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Biomedical subjects

P Sherman

Publications and source records attributed to P Sherman.

At least 19 recordsLinked to original sources
PubMed2001

JlpA, a novel surface-exposed lipoprotein specific to Campylobacter jejuni, mediates adherence to host epithelial cells.

A 1116 bp open reading frame (ORF), designated jlpA, encoding a novel species-specific lipoprotein of Campylobacter jejuni TGH9011, was identified from recombinant plasmid pHIP-O. The jlpA gene encodes a polypeptide (JlpA) of 372 amino acid residues with a molecular mass of 42.3 kDa. JlpA contains a typical signal peptide and lipoprotein processing site at the N-terminus. The presence of a lipid moiety on the JlpA molecule was confirmed by the incorporation of [3H]-palmitic acid. Immunoblotting analysis of cell surface extracts prepared using glycine-acid buffer (pH 2.2) and proteinase K digestion of whole cells indicated that JlpA is a surface-exposed lipoprotein in C. jejuni. JlpA is loosely associated with the cell surface, as it is easily extracted from the C. jejuni outer membrane by detergents, such as sarcosyl and Triton X-100. JlpA is released to the culture medium, and its concentration increases in a time-dependent fashion. The adherence of both insertion and deletion mutants of jlpA to HEp-2 epithelial cells was reduced compared with that of parental C. jejuni TGH9011. Adherence of C. jejuni to HEp-2 cells was inhibited in a dose-dependent manner when the bacterium was preincubated with anti-GST-JlpA antibodies or when HEp-2 cells were preincubated with JlpA protein. A ligand-binding immunoblotting assay showed that JlpA binds to HEp-2 cells, which suggests that JlpA is C. jejuni adhesin.

Adhesins, Bacterial↗
PubMed2001

Distinct outcomes of chloride diarrhoea in two siblings with identical genetic background of the disease: implications for early diagnosis and treatment.

BACKGROUND: Congenital chloride diarrhoea (CLD, OMIM 214700) is a serious inherited defect of intestinal electrolyte absorption transmitted in an autosomal recessive fashion. The major clinical manifestation is diarrhoea with high chloride content which can be balanced by substitution. The molecular pathology involves an epithelial Cl(-)/HCO(3)(-) exchanger protein, encoded by the solute carrier family 26, member 3 gene (SLC26A3), previously known as CLD or DRA (downregulated in adenomas). To date, almost 30 different mutations in the SLC26A3 gene have been identified throughout the world. No clear genotype-phenotype correlation has been established. PATIENTS/METHODS: Two siblings presenting with CLD were studied for disease history, supplementation, or other treatments, and for mutations in the SLC26A3 gene. RESULTS: Mutation analysis revealed a homozygous I544N mutation in both patients. However, despite the uniform genetic background of CLD in this family, the clinical picture and outcome of the disease were remarkably different between siblings. The older sibling had a late diagnosis and chronic course of the disease whereas the younger one, who was diagnosed soon after birth and immediately received supplementation therapy, grows and develops normally. CONCLUSION: Time of diagnosis, substitution therapy, compliance, and compensatory mechanisms are more important modulators of the clinical picture of CLD than the type of mutation in the SLC26A3 gene.

Chloride Channels↗
PubMed2001

Total knee arthroplasty after open reduction and internal fixation of fractures of the tibial plateau: a minimum five-year follow-up study.

BACKGROUND: There is little information in the literature regarding the outcome of total knee arthroplasty following open reduction and internal fixation of fractures of the tibial plateau. The goal of this study was to evaluate the results of such procedures after a minimum of five years of follow-up. METHODS: We retrospectively analyzed the outcomes of fifteen total knee arthroplasties performed at an average of 38.6 months (range, eight months to eleven years) after open reduction and internal fixation of a fracture of the tibial plateau in fifteen consecutive patients. The average duration of follow-up after the total knee arthroplasty procedures was 6.2 years (range, 5.4 to 11.1 years). The average age of the patients was fifty-six years (range, thirty-seven to sixty-eight years) at the time of the arthroplasty. We evaluated the outcomes on the basis of the Hospital for Special Surgery knee score, the Short Form-36 score, and radiographs of the knees. RESULTS: The average Hospital for Special Surgery knee score was 51 points (range, 20 to 74 points) before the arthroplasty, and it increased to 80 points (range, 44 to 91 points) postoperatively. Four knees were scored as excellent, eight had a good result, one was rated as fair, and two had a poor result. The average Short Form-36 scores were 58.0 points for general health, 72.4 points for bodily pain, 72.1 points for mental health, 58.3 points for physical functioning, 84.6 points for physical role functioning, 81.0 points for social functioning, and 57.7 points for vitality. The average active postoperative arc of motion was 105 degrees (range, 70 degrees to 135 degrees ) compared with 87 degrees (range, 20 degrees to 125 degrees ) preoperatively. Incomplete radiolucencies were noted on all of the postoperative radiographs made after the total knee arthroplasties. There was a high rate of infection (three patients), patellar tendon disruption (two patients), and postoperative secondary procedures (three patients required closed manipulation). The patients with infection were considered to have a failure of treatment: two required arthrodesis, and one required a two-stage exchange. CONCLUSION: On the basis of our results, we concluded that total knee arthroplasty after open reduction and internal fixation of a fracture of the tibial plateau decreases pain and improves knee function, but the procedure is technically demanding and is associated with a high failure rate (five of fifteen).

Adult↗
PubMed2000

Rapid and differential losses of in vivo dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) radioligand binding in MPTP-treated mice.

The dose- and time-dependent changes of in vivo radioligand binding to the neuronal membrane dopamine transporter (DAT) and vesicular monoamine transporter type 2 (VMAT2) were examined in mouse brain after MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administrations. Regional brain distribution studies were done in male C57BL/6 mice using simultaneous injections of d-threo-[(3)H]methylphenidate (DAT) and (+)-alpha-[(11)C]dihydrotetrabenazine (VMAT2). Single (55 mg/kg i.p. ) or multiple (4 x 10 mg/kg i.p., 1-hour intervals) administration of MPTP caused significant reductions in [(3)H]methylphenidate and [(11)C]dihydrotetrabenazine specific striatal binding, measured 14 days later. The single high dose of MPTP produced greater losses of [(11)C]dihydrotetrabenazine binding than did the multiple MPTP dosing regimen. Using the single high dose of MPTP, changes of in vivo binding of the two radioligands were determined at 1, 3, and 14 days after neurotoxin injection. At 1 day, there are large losses of [(3)H]methylphenidate binding (DAT) but no changes in [(11)C]dihydrotetrabenazine binding to the VMAT2 site in the striatum. At 3 and 14 days, there were >50% losses of binding of both bot radioligands, but significantly (P < 0.001) greater losses of VMAT2 binding of [(11)C]dihydrotetrabenazine. These studies indicate that the losses of the neuronal membrane and vesicular transporters are not always equal, and do not occur in the same time frame, after administration of the neurotoxin MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Magnetic resonance imaging to distinguish the type and severity of pediatric inflammatory bowel diseases.

BACKGROUND: The distinction between ulcerative colitis and Crohn's disease is important, because treatment options and clinical course may vary. Magnetic resonance imaging (MRI) allows noninvasive transmural assessment of the intestine and may facilitate differentiation of ulcerative colitis from Crohn's disease. The objective of this prospective study was to determine whether MRI differentiates Crohn's disease from ulcerative colitis in children as effectively as colonoscopy with mucosal biopsies. METHODS: Fifteen patients underwent colonoscopy with biopsies followed by abdominal MRI. The MRI diagnosis, determined by two radiologists independently completing a standardized form was compared with the gastroenterologic diagnosis. RESULTS: After colonoscopy and review of histology, Crohn's disease was diagnosed in nine patients, ulcerative colitis in five, and indeterminate colitis in one, who was excluded from study. Agreement of the MRI diagnosis with the gastroenterologic diagnosis was 4 of 4 (100%) for ulcerative colitis, 4 of 10 (40%) for Crohn's disease considering both radiologists, and 5 of 10 (50%) for Crohn's disease for each radiologist individually. Percentage of enhancement by MRI did not correlate with the severity of inflammation determined at endoscopy among the patients with Crohn's disease (r = -0.3, P = 0.366). There was agreement on severity of inflammation in three of four patients with ulcerative colitis. CONCLUSIONS: Current MRI interpretation of inflammatory bowel disease did not adequately recognize Crohn's disease in children. Therefore, colonoscopy with biopsy remains the most accurate tool for determining the type and severity of inflammatory bowel disease in children and adolescents.

Adolescent↗
PubMed2000

ICTS, an interventional cardiology training system.

In this article, we present an Interventional Cardiology Training System developed by the Medical Application Group at Mitsubishi Electric in collaboration with the Center for Innovative Minimally Invasive Therapy. The core of the ICTS is a computer simulation of interventional cardiology catheterization. This simulation integrates clinical expertise, research in learning, and technical innovations to create a realistic simulated environment. The goal of this training system is to augment the training of new cardiology fellows as well as to introduce cardiologists to new devices and procedures. To achieve this goal, both the technical components and the educational content of the ICTS bring new and unique features: a simulated fluoroscope, a physics model of a catheter, a haptic interface, a fluid flow simulation combined with a hemodynamic model and a learning system integrated in a user interface. The simulator is currently able to generate--in real-time--high quality x-ray images from a 3D anatomical model of the thorax, including a beating heart and animated lungs. The heart and lung motion is controlled by the hemodynamic model, which also computes blood pressure and EKG. The blood flow is then calculated according to the blood pressure and blood vessel characteristics. Any vascular tool, such as a catheter, guide wire or angioplasty balloon can be represented and accurately deformed by the flexible tool physics model. The haptics device controls the tool and provides appropriate feedback when contact with a vessel wall is detected. When the catheter is in place, a contrast agent can be injected into the coronary arteries; blood and contrast mixing is computed and a visual representation of the angiogram is displayed by the x-ray renderer. By bringing key advances in the area of medical simulation--with the real-time x-ray renderer for instance--and by integrating in a single system both high quality simulation and learning tools, the ICTS opens new perspectives for computer based training systems.

Angioplasty, Balloon, Coronary↗
PubMed1999

Dynamics of a shallow fluidized bed.

The results of the experimental study of the dynamics of a shallow fluidized bed are reported. The behavior of granular material is controlled by the interplay of two factors--levitation due to the upward airflow, and sliding back due to gravity. Near the threshold of instability, the system shows critical behavior with remarkably long transient dynamics. The experimental observations are compared with a simple cellular automata model.

Journal Article↗
PubMed1999

Canadian Helicobacter Study Group Consensus Conference on the Approach to Helicobacter pylori Infection in Children and Adolescents.

Gastric infection with Helicobacter pylori is common in both children and adults, but children are considerably less susceptible to peptic ulcers and other pathological sequelae. As a result, the risk to benefit ratio of diagnostic studies and therapeutic regimens for H pylori in adults are likely different from those in pediatric populations. These guidelines for the management of pediatric H pylori infection, developed by the Canadian Helicobacter Study Group, are designed to identify when the diagnosis and treatment of H pylori may improve patient care. Given the low prevalence of this infection in Canada, it is important to recognize that indiscriminate testing and treatment programs in children are not recommended, and indeed may threaten the optimal care of children. Diagnostic tests should be employed judiciously and be reserved for children who are most likely to derive measurable benefit, such as those likely to have peptic ulcer disease. At this time a test and treat strategy in children cannot be considered prudent, evidence based or cost effective. It is appropriate to limit diagnosis and treatment to children and adolescents in whom H pylori has been identified during endoscopic investigation.

Adolescent↗
PubMed1998

Reduced MPTP neurotoxicity in striatum of the mutant mouse tottering.

The effects of MPTP treatment (4 x 10 mg/kg, 2-h intervals) on in vivo striatal binding of (+)-alpha-[3H]dihydrotetrabenazine ((+)-[3H]DTBZ) to the vesicular monoamine transporter type 2 (VMAT2) were examined in wild type (+,+) and tottering (tg/tg) mice of the C57BL/6J strain. The tottering mutant has been previously characterized as having hyperinnervation of noradrenergic terminals in the brain, with increased concentrations of norepinephrine and increased numbers of VMAT2 binding sites. In wild-type mice, MPTP caused a significant decrease in specific striatal (+)-[3H]DTBZ binding in both males (-71%) and females (-57%), consistent with dopaminergic terminal losses. In the tottering mice, the neurotoxic effects of MPTP were diminished, with smaller losses of (+)-[3H]DTBZ binding observed both in males (-45%) and females (-26%). These results are consistent with the hypothesis that vesicular storage (as a result of hyperinnervation) offers neuroprotection toward MPTP toxicity, although the confounding effects of increases in norepinephrine concentrations or changes in calcium ion channel function (both also characteristics of the tottering mutant) cannot be ruled out. The tottering mutant does, however, offer another animal model to examine the biochemical features responsible for MPTP toxicity.

Animals↗
PubMed1998

Lack of correlation between vacuolating cytotoxin activity, cagA gene in Helicobacter pylori, and peptic ulcer disease in children.

To determine the prevalence of the cagA gene and vacuolating cytotoxin in Helicobacter pylori isolates obtained from children and to characterize the relationship between cagA, cytotoxin production, and ulcerogenesis, pediatric Helicobacter pylori isolates were tested for cagA by the polymerase chain reaction and for vacuolating cytotoxin by a cell culture assay. Helicobacter pylori isolates were obtained from 33 children referred for upper gastrointestinal endoscopy. Twenty-six of these isolates were tested for cagA by the polymerase chain reaction; all 26 (100%) were positive. Of the 26 children from whom these isolates were obtained, 26 (100%) had chronic gastritis and 12 (46%) had duodenal ulcers. Nine (30%) of 30 isolates tested showed expression of vacuolating cytotoxin, only three of which came from patients with duodenal ulceration (odds ratio 0.81, 95% confidence interval 0.1-5.3). Of the 23 cagA-positive isolates tested for cytotoxin, only nine (39%) were positive. There was no association between vacuolating cytotoxin and clinical symptoms, nor was cytotoxicity associated with ulcerogenesis. In summary, the findings suggest that cagA is not a marker of duodenal ulceration or of vacuolating cytotoxin production in children referred for endoscopy.

Adolescent↗
PubMed1998

N-[11C]methylpiperidine esters as acetylcholinesterase substrates: an in vivo structure-reactivity study.

A series of simple esters incorporating the N-[11C]methylpiperidine structure were examined as in vivo substrates for acetylcholinesterase in mouse brain. 4-N-[11C]Methylpiperidinyl esters, including the acetate, propionate and isobutyrate esters, are good in vivo substrates for mammalian cholinesterases. Introduction of a methyl group at the 4-position of the 4-piperidinol esters, to form the ester of a teritary alcohol, effectively blocks enzymatic action. Methylation of 4-N-[11C]methylpiperidinyl propionate at the 3-position gives a derivative with increased in vivo reactivity toward acetylcholinesterase. Esters of piperidinecarboxylic acids (nipecotic, isonipecotic and pipecolinic acid ethyl esters) are not hydrolyzed by acetylcholinesterase in vivo, nor do they act as in vivo inhibitors of the enzyme. This study has identified simple methods to both increase and decrease the in vivo reactivity of piperidinyl esters toward acetylcholinesterase.

Acetylcholinesterase↗
PubMed1998

Ketotifen therapy for acute ulcerative colitis in children: a pilot study.

Eosinophils contribute to the inflammatory process in a variety of chronic inflammatory bowel diseases. Ketotifen is beneficial in experimental models of colitis and in patients with eosinophilic gastroenteritis. Therefore, we investigated the efficacy of ketotifen therapy for the treatment of active ulcerative colitis. Children with newly or previously diagnosed ulcerative colitis with mild-moderate disease activity were treated with ketotifen at a dosage of 4 mg daily for eight weeks. Efficacy was determined by a physician disease severity index and by endoscopic and histologic examinations. Ten patients were enrolled. Symptoms improved in four patients and resolved completely in one patient. There was endoscopic improvement in three patients and histologic improvement in one. Increased eosinophils on rectal biopsy at entry were present in two of the responders. Five patients withdrew due to a lack of symptomatic improvement. No adverse events were identified. Low-dose ketotifen offers a limited therapeutic advantage in active ulcerative colitis that may be enhanced in the subgroup of patients with a high eosinophil count in the colonic mucosa. Further study of therapeutic efficacy with increased dosages of the mast cell stabilizer for acute and maintenance therapy is warranted.

Child↗
PubMed1998

Outcome after ileoanal anastomosis in pediatric patients with ulcerative colitis.

BACKGROUND: To review the outcome after restorative proctocolectomy among children and adolescents with ulcerative colitis at a pediatric inflammatory bowel disease center. METHODS: The records of all patients with ulcerative colitis undergoing colectomy and ileoanal anastomosis at The Hospital for Sick Children, Toronto, Canada, were reviewed. Questionnaires concerning functional results were sent to patients with restored transanal defecation. RESULTS: Seventy three patients (mean age, 13.2 years; range, 2.6-18.8 years) underwent ileoanal anastomosis (19 straight ileoanal anastomosis, 41 J pouch, 13 S pouch) between January 1980 and June 1995 and were observed 5.8+/-3.3 years. The ileoanal anastomosis is nonfunctional in 19 (26%) patients. Excision rates according to type of restorative procedure were J pouch, 7% (3 of 41); S pouch, 32% (4 of 13); and straight ileoanal anastomosis, 32% (6 of 19). Failure was usually attributable to intractable diarrhea among patients with straight ileoanal anastomosis but was caused by anastomotic leak or pelvic-perianal sepsis among patients with pouch procedures. Failure rates did not vary with age at ileoanal anastomosis. Among patients retaining ileoanal continuity, continence problems reported in the questionnaire were frequent and tended to be more extreme among younger patients. Overall, 90% of respondents reported satisfaction with the functional outcome of the restorative operation. CONCLUSIONS: The success rate of the ileoanal anastomosis/J-pouch procedure is comparable to that in adult series. The ileoanal anastomosis/J-pouch procedure is the operation of choice for children and adolescents who want ileoanal continuity restored after colectomy for ulcerative colitis.

Adolescent↗
PubMed1998

Campylobacter upsaliensis: waiting in the wings.

Despite strong epidemiological evidence supporting an important role for Campylobacter upsaliensis as a human enteropathogen, it remains relatively unknown in the realm of clinical microbiology. Clinical studies indicate that infection with this organism usually is associated with benign self-limiting diarrhea. However, more serious illnesses, including spontaneous abortion and hemolytic-uremic syndrome, recently have been associated with human infections. Understanding of the virulence properties and molecular biology of C. upsaliensis is beginning to evolve. There is now a pressing need for controlled, prospective epidemiologic studies in addition to further in-depth investigation of the pathogenesis of this enteric campylobacter to more precisely define its role in human disease. Furthermore, since C. upsaliensis is sensitive to the antibiotics routinely used in Campylobacter selective media, widespread appreciation of the importance of this organism will rely on the development of widely applicable, effective techniques for its isolation.

Adult↗