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Biomedical subjects

J McNally

Publications and source records attributed to J McNally.

At least 19 recordsLinked to original sources

Poison Control Center--based syndromic surveillance for foodborne illness.

OBJECTIVES: This retrospective study evaluated the usefulness of a poison control center (PCC) data collection system in Tucson, Arizona for early detection of foodborne disease outbreaks. METHODS: A search of a PCC database identified callers with gastrointestinal symptoms attributable to suspected foodborne illnesses whose calls were received during January 1-March 31, 2000. For each foodborne illness-related call, PCC coding was compared with a predefined diarrhea/gastroenteritis syndrome. PCC calls also were evaluated by using ZIP code, age, sex, and date of symptom onset to determine if call classifications matched any laboratory-confirmed cases reported to a county health department. RESULTS: An independent review generally agreed with the PCC's classification of calls. When calls and cases were compared, only one potential match was identified. CONCLUSION: Although confirmatory diagnostic information was not available, PCC calls were not duplicative of cases evaluated by the county health department, which suggests that they represent two independent data sets. PCC data might provide a useful addition to surveillance data reported to public health agencies for the early detection of foodborne disease outbreaks. These results will now be used to develop collaborative prospective surveillance systems.

Arizona↗

Evaluating the potential of SSR flanking regions for examining taxonomic relationships in the Vitaceae.

Three EST-derived microsatellite loci from Vitis vinifera were amplified and sequenced across eight species of Vitaceae from four different genera. Phylogenetic analysis of the microsatellite's flanking regions produced informative results in congruence with previous studies. Generic relationships were respected and the data produced sufficient inter-specific variation to distinguish between Cayratia acris and Cayratia saponaria, two very closely related species. Overall, the sequence alignments showed that priming sites were conserved, whereas microsatellite repeats were present in most cases but structurally variable. The sequence data provided information on the evolutionary patterns of various microsatellite repeats and their correlation to evolutionary relationships among taxa.

Journal Article↗

Design and in vivo immunogenicity of a polyvalent vaccine based on SIVmac regulatory genes.

Most vaccine modalities for human immunodeficiency virus type 1 (HIV-1) tested for immunogenicity and efficacy in the SIVmac (simian immunodeficiency virus) macaque model do not include the viral regulatory proteins. Because viral regulatory proteins are expressed early during the virus life cycle and represent an additional source of antigens, their inclusion as a vaccine component may increase the overall virus-specific immune response in vaccinees. However, at least two of the early proteins, Tat and Nef, may be immunosuppressive, limiting their usefulness as components of an SIV vaccine. We have constructed a polyvalent chimeric protein in which the open reading frames for Tat and Nef have been reassorted and the nuclear localization sequence for Tat and Rev and the myristoylation site for Nef have been removed. The resulting DNA plasmid (pDNA-SIV-Retanef) (pDNA-SIV-RTN) encodes a protein of 55 kDa (Retanef) that localizes at the steady state in the cytoplasma of transfected cells. Both the DNA-SIV-RTN and the highly attenuated recombinant poxvirus vector NYVAC-SIV-RTN were demonstrated to be immunogenic in SIVmac251-infected macaques treated with ART as well as in naive macaques. An equivalent strategy may be used for the generation of polyvalent antigens encoding the regulatory proteins in a HIV-1 vaccine candidate.

Animals↗

A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States.

BACKGROUND: Current therapy for crotaline snakebite includes antivenin (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae polyvalent immune Fab (Fab AV). METHODS: A single dose of Fab AV alone (as-needed [PRN] group) was compared with an initial dose plus repeated treatments during 18 hours (scheduled group) in a multicenter randomized trial. The study included patients with minimal or moderate envenomation by a crotaline snake within the preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation syndrome was observed before Fab AV treatment. After treatment with Fab AV to achieve initial control, patients were randomized to the scheduled or PRN treatment group. Scheduled group patients received additional doses of Fab AV every 6 hours for 3 doses. The PRN group received no planned additional doses of antivenom. RESULTS: The mean severity score of the 31 patients decreased from 4.35 to 2.39 points (P<.001); there was no difference between scheduled and PRN groups. No patient in the scheduled group received unplanned Fab AV doses, but 8 of 16 patients in the PRN group received unplanned doses (P =.002). Acute reactions occurred in 6 patients (19%), and serum sickness occurred in 6 (23%) of 26 patients who returned for follow-up. CONCLUSIONS: In the first randomized trial of antivenom in the United States, Fab AV effectively terminated venom effects. Since the unplanned use of Fab AV in the PRN group was common, the treatment regimen may require more than 1 initial dose.

Adolescent↗

Characterization of RNA synthesis and translation of bovine viral diarrhea virus (BVDV).

Full length and replicon genomes of various strains of bovine viral diarrhea virus (BVDV) have been characterized. Analysis of growth kinetics for a pair of cytopathogenic (cp) and noncytopathogenic (ncp) strains revealed that ncp strain synthesized viral RNA at much reduced level compared to the cp strain. Kinetics of translation and replication, the effects of bi-cistronic versus mono-cistronic genomes, and cis requirements for viral replication were also examined in a BVDV replicon D19c. Importantly, our results suggest a tight regulation and a switch from translation to replication, and demonstrated the cis requirements of NS4B and NS5A in replication.

Diarrhea Viruses, Bovine Viral↗

Mixed foregut cyst associated with esophageal atresia.

The authors report an unusual case of a thoracoabdominal foregut malformation with components of bronchogenic, esophageal duplication, and pancreatic enterogenous cysts, that presented in a child with esophageal atresia. J Pediatr Surg 36:939-940.

Abnormalities, Multiple↗

Efficacy, safety, and use of snake antivenoms in the United States.

The mainstay of hospital treatment for venomous snakebite is antivenom. There is currently only one antivenom available in the United States for the treatment of pit viper envenomation, Antivenin (Crotalidae) Polyvalent (ACP). The general indication for the administration of antivenom is presence of progressive venom injury. Progressive injury is defined as worsening local injury (eg, swelling, ecchymosis), a clinically important coagulation abnormality, or systemic effects (eg, hypotension, altered mental status). Unfortunately, there are no prospective data available regarding the efficacy of ACP. The efficacy of a new antivenom (CroFab; FabAV) composed of purified Fab specific to indigenous snake species has been demonstrated in prospective trials. FabAV appears as effective as IgG antivenoms. However, Fab molecules have a shorter half-life than IgG molecules and may allow recurrence of venom effects, if additional doses are not administered. It has also been found that other antivenoms, including ACP, also allow recurrence of venom effects. The Fab preparation has produced fewer acute or delayed (serum sickness) allergic reactions; however, further experience is needed to confirm this observation. Evaluation of this new antivenom has led to advances in our understanding of antivenoms in terms of solubility and durability. Fab fragments enter solution quickly, thereby shortening the time to antivenom administration and are remarkably stable under extreme conditions of heat and handling.

Animals↗

Congenital megaprepuce: an emerging condition--how to recognize and treat it.

OBJECTIVE: To highlight the clinical presentation, pathological anatomy and surgical management of an emerging condition, the congenital megaprepuce (CM). PATIENTS AND METHODS: All patients with CM treated at Southampton between 1994 and 1998 were reviewed retrospectively; 20 patients underwent surgery (mean age at operation 16 months, range 6-43). Surgical correction developed over this period and variations on a basic technique are now used, depending on the precise pathological anatomy. These techniques are described and illustrated. Cosmetic and functional success, and parental satisfaction, were assessed by a review of the case-notes. RESULTS: After a follow-up of >/= 6 months, the cosmetic and functional outcome was very successful, with the parents of 19 of the 20 patients satisfied. Five patients underwent re-operation, all requiring excision of redundant penile skin. CONCLUSIONS: CM is a striking condition which cannot be easily missed or hidden; we propose that it is a newly emerging and distinct condition which should not be confused with a buried, concealed, webbed, trapped or micropenis. Early surgical correction is recommended and circumcision should be avoided.

Attitude to Health↗

Recurrent coagulopathy after antivenom treatment of crotalid snakebite.

BACKGROUND: We studied whether recurrence of coagulopathy, defined as the return of a coagulation abnormality after initial normalization, occurred after the use of antivenin (Crotalidae) polyvalent. METHODS: A retrospective, blinded, descriptive analysis of 354 consecutive cases of North American crotalid snake envenomation was done. Inclusion criteria were documented clinical evidence of crotalid snakebite, presence of a coagulopathy (platelet count <150,000/mm3, prothrombin time above normal, or fibrinogen level <150 mg/dL), and treatment with antivenin (Crotalidae) polyvalent. RESULTS: Of 112 cases with a coagulopathy extending beyond 6 hours after envenomation, 31 had sufficient coagulopathy testing to detect recurrence. Fourteen of these patients (45%) had recurrence of coagulopathy, and two cases were severe (fibrinogen level 29 mg/dL; platelet count 36,000/mm3). CONCLUSION: Recurrence of coagulopathy after envenomation by North American crotalid snakes may occur after use of antivenin (Crotalidae) polyvalent and can result in severe coagulation abnormalities.

Adult↗

Continuous intravenous midazolam infusion for Centruroides exilicauda scorpion envenomation.

STUDY OBJECTIVE: We sought to describe the effects of continuous intravenous midazolam infusion as therapy for severe bark scorpion (Centruroides exilicauda) envenomation. METHODS: A retrospective chart review from July 1, 1993, through January 1, 1998, identified all patients treated at a university hospital with International Classification of Diseases, Ninth Revision, codes 989.5 (toxic effect of venom) or E905.2 (scorpion sting causing poisoning). By using standardized collection forms, data were extracted from the medical record of every patient who had a grade III or IV envenomation and was treated with a continuous intravenous midazolam infusion. RESULTS: Our search identified 104 patients; 34 had grade III or IV envenomation. Of these, 33 were treated in the ICU with continuous intravenous midazolam infusion. Median patient age was 4 years (range, 1 to 68 years). Midazolam dosage was adjusted to induce a light sleep state to control agitation and involuntary motor activity. The median amount of midazolam resulting in the first recorded decrease in agitation and involuntary motor activity was 0.30 mg/kg (range, 0.03 to 1.76 mg/kg). This first evidence of clinical improvement was recorded as 1.00 hour (median), with a range of 0.00 to 3.75 hours. The initial midazolam infusion rate was 0.10 mg x kg(-1) x h(-1) (median), with a range of 0.01 to 0.31 mg x kg(-1) x h(-1). The maximal midazolam infusion rate was 0.30 mg x kg(-1) x h(-1) (median), with a range of 0.06 to 1.29 mg x kg(-1) x h(-1). The median time until the maximal midazolam infusion rate was 2.5 hours (range, 0.00 to 8.50 hours). The median duration of infusion was 9. 50 hours (range, 4.25 to 20.50 hours). The median length of stay in the ICU was 15.17 hours (range, 6.0 to 28.0 hours), and 85% of patients were discharged directly home. All patients had resolution of abnormal motor activity and agitation during their midazolam infusion. Transient hypoxemia without evidence of end-organ dysfunction was documented in 4 patients during midazolam therapy. CONCLUSION: A continuous intravenous midazolam infusion can be a safe, effective, and readily available treatment option for patients with grade III or IV C exilicauda envenomation.

Adolescent↗

Fas ligand expression and function in systemic lupus erythematosus.

Mutations in the Fas receptor or its ligand (FasL) lead to lupus-like systemic autoimmune diseases in mice and in some humans. To determine whether a significant number of patients with systemic lupus erythematosus (SLE) have impaired FasL function, we compared T cell effector function by superantigen-activated CD4+ T cell lines or by anti-CD3- and IL-2-generated cytotoxic T cells. No differences were observed between SLE and normal control superantigen-derived CD4+ T cells in either the ability of these cells to up-regulate Fas expression or to induce apoptosis of the Fas-sensitive target B cells. When anti-CD3/IL-2-activated T cells were examined, SLE T cells had a modest reduction (-8%) in T cell cytotoxicity compared with normal controls, but the reduction was similar to the rheumatoid arthritis disease controls. A modest reduction in cytotoxicity was evident in both the Fas and perforin/granzyme pathways as determined by testing Fas-positive and -negative targets as well as by selective blockade of the perforin/granzyme pathway with concanamycin. These results indicate that no specific defects in FasL function are evident in the majority of SLE patients under the in vitro conditions tested. The proportional reduction in FasL and perforin/granzyme function in SLE and rheumatoid arthritis patients following anti-CD3/IL-2 stimulation most likely reflects subtle differences in activation in patient-derived vs normal control T cells.

Animals↗

Unusual presentation of bilateral abdominoscrotal hydrocele in a child.

An 18-month-old boy who had bilateral abdominoscrotal hydroceles presented with an acute inflammation of the left hydrocele followed 1 week later by similar spontaneous inflammation of the right side. He was treated with excision of both hydrocele sacs. A review of the literature shows that this is the first report of an abdominoscrotal hydrocele presenting in this unusual fashion.

Abdomen↗

Enhanced monocyte generation of reactive oxygen species in primary systemic vasculitis.

OBJECTIVE: Little is known about the role of mononuclear phagocytes in systemic vasculitis. We examined the hypothesis that monocytes from patients with primary systemic vasculitis have increased capacity to generate reactive oxygen species. METHODS: We studied patients with primary systemic vasculitis (n = 24) and compared them with patients with autoimmune related vasculitis (20), peripheral vascular disease (12), and postrenal transplantation (8). Healthy controls were also studied (56). Peripheral blood monocytes were stimulated using phorbol myristate acetate (PMA). We measured the generation of superoxide by cytochrome c reduction and myeloperoxidase (MPO) dependent products using peak luminol chemiluminescence. RESULTS: Patients with primary systemic vasculitis generated significantly more superoxide than all 3 non-vasculitis groups. Superoxide generation in the autoimmune vasculitis group was also higher than other groups but failed to reach significance versus controls (p = 0.07). Generation of MPO dependent products was also significantly higher in patients with primary vasculitis compared to all other groups. Subgroup analysis within the primary vasculitis group showed no correlation of these findings with disease activity, antineutrophil cytoplasmic antibodies, or American College of Rheumatology classification. CONCLUSION: Mononuclear phagocytes act as a source of reactive oxygen species in primary systemic vasculitis. Further study is required to determine if the reactive oxygen species generated act as a mechanism to promote vessel wall injury, or healing in this condition.

Adult↗

Nitric oxide synthase activity and expression in retinal capillary endothelial cells and pericytes.

The purpose of this study was to examine nitric oxide synthase (NOS) expression in the retinal vasculature in vivo and to study nitric oxide (NO) synthesis in vitro in retinal microvascular endothelial cells and pericytes. Immunoreactivity was examined using a polyclonal antibody raised against porcine cerebellar nitric oxide synthase on frozen sections cut from postmortem human retina and trypsin digests of rat retinal vasculature. The synthesis of nitrite, a stable end product from the interaction of NO with molecular oxygen, was measured in culture supernatants of retinal microvascular cells under basal and stimulated conditions. Expression of constitutive NOS (cNOS) in these cells was examined using the polymerase chain reaction (PCR). Strong NOS immunoreactivity was seen in the endothelium of choroidal and retinal vessels. Nitrite synthesis was documented in supernatants from cultured microvascular endothelial cells which increased significantly following exposure to A23187 and cytokines. Nitrite synthesis by pericytes was not detectable under basal conditions or following stimulation with A23187. Bacterial lipopolysaccharide (LPS), a potent inducer of NOS, caused an increase in nitrite concentrations in pericyte supernatants 24 h after stimulation suggesting the presence of inducible NOS (iNOS). PCR amplification confirmed the presence of the cNOS gene in endothelial cells but not in pericytes. Retinal vascular endothelial cells express significant amounts of NOS constitutively in vivo and in vitro which is activated by Ca++. Also, endothelial cells can be stimulated to synthesize iNOS by cytokines. Retinal pericytes too show iNOS activity following exposure to bacterial LPS. These results suggest that the nitric oxide synthase/nitric oxide pathway may be involved in the regulation of microcirculatory haemodynamics in the retina.

Amino Acid Oxidoreductases↗