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Biomedical subjects

T Halvorsen

Publications and source records attributed to T Halvorsen.

At least 19 recordsLinked to original sources
PubMed2004

Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study.

AIMS: The pulmonary outcome of extreme prematurity remains to be established in adults. We determined respiratory health and lung function status in a population-based, complete cohort of young preterms approaching adulthood. METHODS: Forty-six preterms with gestational age < or = 28 wk or birthweight < or = 1000 g, born between 1982 and 1985, were compared to the temporally nearest term-born subject of equal gender. Spirometry, plethysmography, reversibility test to salbutamol and methacholine bronchial provocation test were performed. Neonatal data were obtained from hospital records and current symptoms from validated questionnaires. RESULTS: When entering the study at a mean age of 17.7 (SD: 1.2) y, a doctor's diagnosis of asthma and use of asthma inhalers were significantly more prevalent among preterms than controls (one asthmatic control compared to nine preterms, all but one using asthma inhalers). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) were decreased and the discrepancies relative to controls increased parallel to increased severity of neonatal lung disease. Parameters of increased neonatal oxygen exposure significantly predicted FEV1. Adjusted for height, gender and age, FEV1 was reduced by a mean of 580 ml/s in subjects with a history of bronchopulmonary dysplasia. Fifty-six percent of preterms had a positive methacholine provocation test compared to 26% of controls. CONCLUSION: A substantially decreased FEV1, increased bronchial hyperresponsiveness and a number of established risk factors for steeper age-related decline in lung function were observed in preterms. A potential for early onset chronic obstructive pulmonary disease is present in subsets of this group.

Adolescent↗
PubMed2001

Beta-cell differentiation from a human pancreatic cell line in vitro and in vivo.

Cell transplantation therapy for diabetes is limited by an inadequate supply of cells exhibiting glucose-responsive insulin secretion. To generate an unlimited supply of human beta-cells, inducibly transformed pancreatic beta-cell lines have been created by expression of dominant oncogenes. The cell lines grow indefinitely but lose differentiated function. Induction of beta-cell differentiation was achieved by stimulating the signaling pathways downstream of the transcription factor PDX-1, cell-cell contact, and the glucagon-like peptide (GLP-1) receptor. Synergistic activation of those pathways resulted in differentiation into functional beta-cells exhibiting glucose-responsive insulin secretion in vitro. Both oncogene-expressing and oncogene-deleted cells were transplanted into nude mice and found to exhibit glucose-responsive insulin secretion in vivo. The ability to grow unlimited quantities of human beta-cells is a major step toward developing a cell transplantation therapy for diabetes.

Activating Transcription Factor 1↗
PubMed2001

Diabetes mellitus-cell transplantation and gene therapy approaches.

Diabetes mellitus affects millions of people in the United States and worldwide. It has become clear over the past decade that the chronic complications of diabetes result from lack of proper blood glucose concentration regulation, and particularly the toxic effects of chronic hyperglycemia on organs and tissues. Pancreas transplants can cure insulin-dependent diabetes mellitus (IDDM). Furthermore, recent advances in pancreatic islet isolation and immunosuppressive regimens have resulted in dramatic improvements in the survival and function of islet allografts. Therefore, islet replacement strategies are becoming increasingly attractive options for patients at risk for severe diabetic complications. A major limitation of these approaches is the small number of organs available for transplantation or islet isolation. Thus, an important next step in developing curative treatments for type I diabetes will be the generation of a replenishable source of glucose-responsive, insulin-secreting cells that can be used for beta cell replacement. This review focuses on approaches to developing robust and widely applicable beta-cell replacement strategies with an emphasis on manipulating beta-cell growth and differentiation by genetic engineering.

Animals↗
PubMed2001

Eosinophil counts and urinary eosinophil protein X in children hospitalized for wheezing during the first year of life: prediction of recurrent wheezing.

UNLABELLED: Early identification of wheezing children with an increased risk of recurrent wheezing or subsequent asthma is important. The aim of the study was to determine the role of markers of eosinophil activation, along with other parameters, in the prediction of recurrent wheezing and allergic sensitization in children with early and severe wheezing. We examined 105 children without atopic dermatitis, hospitalized for wheezing during the first year of life. At a 20-mo follow-up, 101 of the children were assessed for the occurrence of recurrent wheezing (at least 3 episodes, including 1 in the previous 6 mo) and allergic sensitization (positive skin-prick test). By univariate analysis, levels of eosinophil counts at the time of hospitalization (p = 0.005, OR = 18.9), age in months (p < 0.0001, OR = 1.5), respiratory syncytial virus (RSV)-negative disease (p < 0.0001, OR = 8.8), parental atopy (p = 0.006, OR = 3.3) and male sex (0.02, OR = 2.7) were all predictive factors for recurrent wheezing at follow-up. With all parameters included in a multiple regression analysis, RSV-negative disease was not a predictive factor for recurrent wheezing. A simple model including eosinophil counts > or = 0.1 x 10(9)/L and age had a predictive accuracy of 79%, with only a 6% chance of a child being wrongly predicted as symptomatic. Urinary protein X (U-EPX) was not a predictive factor for recurrent wheezing. When included in a multiple logistic regression analysis, a level of U-EPX > or = 100 microg/mmol creatinine was the only parameter with a positive predictive value for allergic sensitization (p = 0.007, OR = 18.9), whereas age, parental allergy or parental asthma were not. CONCLUSION: Children with severe wheezing during the first year of life and subsequent recurrent wheezing are characterized by a normal or high eosinophil count in response to viral infections.

Asthma↗
PubMed2000

Primary treatment of cervical carcinoma. Ten years experience from one Norwegian health region.

OBJECTIVE: To study the primary care of cervical carcinoma with regard to clinical and pathological factors, treatment decisions, complications and survival. DESIGN: A historical cohort comprising all women hospitalized with invasive cervical carcinoma (n=293) during the period 1987-1996. RESULTS: Median age was 52 years (range 23-90). FIGO stage distribution was 62%, 15%, 18% and 5% in stages I, II, III and IV, respectively. Early stage disease correlated with young age. Histologic types were: squamous cell carcinoma 84%, adenocarcinoma 11%, adenosquamous carcinoma 4% and small cell/anaplastic carcinoma 1%. Primary therapies were: surgery 188 women (64%), radiotherapy 99 women (34%), chemotherapy two women (0.7%); four women not treated (1.3%). Complications after surgery in 25 women (13%), none were fatal. Acute or late complications after primary or postoperative radiotherapy in 39 women (25%), seven (4.6%) were late serious complications. Three women died from complications related to radiotherapy. Mean follow-up of surviving patients was 58 months. Overall disease specific five-year survival was 70%. Five-year survival in stages IA, IB, II and III was 100%, 88%, 58% and 20%, respectively. One-year survival in stage IV was 31%. Median survival in stages III and IV according to curative or palliative aim of treatment was 20 and 6 months, respectively (p<0.005). CONCLUSION: Satisfactory quality of diagnosis and therapy have been maintained through regional care for cervical cancer patients.

Adenocarcinoma↗
PubMed1999

The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals.

OBJECTIVE: To assess the risk-of-malignancy index (a scoring system based on menopausal status, ultrasound features, and serum CA 125) at district hospitals for referral of women with suspected malignant pelvic masses for primary surgery at a central gynecologic oncology unit. METHODS: All seven hospitals in Health Region IV, Norway, agreed to refer women with pelvic masses and risk-of-malignancy indices of 200 or more for centralized primary surgery. In total, 365 women 30 years of age or older, admitted consecutively at the local hospitals, were enrolled in the study from February 1, 1995, to January 31, 1997. RESULTS: Compliance with the study was satisfactory; 84% (65 of 77) of women with risk-of-malignancy indices of at least 200 were referred for centralized primary surgery. Sensitivity and specificity to malignancy were 71% and 92%, respectively, which is in agreement with previous validation of the risk-of-malignancy index in teaching hospital settings. False negatives were due mainly to stage Ia (18 of 24) ovarian cancer, whereas 27 of 28 stage II-IV ovarian cancer cases were identified correctly. CONCLUSION: The risk-of-malignancy index identified women with malignant pelvic masses efficiently. Our study showed the risk-of-malignancy index strategy in a practical setting to be able to centralize primary surgery for advanced ovarian cancer from local hospitals to a subspecialty unit. We recommend the risk-of-malignancy index for detection of patients with advanced ovarian cancer for centralized primary surgery.

Adult↗
PubMed1997

Expression of colonization factor antigen I fimbriae by enterotoxigenic Escherichia coli; influence of growth conditions and a recombinant positive regulatory gene.

Enterotoxigenic Escherichia coli (ETEC) may spontaneously lose the positive regulatory cfaR gene and thereby the capacity to express colonization factor antigen I (CFA/I). A recombinant plasmid harbouring the cfaR gene was transformed into cfaR-negative mutant ETEC strains. CFA/I expression of wild-type and cfaR-transformed ETEC cultivated in different liquid media was quantified. At 37 degrees C, a high level of CFA/I expression from wild-type and cfaR-transformed strains was observed after growth in CFA broth. Transformation enhanced CFA/I expression only marginally. The transformant cultures showed a considerable variation in CFA/I expression which was paralleled by the proportion of individual bacteria producing CFA/I. This heterogeneity could be explained by a variable tendency to structural CFA/I gene loss among individual cfaR-transformed bacteria.

Bacterial Proteins↗
PubMed1996

Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses.

OBJECTIVE: To evaluate the ability of a risk of malignancy index (RMI), based on a serum CA125 level, ultrasound findings and menopausal status, to discriminate a benign from a malignant pelvic mass and to discriminate early stage (Figo Stage I) from Stages II, III and IV of ovarian cancer. DESIGN: A prospective study. SETTING: Department of Gynaecology, Trondheim University Hospital, Trondheim, Norway. PARTICIPANTS: One hundred and seventy-three women, 30 years or older, consecutively admitted between February 1992 and February 1994 for primary laparotomy of a pelvic mass. MAIN OUTCOME MEASURES: The sensitivity, specificity and positive predictive value of serum CA125 level, ultrasound findings and menopausal status, separately and combined into the RMI, to diagnose ovarian cancer. RESULTS: The RMI was more accurate than any individual criterion in diagnosing cancer. Using a RMI cut-off level of 200 to indicate malignancy, the RMI derived from this dataset gave a sensitivity of 80%, specificity of 92% and positive predictive value of 83%. Applying RMI criteria developed by others, the following test performance was found: sensitivity 71%, specificity 96% and positive predictive value 89%. For the Stages II, III and IV of ovarian cancer the sensitivity increased to approximately 90% without any substantial loss in specificity. CONCLUSIONS: The risk of malignancy index is able to correctly discriminate between malignant and benign pelvic masses. It is a scoring system which can be introduced easily into clinical practice to facilitate the selection of patients for primary surgery at an oncological unit.

Adult↗
PubMed1995

[Preoperative identification of malignancy among women with a pelvic mass. Evaluation of a risk index based on ultrasound findings. CA 125 in serum and menopausal status].

A risk of malignancy index (RMI) based on vaginal ultrasound, the tumour marker CA 125 level in serum, and menopausal status was calculated in 134 consecutive patients with a pelvic mass. 41 patients harboured a malignancy, while in 93 the condition was benign. The specificity according to the presence of a malignancy was 95% using the risk of malignancy index, compared with 78% when ultrasound was used alone, and 78% when CA 125 was used alone. The corresponding sensitivities were 73, 71 and 83% respectively. The majority of patients with a false negative index score had early stage ovarian cancer. Only one of the 21 patients with advanced ovarian cancer had a score below the limit of 200. The use of the risk malignancy index is a convenient method for pre-operative identification of cases of advanced ovarian cancer.

Adult↗
PubMed1995

Neuroendocrine differentiation in colorectal carcinomas.

OBJECTIVE: To evaluate neuroendocrine differentiation in tumours from patients with colorectal carcinomas by immunostaining with antibodies against human chromogranin A (CgA) and neuron-specific enolase (NSE), and to correlate these finding with serum levels of CgA and pancreastatin-like immunoreactivity (PST-LI). We also investigated the degree of neuroendocrine differentiation found in colorectal carcinomas of different embryonic origins (hindgut and midgut). PATIENTS AND METHODS: The presence of CgA and NSE in tumours from 91 patients with colorectal carcinoma was investigated using immunohistochemistry; levels of CgA and PST-LI in sera from 55 of these patients were determined using radioimmunoassays. RESULTS: Immunostaining for CgA and NSE was found in 15 and 36% of tumours, respectively. One or both markers of neuroendocrine differentiation were demonstrated in 40% of the colorectal carcinomas. In patients who died during the study, 23 and 51% expressed CgA and NSE in their tumours, respectively, while the corresponding values in survivors were 11 and 27% (P = 0.14 and P = 0.025, respectively). The median survival time tended to be lower in patients with neuroendocrine differentiation of their tumours than in those without such differentiation (P = 0.1). The expression of NSE was significantly higher in colorectal carcinomas derived from the midgut than in those of hindgut origin. Elevated serum levels of CgA and PST-LI were found in 38 and 43% of the patients, respectively; 62% had elevated levels of one or both markers. Of the patients with elevated serum levels of CgA or PST-LI, 44% had positive immunohistochemistry for either NSE or CgA compared with 29% of those with normal serum levels of CgA and PST-LI (P = 0.27). Serum levels of CgA were increased in a significantly higher percentage of patients with colorectal carcinomas of midgut than of hindgut origin (63 and 28%, respectively, P = 0.03). Of patients with hindgut-derived carcinomas who died during the study, 64% had raised serum values of CgA compared with 19% of those who survived (P = 0.023). The corresponding figures for PST-LI elevation were 75 and 44%, respectively (P = 0.096). In the midgut group, no difference was demonstrated for these parameters between survivors and non-survivors. CONCLUSION: Neuroendocrine differentiation was demonstrated in 40% of the colorectal carcinomas investigated and was more frequent in midgut-derived carcinomas than in those of hindgut origin. We have shown for the first time that serum levels of CgA and PST-LI are elevated in patients with colorectal carcinomas. In accordance with previous studies, our data support the value of neuroendocrine differentiation as an indicator of poor prognosis; they also suggest a role for serum CgA and PST-LI as prognostic markers.

Biomarkers, Tumor↗
PubMed1994

[Surgical treatment of cervix cancer. A 6-year material from a regional hospital].

The results are reported for 75 patients treated with radical hysterectomy and pelvic lymphadenectomy (Wertheim-Meigs' operation) for cervical carcinoma. There was no per- or postoperative death. Ten patients suffered immediate postoperative complications. One case of lower limb lymphoedema was observed. 17 patients (23%) had pelvic lymph node metastases. In eight patients the disease has recurred (median observation time 43 months). Overall recurrence-free survival was 89%: for patients without lymph node metastases 91%, and for patients with metastases 82%. Using a prognostic score based on stage, presence of lymph node metastases, blood or lymph vessel invasion, low differentiation, and tumour-involved resection margins; two groups could be identified, with a recurrence-free survival of 94% (score < or = 2) and 75% (score > or = 3), respectively (p < 0.02).

Adult↗
PubMed1993

[Eosinophilic gastroenteritis].

We describe the case of a 33 year-old woman who was hospitalized for ascites, abdominal pain and food allergy. Blood samples and histologic examination of a jejunal specimen removed by laparotomy revealed that the patient suffered from eosinophilic gastroenteritis. This disease is classified among the hypereosinophilic syndromes, and food allergy may be of etiologic importance. Clinically eosinophilic gastroenteritis may present with ascites, malabsorption or gut obstruction. The eosinophilic blood cell count is usually elevated and the erythrocyte sedimentation rate is usually normal or slightly increased. Polyarteritis nodosa, Crohn's disease and nematodal infections of the gut must be excluded. Most patients respond well to corticosteroid therapy and the long-term prognosis is good, even though the disease is chronic in nature.

Adult↗
PubMed1990

The benefit of colonoscopy.

In a prospective study involving 833 consecutive outpatient and open-access colonoscopies, attempts were made to characterize the benefit of colonoscopy in terms of both predicted and unpredicted findings and therapeutic procedures. The endoscopist therefore predicted the endoscopic findings before the endoscopy. The results were compared for the different indications for colonoscopy. The overall agreement between the predictions and the colonoscopic findings was 61%. Clinically significant abnormalities were found in about half the examinations. The most frequent abnormal findings were benign polyps (24%), inflammatory bowel disease (17%), and malignancy (5%). In about half the patients with a malignancy the indication for colonoscopy was rectal bleeding, and half of the malignancies were not predicted. The greatest benefit of colonoscopy was found in patients referred because of overt rectal bleeding or occult faecal blood, and abnormal barium enema or endoscopy findings. The importance of complete colonoscopy in connection with operation for colorectal carcinoma is emphasized.

Colonic Polyps↗
PubMed1988

Cimetidine responders in non-ulcer dyspepsia.

The effect of cimetidine and placebo was examined in 123 patients with non-ulcer dyspepsia (NUD) by means of a 12-day multi-crossover model with 5 regular interchanges between cimetidine and placebo. The evaluation of effect in individual patients was based on the number of times cimetidine was associated with less symptoms than the preceding or following placebo period. If cimetidine had no effect, the probability of being defined as a cimetidine responder was 25%. In general, cimetidine was associated with less symptoms than placebo (p less than 0.0001). Forty patients were identified as cimetidine responders (R) and the remaining patients were termed non-responders (NR). Symptoms compatible with gastroesophageal reflux were significantly more frequent in R than in NR, whereas the opposite was true for symptoms of the irritable colon syndrome. The ability of symptoms selected by stepwise logistic regression to predict response to cimetidine showed at best a sensitivity of 75% and a specificity of about 65%. No differences were found between R and NR with regard to acid secretion, endoscopic and histologic findings, or the result of an acid perfusion test. The present study supports the existence of a subgroup of cimetidine responders among patients with NUD characterized by symptoms suggestive of gastroesophageal reflux disease in the absence of confirmatory objective evidence.

Adult↗
PubMed1987

Dyspepsia: Therapeutic response as a diagnostic tool.

Non-ulcer dyspepsia (NUD) is a poorly defined heterogenous condition less well suited for the conventional randomized and placebo controlled parallel type trials. We have designed a multi cross-over model (MCO-model) with the facility of providing information about drug responses in individual patients. A pilot study suggested that the model may identify individual cimetidine responders among patients with dyspepsia. Preliminary findings from an ongoing study in patients with NUD supports the existence of a subgroup of cimetidine responders characterized by gastroesophageal reflux symptoms and possibly an increased basal acid secretion.

Cimetidine↗