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Biomedical subjects

P Byers

Publications and source records attributed to P Byers.

At least 19 recordsLinked to original sources
PubMed2006

Endoscopic retrograde cholangiopancreatography and gastroduodenoscopy after Roux-en-Y gastric bypass.

BACKGROUND: The use of Roux-en-Y gastric bypass (RYGB) for morbid obesity has raised concern that subsequent endoscopic evaluation of the gastric remnant and duodenum is difficult. By gaining percutaneous access to the gastric remnant, however, both gastroduodenoscopy and endoscopic retrograde cholangiopancreatography (ERCP) can be performed easily. This report describes the results of a novel technique for performing "transgastrostomy" gastroduodenoscopy and ERCP. METHODS: Six patients with a RYGB for morbid obesity underwent transgastric remnant endoscopic evaluations. If a gastric remnant tube had not been placed during prior surgery, one was placed percutaneously by an interventional radiologist. The tube tract then was dilated to either 20- or 24-Fr. At the time of endoscopy, the gastrostomy tube was removed and the skin anesthetized. Then either a pediatric duodenoscope (outer diameter, 7.5 mm) or a slim gastroscope (outer diameter, 5.9 mm) was inserted through the gastrostomy tube tract. RESULTS: Percutaneous gastroduodenoscopy was successfully performed for all six patients. The findings included two patients with prepyloric ulcers identified and assessed with a biopsy, one patient with intestinal metaplasia and a benign gastric polyp, and three patients with a normal gastric remnant and duodenum. A nonstrictured enteroenterostomy was noted in one of the three patients with a normal endoscopic evaluation. Percutaneous transgastrostomy ERCP was performed for three of the six patients who underwent gastroduodenoscopy. The findings included one patient who had papillary fibrosis treated with a sphincterotomy, a second patient with a normal biliary tree, and a third patient with a normal pancreatic duct. Selective cannulation of the common bile duct was not successful in the third patient. CONCLUSION: The transgastrostomy endoscopic route ensures access to the excluded stomach and proximal small bowel after RYGB. This route is safe and effective, allowing the use of a duodenoscope to improve the cannulation success rate for ERCPs in this patient population.

Anastomosis, Roux-en-Y↗
PubMed1999

Reliable and sensitive detection of premature termination mutations using a protein truncation test designed to overcome problems of nonsense-mediated mRNA instability.

The protein truncation test (PTT) is a mutation-detection method used to scan for premature termination (nonsense) mutations. PCR amplification of the DNA or mRNA source material is performed using forward primers containing a T7-promoter sequence and translation initiation signals such that the resultant products can be transcribed and translated in vitro to identify the smaller truncated protein products. mRNA is commonly used as the source material, but success of the PTT and other RNA-based mutation detection methods can be severely compromised by nonsense mutation-induced mRNA decay, a well-documented process that is often overlooked in mutation detection strategies. In this study, we develop an RNA-based PTT that overcomes the problem of mRNA decay by preincubating cells with cycloheximide to stabilise the mutant mRNA. The effectiveness of this method for mutation detection in abundant mRNAs was demonstrated in osteogenesis imperfecta fibroblasts by the protection of type I collagen (COL1A1) mRNA containing nonsense mutations that normally resulted in mutant mRNA degradation. Stabilisation of mutant mismatch repair gene (MLH1) mRNA was also observed in transformed lymphocytes from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Importantly, our strategy also stabilised very low-level (or illegitimate) nonsense-containing transcripts in lymphoblasts from patients with Bethlem myopathy (COL6A1), familial adenomatous polyposis (APC), and breast cancer (BRCA1). The greatly increased sensitivity and reliability of this RT-PCR/PTT protocol has broad applicability to the many genetic diseases in which only blood-derived cells may be readily available for analysis.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Preferential presentation of herpes simplex virus T-cell antigen by HLA DQA1*0501/DQB1*0201 in comparison to HLA DQA1*0201/DQB1*0201.

The HLA DQA1 locus is polymorphic. Haplotypes containing HLA DQA1*0501, but not HLA DQA1*0201, together with HLA DQB1*0201 are associated with Grave's disease and celiac sprue. In this report, we demonstrate a functional correlate of DQA1 polymorphism. T cells infiltrating a herpes simplex virus (HSV) lesion from a HLA DQ 2,7 individual yielded a virus-specific CD4+ clone restricted by DQ2. Presentation of viral peptide and protein segregated with DQA1 allele, because cell lines bearing DQA1*0501/DQB1*0201 heterodimers presented antigen in proliferation and cytotoxicity assays much more efficiently than cell lines bearing DQA1*0201/DQB1*0201. Binding of viral peptide to cell lines bearing DQA1*0201, in comparison to DQA1*0501, was only moderately reduced and may not explain this effect. Truncation and substitution analyses of peptide binding and T-cell activation were performed to determine which viral peptide residues contacting TCR might therefore be presented in an altered conformation by DQA1*0201/DQB1*0201. Residues 432, 435, 437, 438, and 440 (position P1, P4, P6, P7, and P9) contributed to DQ2 binding, whereas residues 431, 433, 434, and 436 (positions P 1, P2, P3, and P5) contributed to TCR contact. Differential presentation of peptide by HLA DQ2 heterodimers varying at the DQA1 locus may have relevance to host defense and the pathogenesis of HLA DQ2-associated autoimmune diseases.

Alleles↗
PubMed1996

Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase.

Polymorphic residues of HLA class II molecules influence immune activation in part by determining specific structural constraints for binding antigenic peptides. We identified a peptide from glutamic acid decarboxylase, a diabetes-associated autoantigen that preferentially bound to HLA-DQ3.2 molecules, one of the HLA determinants highly associated with insulin-dependent diabetes. We analyzed interactions of specific HLA-DQ residues with modified peptide analogues and found a pattern of permissive site-specific amino acids that accommodated allele-specific binding. Four anchor residues constrain binding to different DQ alleles; limited variation at two of these sites, residues 4 and 9, accounts for the unique pattern of peptide binding to HLA-DQ3.1 or HLA-DQ3.2.

Alleles↗
PubMed1995

A second autosomal split hand/split foot locus maps to chromosome 10q24-q25.

Ectrodactyly (split hand/split foot malformation, SHSF) is a human limb malformation characterized by absent central digital rays, deep median cleft, and syndactyly of remaining digits. The disorder is genetically heterogeneous, with at least two loci thus far determined: an autosomal locus at 7q21 designated SHFM1 and an X-linked locus at Xq26 designated SHFM2. Cytogenetic analysis of sporadic SHSF patients and linkage studies in extended pedigrees both suggest more than one autosomal locus exists. We report a novel SHSF locus suggested by a stillborn infant with ectrodactyly and other malformations who inherited an unbalanced translocation resulting in monosomy 4p15.1-4pter and trisomy for 10q25.2-qter. To investigate 10q25 as a possible split hand/split foot locus, microsatellite markers spanning 52 cM of 10q were utilized for linkage analysis of a large autosomal dominant SHSF pedigree in which the region encompassing SHFM1 previously was excluded as containing the causative mutation. The marker D10S583 was fully informative in the family, giving a maximum LOD score of 4.21 at recombination theta = 0.00. Recombination haplotypes define the 9 cM region between D10S541 and D10S574 as inclusive for this second autosomal SHSF locus, for which we propose the designation SHFM3.

Abnormalities, Multiple↗
PubMed1992

Initial observations of human dermatosparaxis: Ehlers-Danlos syndrome type VIIC.

We describe initial observations of an infant with dermatosparaxis (another form of Ehlers-Danlos syndrome, designated as type VIIC), an autosomal recessive disorder characterized by skin fragility and described in several species of domesticated animals. Electron microscopic examination of the skin shows collagen sheets rather than fibrils, and characteristic distortions resembling hieroglyphs. In addition to skin fragility, the disorder is characterized by redundant skin folds and edema, healing with minimal scar formation, large fontanels and wide sagittal and metopic sutures, blue sclerae, micrognathia, and umbilical hernia; after the neonatal period there are joint laxity, growth failure, short limbs, and normal mineralization of the skeleton except for the cranial vault. This disorder may also be a cause of premature rupture of placental membranes and myopia.

Ehlers-Danlos Syndrome↗
PubMed1991

The role of the Peyer's patch in the carcinogenesis of lymphoid cells.

The dose response to 3-methylcholanthrene (3-MC), the promoter effects of 2,6,10,14-tetramethylpentadecane (pristane) and the target-organ specificity in the preferential induction of B-lymphoid malignancies versus thymic tumors were examined. Lymphoid malignancies were induced in approximately 30% of the Copenhagen rats treated with injections in Peyer's patches (PP) of low, intermediate or high doses of 3-MC. A low dose of 3-MC induced B-lymphocytic leukemias or B lymphomas, whereas thymic tumors were detected in rats treated with high doses. Co-treatment of rats with pristane and 3-MC resulted in increased incidences and decreased latency of the lymphoid malignancies observed, suggesting that pristane acts as a tumor promoter. To address the possible role of PP in the induction events, PP were surgically removed after 3-MC treatment and the remaining small intestine anastomosed. Thymic tumors, but no B-lymphoid malignancies, were observed, indicating that the PP environment was important in the induction of the B-lymphoid malignancies. Radiotracer studies also revealed that appreciable amounts of 3-MC were disseminated to the thymus within 24 hr after treatment of PP with a high dose of 3-MC. Furthermore, direct intrathymic injection of the thymus with 3-MC resulted in the development of thymic tumors only. These results support the hypothesis that the PP has an important role in early events in the carcinogenesis of B lymphocytes and in the dissemination of 3-MC to the thymus.

Animals↗
PubMed1990

The use of serum amylase and lipase in evaluating and managing blunt abdominal trauma.

In order to determine the usefulness of serum amylase and lipase in the initial evaluation and subsequent management of blunt abdominal trauma (BAT) patients, we collected serum amylase and lipase on 85 consecutive BAT patients at admission, hospital day 1, hospital day 3, and hospital day 7. Only one patient had a pancreatic injury. A total of 45 patients (53%) had at least one enzyme abnormality during the study. There was no correlation between amylase or lipase values and age, sex, type of injury, diagnostic tests, operation, and outcome. In a control group of nonabdominal-trauma patients with admit studies only, all enzyme values were normal. We conclude that serum amylase and lipase are randomly elevated in patients with nonpancreatic-BAT both initially and during subsequent hospitalization and are not useful clinical tools in these patients.

Abdominal Injuries↗
PubMed1989

HLA genes associated with rheumatoid arthritis. Identification of susceptibility alleles using specific oligonucleotide probes.

We examined the association of individual HLA genes with rheumatoid arthritis (RA), using oligonucleotide probes that identified both DR4-associated and non-DR4-associated genes. Two distinct HLA-DR beta alleles (Dw4 and Dw14) were found in DR4+ RA patients compared with controls (Dw4 50% versus 17%; Dw14 35% versus 5%; total DR4 73% versus 30%), indicating that these 2 alleles are independent susceptibility genes. Remarkably, the majority of the DR4- RA patients also demonstrated a linear DNA sequence, apparently "shuffled" between different susceptibility alleles, identified with an oligonucleotide probe to a key portion of the Dw14 gene.

Adult↗
PubMed1989

HLA class II typing using oligonucleotide probes.

A DQ beta locus-specific oligonucleotide probe is used to identify DQ beta alleles present in six insulin-dependent diabetes mellitus (IDDM) multiplex families. Results of genotyping using this technique agree with those from cDNA probes and are often clearer. Allele-specific oligonucleotide probes for the DR beta locus are used to identify subtypes (Dw4 and Dw14) of the DR4 specificity in five IDDM multiplex families. This distinction cannot be made with available cDNA probes.

Blotting, Southern↗
PubMed1989

Blunt pancreatic trauma: prospective evaluation of early endoscopic retrograde pancreatography.

Major ductal injury is a determining factor in the outcome after pancreatic trauma. The purpose of this study was to determine the value of early endoscopic retrograde pancreatography (ERP) in patients with blunt pancreatic trauma. We attempted ERP in nine patients. Indications were abnormal pancreatic findings on CT scanning in five patients, a suboptimal view on CT scanning in three patients, and a high index of suspicion in one patient. ERP was successful in eight patients. Two had major ductal injury treated operatively and were discharged without complications. In six, ERP showed a normal pancreatic duct. These patients were treated conservatively; five were eventually discharged, and one died of necrotizing pneumonia. Our results suggest that ERP is safe and accurate in the diagnosis of blunt pancreatic ductal injuries. If the pancreatic ductal system is intact, conservative management is appropriate, but if ERP shows major ductal injury, surgical intervention is indicated.

Adolescent↗
PubMed1987

Diagnostic peritoneal lavage in the management of blunt abdominal trauma: a reassessment.

In order to reassess the value of diagnostic peritoneal lavage (DPL) in patients with blunt abdominal trauma, we conducted a prospective study over a 15-month period involving 138 patients. There were 29 (28.3%) patients with positive DPL and 103 (71.7%) with negative DPL in this series. Of the 29 patients with positive DPL, 28 (96.5%) were found to have significant intra-abdominal injuries; 27 by exploratory laparotomy and in one case at autopsy. One patient with a grossly positive DPL had a negative exploratory laparotomy (3.4% false positive rate). All 109 patients with negative DPL were admitted. In only one case a significant intra-abdominal injury was demonstrated (0.9% false negative rate). The overall mortality in this series was 11.6% and there were no complications related to the DPL. Our results suggest that DPL is indeed an accurate indicator of significant intra-abdominal injuries in patients with blunt abdominal trauma.

Abdominal Injuries↗
PubMed1987

Prevalence of cartilage lesions in foot joints: a test of the concept of limited and progressive lesions.

Lesions in the articular cartilage of the joints of the first ray of feet amputated from 54 patients in the age range 10-79 years have been categorised by site, size, and stage of development. The large number of small lesions in early stages of development, appearing from an early age, and the few lesions with extensive bone exposure, occurring only in later years, lend corroboration to the concept of limited and progressive lesions, as established for the hip joint.

Adolescent↗
PubMed1986

Preventable trauma deaths: Dade County, Florida.

We reviewed 1,201 trauma deaths that occurred in Dade County, Florida, in 1982 in order to evaluate the need for an organized trauma network. There were 715 deaths (59.5%) at the scene. Of the remaining 486 patients who were transported to hospitals for treatment there were 240 central nervous system (CNS) deaths and 246 non-CNS deaths. Fifty-two (21.1%) preventable non-CNS trauma deaths were identified out of the 246 non-CNS deaths. The lack of an appropriate surgical procedure or a delay to surgery accounted for 82.7% of the preventable deaths. The preventable non-CNS death rate was 12.1% at the then functional Level I hospital and 26.4% at the other 22 hospitals (p less than 0.01). The ISS scores were similar for both the functional Level I hospital and the other hospitals. A trauma network involving seven hospitals is currently being established in Dade County, Florida. Applying the 1982 data to these hospitals reveals a preventable non-CNS death rate of 12.1% for the Level I hospital, 21.5% for the six planned Level II hospitals, and 30.0% for the other 16 hospitals. We conclude that: the severely injured should be triaged directly to trauma centers, and there is a need in Dade County, Florida, for an organized trauma system.

Adolescent↗
PubMed1986

A prospective randomized study of moxalactam versus gentamicin and clindamycin in penetrating abdominal trauma.

We conducted a randomized, prospective study of moxalactam versus gentamicin plus clindamycin in 42 patients with penetrating abdominal trauma. Patients were randomized to receive intravenously either 2 grams of moxalactam every 12 hours or 80 milligrams of gentamicin every eight hours and 600 milligrams of clindamycin every six hours. Antibiotics were administered preoperatively and continued for a minimum of five days if hollow viscus injury occurred. For those without hollow viscus injury, only those patients receiving a minimum of three days of antibiotics were evaluated. A single intramuscular dose of 10 milligrams of vitamin K was also administered to all patients in the moxalactam group. There were 39 males and three females with a mean age of 33 years. Twenty patients received moxalactam and 22 received gentamicin plus clindamycin. The mechanism of injury was gunshot wound in 32 patients and stab wounds in ten patients. Eight patients in each group sustained injuries to the small intestine or colon, or both. The mean injury severity score was 22.6 and 21.2 in the single and double antibiotic regimen, respectively. The mean duration of antibiotic therapy was 5.8 and 7.0 days in the single and double antibiotic group, respectively. No infectious complications occurred in the moxalactam group whereas five infections occurred in four patients in the gentamicin plus clindamycin group (p less than 0.05). These infections included one intra-abdominal abscess, two wound infections and two episodes of necrotizing fasciitis of the wound and abdominal wall. There were no complications attributable to moxalactam therapy. The over-all mortality rate was zero per cent. The total pharmacy cost of a five day course of moxalactam plus a single dose of vitamin K is $204.67 compared with $226.00 for a similar course of gentamicin plus clindamycin. We conclude that: moxalactam is at least, if not more, effective in preventing infectious complications after penetrating abdominal trauma compared with gentamicin plus clindamycin; moxalactam is safe in the doses used when combined with vitamin K, and 3, moxalactam is more cost-effective than gentamicin plus clindamycin dual antibiotic therapy.

Abdominal Injuries↗