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Biomedical subjects

V Johnson

Publications and source records attributed to V Johnson.

At least 19 recordsLinked to original sources
PubMed2005

Analysis of somatic molecular changes, clinicopathological features, family history, and germline mutations in colorectal cancer families: evidence for efficient diagnosis of HNPCC and for the existence of distinct groups of non-HNPCC families.

OBJECTIVE: To analyse somatic molecular changes, clinicopathological features, family history, and germline mutations in families with colorectal cancer (CRC). METHODS: Molecular changes (K-ras and beta-catenin mutations, chromosome 18q allele loss (LOH), APC LOH, microsatellite instability (MSI), and expression of beta-catenin and p53) were examined in four series of CRC patients with proven or probable hereditary disease: hereditary non-polyposis colon cancer (HNPCC); MYH associated polyposis (MAP); multiple (>5) colorectal adenomas without familial adenomatous polyposis (FAP); and other families/cases referred to family cancer clinics (FCC series). HNPCC was diagnosed using a combination of germline mutation screening and tumour studies. A series of unselected CRC patients was also studied. RESULTS: There was overlap between genetic pathways followed by each type of CRC, but significant differences included: increased frequency of K-ras mutation and reduced frequency of APC LOH in cancers from MAP, but not from multiple adenoma patients; reduced frequency of LOH in HNPCC CRCs; and increased MSI in CRCs from HNPCC, but not from FCC or multiple adenoma patients. HNPCC was apparently detected efficiently by combined germline and somatic analysis. Cancers from the FCC, unselected, and multiple adenoma series shared similar molecular characteristics. In the FCC and multiple adenoma series, hierarchical cluster analysis using the molecular features of the cancers consistently identified two distinct groups, distinguished by presence or absence of K-ras mutation. CONCLUSIONS: While K-ras mutation status is known to differentiate hereditary bowel cancer syndromes such as MAP and FAP, it may also distinguish groups of non-HNPCC, FCC patients whose disease has different, as yet unknown, genetic origins.

Adult↗
PubMed2005

Exon 3 beta-catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome.

BACKGROUND AND AIMS: Activating beta-catenin mutations in exon 3 have been implicated in colorectal tumorigenesis. Although reports to the contrary exist, it has been suggested that beta-catenin mutations occur more often in microsatellite unstable (MSI+) colorectal carcinomas, including hereditary non-polyposis colorectal cancer (HNPCC), as a consequence of defective DNA mismatch repair. We have analysed 337 colorectal carcinomas and adenomas, from both sporadic cases and HNPCC families, to provide an accurate assessment of beta-catenin mutation frequency in each tumour type. METHODS: Direct sequencing of exon 3 of beta-catenin. RESULTS: Mutations were rare in sporadic (1/83, 1.2%) and HNPCC adenomas (1/37, 2.7%). Most of the sporadic adenomas analysed (80%) were small (<1 cm), and our data therefore differ from a previous report of a much higher mutation frequency in small adenomas. No oncogenic beta-catenin mutations were identified in 34 MSI+ and 78 microsatellite stable (MSI-) sporadic colorectal cancers but a raised mutation frequency (8/44, 18.2%) was found in HNPCC cancers; this frequency was significantly higher than that in HNPCC adenomas (p=0.035) and in both MSI- (p<0.0001) and MSI+ (p=0.008) sporadic cancers. Mutations were more common in higher stage (Dukes' stages C and D) cancers (p=0.001). CONCLUSION: Exon 3 beta-catenin mutations are associated specifically with malignant colorectal tumours in HNPCC; mutations appear not to result directly from deficient mismatch repair. Our data provide evidence that the genetic pathways of sporadic MSI+ and HNPCC cancers may be divergent, and indicate that mutations in the HNPCC pathway of colorectal tumorigenesis may be determined by selection, not simply by hypermutation.

Adenoma↗
PubMed2004

Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic.

PURPOSE: Hereditary nonpolyposis colon cancer (HNPCC) is a Mendelian dominant syndrome of bowel, endometrial, and other cancers and results from germline mutations in mismatch repair (MMR) genes. HNPCC is now best diagnosed on molecular grounds using MMR mutation screening, aided by microsatellite instability (MSI) and immunohistochemistry in tumors. Selection of families for molecular investigation of HNPCC is usually based on suboptimal methods (Amsterdam Criteria or Bethesda Guidelines), but these can be improved using additional clinical data (mean ages of affected persons and presence of endometrial cancer) in a quantitative model. METHODS: We have verified the performance of the Wijnen model and have shown that it remains valid when HNPCC is diagnosed using mutation screening, MSI, and immunohistochemistry. We have also set up and verified our own models (Amsterdam-plus and Alternative), which perform at least as well as the Wijnen model. RESULTS: The Amsterdam-plus model improves on the Amsterdam Criteria by using five extra variables (numbers of colorectal and endometrial cancers in the family, number of patients with five or more adenomas, number with more than one primary cancer of the colorectum or endometrium, and mean age of presentation) and performs better than the Wijnen model. The Alternative model avoids the need to evaluate the Amsterdam Criteria and performs nearly as well as the other models. CONCLUSION: We believe that a quantitative model, such as the Amsterdam-plus model, should be the first choice for selecting families or patients for evaluation of HNPCC using molecular tests. We present an algorithm for this process.

Adult↗
PubMed2004

Phase I study for poor-prognosis lymphoma: augmentation of the "BEAM" regimen with escalating dose melphalan using amifostine cytoprotection and autologous hematopoietic stem cell transplantation--a preliminary report.

We and others have previously shown that the use of amifostine (Ethyol; MedImmune Inc, Gaithersburg, MD) can ameliorate certain regimen-related toxicities of high-dose melphalan (HD-MEL) in the autologous hematopoietic stem cell transplant setting. Our recent experience indicated that the maximum tolerated dose of HD-MEL plus autologous hematopoietic stem cell transplant could be increased from approximately 200 mg/m2 to at least 280 mg/m2 with amifostine. Although a dose-limiting toxicity was not clearly identified, atrial fibrillation was noted in several patients. Phase II trials using this regimen have been reported in lymphoma and myeloma. Nonetheless, it is unlikely that single agent therapy, regardless of dose, will be highly curative in advanced hematologic malignancy. Thus, we used amifostine to permit dose escalation of HD-MEL within the BEAM (BCNU/etoposide/arabinosylcytosine/HD-MEL) combination chemotherapy regimen before autologous hematopoietic stem cell transplant in selected patients with lymphoma. Patient entry at the starting dose (ie, HD-MEL 140 mg/m2) has been completed without the development of severe regimen-related toxicities. This trial is ongoing.

Adult↗
PubMed2001

Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network.

PURPOSE: To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma of the urothelial tract. PATIENTS AND METHODS: Fifty-four patients with advanced unresectable urothelial carcinoma entered this multi-centered, community-based, phase II trial between May 1997 and December 1999. All patients were treated with paclitaxel 200 mg/m(2) by 1-hour intravenous (IV) infusion on day 1 and gemcitabine 1,000 mg/m(2) IV on days 1, 8, and 15; courses were repeated every 21 days. Patients who had objective response or stable disease continued treatment for six courses. RESULTS: Twenty-nine of 54 patients (54%; 95% confidence interval, 40% to 67%) had major responses to treatment, including 7% complete responses. With a median follow-up of 24 months, 16 patients (30%) remain alive and nine (17%) are progression-free. The median survival for the entire group was 14.4 months; 1- and 2-year actuarial survival rates were 57% and 25%, respectively. Seven (47%) of 15 patients previously treated with platinum-based chemotherapy responded to paclitaxel/gemcitabine. Grade 3/4 toxicity was primarily hematologic, including leukopenia (46%), thrombocytopenia (13%), and anemia (28%). Ten patients (19%) required hospitalization for neutropenia and fever, and one patient had treatment-related septic death. CONCLUSION: The combination of paclitaxel and gemcitabine is active and well tolerated in the first- or second-line treatment of patients with advanced transitional-cell carcinoma of the urothelial tract. Response rate and duration compare favorably with those produced by other active, first-line regimens. This regimen should be further evaluated in phase II and III studies, as well as in patients with compromised renal function.

Actuarial Analysis↗
PubMed2001

CEO perceptions of competition--and strategic response in hospital markets.

Physician-organization integration (POI) has emerged as a key issue for hospitals and health systems seeking to improve the quality and cost-effectiveness of care. Although competition and managed care are often cited as primary market drivers of the adoption of POI strategies, prior research has shown only weak associations between these market attributes and POI. This article argues that the role of key organizational decision makers has not been adequately accounted for in explaining strategic change. The study examines the role of hospital CEO perceptions of competition in predicting the adoption of five different approaches to POI. CEO perceptions of general market competition are explained by a combination of market and organizational attributes. Furthermore, when controlling for objective characteristics of the environment and organization, CEO perceptions of competition have consistent, statistically significant associations with four of five measures of POI examined.

Attitude of Health Personnel↗
PubMed2001

Urinary diversions: a review of nursing care.

The nurse plays an important part in the preoperative and postoperative management of the patient with a urinary diversion. Although urinary diversion as a surgical alternative has been performed since the mid 1800s, improvements in technique and management over the past 10 years warrant discussion. Three types of urinary diversion procedures are discussed along with suggestions for optimal nursing management during the postoperative period.

Humans↗
PubMed2000

Parental modeling and parenting behavior effects on offspring alcohol and cigarette use. A growth curve analysis.

PURPOSE: This paper examined the effects of parental drinking and smoking, parental warmth and hostility, and their interactions on offsprings' drinking and smoking over time. METHODS: We used four waves of prospective longitudinal data collected from 218 males and 214 females who were age 15 at Time 1 and age 28 by Time 4. Growth mixture modeling was used to develop offspring trajectory groups of cigarette smokers and alcohol drinkers. Logistic regression analyses were conducted to determine whether parent behaviors could predict offspring heavy drinking and smoking trajectories. RESULTS: Four drinking and three smoking trajectory groups were identified for females and males. Parent drinking rather than parenting behavior predicted heavy drinking by offsprings and mothers' drinking was a slightly better predictor than fathers' drinking for both daughters and sons. Fathers' warmth and hostility was the best predictor of heavy smoking by sons. Neither modeling nor parenting significantly predicted female heavy smoking. For the most part, parent modeling did not interact with parenting behavior to predict smoking or drinking in offspring. IMPLICATIONS: Parents affected their offspring's use of alcohol and cigarettes both through modeling and parenting behavior. However, the importance of modeling relative to parenting behavior differed by the type of substance. Prevention programs that focus on both the modeling of parental behaviors, as well as enhancing parenting skills, should be effective in influencing trajectories of substance use throughout adolescence and young adulthood.

Adolescent↗
PubMed2000

Vibrio cholerae O139 conjugate vaccines: synthesis and immunogenicity of V. cholerae O139 capsular polysaccharide conjugates with recombinant diphtheria toxin mutant in mice.

Epidemiologic and experimental data provide evidence that a critical level of serum immunoglobulin G (IgG) antibodies to the surface polysaccharide of Vibrio cholerae O1 (lipopolysaccharide) and of Vibrio cholerae O139 (capsular polysaccharide [CPS]) is associated with immunity to the homologous pathogen. The immunogenicity of polysaccharides, especially in infants, may be enhanced by their covalent attachment to proteins (conjugates). Two synthetic schemes, involving 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) as activating agents, were adapted to prepare four conjugates of V. cholerae O139 CPS with the recombinant diphtheria toxin mutant, CRMH21G. Adipic acid dihydrazide was used as a linker. When injected subcutaneously into young outbred mice by a clinically relevant dose and schedule, these conjugates elicited serum CPS antibodies of the IgG and IgM classes with vibriocidal activity to strains of capsulated V. cholerae O139. Treatment of these sera with 2-mercaptoethanol (2-ME) reduced, but did not eliminate, their vibriocidal activity. These results indicate that the conjugates elicited IgG with vibriocidal activity. Conjugates also elicited high levels of serum diphtheria toxin IgG. Convalescent sera from 20 cholera patients infected with V. cholerae O139 had vibriocidal titers ranging from 100 to 3,200: absorption with the CPS reduced the vibriocidal titer of all sera to < or =50. Treatment with 2-ME reduced the titers of 17 of 20 patients to < or =50. These data show that, like infection with V. cholerae O1, infection with V. cholerae O139 induces vibriocidal antibodies specific to the surface polysaccharide of this bacterium (CPS) that are mostly of IgM class. Based on these data, clinical trials with the V. cholerae O139 CPS conjugates with recombinant diphtheria toxin are planned.

Animals↗
PubMed2000

An elementary school-based health clinic: can it reduce medicaid costs?

OBJECTIVE: School-based health services have evolved from primarily controlling communicable disease to comprehensive programs with direct services, education, and improvement of the school environment. School-based health clinics (SBHCs), currently 1157 in number, are used to reach children for preventive and other routine care. Although several studies have examined the costs and effects of such programs, few, if any, have examined their potential to save Medicaid program outlays. The objective of this study was to assess the effect of the Whitefoord Elementary School-Based Health Clinic (WESBHC), located in Atlanta, Georgia, on health care costs paid by Georgia Medicaid over the 1994-1996 period. This clinic has been in operation since late 1994. DESIGN: The analysis uses 1994-1996 claims data for Medicaid-enrolled children 4 through 12 years old served by the WESBHC and similar children in a comparison school district without such a clinic. Descriptive and multivariate analyses are used to discern the differences in the changes in Medicaid expenses per child-year enrolled for these 2 groups of children. Both those who only used the WESBHC sporadically and those for whom it was their medical home were identified for analysis. RESULTS: The descriptive analysis shows that although there were no significant differences in the Medicaid expenses for the WESBHC and comparison children in 1994, before the operation of the WESBHC, by 1995, the WESBHC children had significantly lower emergency department expenses. In addition, they had higher Early Periodic Screening Diagnosis and Treatment preventive care expenses. By 1996, the WESBHC children had significantly lower inpatient, nonemergency department transportation, drug, and emergency department Medi- caid expenses. Multivariate analysis confirmed the effect of the WESBHC on lowering emergency department expenses. CONCLUSIONS: The results strongly suggest that the operation of a SBHC can have effects on the child's use of services and health care expenses. Given that these clinics serve all those who come for care and many of these are low-income children, these savings are likely to accrue to the Medicaid program of the state. As states continue to implement Medicaid-managed care for their child populations, they will need to consider the ability of SBHCs to participate in and receive Medicaid revenues through health maintenance organization networks.

Child↗
PubMed2000

Alcohol problems among a community sample: longitudinal influences of stress, coping, and gender.

This study examined the relationships among stress, coping methods, and alcohol-use associated problems within a longitudinal, community sample of males and females who were followed from adolescence through young adulthood. While fewer females than males were categorized as "dependent users," these females were more debilitated in terms of the number of alcohol-related problems experienced from age 15 through age 25. Measures of both chronic and proximal levels of personal stress and negative coping styles were most helpful in explaining problems with alcohol use. Distal measures of stress and coping, while perhaps serving as mediators or moderators of other important constructs, did not appear to have a direct effect on the outcome measure.

Adaptation, Psychological↗
PubMed1999

Low prenatal weight gain among adult WIC participants delivering term singleton infants: variation by maternal and program participation characteristics.

OBJECTIVE: To determine the association of maternal and prenatal WIC program participation characteristics with low prenatal weight gain among adult women delivering liveborn, singleton infants at term. METHODS: WIC program data for 19,017 Black and White Alabama women delivering in 1994 were linked with birth certificate files to examine the association of anthropometric, demographic, reproductive, hematologic, behavioral and program participation characteristics with low prenatal weight gain. RESULTS: One third (31.0%) had low prenatal weight gain as defined by the Institute of Medicine. The incidence of low weight gain was increased among women who had < 12 years of education, were single, Black, anemic, had low or normal prepregnancy body mass index (BMI), increased parity, interpregnancy intervals < or = 24 months, used tobacco or alcohol, or entered prenatal care or WIC programs after the first trimester. After adjusting for selected maternal characteristics, the adjusted odds ratios (AOR) for low weight gain were increased with short interpregnancy intervals (AOR 1.21 to 2.20); tobacco use (AOR 1.16 to 1.40), anemia (AOR 1.20 to 1.25), and second trimester entry into prenatal care (AOR 1.14 to 1.20); the size of the AORs and 95% confidence intervals varied by BMI and racial subgroup. CONCLUSIONS: The results of this study suggest that WIC interventions targeting low prenatal weight gain be focused on risk factors present not only during pregnancy, but during the pre- and interconceptional periods as well. Interventions should target low BMI, tobacco use, and anemia, and include attention to nutrition screening and risk reduction among women in postpartum and family planning clinic settings.

Adult↗
PubMed1999

The type of somatic mutation at APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson's 'two-hit' hypothesis.

APC is often cited as a prime example of a tumor suppressor gene. Truncating germline and somatic mutations (or, infrequently, allelic loss) occur in tumors in FAP (familial adenomatous polyposis). Most sporadic colorectal cancers also have two APC mutations. Clues from attenuated polyposis, missense germline variants with mild disease and the somatic mutation cluster region (codons 1,250-1,450) indicate, however, that APC mutations might not result in simple loss of protein function. We have found that FAP patients with germline APC mutations within a small region (codons 1,194-1,392 at most) mainly show allelic loss in their colorectal adenomas, in contrast to other FAP patients, whose 'second hits' tend to occur by truncating mutations in the mutation cluster region. Our results indicate that different APC mutations provide cells with different selective advantages, with mutations close to codon 1,300 providing the greatest advantage. Allelic loss is selected strongly in cells with one mutation near codon 1,300. A different germline-somatic APC mutation association exists in FAP desmoids. APC is not, therefore, a classical tumor suppressor. Our findings also indicate a new mechanism for disease severity: if a broader spectrum of mutations is selected in tumors, the somatic mutation rate is effectively higher and more tumors grow.

Adenoma↗
PubMed1999

Factor structure of the Neurobehavioral Cognitive Status Exam (COGNISTAT) in healthy, and psychiatrically and neurologically impaired, elderly adults.

This study reports the results of factor analyses of COGNISTAT (NCSE) in a sample of elderly persons comprised of "healthy" participants with no psychiatric or neurological impairments (n = 153), individuals with psychiatric impairments (n = 70), and those with neurological impairments (n = 80). Our findings support a unitary factor structure for COGNISTAT, though a separate factor of unclear clinical or theoretical significance was suggested.

Adult↗
PubMed1999

Comparison of linear equating and prorated short forms for estimating WAIS-R FSIQ in a neuropsychological population.

Comparisons were made of estimates of the Wechsler Adult Intelligence Scale - Revised Full Scale IQ using the two-,three- and four-subtest linear equating procedures of Kaufman (1990) and Booker and Cyr (1986) with FSIQ estimates using prorating to obtain FSIQ scores. The advantage of prorating is that it affords greater clinical flexibility in selection of subtests. The participants were 64 neuropsychiatric patients who completed the full WAIS-R from which short form and FSIQ were calculated. Prorating yielded estimates of mean IQ and categorization of IQ comparable to IQs obtained by linear equating, though there was an increased likelihood of disparate results with extreme IQ scores. Prudent clinical judgment is recommended for situations involving unusual or extreme scaled score patterns, particularly when the number of subtests is small.

Adult↗