Biomedical subjects

J W McCall

Publications and source records attributed to J W McCall.

At least 37 records · Page 2Linked to original sources

PubMed1998

Bis-cationic heteroaromatics as macrofilaricides: synthesis of bis-amidine and bis-guanylhydrazone derivatives of substituted imidazo[1,2-a]pyridines.

A series of guanylhydrazone, amidine, and hydrazone derivatives of 2-phenylimidazo[1,2-a]pyridine have been prepared and evaluated for macrofilarial activity against Acanthocheilonema viteae and Brugia pahangi in jirds. Compounds with 4',6-bis-substitution by cyclic guanylhydrazone groups show activity. 4',6-Bis-amidines show some activity but are more toxic; 4'- or 6-monosubstituted compounds are inactive. 2,6-Bis-substituted compounds lacking the phenyl ring are inactive. 4',6-Bis-substituted compounds having additional double bonds inserted between the heterocyclic ring and the phenyl ring or between the substituent and the ring system show reduced activity.

Amidines↗

PubMed1998

Dirofilariasis in the domestic ferret.

The popularity of pet ferrets in heartworm-endemic and -nonendemic areas is growing, with ferret ownership in the United States currently exceeding 10 million. The domestic ferret (Mustela putorius furo) has been reported to be susceptible to naturally-acquired and experimentally-induced infections of Dirofilaria immitis. Host-parasite relationships between D. immitis and domestic dogs and cats have been well studied, but there have been relatively few reports on infections in ferrets. Laboratory studies have shown the ferret to be highly susceptible, with infection and recovery rates similar to those achieved in the dog and higher than those seen in cats. Microfilaremia is characteristically of low concentration and transient in nature, similar to that seen in heartworm-infected cats. A definitive diagnosis can be made from ELISA-based antigen tests, echocardiography, and angiography, but suggestive radiographic findings require additional supportive information to confirm a tentative diagnosis. Prevention has been shown to be effective with currently used canine prophylactic pharmaceutics, but effective treatment of adult heartworms in ferrets has not yet been confirmed by controlled studies. There is currently no approved drug for prevention or treatment of D. immitis in ferrets.

Animals↗

PubMed1998

Pharmacokinetics, formulation, and safety of insect repellent N,N-diethyl-3-methylbenzamide (deet): a review.

This review is intended to provide the reader with an overview of the all-purpose topical insect repellent N,N-diethyl-3-methylbenzamide (deet), with emphasis on its pharmacokinetics, formulation, and safety aspects. N,N-diethyl-3-methylbenzamide is effective against a variety of mosquitoes, flies, fleas, and ticks, and its protection efficacy depends on factors such as type of formulation, application pattern, physical activity of the user, environment, and species and feeding behavior of the insects. It offers an inexpensive and practical means of preventing the attack of biting insects and, more importantly, the transmission of vector-borne diseases. In both humans and animals, deet skin penetration and biodistribution are rapid and extensive, and metabolism and elimination appear to be complete. As evidenced by over 4 decades of human experience and rigorous animal testing, deet is generally safe for topical use if applied as recommended, although it has occasionally been related to side effects such as toxic encephalopathy, seizure, acute manic psychosis, cardiovascular toxicity, and dermatitis, along with a few cases of death due to extensive skin absorption. N,N-diethyl-3-methylbenzamide may compete in metabolism with and alter the biodistribution properties of other compounds to which a subject is simultaneously exposed, resulting in an added risk of side effects. The appropriate use of formulation techniques and new formulation excipients not only offers a way to extend the duration of protection, but also reduces deet skin penetration. In addition to extended repellency, minimal skin penetration of deet should be an important consideration in the evaluation of a deet formulation during new product development.

Animals↗

PubMed1996

Evaluation of ivermectin and milbemycin oxime efficacy against Dirofilaria immitis infections of three and four months' duration in dogs.

OBJECTIVES: To determine the efficacy of ivermectin (IVM) and milbemycin oxime (MBO) against induced heartworm infection, where monthly treatment is started 3 or 4 months after infection, and to monitor microfilaremia and antigenemia. ANIMALS: 21 heartworm-naive Beagles. PROCEDURES: Each of 21 dogs was given 50 infective larvae of Dirofilaria immitis by SC inoculation. One group of 5 dogs served as nonmedicated controls, 2 groups of 5 dogs received IVM at 6 micrograms/kg of body weight or MBO at 500 micrograms/kg for 12 months beginning at postinfection (PI) month 4, and 2 groups of 3 dogs received IVM or MBO for 13 months beginning at PI month 3. Blood collected at intervals not > 1 month beginning at PI month 4 was examined for microfilariae and antigen. Dogs were euthanatized at PI month 16. RESULTS: Adult worm counts, relative to controls, were reduced in the 4-month treatment groups by 95.1 (P < 0.01) and 41.4% for IVM and MBO, respectively. The difference between the IVM and MBO groups was significant (P < 0.01). Live worms were found in all MBO-treated (range, 8 to 27) and control dogs (range, 12 to 39) and in 3 of 5 IVM-treated dogs (range, 2 to 4). In the 3-month treatment groups, worm counts were reduced by 97.7 (P < 0.01) and 96.8% (P < 0.01) for IVM and MBO, respectively. Microfilariae were seen in all control dogs and in only 2 of the 16 treated dogs. The antigen response of MBO-treated dogs in the 4-month treatment group was only slightly weaker than that for control dogs. In all other treated dogs, this response was delayed and weaker. CONCLUSION: Ivermectin is highly (> or = 95%) and significantly more effective than MBO against induced heart-worm infection when 1 year of monthly prophylactic dosing is started 4 months after infection. CLINICAL RELEVANCE: In some cases of owner compliance failure, monthly administration of IVM gives a high level of protection against young adult heartworms.

Animals↗

PubMed1995

Pharmacokinetic studies of methotrexate in plasma and synovial fluid following i.v. bolus and topical routes of administration in dogs.

PURPOSE: The pharmacokinetic properties of methotrexate (MTX) in the plasma and synovial fluid (SF) after bolus i.v. and topical administration were studied in dogs to assess the feasibility of topical delivery of MTX for the treatment of rheumatoid arthritis. METHODS: A MTX gel in Poloxamer 407 containing an absorption enhancer was formulated and topically applied on the elbow and stifle joints of dogs. SF was collected by inserting a needle with syringe into the joint space. Drug concentrations in the plasma, SF and muscle tissues were determined using a HPLC method with fluorimetric detection. RESULTS: Peak MTX concentrations in SF occurred at 38 +/- 5 min following bolus i.v. dose, indicating the presence of a substantial diffusion barrier between the plasma and SF. The plasma/SF concentration ratios of 1.16 +/- 0.25 were maintained after the attainment of distribution equilibrium between the two compartments. The t1/2 values in the plasma (11.2 +/- 1.2 hr) and SF (12.7 +/- 3.7 hr) were similar during the elimination phase, while the MRT in SF (3.24 +/- 0.21 hr) was longer than that in plasma (2.56 +/- 0.20 hr), probably due to the slow distribution of MTX to SF. After topical dose, MTX concentrations in plasma reached the steady state at approximately 4 hr, lasting for approximately 20 hr. The bioavailability of MTX from the gel was 11.8 +/- 3.3% of the applied dose, but muscle tissues beneath the gel application site had significantly higher levels of MTX than untreated muscle tissues. There was no statistical difference in SF concentrations of MTX between drug treated and untreated joints 24 hr after topical dose. CONCLUSIONS: Topical delivery of MTX in a hydrophilic gel achieved a sustained C/t profile in plasma and higher drug levels in muscle tissues underneath the dosing site, implicating the potential therapeutic value of the topical formulation.

Administration, Topical↗

PubMed1994

Clinical prophylactic activity of melarsomine dihydrochloride (RM 340) against Dirofilaria immitis in heartworm-naive beagles exposed to natural infection in three southeastern states.

Melarsomine dihydrochloride (RM 340), a drug being developed as an adulticide for treatment of heartworm (Dirofilaria immitis) infection in dogs, was safe and highly effective as a clinical prophylactic agent against naturally acquired infections using Strategic and Tactical Treatment Programs. The Strategic Program involved treatment every 4 months (three series of treatments per year), disregarding the mosquito season (MS), to clear the existing infection at each treatment. The Tactical Program consisted of two series of treatments per year, 4 months apart, with the first one given about the middle of the MS (August) and the second one given after the end of the MS (December). Melarsomine was administered as two i.m. injections (lumbar muscles) of 2.2 mg kg-1 given 3 h apart. A total of 90 heartworm-naive beagles and a number of microfilaremic 'seed' dogs were used. Three similar experiments (30 beagles per experiment) were conducted at selected areas (Georgia, Florida, Louisiana) known to be enzootic for heartworm. At each site, 30 beagles were allocated to six groups of five dogs each, and four of these groups were placed outdoors in April of 1988. Two groups (control and treated) were exposed for 12 months, and the treated group was given melarsomine at 4, 8, and 12 months after exposure was started (Strategic Program). Another group was exposed for 8 months and treated with melarsomine at 4 and 8 months (Tactical Program). One group of tracer (sentinel) beagles was exposed from April to August 1988, one group from August to December 1988, and another from December 1988 to April 1989. April-August and August-December tracers served as controls for the tactically treated dogs. After exposure, all dogs were held indoors for 5 months before necropsy. Blood was collected at 4-5 month intervals and examined for microfilariae (MF) and adult heartworm antigen (enzyme-linked immunosorbent assay, ELISA). Treatment by the Strategic Program was 99% effective, with only one of the total of 15 treated dogs harboring any worms (a single female) at necropsy. Thirteen of the 14 control dogs (93%) exposed for 12 months became infected, with average worm recoveries of 6.8, 5.4, and 25.2 (range 1-45) for the Georgia, Florida, and Louisiana sites, respectively. All of the 13 heartworm-infected control dogs were antigen-positive, and 12 of these were also MF-positive, while none of the strategically treated dogs was either antigen- or MF-positive at necropsy. Tactical treatment of the total of 14 dogs twice per year was 100% effective.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Use of melarsomine dihydrochloride (RM 340) for adulticidal treatment of dogs with naturally acquired infections of Dirofilaria immitis and for clinical prophylaxis during reexposure for 1 year.

Heartworm-infected dogs were treated therapeutically with a new heartworm adulticide (melarsomine dihydrochloride, RM 340) and then put on a Strategic Program with treatment every 4 months for clinical prophylaxis to take advantage of the drug's potent activity against 4-month-old immature as well as adult Dirofilaria immitis. Ten random-source dogs with naturally acquired heartworm infections (microfilariae- and antigen-positive) were given melarsomine (2.2 mg kg-1 twice 3 h apart) by i.m. injection in the lumbar muscles to clear their existing infections. They were then placed outdoors (August 1988) in a high-risk area in Georgia (USA) for heartworm transmission and given melarsomine at the same posology every 4 months (Strategic Program) for 12 months as a clinical prophylactic measure. Five nontreated heartworm-naive beagles placed at this site during the same period served as 'controls' to monitor heartworm transmission. After exposure for 12 months, the ten treated and five 'control' dogs were taken indoors and held for 5 months. Microfilaremia and antigenemia levels were monitored in both groups by testing at 4-5 month intervals throughout the study and the intensity of infection was determined at necropsy. Microfilaremia levels in treated dogs dropped dramatically following the initial therapeutic treatment and remained either negative or low. Only two of the five 'control' dogs became microfilaremic, and this occurred near the end of the study. Nine of the ten treated dogs were antigen-negative 4 months after the initial therapeutic treatment, and all of them were antigen-negative at all bleedings thereafter. Four of the five 'control' dogs were antigen-positive at necropsy, and only one of these was positive 4 months earlier. Based on these antigen data, the initial treatment cleared 90% of the dogs of worms, and no worms were detected in any of the treated dogs thereafter. However, it is possible that undetectable immature heartworms were present. Although all of the treated dogs were antigen-negative at necropsy, three of them had a total of eight heartworms, seven of which were clearly immature, as determined by worm length measurements, and the remaining worm was a young adult female that was probably too young to be detected. All of the five 'control' dogs had heartworms (average 7.4; range 1-16), and about half of these worms were clearly immatures. Therapeutic treatment followed by strategic treatment with melarsomine every 4 months during reexposure was at least 89.2% effective overall.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of anthelmintics for dogs and cats.

Guidelines have been designed to assist in the planning, operation and interpretation of studies for the assessment of the efficacy of drugs against helminth parasites of dogs and cats. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on the selection of animals, housing, feeding, dose-titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities involved in the evaluation of anthelmintics to employ comparable and standard procedures and will have the added benefit of minimising the numbers of animals needed for such tests.

Animal Husbandry↗

PubMed1994

Cutaneous exposure to warfarin-like anticoagulant causing an intracerebral hemorrhage: a case report.

A case of intercerebral hematoma due to warfarin-induced coagulopathy is presented. The 39-year-old woman had spread a warfarin-type rat poison around her house weekly using her bare hands, with no washing post application. Percutaneous absorption of warfarin causing coagulopathy, reported three times in the past, is a significant risk if protective measures, such as gloves, are not used. An adverse drug interaction with piroxicam, which she took occasionally, may have exacerbated the coagulopathy.

Administration, Cutaneous↗

PubMed1994

Filariasis testing in a jird model: new drug leads from some old standbys.

A total of 65 compounds, most of which were from chemical classes having members known to be active against one or more parasitic organisms, were evaluated against Brugia pahangi and Acanthocheilonema viteae for macrofilaricidal activity in male Mongolian jirds (Meriones unguiculatus). Sixteen of the 65 compounds tested suppressed the number of parasites. Of these 16, three were suppressive for B. pahangi, 10 for A. viteae, and three for both parasites. The antibiotic nigericin and the antihistaminic isothipendyl were found to be most active.

Animals↗

PubMed1994

A new class of anti-filariasis compounds: a preliminary look.

Parasitic nematode worms which produce filariasis in humans place approximately one billion people at risk in more than 75 countries. More than 100 million people are infected with these diseases and are recognized as being of significant military importance. During World War II, filariasis was among the leading causes of medical evacuation from the entire South Pacific area. Agents available to treat the diseases exhibit significant toxicity. Better drugs are urgently needed. Data are reported from work using a Mongolian jird animal model on a new class of potential drugs, thiosemicarbazones. These compounds exhibit activity against the parasites which cause both lymphatic filariasis and the "onchocerciasis type" of the disease.

Animals↗

PubMed1994

Early migration and development of Dirofilaria immitis in the ferret, Mustela putorius furo.

Twenty-four female ferrets, approximately 4 mo of age, were subcutaneously inoculated with 60 infective larvae of Dirofilaria immitis to determine migration and development of the worms until they became young adults in the heart and associated vessels. Twelve groups of 2 ferrets each were examined at 3, 5, 11, 15, 21, 49, 56, 63, 70, 91, 119, and 140 days postinoculation, respectively, to recover worms. Total worm recovery from each ferret varied from 1.6 to 79.3%. Worms were found mostly in subcutaneous tissue and muscle from the beginning of infection up to and including day 91. Worms were first recovered from the heart at day 70, when 3.8% of the worms had reached this site. By day 119, essentially all of the worms had migrated to the heart, as indicated by similar overall worm recoveries at 119 (mean 59.0%) and 140 days (mean 65.8%). Some worms remained in the tissues even at day 140. The third and fourth molts occurred as early as days 3 and 56, respectively. On day 91, i.e., soon after the worms reached the heart, the mean lengths of males and females were 58.8 mm (range 43.0-75.0 mm) and 63.3 mm (range 55.0-69.0 mm), respectively. At 140 days, male and female worms from the heart measured 118 mm (range 62.0-146.0 mm) and 144 mm (range 105.0-168.0 mm), respectively.

Animals↗

PubMed1993

Characterization of the N-linked oligosaccharides in glycoproteins synthesized by microfilariae of Dirofilaria immitis.

In this report, we describe studies on the structures of the N-linked oligosaccharides contained in glycoproteins synthesized by microfilariae of the canine heartworm, Dirofilaria immitis. Microfilariae were incubated in media containing either 2-[3H]mannose, 6-[3H]glucosamine, or 6-[3H]galactose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorographic analyses indicated that many glycoproteins were radiolabeled by both the mannose and glucosamine, whereas glycoproteins were not radiolabeled by the galactose. Glycopeptides from these total glycoproteins were fractionated and purified by serial lectin affinity chromatography, and the structures of the oligosaccharides in the isolated glycopeptides were analyzed by a variety of techniques. The N-linked oligosaccharides were shown to contain mannose (Man), fucose, N-acetylglucosamine (GlcNAc), and N-acetylgalactosamine (GalNAc). However, they lacked sialic acid and galactose, which are commonly found in mammalian glycoproteins. GalNAc was shown to be in an unusual terminal position and beta-linked in the sequence GalNAc beta GlcNAc beta Man-R, where R is the typical branch of complex-type N-linked oligosaccharides. Similar structures were recently found by us to be synthesized by the helminthic parasite Schistosoma mansoni. These results demonstrate that glycoproteins synthesized by microfilariae of D. immitis have unusual carbohydrate moieties and may lead to a better understanding of the specific roles of glycoprotein oligosaccharides in host-parasite interactions.

Animals↗

PubMed1993

Prophylactic activity of tetracycline against Brugia pahangi infection in jirds (Meriones unguiculatus).

The ability of oral tetracycline to inhibit the development of third-stage infective larvae (L3) of Brugia pahangi to adult worms in jirds was studied using 2 experimental protocols. Jirds treated with 1.4% tetracycline in drinking water for a period beginning 30 days before inoculation of L3 until 30 days post-inoculation (DPI) had 97% reduction in adult worm recovery compared to untreated controls. Jirds that received 1.2% tetracycline in drinking water beginning 1 day before until either 12 or 26 DPI had adult worm recoveries of 11% and < 1%, respectively. Untreated jirds and those given tetracycline beginning at or later than 13 DPI had similar adult worm recovery (27-29%). Prepatent periods were prolonged, and circulating microfilariae were reduced in jirds given tetracycline from 27 to 54 DPI compared to controls. These data indicate that tetracycline administered to jirds in drinking water inhibits B. pahangi development from L3 to adult worms and suggest that this effect occurs during early larval development. Tetracycline administered to infected jirds prior to and continuing through the onset of patency can also affect development of microfilaremia.

Administration, Oral↗

PubMed1992

Synthesis and biological activity of certain alkyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates and related derivatives: a new class of potential antineoplastic and antifilarial agents.

A series of methyl and ethyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates (7-19) and methyl 5-carbamoyl-1H-benzimidazole-2-carbamates (24-34) have been synthesized via the reaction of an appropriate alcohol or amine with the acid chloride derivatives 6a or 6b at room temperature. Reaction of an alcohol with acid chloride 6a at reflux temperature afforded transesterified products 20-23 in good yield. Treatment of methyl 5-amino-1H-benzimidazole-2-carbamate with substituted benzoyl chlorides furnished the methyl 5-benzamido-1H-benzimidazole-2-carbamates (36-38). Compounds 9, 16, 20, and 22 demonstrated significant growth inhibition in L1210 cells with IC50's less than 1 microM. Growth inhibition by this series of compounds appears to be associated with mitotic spindle poisoning. All the compounds tested, 9, 10, 19, 20, 22, and 23, caused significant accumulation of L1210 cells in mitosis. Compounds 7, 9, 19, 25, 26, 27, and 36 showed significant in vivo antifilarial activity against adult worms of Brugia pahangi, Litomosoides carinii, and Acanthocheilonema viteae in experimentally infected jirds.

Animals↗

PubMed1992

Colposcopy in family practice: pilot studies of pain prophylaxis and patient volume.

In a family practice office with volume representative of an average one-person practice, the implementation of colposcopy services was studied. During six months, 257 patients received Papanicolaou (PAP) smears. These patients represented 16.2% of the total 1,585 female patient visits for ages greater than 16. Of the 257 cytology specimens, 10.1% (26) revealed dysplasia or evidence of Human Papilloma Virus (HPV), indicating the need for colposcopic examination. Pathology reports of all biopsied cases confirmed the presence of dysplasia or HPV. These results suggest that the average family physician might reasonably anticipate about 100 colposcopy sessions per year, assuming each patient receives a diagnostic and a therapeutic colposcopic evaluation. In the course of colposcopy services in a family practice, 46 patients underwent 67 colposcopic examinations with cervical biopsy and/or cryotherapy in the office. Some patients received nonsteroidal anti-inflammatory medication 30-60 minutes before the procedure, with selection according to physician preference. All patients rated the pain experienced during the procedure on a 10-point visual-analog scale. Pain scores were significantly lower in those who received medication. Overall, patients tolerated the procedure well and there were no reported complications. Because of the possibility of such factors as the placebo effect influencing these results, a randomized, placebo-controlled, double-blind study will be needed to verify the findings.

Adolescent↗

PubMed1992

Salmonellosis in gerbils induced by nonrelated experimental procedure.

An outbreak of salmonellosis in a gerbil colony was investigated. The clinical, bacteriologic, and pathologic findings are reported. Clinical signs included an occasional sudden death, depression, emaciation, dehydration, rough hair coat, and testicular enlargement. Not every sign was observed in every infected gerbil. At necropsy, 11 animals had lesions consistent with salmonellosis. Histopathologic lesions consisted of interstitial pneumonia, hepatic and splenic necrosis, meningitis, and suppurative orchitis. Splenic and intestinal amyloidosis were also noted. Salmonella, group D, was recovered from gerbil feces, a container in which adult mosquitos were reared, filarial inoculum, and a cockroach. An epizootiologic investigation led to salmonella-infected cockroaches as the possible source of animal contamination via mosquitos and the subsequent filarial inoculum.

Animals↗

PubMed1991

2-acetylpyridine thiosemicarbazones. 13. Derivatives with antifilarial activity.

Several members of a series of 2-acetylpyridine thiosemicarbazones possess in vivo and in vitro macrofilaricidal properties. The most promising of the group tested is N4-(2-aminophenyl)-2-[1-(2-pyridinyl)ethylidene]-hydrazinecarbothioam ide (4), which suppressed 100% of the macrofilariae of Brugia pahangi and 94% of those of Acanthocheilonema viteae in the jird at a dose of 25 mg/kg per day x 5. Compounds 4 and 14 were also shown to inactivate or kill Onchocerca gutturosa and Onchocerca volvulus adult worms as measured by the loss of their motility or the inhibition of the conversion by the worms of the dye MTT to formazan.

Animals↗