Lessons learned from the development of a hidradenitis suppurativa xenograft mouse model.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease originating from the pilosebaceous unit, in which patients develop painful abscesses, sinus tracts, nodules and scarring, typically in intertriginous areas. Major gaps in our understanding of HS exist, and these may be partially due to the lack of an animal model for experimental studies. We developed an HS xenograft mouse model using human HS lesions grafted onto immunocompromised mice. Although the model had its limitations, several informative lessons were learned, which may contribute to future attempts at an HS animal model.

Molecular identification of Austrobilharzia species parasitizing Cerithidea cingulata (Gastropoda: Potamididae) from Kuwait Bay.

Avian schistosomes belonging to the genus Austrobilharzia (Digenea: Schistosomatidae) are among the causative agents of cercarial dermatitis in humans. In this paper, ribosomal and mitochondrial DNA sequences were used to study schistosome cercariae from Kuwait Bay that have been identified morphologically as Austrobilharzia sp. Sequence comparison of the ribosomal DNA (rDNA) 28S and 18S regions of the collected schistosome cercariae with corresponding sequences of other schistosomes in GenBank revealed high sequence similarity. This confirmed the morphological identification of schistosome cercariae from Kuwait Bay as belonging to the genus Austrobilharzia. The finding was further supported by the phylogenetic tree that was constructed based on the combined data set 18S-28S-mitochondrial cytochrome oxidase I (mtCO1) sequences in which Austrobilharzia sp. clustered with A. terrigalensis and A. variglandis. Sequence comparison of the Austrobilharzia sp. from Kuwait Bay with A. variglandis and A. terrigalensis based on mtCO1 showed a variation of 10% and 11%, respectively. Since the sequence variation in the mtCO1 was within the interspecific range among trematodes, it seems that the Austrobilharzia species from Kuwait Bay is different from the two species reported in GenBank, A. terrigalensis and A. variglandis.

Meta-analysis: Helicobacter pylori eradication treatment efficacy in children.

BACKGROUND: Several meta-analyses assessing the efficacy of anti-Helicobacter pylori treatment in adults have been published but a comparable meta-analysis in children is lacking. AIMS: To summarize the efficacy of treatments aimed at eradicating H. pylori in children and to identify sources of variation in treatment efficacy across studies. METHODS: We searched Medline, reference lists from published study reports, and conference proceedings for anti-H. pylori treatment trials in children. Weighted meta-regression models were used to find sources of variation in efficacy. RESULTS: Eighty studies (127 treatment arms) with 4436 children were included. Overall, methodological quality of these studies was poor with small sample sizes and few randomized-controlled trials. The efficacy of therapies varied across treatment arms, treatment duration, method of post-treatment assessment and geographic location. Among the regimens tested, 2-6 weeks of nitroimidazole and amoxicillin, 1-2 weeks of clarithromycin, amoxicillin and a proton pump inhibitor, and 2 weeks of a macrolide, a nitroimidazole and a proton pump inhibitor or bismuth, amoxicillin and metronidazole were the most efficacious in developed countries. CONCLUSIONS: Before worldwide treatment recommendations are given for eradication of H. pylori, additional well-designed randomized placebo-controlled paediatric trials are needed, especially in developing countries where both drug resistance and disease burden is high.

Interleukin-6-associated laboratory parameters and immunohistochemistry in symptomatic stage A and B nodular sclerosing Hodgkin's disease in children.

Interleukin (IL)-6-associated laboratory parameters obtained at diagnosis on 17 children with histologically confirmed nodular sclerosing Hodgkin's disease (NSHD) are reported. When these patients were grouped as either symptomatic stage A or B, they were found to be similar in extent of disease, age, and gender. However, statistically significant differences between these two groups were observed for the means of the following IL-6-associated laboratory parameters: hematocrit (p = 0.019), platelet count (p = 0.009), serum albumin (p = 0.001), and ferritin (p = 0.037) concentrations. Moreover, trend analysis of abnormalcy revealed an increasing frequency of anemia, thrombocytosis, hypoalbuminemia, and hyperferritinemia between stage A and B patients and, when available, febrile controls (p values = 0.0012, 0.0009, 0.0406, and 0.0011, respectively). Correspondingly, IL-6 immunohistochemistry performed on archival material from representative cases in each group showed greater overall reactivity in specimens from stage B patients. A variety of cells accounted for this positivity for IL-6 antigen including Reed-Sternberg cells and their variants, lacunar cells, dendritic interdigitating cells, endothelial cells, fibroblasts, and vascular smooth muscle cells. In summary, greater and more frequent abnormalities in IL-6-associated laboratory parameters and increased immunohistochemical reactivity for IL-6 antigen coincide with the presence of fever in helping to identify children with clinical stage B NSHD.

Growth patterns of human neuroblastoma xenografts and their relationship to treatment outcome.

BACKGROUND: Several investigators have reported the ability to establish xenografts in nude mice from children with neuroblastomas, but a correlation of prognosis with this establishment and the growth patterns of the neuroblastomas has not been reported. METHODS: Tumor specimens from 58 children with neuroblastomas were heterotransplanted into BALB/c nude mice. In 34 patients, heterotransplantation was done before therapy; in 24 patients, tumors were obtained after at least one course of chemotherapy or radiation therapy. The histology, cytogenetics, and growth characteristics of serial passages of the xenografts were studied. RESULTS: The engraftment rate was 34%. Neuroblastomas with diploid chromosome numbers did not engraft. Chromosomal abnormalities involving 1p were seen in more than 50% of the xenografts. Cytogenetic features were retained between original tumors and resultant xenografts. Xenografts could be established only from tumors with unfavorable histology, as defined by Shimada classification criteria. The histology of each xenograft line was strikingly similar, and each was highly undifferentiated. Engraftment rates, doubling times, and lag times did not vary appreciably between xenografts established from treated tumors compared with xenografts established from untreated tumors. There was no correlation between doubling or lag times and prognosis. Patients whose tumors engrafted had only a 5% 3-year survival rate. CONCLUSIONS: From these results, it appears that successful engraftment is the most important prognostic indicator for patients with neuroblastomas. Because of the commonality of the histologic features and the stability of the tumor clones from patients before and after heterotransplantation, these xenografts may be useful as an in vivo model for studying drug resistance and for designing treatment regimens.

Comparison of two double labeling techniques to measure cell cycle kinetics in myeloid leukemias.

Five patients with acute myeloid leukemia (AML) received a one hour infusion of iododeoxyuridine (IUdR) 100 mg/M2 to label S-phase cells in vivo. The aspirate was labeled in vitro either with tritiated thymidine (3HTdr) or bromodeoxyuridine (BrdU) to measure the duration of S-phase (Ts). The mean Ts using 3HTdr (Ts1) was 15.9h (13.1-19.8h) and using BrdU (Ts2) was 17.1h (14.5-20.6h). Total cell cycle time (Tc) ranged between 44.7h to 158.8h using Ts1 and 54.0h to 170.5h using Ts2. Based on this close approximation between the results, we confirm the reliability of the newly developed method that relies purely on immunohistochemical reaction.

Effect of bambermycins, in vitro, on plasmid-mediated antimicrobial resistance.

The potential of bambermycins (a growth-promoting antimicrobial approved for turkeys, broilers, and swine) to overcome or control plasmid-mediated antimicrobial resistance was determined in a series of in vitro experiments. Four possible modes of action of bambermycins were studied: synergistic effect with 12 other antimicrobials, elimination of resistance (R) plasmids from Escherichia coli, selective killing or inhibition of E coli carrying R plasmids, and inhibition of R plasmid transfer. Bambermycins had no synergistic activity with the other drugs tested and had little effect on eliminating plasmids from host bacteria. Dependent on plasmid type, bambermycins decreased or increased transfer frequency of R plasmids. Bambermycins also selectively inhibited growth of bacteria harboring certain R plasmids.

Influence of salinomycin on antimicrobial resistance of coliforms and streptococci from broiler chickens.

An experiment was conducted to evaluate antimicrobial resistance of coliforms and streptococci isolated from feces of chickens fed salinomycin. Two groups of 20 chickens were fed either a control feed or feed supplemented with 80 g/ton salinomycin. Chicken fecal coliforms and streptococci were isolated at 5, 15, 19, 22, 26, 33, 40, and 47 days of age and their resistance to 11 or 12 antibacterial agents (coliforms and streptococci, respectively) were determined in both groups of chickens. Salinomycin significantly reduced the number of coliforms resistant to sulfadiazine and reduced the number of streptococci resistant to erythromycin and lincomycin. Streptococci from birds fed salinomycin had lower minimum inhibitory concentrations for streptomycin. No streptococci isolates developed resistance to salinomycin. Coliforms from birds fed salinomycin had more (P less than .05) resistance patterns involving two, five, and six drugs. Numbers of coliforms resistant to streptomycin, ampicillin, carbenicillin, and cephalothin were greater (P less than .05) from birds fed salinomycin.

Virginiamycin effects on controlling necrotic enteritis infection in chickens.

Duplicate trials were conducted with male broiler chickens to evaluate virginiamycin as treatment against experimentally induced necrotic enteritis infection. Each trial consisted of seven treatments, each replicated four times, with 10 birds per replicate. Two treatments were fed control ration (noninfected control and infected control) and the five remaining treatments were fed virginiamycin at 5, 10, 15, 20, or 40 g/ton. Birds were orally dosed with 10 ml of Clostridium perfringens culture at 14 days of age. At 5 weeks of age, surviving birds were killed and necropsied to obtain lesion scores. Birds fed virginiamycin had significantly less mortality and lower intestinal lesion scores than nonmedicated birds when experimentally infected with necrotic enteritis.

Effect of bambermycins on quantity, prevalence, duration, and antimicrobial resistance of Salmonella typhimurium in experimentally infected broiler chickens.

Twenty broiler chickens were fed bambermycins (Flavomycin; an antibiotic produced by Streptomyces) at the rate of 3 g/ton (US) for 63 days, and 20 control birds were fed nonmedicated feed. The birds were inoculated (dosed) on the 10th and 11th feeding day with Salmonella typhimurium. The study evaluated the effects of bambermycins on Salmonella incidence, shedding, and antimicrobial resistance. Bambermycins had no effect on body weights, duration of shedding of salmonellae, number of salmonellae shed on postdosing day 3, tissue recoverability of salmonellae, and total number of resistance patterns. Bambermycins resulted in the decrease of salmonellae to be more gradual; however, both treatments were comparable at the end of the study. The majority of S typhimurium from bambermycins-treated birds maintained the original antibiogram of streptomycin, sulfadiazine, and nalidixic acid. The salmonellae isolated from the control birds were more resistant to 2 drugs (varying antibiograms). Bambermycins as a feed additive in broiler diets given at the dose level of 3 g/ton had no detrimental effects based on salmonellae shedding and antimicrobial resistance.

Laboratory evaluation of the Anderson Technical semiautomated susceptibility testing system.

Anderson Technical, Inc. has developed rapid, semiautomated equipment for antimicrobial susceptibility testing. A total of 310 fresh clinical bacterial isolates (226 gram-negative and 75 gram-positive) were tested with the Anderson Technical system and compared with those of Micro-Media Systems, Inc. For the gram-positive organisms, 74.3% of the test pairs had identical minimum inhibitory concentration values, whereas 99.1 and 0.9% of the test pairs had minimal inhibitory concentration values differing by less than or equal to 1 and greater than 1 dilution level, respectively. Identical minimum inhibitory concentration values were obtained for 67.2% of the gram-negative test pairs, whereas 97.6 and 2.4% differed by less than or equal to 1 and greater than 1 dilution level, respectively. For all organisms tested, 98.0% differed by less than or equal to 1 dilution level. The Anderson Technical equipment proved to be a rapid and flexible system for microdilution testing.

Influence of salinomycin on incidence, shedding, and antimicrobial resistance of Salmonella typhimurium in experimentally infected broiler chicks.

Twenty broiler chickens were fed 80 g/T salinomycin, an antibiotic produced by Streptomyces albus, and 20 birds were fed a control, unmedicated feed. The birds were experimentally infected with Salmonella typhimurium. The study evaluated the effects of salinomycin on Salmonella incidence, shedding, and antimicrobial resistance. Salinomycin had no effect on body weights, length of time salmonellae were shed, number of salmonellae shed on postdosing day 3, salmonellae tissue recoverability, or on the total number of resistance patterns. Salinomycin caused the decline of salmonellae to be more gradual; however, both treatments were comparable at the end of the study. The majority of isolated from birds receiving salinomycin maintained the original S. typhimurium antibiogram of streptomycin, sulfadiazine, and nalidixic acid. The salinomycin salmonellae were more susceptible to tetracycline, amikacin, carbenicillin, gentamicin, and cephalothin. The multiple resistance patterns of eight and nine drugs tended to be more prevalent among salmonellae from control birds than salinomycin treated birds. The antibiotic salinomycin appears to be an acceptable feed additive in broilers at the level of 80 g/T based on these results of its effects on salmonellae shedding and antimicrobial resistance.

Antimicrobial resistance transfer in transport media.

Five different transport media (buffered glycerol saline, Amies, Cary and Blair, Stuart, and modified Stuart) were tested to determine if antimicrobial resistance transfer could occur among bacteria in the media. Transfer of resistance occurred in all of the media, except buffered glycerol saline, within 2 h of holding both at room temperature and 4 degrees C.

Incidence of salmonellae in fecal samples of production swine and swine at slaughter plants in the United States in 1978.

Nine swine slaughter plants and 19 swine production units were randomly selected for sampling from the six highest swine-producing states representing a total of 64% of the United States swine production. Three composites of 10 fresh swine fecal samples were obtained from each slaughter plant, representing three different farm sources of swine. Two composite fecal samples were collected from two different production pens from each production unit. Samples were analyzed for salmonellae. Isolated salmonellae were biochemically and serologically identified and tested for antibiotic susceptibility and resistance transfer ability. Salmonellae were recovered from swine at seven of the nine slaughter plants and 16 of the 27 composites of slaughter swine. Of the 19 production units, 3 had swine shedding salmonellae. Resistances found included streptomycin, tetracycline, and sulfadiazine. Of the 52 total isolates tested, 71% had some level of antibiotic resistance. Only 3 of 37 resistant isolated could transfer resistance under the conditions used.

Comparison of therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin on E. coli infection of young chickens.

Three replicate trials were conducted with broiler male chicks to test the therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin in water against an artifically induced Escherichia coli infection. Mortality, lesion scores (heart, liver and air sac), and performance data were the criteria in evaluating therapeutic efficacy of these drugs. Results indicated the therapeutic efficacy of doxycycline was greater than chlortetracycline and lincomycin-spectinomycin.