Earlier discharge with community-based intervention for low birth weight infants: a randomized trial.

BACKGROUND: Prolonged hospitalization of low birth weight infants increases the risk of medical and psychosocial complications. The feasibility of earlier discharge with community-based follow-up of infants of < or = 2000 g birth weight, without the use of home apnea monitors, was investigated. METHODS: One hundred infants of < or = 2000 g birth weight were randomized to either an intervention or control group. Intervention infants were discharged when readiness criteria were met. Based on assessed need, intervention group families received public health nursing and homemaker services for up to 8 weeks. Control infants were discharged to their homes at the discretion of the attending physician. All infants were assessed blindly at age 1 year with the Bayley and Home Observation for Measurement of the Environment (HOME) scales. RESULTS: There were no group differences in baseline infants' characteristics or in neonatal complications. Infants in the intervention group were discharged from the hospital at an earlier postconceptional age (mean +/- SD 36.6 +/- 1.5 weeks vs 37.3 +/- 1.6 weeks; P < .04). Median length of hospital stay (23 days vs 31.5 days) and mean weight at the time of discharge (2200 +/- 288 g vs 2275 +/- 301 g) were lower, but not significantly, for infants in the intervention group. A secondary analysis by birth weight strata (< or = 1500 g and 1501 through 2000 g) revealed that the most significant reductions in hospital stay and weight at discharge were realized in infants of 1501 through 2000 g birth weight. The persistence of apneic episodes and need for electronic monitoring prevented earlier discharge of infants of < or = 1500 g birth weight. Postdischarge services to the intervention group included 185 public health nurse home visits (3.8 +/- 0.91), 410 phone contacts (8.4 +/- 5), and 2298 homemaker hours (46 +/- 78) of service. At 1 year, there were no deaths and no group differences in rehospitalization rates, use of ambulatory services, or Bayley scores. Intervention families had significantly higher 1-year HOME scores. Minimum cost of hospital care was $873 per day, while the total cost of community-based services averaged $626 per infant. CONCLUSIONS: A significant reduction in average length of hospital stay was achieved for infants of 1501 through 2000 g birth weight. Earlier discharge of infants weighing < or = 1500 g at birth was hampered by persistent apneic episodes and feeding difficulties. A community-based program designed to provide individualized support and education for families of low birth weight infants was cost-effective and had a positive influence on the home environment.

The potential of monoclonal antibodies to reduce reperfusion injury in myocardial infarction.

Reperfusion injury is mediated, in part, by the accumulation of platelets and leucocytes in the microvasculature after reflow. These components of the blood pool form aggregates that can obstruct flow in small vessels. In addition, mediators released from leucocytes and platelets further damage the reperfused myocardium. A strategy to limit reperfusion injury exploits the important role of membrane-bound adhesion molecules that attach platelets and leucocytes to themselves and to the vascular endothelium. Monoclonal antibodies against specific adhesion receptors effectively eliminate the function of the receptor. The most widely investigated receptors are P-selectin, present on platelets and the endothelium, CD11/CD18, present on leucocytes, and the fibrinogen receptor on platelets. Numerous animal studies have strongly supported the use of these monoclonal antibodies to block adhesion receptors as adjunctive reperfusion therapy. However, recent human trials have yielded disappointing results.

Pathophysiology and therapeutic modification of thrombin generation in patients with coronary artery disease.

Thrombin plays a central role in thrombogenesis: it activates platelets, converts fibrinogen to fibrin, and activates factor XIII, which then crosslinks and stabilizes the fibrin clot. In addition, thrombin amplifies coagulation by activating factors VIII and V, key cofactors in the generation of activated factor X and thrombin, respectively. Even platelet function is influenced by thrombin. Hence, thrombin generation is most important both in the chronic progression of coronary atherosclerotic disease and in its conversion to acute events. To date, various therapeutic approaches capitalize on this knowledge by targeting specific thrombin-related pathways. Among the successful and carefully documented pharmacologic strategies in acute or chronic coronary heart disease are the use of unfractioned heparin, low-molecular-weight heparin, thrombolysis, hirudin, and/or inhibition of thrombin generation by glycoprotein IIb/IIIa antagonists, most often utilized on top of antiplatelet therapy (e.g., with acetylsalicylic acid) and/or vitamin K antagonism. The present review provides insights into the pathophysiology of thrombin generation in coronary atherosclerosis and gives an overview over the above mentioned therapeutic thrombin modifications.

Evaluation of the therapeutic and protective efficacy of doramectin against psoroptic scabies in cattle.

Three studies were conducted to evaluate the therapeutic and protective efficacy of doramectin when given by injection at a dose of 200 micrograms/kg against induced Psoroptes otis infestations of cattle. The first study investigated therapeutic efficacy. Mite infestations were established on 15 test animals held in stanchions by transfer of material from infested donor calves. Test animals were then allotted on the basis of mite counts to a treatment group (10 animals) which received doramectin and a control group (5 animals) which received saline. Skin scrapings were collected for mite counts on the day before treatment and on days 7, 14, 21 and 28 after treatment. Efficacy assessed on the basis of the proportion of animals cured by day 28 was 100%. The second study was designed to determine the duration of protective efficacy. Forty-eight scabies-free heifers were allotted to a treated group of 32 which received doramectin, and a control group of 16 which remained untreated. These treatment groups were each divided into eight subgroups. Commencing on treatment day and continuing at weekly intervals for 7 weeks, a subgroup of animals from each treatment was placed in stanchions and challenged by transfer of material from infested donor calves. Skin scrapings for mite counts were collected 7 and 14 days later. Infestations were successfully established on all untreated control calves. Doramectin prevented the establishment of infestation for three weeks and significantly (P < 0.05) reduced infestation levels for an additional two weeks. The third study established the duration of residual protection conferred by doramectin and ivermectin under contact transmission. Ninety-six scabies-free heifers were divided into two equal treatment groups. Animals in one group received doramectin and animals in the other group received ivermectin at its recommended dose of 200 micrograms/kg by subcutaneous injection. Each treatment group was then divided into eight subgroups of six animals. Commencing on treatment day and continuing at weekly intervals for 7 weeks a subgroup of animals from each treatment was exposed to purposely infested seeder animals for one week. Three animals from each treatment subgroup were then placed in individual stanchions in which grooming was prevented and the other three were placed together in a pen where normal grooming behavior was permitted. Skin scrapings for mite counts were collected at weekly intervals for up to 4 weeks. Doramectin provided complete protection against infestation for five weeks compared to four weeks for ivermectin. These periods were not influenced by grooming behavior.

Comparative pharmacokinetics of doramectin and ivermectin in cattle.

Plasma pharmacokinetics were compared for 40 cattle dosed by subcutaneous injection with doramectin or ivermectin (200 micrograms kg-1), commercial formulations of doramectin or ivermectin, 20 cattle per product). Doramectin exhibited a similar peak plasma concentration to ivermectin (about 32 ng ml-1), but the time to Cmax was longer for doramectin (5.3 +/- 0.35 days) than for ivermectin (4.0 +/- 0.28 days). The area under the curve from time 0 to infinity post-injection was significantly higher (p < 0.001) for doramectin (511 +/- 16 ng day ml-1) than for ivermectin (361 +/- 17 ng day ml-1). This was explained by a lower clearance, a lower volume of distribution and, probably, a higher bioavailability of doramectin over ivermectin. It is concluded that the pharmacokinetic differences between doramectin and ivermectin may explain the longer duration of preventive efficacy of doramectin.

Comparative persistent efficacy of doramectin, ivermectin and fenbendazole against natural nematode infections in cattle.

A study was conducted in Argentina, to investigate the period of protection of a single injection of doramectin administered subcutaneously (s.c.) at 200 micrograms kg-1 (1 ml/50 kg) compared with single treatments of ivermectin (200 micrograms kg-1 s.c.) and fenbendazole (5 mg kg-1 p.o.), against field infections of gastrointestinal parasites of cattle. Eighty-three animals were selected and ranked on the basis of serial fecal egg counts (e.p.g.'s). From this group, three animals were slaughtered before treatment and their lungs, abomasum, small and large intestines, were processed for parasite counts and identification. The remaining 80 animals were allocated in ranked groups of four to a control or one of three treated groups. Animals of the four groups were grazed together in the same pasture for the duration of the study. Treatments were administered on Day 0. Individual fecal samples were collected at weekly intervals for the first 49 days post-treatment and twice a week from Day 52 to Day 84 (end of study). At each collection day fecal samples were pooled for coprocultures. On Day 28 and 56, two animals from each group, previously identified on Day 0, were killed and their parasite burdens determined. The duration of protection of a single injection of doramectin was longer than ivermectin or fenbendazole treatment. On Day 56, the total number of parasites found in doramectin-treated animals was significantly (P < 0.05) lower than parasite burdens found in either ivermectin- or fenbendazole-treated animals. The longer persistent activity of doramectin was expressed by the lower number of adults and L4 stages of Ostertagia ostertagi. Data from this experiment demonstrated the limitations of using fecal egg counts to evaluate the persistent efficacy of anthelmintics. The duration of activity of doramectin was demonstrated more accurately by parasite counts in cattle from each group since decreasing e.p.g.'s were seen in non-medicated animals without changes in total parasite burdens.

Protective efficacy of doramectin and ivermectin against Cochliomyia hominivorax.

Two studies were conducted in Brazil using induced infestations of the New World screwworm, Cochliomyia hominivorax, to investigate: a) the comparative prophylactic efficacy of doramectin and ivermectin at their recommended use levels (200 micrograms kg-1 s.c.), and b) the duration of protection of a single injection of doramectin. In the comparative efficacy study, two groups of six animals each were treated with ivermectin or doramectin. Two hours after treatment, four incisions were made. Each incision was infested with 30 first instar C. hominivorax larvae and their status evaluated daily for 7 days post-treatment (p.t.). Doramectin treatment was 100% effective in prevention of C. hominivorax infestations whereas ivermectin efficacy was incomplete. First instar larvae were eliminated in doramectin-treated calves by 48 h p.t., while in the ivermectin group, C. hominivorax developed in over 29% of the incisions. Healing began in wounds of doramectin-treated animals at 24 h p.t. and was in progress in 100% of all wounds at 2 days p.t., while 50% of ivermectin-treated calves showed incisions with active lesions. In the duration of protection study, 24 calves were allocated to six groups (T1-T6) of four animals each. Three groups (T1, T3 and T5) were treated with saline and three groups (T2, T4 and T6) with doramectin. Animals were infested as described previously according to the following schedule: T1 and T2 at day 14, T3 and T4 at day 21, and T5 and T6 at day 28 p.t. Incisions were evaluated daily for 8 days post-infestation. Screwworm infestations and viable third-instar larvae developed of all incisions of saline-treated calves, while doramectin was 100% effective preventing development of C. hominivorax for 21 days p.t. and showed partial activity at 28 days p.t.

World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of anticoccidial drugs in chickens and turkeys.

These guidelines have been written to aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against Eimeria species in chickens and turkeys. The information provided deals with many aspects of how to conduct controlled studies in battery cages (dose determination), floor pens (dose confirmation), and commercial facilities (field effectiveness studies), the selection of birds, housing, feeding, preparation of medicated rations, record keeping, diagnostic techniques, and methods for the preparation, maintenance and use of parasites. These guidelines are also intended to assist investigators in conducting specific studies, provide specific information for registration authorities involved in the decision-making process, assist in the approval and registration of new anticoccidial drugs, and facilitate the world-wide adoption of standard procedures.

Helminth parasites of intermingling axis deer, wild swine and domestic cattle from the island of Molokai, Hawaii.

Helminth infections of axis deer (Cervus axis), wild swine (Sus scrofa) and domestic cattle (Bos taurus) were studied among intermingling herds on the Puu-O-Hoku Ranch, Molokai, Hawaii. Twenty-four species of helminths were collected from the 10 deer, 10 swine and 10 cattle. Capillaria bovis, Cooperia punctata, Haemonchus contortus and Trichostrongylus axei infected both axis deer and cattle, whereas Gongylonema pulchrum infected both axis deer and wild swine. None of the species of helminths occurred in both wild swine and cattle nor was any species found in all three hosts. Wild swine and domestic cattle supported separate and distinct helminth communities. In contrast, the helminth community of axis deer appeared to be derived from the helminth communities of cattle and wild swine and consisted only of those species capable of parasitizing either a broad range of ruminants or many mammalian taxa.

Immunization of chickens against coccidiosis with extracts of Eimeria-infected tissues.

Immunization of chickens with extracts prepared from Eimeria-infected tissues was attempted. Significant protection against weight depression was conferred when chickens were inoculated intra-abdominally with tissue extracts prepared from ceca infected with two different strains of E. tenella. When extracts were given intravenously, with or without the adjuvant, polyandenylic-polyuridylic acid, weight depression was not ameliorated after challenge. Experiments using extracts from two strains of E. acervulina- and E. maxima- and one strain of E. brunetti-infected tissues failed to protect against weight gain depression after challenge.

Anticoccidial activity of combinations of narasin and nicarbazin.

The efficacy of mixtures of narasin and nicarbazin were evaluated by comparing broiler performance, susceptibility to heat stress, and the mode of action against Eimeria. In a floor pen trial, narasin (70 ppm) alone or in combination with nicarbazin at levels between 10/10 and 50/50 ppm gave significantly better performance than unmedicated birds or birds given nicarbazin at 125 ppm alone. Amelioration of nicarbazin-associated mortality with heat as a stressor was observed in birds given the 50/50 ppm mixture of narasin and nicarbazin: mortality in these birds was similar to that of unmedicated birds and was reduced by 15 to 20% of that occurring in birds in the nicarbazin (125 ppm) treatment. The narasin/nicarbazin mixture (50/50) appears primarily to prevent further development of sporozoites. However, in birds treated with 25/25 ppm of narasin and nicarbazin, both the deleterious action of nicarbazin on merogeny and the antisporozoite activity of narasin were observed.

Comparative testing of anticoccidials in broiler chickens: the role of coccidial lesion scores.

The relationship between oocyst dose and lesion score was evaluated in trials involving five field isolates each of Eimeria acervulina, Eimeria maxima, and Eimeria tenella. Each trial included an uninfected, unmedicated treatment, and at least three treatments of unmedicated birds given different doses of oocysts from a single isolate. In four trials each with E. acervulina and E. tenella, and all five trials with E. maxima, infected, salinomycin-medicated (60 ppm) treatments were included. Each treatment consisted of five cages with eight male broiler birds per cage using a randomized complete block design. The relationship between oocyst dose and lesion score was examined within each coccidial species using the linear model: Y = beta0 + beta1(log(n) oocyst dose + 1). The results demonstrated that in unmedicated birds, low oocyst doses caused mean lesion scores up to 2.0, but the numbers required to cause higher mean scores were many times greater. Second, the estimated oocyst dose in salinomycin-medicated birds for any given mean lesion score was substantially more than the corresponding estimate for unmedicated birds. These results indicated that there could be wide differences in levels of oocyst dose between unmedicated and medicated birds that lesion scores failed to measure. If lesion scores are used in trials comparing anticoccidial drugs, an alternative design may be to include three infected, unmedicated treatments each given a different level of inoculum (e.g., low, medium, and high). Medicated treatments, given the highest oocyst dose only, would then be compared to each of the infected, unmedicated treatments.

Anticoccidial efficacy of semduramicin. 1. Evaluation against field isolates by dose titration in battery tests.

Semduramicin (AVIAX), a novel polyether ionophore, was titrated in a series of five battery tests at 20, 25, and 30 ppm in feed to determine the optimum level for use. Twelve-day-old broiler chicks were medicated for 48 h prior to inoculation in each 9-day test. The inocula included monospecific field isolates of Eimeria tenella, Eimeria brunetti, Eimeria necatrix, and Eimeria maxima, and a mixture of these species with Eimeria acervulina and Eimeria mitis. The numbers of oocysts inoculated were selected after titration of each species and the mixture of species. All three concentrations of semduramicin significantly (P < .05) reduced coccidiosis mortality and lesion scores and achieved lower feed:gain ratios and greater weight gains than the infected, unmediated treatments. A concentration of 25 ppm semduramicin was determined to be optimal based on improved lesion control compared with 20 ppm and improved weight gain compared with 30 ppm.

Anticoccidial efficacy of semduramicin. 2. Evaluation against field isolates including comparisons with salinomycin, maduramicin, and monensin in battery tests.

The efficacy of semduramicin (AVIAX), a novel polyether ionophore, was profiled in a series of 57 battery tests conducted in the United States and the United Kingdom. The studies employed mixed and monospecific infections of Eimeria acervulina, Eimeria mivati/Eimeria mitis, Eimeria brunetti, Eimeria maxima, Eimeria necatrix, and Eimeria tenella derived from North American and European field isolates. Ten-day-old broiler cockerels in pens of 8 to 10 birds were continuously medicated in feed beginning 24 h before challenge in tests of 6 to 8 days' duration. At the use level of 25 ppm, semduramicin effectively controlled mortality, lesions, and weight gain depression that occurred in unmedicated, infected controls for all species. In comparison with 60 ppm salinomycin, semduramicin significantly (P < .05) improved weight gain against E. brunetti and E. tenella, lesion control against E. brunetti and E. maxima, and the control of coccidiosis mortality against E. tenella. Salinomycin was superior (P < .05) to all treatments in maintenance of weight gain and control of lesions for E. acervulina. Maduramicin at 5 ppm was inferior (P < .05) to semduramicin in control of E. acervulina and E. maxima lesions, but was superior (P < .05) to all treatments in maintenance of weight gain and control of lesions in E. tenella infections. The data indicate that semduramicin at 25 ppm is well tolerated in broilers and possesses broad spectrum anticoccidial activity.

Gut stasis in chickens infected with Eimeria.

The duration and locations of gut stasis were examined in chickens infected with either Eimeria acervulina or E. maxima. Gut passage time (GPT) was used to determine gut stasis. The location of feed retention was determined qualitatively and quantitatively. Infections with both species were associated with increased GPT from Days 5 to 13 postinoculation. Feed appeared to be retained in the crop and gizzard of infected birds when judged visually. However, measurements of total dry matter retained in various regions of the gastrointestinal tract did not differ significantly from each other.