Susceptibility of cat fleas (Siphonaptera: Pulicidae) to fipronil and imidacloprid using adult and larval bioassays.

The monitoring of the susceptibility offleas to insecticides has typically been conducted by exposing adults on treated surfaces. Other methods such as topical applications of insecticides to adults and larval bioassays on treated rearing media have been developed. Unfortunately, baseline responses of susceptible strains of cat flea, Ctenocephalides felis (Bouchè), except for imidacloprid, have not been determined for all on-animal therapies and new classes of chemistry now being used. However, the relationship between adult and larval bioassays of fleas has not been previously investigated. The adult and larval bioassays of fipronil and imidacloprid were compared for both field-collected isolates and laboratory strains. Adult topical bioassays of fipronil and imidacloprid to laboratory strains and field-collected isolates demonstrated that LD50s of fipronil and imidacloprid ranged from 0.11 to 0.40 nanograms per flea and 0.02 to 0.18 nanograms per flea, respectively. Resistance ratios for fipronil and imidacloprid ranged from 0.11 to 2.21. Based on the larval bioassay published for imidacloprid, a larval bioassay was established for fipronil and reported in this article. The ranges of the LC50s of fipronil and imidacloprid in the larval rearing media were 0.07-0.16 and 0.11-0.21 ppm, respectively. Resistance ratios for adult and larval bioassays ranged from 0.11 to 2.2 and 0.58 to 1.75, respectively. Both adult and larval bioassays provided similar patterns for fipronil and imidacloprid. Although the adult bioassays permitted a more precise dosage applied, the larval bioassays allowed for testing isolates without the need to maintain on synthetic or natural hosts.

Genome sequences of Mycoplasma alligatoris A21JP2T and Mycoplasma crocodyli MP145T.

Mycoplasma alligatoris and Mycoplasma crocodyli are closely related siblings, one being highly virulent and the other relatively attenuated. We compared their genomes to better understand the mechanisms and origins of M. alligatoris' remarkable virulence amid a clade of harmless or much less virulent species. Although its chromosome was refractory to closure, M. alligatoris differed most notably by its complement of sialidases and other genes of the N-acetylneuraminate scavenging and catabolism pathway.

Efficacy of imidacloprid (8.8% w/w) plus permethrin (44% w/w) spot-on topical solution against Amblyomma americanum infesting dogs using a natural tick exposure model.

This study evaluated the efficacy of an imidacloprid 8.8% w/w + permethrin 44% w/w spot-on topical solution (K9 Advantix, Bayer Animal Health) against Amblyomma americanum using a natural field exposure model. Sixteen beagles were divided into two groups of eight dogs each. One group of dogs was treated with K9 Advantix and the other group served as untreated controls. On day -1 and at 3, 7, 14, 21 and 28 days after treatment, the dogs were walked for 80 minutes in an A. americanum-infested habitat at the Konza Prairie Biological Station in Northeastern Kansas. Postexposure tick counts (efficacy evaluations) were conducted on each dog at 3 and 48 hours after exposure. At 3 days after treatment, the efficacy of K9 Advantix within 3 hours of natural tick exposure was 88.0% and declined slowly during the study. The 48-hour postexposure efficacy remained above 93.5% throughout the study.

Evaluation of an imidacloprid (8.8% w/w)--permethrin (44.0% w/w) topical spot-on and a fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w) topical spot-on to repel, prevent attachment, and kill adult Ixodes scapularis and Amblyomma americanum ticks on dogs.

This study evaluated the effectiveness of two topical spot-on formulations -- imidacloprid(8.8% w/w)-permethrin (44.0% w/w) and fipronil (9.8% w/w)-(S)-methoprene (8.8% w/w)--to repel, prevent the attachment of, and kill adult Ixodes scapularis and Amblyomma americanum on dogs. Twelve purpose-bred beagles were distributed into three groups of four dogs each; one group served as untreated controls, and each of the other two groups received one of the test products. Dogs were exposed to 25 adult ticks of each species for 10 minutes on posttreatment days 3, 7, 14, 21, and 28. Unattached or repelled ticks were collected and evaluated for viability, and on-dog tick counts were conducted at 3, 24, and 48 hours after tick exposure. The imidacloprid-permethrin formulation provided significant repellency against I. scapularis for up to 3 weeks after treatment, and both formulations provided good overall control of I. scapularis and A. americanum during the study period.

Evaluation of an imidacloprid (8.8% w/w)--permethrin (44.0% w/w) topical spot-on and a fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w) topical spot-on to repel, prevent attachment, and kill adult Rhipicephalus sanguineus and Dermacentor variabilis ticks on dogs.

This study evaluated the effectiveness of two topical spot-on formulations, imidacloprid (8.8% w/w)--permethrin (44.0% w/w) and fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w), to repel, prevent the attachment of, and kill adult Rhipicephalus sanguineus and Dermacentor variabilis on dogs. Twelve purpose-bred beagles were distributed into three groups of four dogs each; one group served as untreated controls and each of the other two groups received one of the test products. Dogs were exposed to 25 adult ticks of each species for 10 minutes on posttreatment days 3, 7, 14, 21, and 28. Nonattached or repelled ticks were collected and evaluated for viability, and on-dog tick counts were conducted at 3, 24, and 48 hours after tick exposure. The imidacloprid-permethrin formulation provided significant repellency of R. sanguineus and D. variabilis for up to 3 and 4 weeks after treatment, respectively; and provided good overall control for R. sanguineus and D. variabilis during the study period. The fipronil--(S)-methoprene formulation provided good overall tick control during the study period.

Cortisol regulates secretion and pituitary content of the two gonadotropins differentially in female rats: effects of gonadotropin-releasing hormone antagonist.

To determine if LH and FSH respond to cortisol exposure the same way in females as they do in males, metestrous females were implanted with cholesterol or cortisol (F) subcutaneously, and either ovariectomized or left intact 4 days later. Tail vein injections of 1000 ng of GnRH in saline, or saline alone, were given 4.5, 23.5, or 47.5 h after the time of ovariectomy. Animals were killed 30 min after the injections at 5, 24, and 48 h after surgery. F attenuated the postovariectomy increase in serum LH at 48 h. F also suppressed GnRH-stimulated LH release 24 and 48 h after surgery in ovariectomized animals and in intact animals at 48 h. Pituitary content of LH was increased moderately by F at 5 h. These effects of F are similar to those seen in males. In contrast to LH, F increased serum FSH in intact females and suppressed levels in ovariectomized animals at 24 and 48 h, while inducing a remarkable increase in pituitary FSH content at all three times. These divergent effects of F on serum FSH (suppression in gonadectomized and stimulation in intact groups) were not seen in males, and the increase in pituitary FSH as a result of exposure to F was much more profound and reliable in females than in males. To determine if the F-induced increase in pituitary FSH was dependent on endogenous secretion of GnRH, intact metestrous females were implanted with either cholesterol or F pellets. Each implant group received sc injections of 100 micrograms GnRH antagonist or control injections every 48 h beginning at the time of steroid implantation. Animals were killed 5 days after implantation. The antagonist suppressed both serum and pituitary LH. F also suppressed serum LH levels, but had no effect on pituitary content of LH. Neither the antagonist nor F affected serum FSH. F greatly increased pituitary content of FSH in the presence or absence of GnRH antagonist. These data suggest that 1) LH responds to F treatment in a similar way in females and males; 2) pituitary FSH content is more sensitive to the enhancing effect of F in females than in males; 3) the ability of F to increase pituitary FSH in females is not dependent on GnRH.

Time course of diet-exacerbated carotid artery atherogenesis in the White Carneau pigeon.

The carotid arteries of White Carneau pigeons fed an atherogenic diet developed fatty streaks, proliferative and atheromatous lesions. The carotid bifurcation had accelerated lesion development when compared to either the proximal internal carotid or the dorsal carotid artery. After 4 weeks of being fed an atherogenic diet, the bifurcation region of all birds showed some lesion involvement. Lesions at the bifurcation initially involved the medial and lateral walls; flow dividers became involved slightly later, with the anterior flow divider consistently developing thicker lesions than the posterior flow divider. Lesions progressed in terms of length of circumference, mean thickness, cross-sectional area, and percent lumen stenosis as the time fed the atherogenic diet increased.20

Treatment of sporotrichosis with itraconazole. NIAID Mycoses Study Group.

PURPOSE: To describe the clinical presentation and outcomes of treatment with itraconazole in patients with sporotrichosis. METHODS: A culture for Sporothrix schenckii or compatible histopathology was required for inclusion in the study. Patients with both cutaneous and systemic sporotrichosis were treated. Patients received from 100 to 600 mg of itraconazole daily for 3 to 18 months. Patients were classified as responders or nonresponders. Responders were further classified as remaining on treatment, relapsed, or free of disease. Nonresponders included patients who failed to respond or progressed during treatment with itraconazole. RESULTS: Twenty-seven patients (mean age: 53 years) were treated with 30 courses of itraconazole. Diabetes mellitus and alcoholism were present in eight and seven patients, respectively. Sites of involvement included lymphocutaneous alone in 9 patients, articular/osseous in 15 (multifocal in 3), and lung in 3. Prior therapy was unsuccessful in 11 patients. Among the 30 courses, there were 25 responders and 5 nonresponders. All 5 nonresponders received at least 200 mg daily of itraconazole for durations that ranged from 6 to 18 months. Of the 25 responders, 7 relapsed 1 to 7 months after treatment durations of 6 to 18 months. Of the 7 who relapsed, 2 are responding to a second course. One responder was lost to follow-up after 10 months of treatment with itraconazole. Of the remaining 17 responders, 3 remain on treatment, and 14 are free of disease over follow-up durations of 6 to 42 months (mean: 17.6 months). Itraconazole was well tolerated with few side effects noted. CONCLUSIONS: These results document the efficacy of itraconazole in the treatment of cutaneous and systemic sporotrichosis.

NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis.

BACKGROUND: Invasive aspergillosis is the most common invasive mould infection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal. METHODS: A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followed by 400 mg/d) in patients with various underlying conditions. Response was based on clinical and radiologic criteria plus microbiology, histopathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failure or overall failure. RESULTS: Our study population consisted of 76 evaluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or partial response, and 3 (4%) had a stable response, and in 20 patients (26%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for other reasons including possible toxicity (7%) and death due to another cause but without resolution of aspergillosis (20%). Itraconazole failure rates varied widely according to site of disease and underlying disease group: 14% for pulmonary and tracheobronchial disease, 50% for sinus disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow transplant patients, and 14% in those with prolonged granulocytopenia (median 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discontinued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed. CONCLUSION: Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates apparently comparable to amphotericin B. Relapse in immunocompromised patients may be a problem. Controlled trials are necessary to fully assess the role of itraconazole in the treatment of invasive aspergillosis.

History and relevance of the Hutterite population for genetic studies.

The social and cultural origins of the Hutterian Brethren, the most inbred population in North America, are described along with the characteristics that make the group useful for genetic studies. The Hutterites represent a closed population, with high levels of fertility and consanguinity. The group maintains a stable residence pattern and keeps extensive genealogic records. The uniform pattern of communal living, the existence of endogamous subgroups within the population, and an orderly design for colony fission facilitates comparisons rarely found in other accessible populations. This inbred population is useful for detecting new recessively inherited diseases, for advancing our knowledge of the effect of inbreeding, and for analyzing human chromosomal variation. Selected demographic and genetic studies are cited.

Intimal changes in arteriovenous bypass grafts. Effects of varying the angle of implantation at the proximal anastomosis and of producing stenosis in the distal runoff artery.

Autologous arteriovenous bypass grafts were constructed between external iliac arteries in 20 mongrel dogs to determine the development of intimal fibromuscular hyperplasia. Animals received grafts at 55, 90 or 120 degree angles relative to the proximal anastomosis. Five animals with 90 degree angle grafts were also subjected to 80% stenosis in the runoff artery. All grafts showed the development of a fibromuscular tunica intima. Qualitative or quantitative intimal differences were not observed among grafts placed at 90 degree angles, 90 degree angles with runoff artery stenosis, or 120 degree angles. Grafts placed at 55 degree angles relative to the proximal anastomosis developed a consistently thicker fibromuscular layer in the tunica intima when compared to the other groups. These changes which were segmental in nature, occurred in the proximal and distal grafts and over the distal anastomosis.

The anatomy of the parotoid gland in Bufonidae with some histochemical findings. II. Bufo alvarius.

The gross and microscopic anatomy of the venom producing parotoid glands of Bufo alvarius has been studied by light and electron microscopy. Histochemical reactions for the presence of venom constituents and of components in biochemical pathways in the synthesis and release of venom were performed. The gland is composed of numerous lobules. Each lobule is an individual unit with a lumen surrounded by a double cell layer. Microvilli of the outer layer interdigitate with microvilli of the inner layer. Cells of the outer layer resemble smooth muscle cells, are rich in adenosine triphosphatase and glucose-6-phosphatase, and contain numerous pinocytotic vesicles, glycogen granules and various organelles. These organelles include "crystalloids" of what seem to be highly organized agranular reticulum. These outer layer cells probably function in some aspects of venom synthesis, active cellular transport and contraction in the discharge of the secretory product. The inner cell layer demonstrates a positive chromaffin reaction, contains steroid material, various organelles, some pinocytotic vesicles and glycogen granules, and appears devoid of a plasmalemma on its inner surface. This layer is probably involved in venom formation and release via an apocrine type of secretion. Bufo alvarius parotid gland shows significant morphological and histochemical differences from that of B. marinus and more nearly resembles a typical steroid producing organ.

[The treatment of aspergillosis, cryptococcosis and histoplasmosis in immunocompromised patients. Report of experience in the United States]. / Die Behandlung von Aspergillosen, Kryptokokkosen und Histoplasmosen bei immungeschwächten Patienten. Erfahrungsbericht aus den Vereinigten Staaten.

Itraconazole has emerged as an important new oral agent in the treatment of systemic fungal infections. We report a summary of available data on its use in aspergillosis, cryptococcosis and histoplasmosis compiled in the United States with particular attention to the immunocompromised host. Data has been accrued in open-label studies including 57 patients with cryptococcal disease where the overall response rate among patients with meningitis was 86%, 28 patients (seven with HIV infection) with invasive aspergillus where the overall response rates were 80% in non-AIDS and 42% in HIV patients. Data is summarized on six patients with allergic bronchopulmonary aspergillosis, all of whom improved on therapy, and twelve patients with histoplasmosis including eight with AIDS, eleven of whom responded (three newly reported cases are included). In summary, itraconazole showed activity in human studies of aspergillosis, cryptococcosis and histoplasmosis with minimal toxicity. Itraconazole offers a new oral alternative to conventional amphotericin B therapy in these infections. Comparative studies are needed to clarify its role.

Preventing substance abuse. An interview paradigm.

In summary, substance use and abuse is a major health problem in the United States affecting adolescents of both sexes and of every socioeconomic level. Family physicians have numerous opportunities to improve the health of future generations by using specific skills and expertise to prevent, identify, and intervene with adolescents' abuse of alcohol and other chemical substances. The first step is taking an effective alcohol and drug-use history.

A note on nursing practices in an American isolate with a high birth rate.

Abstract An unusually short interval between successive births in a non-contracepting and breast-feeding population has been reported by Dr. Mindel C. Sheps (Pop. Studies, 19, 1). Nursing practices that might affect the interval between birth and pregnancy are reported here from systematic observations made in the field. Probable factors are: (1) a maternal diet high in calories and in protein; (2) although infants are nursed for many months, each nursing period is short in a busy and highly patterned community schedule; and (3) supplementary feeding is introduced at an early age.

Effect of hydroxypropyl-beta-cyclodextrin on efficacy of oral itraconazole in disseminated murine cryptococcosis.

The therapeutic efficacy of itraconazole solubilized in either the commonly used vehicle, polyethylene-glycol-200 (PEG) or hydroxypropyl beta-cyclodextrin was compared in a murine model of disseminated cryptococcosis. Itraconazole at doses of up to 120 mg/kg/day solubilized in PEG were found not to be effective. However, itraconazole at doses > or = 30 mg/kg/day solubilized in hydroxypropyl-beta-cyclodextrin markedly prolonged survival and a relationship between dose and survival was seen.

US experience with itraconazole in Aspergillus, Cryptococcus and Histoplasma infections in the immunocompromised host.

Itraconazole has emerged as an important new oral agent in the treatment of systemic fungal infections. This paper summarizes the data available on its use in aspergillosis, cryptococcosis and histoplasmosis, compiled in the United States with particular attention to the immunocompromised host. Data have been accrued in open-label studies including 57 patients with cryptococcal disease where the overall response rate among patients with meningitis was 86%, and in 28 patients (8 with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection) with invasive aspergillosis where the overall response rates were 80% in patients without AIDS and 86% in patients with AIDS. Data are summarized on 6 patients with allergic bronchopulmonary aspergillosis, 5 of whom demonstrated marked improvement on therapy, and 12 patients with histoplasmosis including 8 with AIDS, 11 of whom responded and 1 recrudesced on therapy. In summary, itraconazole showed activity in human studies of aspergillosis, cryptococcosis and histoplasmosis with minimal toxicity. Itraconazole offers a new oral alternative to conventional amphotericin B therapy in these infections. Comparative studies are needed to clarify its role.

Effect of cyclodextrin on the pharmacology of antifungal oral azoles.

Concentrations of oral azoles in serum were compared in a single-dose pharmacologic study in mice. When hydroxypropyl-beta-cyclodextrin was used as a carrier and compared with a standard carrier, polyethylene glycol, drug concentrations determined by bioassay showed that the peak concentration and area under the concentration-time curve were greatly enhanced for itraconazole and saperconazole; moderately enhanced for ketoconazole; but negligibly affected for fluconazole, miconazole, and SCH 42427.

Malignancy in uremia: dialysis versus transplantation.

The incidence of cancer was compared in 499 dialysis patients and 121 renal transplant recipients. De novo malignancy developed in 15 patients on chronic dialysis (3 per cent) and in 6 transplant recipients (4.9 per cent), a significant increase over the expected number in the age-matched general population. There was no difference in the incidence of cancer in uremic patients on dialysis or after transplantation. A total of 10 dialysis patients (67 per cent) and 1 transplant patient (16 per cent) died of cancer. Neoplasms in the dialysis patients were the common types of mesenchymal tumors, while superficial skin cancers were seen more frequently in the transplant recipients. The differences in tumor types accounted for the higher mortality rate from cancer in the dialysis patients and may reflect different patterns of immunosuppression in these 2 patient populations.