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Biomedical subjects

D Whitcomb

Publications and source records attributed to D Whitcomb.

9 recordsLinked to original sources
PubMed2005

Multianalyte profiling of serum cytokines for detection of pancreatic cancer.

Early detection of pancreatic cancer might improve clinical outcome. Significant alterations in the levels of individual serum cytokines have been reported in pancreatic cancer. We hypothesized that a multicytokine panel could serve as biomarkers for pancreatic cancer. To evaluate the diagnostic utility of such a panel, we have utilized a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple markers. In this study, a panel of 31 serological markers including cytokines, chemokines, growth and angiogenic factors in combination with CA 19-9 was analyzed in sera of pancreatic cancer patients, patients with chronic pancreatitis, and matched control healthy subjects. Statistical analysis identified a multicytokine panel that was able to distinguish pancreatic cancer from healthy controls with a sensitivity of 85.7% and specificity of 92.3%, which was superior to performance of CA 19-9 alone. Importantly, a multicytokine panel allowed the discrimination of pancreatic cancer from chronic pancreatitis with high sensitivity of 98% and specificity of 96.4%. In conclusion, we demonstrated that analysis of multiple serum cytokines using a novel LabMAP technology is a promising approach for development of a diagnostic assay for pancreatic cancer.

Biomarkers, Tumor↗
PubMed2004

Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples.

BACKGROUND: Brush cytology of biliary strictures to diagnose pancreaticobiliary malignancy suffers from poor sensitivity. AIM: To improve the diagnostic yield of pancreaticobiliary brush cytology through analysis of tumour suppressor gene linked microsatellite marker loss of heterozygosity (LOH) and k-ras codon 12 mutation detection. METHODS: Twenty six patients with biliary strictures underwent endoscopic retrograde cholangiography with brush cytology. A panel of 12 polymorphic microsatellite markers linked to six tumour suppressor genes was developed. Genomic DNA from cell clusters acquired from brush cytology specimens and microdissected surgical malignant and normal tissue underwent polymerase chain amplification reaction (PCR). PCR products were compared for LOH and k-ras codon 12 mutations. RESULTS: Seventeen patients were confirmed to have pancreaticobiliary adenocarcinoma. Nine patients had benign strictures (eight proven surgically, one by follow up). Cytomorphological interpretation was positive for malignancy (n = 8), indeterminate (n = 10), and negative for malignancy (n = 8). Selected malignant appearing cytological cell clusters and microdissected histological samples from cancer showed abundant LOH characteristic of malignancy while brushings from nine cases without cancer carried no LOH (p<0.001). LOH and k-ras mutations profile of the cytological specimens was almost always concordant with the tissue samples. Presence of k-ras mutation predicted malignancy of pancreatic origin (p<0.001). CONCLUSION: LOH and k-ras codon 12 mutation analysis of PCR amplified DNA from biliary brush cytology discriminates reactive from malignant cells, with 100% sensitivity, specificity, and accuracy. Minor variations in LOH in brushings and in different sites within the same tumour likely reflect intratumoral mutational heterogeneity during clonal expansion of pre- and neoplastic lineages.

Adenocarcinoma↗
PubMed2002

The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease.

BACKGROUND: Mutations in the PRSS1 gene explain most occurrences of hereditary pancreatitis (HP) but many HP families have no PRSS1 mutation. Recently, an association between the mutation N34S in the pancreatic secretory trypsin inhibitor (SPINK1 or PSTI) gene and idiopathic chronic pancreatitis (ICP) was reported. It is unclear whether the N34S mutation is a cause of pancreatitis per se, whether it modifies the disease, or whether it is a marker of the disease. PATIENTS AND METHODS: A total of 327 individuals from 217 families affected by pancreatitis were tested: 152 from families with HP, 108 from families with ICP, and 67 with alcohol related CP (ACP). Seven patients with ICP had a family history of pancreatitis but no evidence of autosomal dominant disease (f-ICP) compared with 87 patients with true ICP (t-ICP). Two hundred controls were also tested for the N34S mutation. The findings were related to clinical outcome. RESULTS: The N34S mutation was carried by five controls (2.5%; allele frequency 1.25%), 11/87 (13%) t-ICP patients (p=0.0013 v controls), and 6/7 (86%) affected (p<0.0001 v controls) and 1/9 (11%) unaffected f-ICP cases. N34S was found in 4/108 affected HP patients (p=0.724 v controls), in 3/27 (11%) with wild-type and in 1/81 (1%) with mutant PRSS1, and 4/67 ACP patients (all p>0.05 v controls). The presence of the N34S mutation was not associated with early disease onset or disease severity. CONCLUSIONS: The prevalence of the N34S mutation was increased in patients with ICP and was greatest in f-ICP cases. Segregation of the N34S mutation in families with pancreatitis is unexplained and points to a complex association between N34S and another putative pancreatitis related gene.

Adult↗
PubMed2001

A new polymorphism for the RI22H mutation in hereditary pancreatitis.

BACKGROUND AND AIMS: Hereditary pancreatitis (HP) is a rare form of recurrent acute and chronic pancreatitis. Mutations in the cationic trypsinogen (protease serine 1, PRSS1) gene have been identified as causing HP. The R122H (previously known as R117H) mutation is the commonest and can be detected by a single and rapid polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) based technique using the AflIII enzyme. This test however may give a false negative result in the presence of a neutral polymorphism within the enzyme recognition site. The frequency of this event was examined by sequencing studies in patients with HP and in healthy controls. METHODS: Of 60 families identified by the UK and Ireland consortium of EUROPAC (European Registry for Hereditary Pancreatitis and Familial Pancreatic Cancer), 51 were screened for R122H, N29I, and A16V mutations using standard techniques, and by sequencing of all five exons of cationic trypsinogen. RESULTS: Twelve families had the N29I mutation, one family had A16V and, on standard testing, 15 families had the R122H mutation. An additional family with the R122H mutation was found on direct sequencing. The false negative result was due to a neutral polymorphism C-->T at the third base of the codon, not affecting the amino acid coded for, destroying the AflIII restriction site. This polymorphism was not observed in 50 DNA specimens (100 chromosomes) from controls nor from 50 individuals from PRSS1 mutation negative HP families. A novel mutation specific PCR was developed to avoid this pitfall. CONCLUSIONS: One of the 16 families with HP and an R122H mutation contained a polymorphism affecting the AflIII restriction site. Adoption of an alternative R122H assay is important for genetic studies in individuals with apparent HP.

Acute Disease↗
PubMed1995

Criminal justice outcomes of prosecution of child sexual abuse: a case flow analysis.

This study examined the progress and disposition of child sexual abuse cases referred for prosecution in four urban jurisdictions. Most cases were accepted for prosecution. The vast majority of cases carried forward for prosecution resulted in guilty pleas. Only 9% of the total sample went to trial. A majority of the small number that went to trial were convicted. Over 3/4 of those convicted were incarcerated. The rate at which cases were carried forward for prosecution and convicted was comparable to that of a national sample of felony arrests overall, but child sexual abuse cases were more likely to go to trial (p < .005) and received more severe sentences (p < .005). Our results are strikingly consistent with those from previous studies of prosecution of child sexual abuse. A new understanding of prosecution of child sexual abuse is recommended that takes into account the large proportion of cases that do not go to trial.

Adolescent↗
PubMed1994

Prosecution of child sexual abuse: which cases are accepted?

This study examined the relationship of case characteristics, maternal support, and child psychopathology to acceptance of child sexual abuse cases for prosecution. Cases referred to prosecutors' offices over a 1-year period in four urban jurisdictions (N = 431) were examined, and a smaller sample of mothers and children (N = 289) were interviewed as well. Background characteristics of the perpetrator and victim, severity of abuse, and nature of available evidence were all significantly related to acceptance for prosecution. Specific independent predictors of acceptance were victim age, presence of oral-genital abuse, use or threat of force, duration of abuse, and presence of physical or eyewitness evidence. With other variables controlled, maternal support was higher and child internalizing psychopathology lower in accepted cases. The results are interpreted in terms of prosecutors' concern for serving justice and protecting children and their perceptions of their ability to prosecute cases successfully.

Adolescent↗
PubMed1994

The Intervention Stressors Inventory: a measure of the stress of intervention for sexually abused children.

This paper describes the development and initial validation of the Intervention Stressors Inventory (ISI), a new scale designed to measure the level of stress sexually abused children experience as a result of societal intervention. Estimates of the relative stress level of various interventions were obtained from 98 professionals; a police interview was the designated anchor with a score of 50 points. Resulting scores from the survey included 35 points for social worker interview, 100 points for placement in foster care, and 111 points for testimony in criminal court. Factors that could potentially modify the stress of any given event were also considered. Interviews with 254 sexually abused children and their parents, 9 months after their cases were reported, provided an opportunity to examine the validity of the instrument. Weighted scores for each child were generated based on their experiences. Validity was supported by higher scores for older children, varying patterns of scores in different jurisdictions and a decline in scores over the one-year period in which jurisdictions were actively seeking to reduce the intrusiveness of intervention. Early results suggest that the ISI is useful as a research tool and as a guide in our efforts to reduce the trauma of intervention.

Adolescent↗
PubMed1990

Results of high dose intravenous urokinase for acute myocardial infarction.

To determine the outcome of patients after treatment with high-dose intravenous urokinase (3 million U) 102 patients were prospectively evaluated in the setting of acute myocardial infarction. The first 61 patients received intravenous urokinase as a continuous infusion and the last 41 patients were treated with an initial 1.5 million U intravenous bolus. Sixty-two percent of all patients had patent infarct-related arteries by the time of immediate angiography (median time 2.2 hours), which was performed in all patients. There was no significant difference in patency rates between patients treated with or without an initial intravenous bolus. Twenty-eight (28%) patients developed clinical evidence of recurrent ischemia (death, reocclusion, emergency angioplasty, urgent bypass surgery) during hospitalization, whereas only 7 (7%) developed angiographically documented reocclusion. Of 28 patients who failed to achieve successful reperfusion at the time of immediate catheterization, rescue angioplasty was technically successful in establishing reperfusion in all but 1 patient. No significant improvement in median global left ventricular function was seen between immediate (48%) and follow-up catheterization (48%). Significant bleeding complications were unusual except in 1 patient who experienced an intracranial hemorrhage. Eight (8%) patients died during hospitalization. Therefore, the use of high-dose intravenous urokinase in patients with acute myocardial infarction is associated with a 62% patency rate, a low incidence of reocclusion and bleeding complications and a high technical success rate with rescue angioplasty at the time of immediate catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗