgo planus to these events. Intrauterine development apart from the genetic considerations just mentioned place the fetus under additional jeopardy. Even extraembryonic membranes can form strands of tissue that can entangle the delicate developing foot plate, and calcaneovalgus deformities could conceivably be established. The developing embryo and fetus first demonstrate a blastema that forms limb buds on the ventral caudal aspect. Anlage of the scleroblastema and myoblastema of the prospective leg and foot develop in the presence of nerve trunks. Such nerves are related to the lumbosacral plexus and they are thought to exert inductive developmental influences. Interference with any of these events may be implicated in pedal deformities such as pes valgo planus. This is also true of subsequent morphogenetic events involving embryonic rotations, osteogenesis, and myogenesis. Many pedal deformities have congenital basis and it is clear that pes valgo planus is one of them. Post-natal structural changes further accentuate underlying etiologies. For example, the calcaneus normally exhibits a varus position at birth, but this feature diminishes until the cessation of bone growth. The adult talar neck-calcaneal angle is normally about 24 degrees, representing a 6-degrees reduction from that of 30 degrees, which is demonstrated at birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromosome Aberrations↗

PubMed1988