Biomedical subjects

A A Hart

Publications and source records attributed to A A Hart.

At least 19 recordsLinked to original sources

PubMed2003

[The prevalence of use of restraints in a Dutch teaching hospital. An exploration in two wards].

UNLABELLED: The use of restraints in The Netherlands has mainly been studied in psychiatric, geropsychiatric, elderly, and retarded persons. No study is known on this subject in Dutch general hospitals. The objective of our study was to determine the prevalence of the use of physical restraints and side-rails and factors associated with restraint and side-rail use in a Dutch teaching hospital. On two acute care wards (internal medicine and neurology) 208 consecutively admitted patients were personally observed for the use of side-rails in February 2001. The use of restraints was abstracted from the nursing records. RESULTS: Of the patients 34% at least one time had side-rails raised, and 9% was subjected to physical restraints at some point during hospitalisation. In the logistic model, the neurology ward (OR: 4; 95% CI: 2-10), age of 80 or over (OR 12; 95% CI 3-51), stroke (OR 7; 95% CI 2-24), disorientation (OR: 9; 95% CI: 3-29) and restlessness or agitation (OR: 68; 95% CI: 7-596) were found to be independently associated with use of side-rails. For the use of restraints restlessness or agitation (OR: 125; 95% CI: 18-856) was found to be an independent factor. Differences in study design make comparisons between institutions and countries difficult.

Accidental Falls↗

PubMed2001

Complexity of lung cancer modifiers: mapping of thirty genes and twenty-five interactions in half of the mouse genome.

BACKGROUND: Numerous low-penetrance genes control susceptibility to cancer in experimental animals, but the overall genetic information on this group of genes (i.e., number of loci and their mutual interactions) is missing. We performed a systematic search, scanning roughly half of the mouse genome for lung cancer susceptibility (Sluc) genes affecting tumor size or number by using mouse recombinant congenic (RC) strains. In each RC strain (OcB), approximately 12.5% of the genome is derived from the lung cancer-resistant strain B10.O20, whereas the rest is derived from the lung cancer-susceptible strain O20. METHODS: A total of 730 F2 hybrids from five (OcB x O20) crosses were tested. Pregnant mice were treated on day 18 of gestation with a single dose of N-ethyl-N-nitrosourea. When offspring were 16 weeks old, whole lungs were removed and sectioned semiserially, and the size of all lung tumors (n = 2658) was determined. Analysis of variance was used for detection of linkage, and models (including main effect and two-way interactions) were tested with a statistical program. RESULTS: We detected a total of 30 Sluc loci (16 new plus 14 previously reported) and 25 two-way interactions. Some of these interactions are counteracting (e.g., Sluc17 and Sluc20), resulting in the partial or total masking of the individual independent effect (main effect) of each involved locus. Seven loci (Sluc1, Sluc5, Sluc12, Sluc16, Sluc18, Sluc20, and Sluc26) and two interactions (Sluc5 x Sluc12 and Sluc5 x Sluc26) were detected in more than one RC strain. CONCLUSIONS: The extrapolation of our results to the whole genome suggests approximately 60 Sluc loci (90% confidence intervals = 42 to 78). Despite the genetic complexity of lung cancer, use of appropriate mapping strategies can identify a large number of responsible loci and can reveal their interactions. This study provides an insight into the genetic control of lung tumorigenesis and may serve as a paradigm for investigating the genetics of other cancer types.

Animals↗

PubMed2001

Apoptosis, proliferation and p53, cyclin D1, and retinoblastoma gene expression in relation to radiation response in transitional cell carcinoma of the bladder.

PURPOSE: To determine whether the apoptotic index, the Ki67 index, and the expression of the p53, cyclin D1, and retinoblastoma genes correlate with local control, overall survival, and time to distant metastases in invasive bladder cancer treated with external beam radiation. METHODS AND MATERIALS: Paraffin-embedded pretreatment biopsies from 83 patients with invasive transitional cell carcinoma of the bladder were scored morphologically for apoptosis and immunohistochemically for Ki67, p53, cyclin D1, and retinoblastoma gene expression. Survival analysis methods were used to assess overall survival, local control, and freedom from distant metastases. A multiple proportional hazard (PH) regression analysis was performed to study the prognostic value of the abovementioned biologic parameters (all divided into two categories, except Ki67) in addition to classical prognostic factors such as T stage, histologic grade, multifocality of the tumor, and completeness of transurethral resection. All patients were treated with external beam radiation as sole treatment. Median follow-up for the 19 patients still living was 7.5 years. RESULTS: Apoptotic index varied from 0% to 3.4% with a mean of 0.8% and a median of 0.6%. Ki67 index varied from 0% to 60% with a mean of 14% and a median of 12%. P53 protein was detectable in 61% of the tumors. Overexpression of cyclin D1 was observed in 39% of the tumors and loss of retinoblastoma protein in 23% of the tumors. High Ki67 index was found to be significantly associated with p53 expression (p = 0.04) and cyclin D1 overexpression (p = 0.023). Cyclin D1 overexpression was found more often in Rb-positive tumors than in Rb-negative tumors (p = 0.006). Other associations between the markers are less clear. Biologic markers were not correlated with T stage or grade. In the PH analysis local control was found to be significantly better for tumors with wild-type p53 (p = 0.028). Also, tumors with an apoptotic index above the median value (0.6%) had a significantly better local control rate (p = 0.035). Ki67 index (p = 0.35), retinoblastoma gene expression (p = 0.30) and cyclin D1 overexpression (p = 0.61) were not found to have an additional predictive value regarding local tumor control. None of the tested biologic parameters were found to be associated with overall survival. Time to distant metastases was significantly shorter for tumors with high Ki67 index (p = 0.01) and tumors with an apoptotic index less than median (p = 0.009). CONCLUSIONS: The results of our study provide evidence for a prognostic value of p53 expression and apoptotic index with respect to the radiation response in bladder cancer in addition to more conventional prognosticators. The value of these parameters as a predictive assay for radiation response warrants confirmation in larger and prospective studies.

Adult↗

PubMed2001

The value of Cloquet's node in predicting melanoma nodal metastases in the pelvic lymph node basin.

BACKGROUND: A selection of melanoma patients with groin metastases can benefit from a pelvic (iliac/obturator) lymph node dissection in addition to the infrainguinal dissection. However, there are no reliable criteria to determine which patients may benefit from such an inguinal-pelvic lymphadenectomy. METHODS: In 142 patients (group A) out of a review of 214 groin dissections performed between 1980 and 1994, the tumor status of Cloquet's node was traced retrospectively. In 52 additional patients (group B), the status of Cloquet's node was registered prospectively. The number of positive lymph nodes and the total numbers of retrieved nodes were recorded as well. All patients underwent a combined therapeutic inguinal-pelvic lymph node dissection between January 1995 and June 1999 in a tertiary referral center. RESULTS: Cloquet's node was free of disease in 18 of 39 patients with involved pelvic nodes in the retrospective study (sensitivity, 54%; negative predictive value, 83%). In the prospective study, 9 of the 20 patients with involved pelvic nodes had a tumor-free Cloquet's node (sensitivity, 55%; negative predictive value, 78%). Additional immunohistochemical staining of Cloquet's node resulted in a sensitivity of 65%. In the combined group A&B, the number of positive nodes in the inguinal region (cutoff point more than three nodes) had a sensitivity of 41% and a negative predictive value of 78% to determine the pelvic nodal status. When we combined the number of positive inguinal nodes and Cloquet's node in group A&B, the best sensitivity was 56% and the best negative predictive value was 82%. CONCLUSIONS: Cloquet's node has a low sensitivity to predict the pelvic nodal tumor status. This was barely improved when we accounted for the number of positive inguinal nodes. Groin lymph node dissections should encompass the iliac and obturator compartments in patients with palpable inguinal node metastases.

Adolescent↗

PubMed2001

Outcome of thoracoscopic pulmonary metastasectomy evaluated by confirmatory thoracotomy.

BACKGROUND: The aim of this study was to determine the feasibility, accuracy, and outcome of thoracoscopic resection of peripherally located pulmonary metastases. METHODS: The 28 patients had three or fewer solitary metastases, located in the periphery of the lung, with a diameter 3 cm or less on computed tomography scan. A thoracoscopic resection was performed to remove all identified lesions evaluated by confirmatory thoracotomy. RESULTS: A thoracoscopic resection was technically impossible in 10 patients. In 1 patient a confirmatory thoracotomy was not performed because the lesion was diagnosed as carcinoid. Among the 17 patients who underwent confirmatory thoracotomy, 12 patients had a complete thoracoscopic resection and 5 patients had residual disease. The success rate appeared to be higher (p = 0.01) in patients with one lesion (11 of 12 patients), than in patients with more than one lesion (1 of 5 patients) found by preoperative computed tomography scan. CONCLUSIONS: Thoracoscopic resection can be considered a viable treatment option for patients who present with a solitary pulmonary metastasis with a diameter of 3 cm or less, when the lesion is located in the periphery of the lung.

Adult↗

PubMed2001

Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53.

BACKGROUND AND PURPOSE: In a recent study on patients with transitional cell cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associated with poor local control. The purpose of this study was to assess the prognostic significance of additional markers implicated in regulation of cell cycle and apoptosis. PATIENTS AND METHODS: Bcl-2, Bax and p21 positivity were detected immunohistochemically on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with radiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were included in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, multifocality and macroscopic completeness of the TUR). Positivity was defined as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53. RESULTS: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be related to poor local control (36 vs. 72% at 3 years; P=0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P=0.017). Evidence for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years;P=0.037, disease-specific survival: 76 vs. 92% at 3 years; P=0.043). In an additional PH analysis, we found poor local control rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs. 65% at 3 years; P=0.0017), and lower disease specific survival (60 vs. 92%; P=0.0024), disease-free survival (7 vs.35%, P=0.0023) and overall survival (39 vs. 80%; P=0.0018). CONCLUSION: This study provides evidence for a poor outcome in patients treated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53. This relationship was found for local control and disease-free, disease-specific and overall survival.

Adult↗

PubMed2001

The prognostic significance of a previous malignancy in operable non-small cell lung cancer.

There is little data in literature on survival of patients with lung cancer as a second primary (SP) malignancy. This retrospective study was undertaken to investigate whether a previous malignancy has prognostic significance in operable non-small cell lung cancer (NSCLC). Sixty-six patients with SP NSCLC were compared with 75 'first primary' (FP) NSCLC patients without a previous malignancy. All the 141 patients had been surgically treated with curative intent at The Netherlands Cancer Institute (NKI) between 1977 and 1996. Patients who had undergone resections for lung metastases were excluded. Clinical and pathological characteristics were collected and a multivariate analysis on all the 141 patients was carried out. All the previous malignancies were invasive cancers associated with metastatic potential and predominantly located in the aerodigestive tract. Female-male ratio was higher in the SP group (29 vs. 15%, P = 0.06). Tumour diameter was smaller in the SP group (3.0 vs. 4.7 cm, P < 0.0001). Pneumonectomy was performed less frequently in the SP group. Five-year survival rate was higher in the SP group (61 vs. 34%, P = 0.04). Univariate favourable prognostic factors were; small tumour diameter, female gender, favourable pTNM-stage, favourable pT-stage, favourable cTNM-stage, no post-operative radiotherapy and a history of previous malignancy. Multivariate analysis showed tumour diameter, female gender and pTNM-stage to be the major potential confounders. When adjustments were made for these three variables, the prognostic advantage of the SP group disappeared. It was concluded that SP NSCLC has a similar prognosis when compared with FP NSCLC. NSCLC diagnosed during the follow-up of a previous malignancy, and deemed operable, therefore, warrants the same diagnostic and therapeutic approach as NSCLC as first malignancy.

Adult↗

PubMed2001

Functional MRI of visual cortex in sedated 18 month-old infants with or without periventricular leukomalacia.

Functional MRI (fMRI) of the visual cortex was evaluated in 42 sedated 18-month-old infants (mean corrected age; 31 males, 11 females) with or without periventricular leukomalacia (PVL). Data from 14 infants could not be evaluated because of movement artefacts. Ten of the remaining 28 infants showed no significant fMRI response upon visual stimulation. In 18 infants, a significant signal change upon stimulation was found in the visual cortex: in 17 a signal decrease and in one a signal increase. Functional changes were located mainly in the anterior part of the visual cortex. Seven of the 28 infants had normal MRI and 21 showed variable occipital PVL. An fMRI response was equally frequent in infants without PVL (4 of 7 infants) and with PVL (14 of 21 infants). In conclusion, fMRI was shown to be feasible in sedated infants. No correlation was found between functional activation and the presence or absence of occipital PVL. Type of fMRI response (signal decrease) and localization (anterior part of the visual cortex) are different from those seen in adults, probably reflecting a combination of sedation effects and immaturity of the visual system. At present, fMRI is a highly promising research tool; its clinical relevance still has to be established.

Case-Control Studies↗

PubMed2001

Impact of mammographic interval on stage and survival after the diagnosis of contralateral breast cancer.

BACKGROUND: Following treatment for primary breast cancer, annual mammography and regular clinical breast examination is advised. The aim of this study was to investigate whether annual mammography resulted in an improvement in stage of contralateral breast cancers compared with mammography performed at a longer interval. METHODS: This was a retrospective analysis of patients treated for breast cancer, who developed a contralateral breast cancer between 1977 and 1998. Patients were stratified into two groups according to mammographic interval. RESULTS: Data were available for 275 patients who developed contralateral breast cancer during follow-up. Annual mammography was performed in 51 per cent; these patients were a mean of 5 years younger at diagnosis. Patients who had annual or biennial mammography had comparable rates of impalpable contralateral breast cancer, 30 and 27 per cent respectively. The tumours were of favourable stages in 60 and 58 per cent respectively. Five-year disease-free survival following diagnosis of contralateral breast cancer was 75 per cent in both groups. When the contralateral lesion was detected by mammography, disease-free survival was better, irrespective of the stage of the ipsilateral breast cancer. CONCLUSION: No difference was found between the two groups in stage distribution and disease-free survival after the diagnosis of contralateral breast cancer. Survival was better in patients in whom the contralateral breast cancer was first detected by mammography.

Adult↗

PubMed2001

Circadian rhythms in systemic hemodynamics and renal function in healthy subjects and patients with nephrotic syndrome.

BACKGROUND: The resemblance of the circadian rhythm of glomerular filtration rate (GFR) to that of arterial blood pressure (BP) suggests that systemic hemodynamic factors contribute to this variation. In the present study, this was investigated using continuous BP monitoring and pulse wave analysis. The study was performed in eight healthy subjects and in seven patients with nephrotic syndrome who had normal or reversed rhythms of GFR. METHODS: Circadian variations of renal function (continuous infusion of inulin/paraaminohippuric acid), noninvasive finger arterial pressure (Portapres), and vasoactive hormone levels were monitored during 27 hours. With stepwise backward regression analysis, the contributions of the measured variables to the circadian variation of GFR were investigated. RESULTS: Both groups showed a reduction of BP at night. In the controls, this was related to a drop in cardiac output, while in the patients, total peripheral resistance decreased at night. None of the hemodynamic variables explained the circadian GFR variation in both groups. In the controls, only 6% of the effective renal plasma flow (ERPF) rhythm was associated with variations in cardiac output (P = 0.03). In the patients, atrial natriuretic peptide and plasma renin activity were responsible for 36% of the variation in GFR (P < 0.01). CONCLUSIONS: These results indicate that the circadian variation of GFR does not result directly from changes in BP or cardiac output. An inverted GFR rhythm in patients with nephrotic syndrome may originate from hormonal mechanisms rather than directly from the hemodynamic effects of edema mobilization.

Adult↗

PubMed2001

Regional toxicity after isolated limb perfusion with melphalan and tumour necrosis factor- alpha versus toxicity after melphalan alone.

AIMS: To determine whether the addition of high-dose tumour necrosis factor-alpha (TNF alpha) to isolated limb perfusion (ILP) with melphalan increases acute regional tissue toxicity compared to ILP with melphalan alone. METHODS: A retrospective, multivariate analysis of toxicity after normothermic (37--38 degrees C) and 'mild' hyperthermic (38--40 degrees C) ILPs for melanoma was undertaken. Normothermic ILP with melphalan was performed in 294 patients (70.8%), 'mild' hyperthermic ILP with melphalan in 71 patients (17.1%) and 'mild' hyperthermic ILP with melphalan combined with TNF alpha in 50 patients (12.0%). Toxicity was nil or mild (grades I--II according to Wieberdink et al.) in 339 patients (81.7%), and more severe acute regional toxicity (grades III--V) developed in 76 patients (18.3%). A stepwise logistic regression procedure was performed for the multivariate analysis of prognostic factors for more severe toxicity. RESULTS: On univariate analysis, 'mild' hyperthermic ILP with melphalan plus TNF alpha significantly increased the incidence of more severe acute regional toxicity compared to normothermic and 'mild' hyperthermic ILP with melphalan alone (36% vs 16% and 17%; P=0.0038). However, after ILP using TNF alpha no grade IV (compartment compression syndrome) or grade V (toxicity necessitating amputation) reactions were seen. Significantly more severe toxicity was seen after ILPs performed between 1991 and 1994 compared with earlier ILPs (33%vs 14%P=0.0001). Also, women had a higher risk of more severe toxicity than men (22% vs 7%; P=0.0007). After multivariate analysis, prognostic factors which remained significant were: sex (P=0.0013) and either ILP schedule (P=0.013) or treatment period (P=0.0003). CONCLUSIONS: Regional toxicity after 'mild' hyperthermic ILP with melphalan and TNF alpha was significantly increased compared to ILP with melphalan alone. This may be caused by increased thermal enhancement of melphalan due to the higher tissue temperatures (39--40 degrees C) at which the melphalan in the TNF alpha-ILPs was administered or by an interaction between high-dose TNF alpha and melphalan.

Adult↗

PubMed2000

Stage as major long term outcome predictor in minor salivary gland carcinoma.

BACKGROUND: The myriad of histologic types and anatomic sites of occurrence make minor salivary gland carcinomas the most heterogeneous group of carcinomas of the upper aerodigestive tract. Many publications addressing this group consider different subsections, making it hard to get a clear picture of long term treatment results and of modifying prognostic factors. METHODS: Overall survival, disease specific survival, and percentage rates for no recurrence in all 55 patients with a minor salivary gland carcinoma, treated at the Netherlands Cancer Institute from 1973 to 1994, were calculated and compared to the results in major salivary gland carcinoma patients. Major prognostic factors were univariately analyzed. The median period of follow-up time for patients alive at the end of follow-up was 134 months. RESULTS: The overall 5- and 10-year survival rates were 66% and 57%, respectively. The 5- and 10-year disease specific survival rates (DSS) were 76% and 74%, respectively; and the 5- and 10-year recurrence-free rates were 63% and 60%, respectively. Prognostic for overall survival were age (P = 0.0005), site of occurrence (P = 0.0001), and the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) Tumor, Node, and Metastases (TNM) classification and stage regrouping system (P = 0.0001). Factors predicting DSS were site of occurrence (P < 0.0001) and the UICC/AJCC TNM classification and stage regrouping (P < 0.0001). In surgical patients, histologic evidence for metastatic lymph nodes (P = 0.0037) and vascular invasion (P = 0.0051) conferred a lower DSS. Tumor recurrence was predicted by the UICC/AJCC TNM classification and stage regrouping (P = 0.0001). In surgical patients, soft tissue invasion (P = 0. 0085) predicted tumor recurrence. CONCLUSIONS: Sixty percent of patients treated for minor salivary gland carcinoma were free of tumor ten years later. This equals the result in major salivary gland carcinoma patients. The recent UICC/AJCC TNM classification and stage regrouping are confirmed as major predictors of outcome.

Adolescent↗

PubMed2000

Primary axillary radiotherapy as axillary treatment in breast-conserving therapy for patients with breast carcinoma and clinically negative axillary lymph nodes.

BACKGROUND: The objective of the current study was to evaluate the effectiveness and morbidity of primary axillary radiotherapy in breast-conserving therapy for postmenopausal, clinically axillary lymph node negative patients with early stage breast carcinoma. METHODS: Between 1983-1997, 105 patients with clinically negative axillary lymph nodes and breast carcinoma were treated with wide local excision followed by radiotherapy to the breast, and axillary and supraclavicular lymph node areas. Adjuvant treatment with tamoxifen was given to 75 patients. The median follow-up of patients still alive was 41 months (range, 8-137 months). Fifty-five patients with no evidence of disease at last follow-up were examined prospectively with respect to late functional damage. RESULTS: The mean age of the patients was 64 years. Three patients developed a local recurrence. No isolated axillary lymph node recurrence was observed. In two patients, axillary recurrence was accompanied by distant metastases. The 5-year disease free interval and the overall survival were 82% (standard error [SE], 6%) and 83% (SE, 6%), respectively. In five patients, arm edema was reported and impaired shoulder function was reported in seven patients. Prospectively scored, arm edema was reported subjectively by the patient in 4% and objectively measured in 11% of cases. Impaired shoulder function was reported subjectively in 35% and objectively measured in 17% of cases. No brachial plexus neuropathy was noted. CONCLUSIONS: Primary axillary radiotherapy for postmenopausal women with clinically lymph node negative, early stage breast carcinoma was found to result in low axillary lymph node recurrence rates with only limited late complications. Therefore, primary axillary radiotherapy should be considered as axillary treatment in selected patients as an alternative to axillary lymph node dissection.

Aged↗

PubMed2000

Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group.

BACKGROUND: Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy. METHODS: The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat. FINDINGS: Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up. INTERPRETATION: Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made.

Aged↗

PubMed2000

Differences in estrogen receptor alpha variant messenger RNAs between normal human breast tissue and primary breast carcinomas.

We evaluated the differences in prevalence and functional activity of human estrogen receptor alpha (hER) variant mRNA between 21 normal breast tissues and 41 primary breast carcinomas using a functional assay in yeast for the hER First, we found that the presence of wild-type hER, relative to the total amount of hER, differs markedly (P < 0.0001) between normal breast tissue (median, 85% wild-type hER) and breast tumors (median, 74% wild-type hER). Second, the hER variants with altered function that are present in normal breast tissue are mainly one-exon deleted splicing variants (median, 100%), whereas in breast tumors only half of all variants lack just one single exon (median, 50%; P < 0.0001). Our results suggest that hER-dependent estrogen responsiveness of breast tissue may change during tumor outgrowth, indicating that specific hER variants may play a role in breast cancer development or progression.

Adult↗

PubMed2000

Toxicity and drug exposure in a quadruple drug regimen in HIV-1 infected patients participating in the ADAM study.

OBJECTIVE: To study the relationship between toxicity and the exposure to nelfinavir and saquinavir as part of a quadruple drug regimen. DESIGN: The ADAM study is a randomized study to investigate the feasibility of induction-maintenance therapy in HIV-1 infection. METHODS: HIV-1-infected patients with no prior use of antiretroviral treatment started induction therapy consisting of stavudine + lamivudine + nelfinavir + saquinavir for a period of 26 weeks. Data regarding toxicity of the quadruple regimen and exposure to the protease inhibitors were collected. RESULTS: Seven of the 65 patients enrolled had to switch therapy for reasons of toxicity within the first 26 weeks. Diarrhoea was frequently reported (49 of 65, one discontinuation), but could be relieved by using antidiarrhoeal agents. Laboratory monitoring revealed elevated liver enzymes (leading to four discontinuations) and mild to moderate elevations of triglycerides and cholesterol (nine and 23 of 65, respectively). The exposure to saquinavir and nelfinavir was lower than expected. Abdominal pain was associated with a higher exposure to nelfinavir or saquinavir. The association of nausea and abdominal distension with drug exposure appeared to vary over time. CONCLUSIONS: The quadruple drug regimen was quite well tolerated. Diarrhoea was frequently reported but could be relieved by the use of antidiarrhoeal agents. In comparison with other protease inhibitor combinations, lipid abnormalities in plasma were infrequent and mild. With the exception of diarrhoea, all gastrointestinal complaints observed were found to be associated with the level of exposure to nelfinavir or saquinavir. The exposure to the protease inhibitors was relatively low, although the virologic efficacy of the regimen used was satisfactory.

Acquired Immunodeficiency Syndrome↗

PubMed2000

The prevalence of mental health problems in Rwandan and Burundese refugee camps.

OBJECTIVE: We examined the prevalence of mental health problems in refugees living in camps that emerged in Tanzania during the Rwanda crisis that started in 1994. METHOD: Using the 28-item version of the General Health Questionnaire (GHQ-28), we examined two samples: a random sample (n = 854) and a sample of clients of a psychosocial support programme in these camps (n = 23). Sensitivity, specificity and positive- and negative predictive values were estimated for several cut-off scores of the GHQ-28. RESULTS: The prevalence of serious mental health problems was estimated at 50% (SE 12%). When using the GHQ-28 as a screener, a cut-off score of 14 is recommended. CONCLUSION: Given the high prevalence of mental health problems, psychosocial programmes for large refugee populations should aim at strengthening community structures and supporting groups instead of focusing at individuals. The screening capacity of the GHQ-28 could be used to identify mentally vulnerable groups.

Adolescent↗

PubMed2000

Susceptibility to Leishmania major infection in mice: multiple loci and heterogeneity of immunopathological phenotypes.

Susceptibility as opposed to resistance of mouse strains (e.g., BALB/c vs C57BL/6) to Leishmania major has been attributed to a defective Th1 and a predominant Th2-response, resulting in increased IL-4 and IgE production, and decreased interferon gamma (IFN gamma) production, macrophage activation and elimination of parasites. Here we report dissection of genetic and functional aspects of susceptibility to leishmaniasis using two contrasting inbred strains BALB/cHeA (susceptible) and STS/A (resistant) and a resistant Recombinant Congenic (RC) Strain, CcS-5/Dem, which carries a random set of 12.5% of genes from the strain STS and 87.5% genes from the susceptible strain BALB/c. Linkage analysis of F2 hybrids between the resistant RC strain CcS-5 and the susceptible strain BALB/c revealed five loci affecting the response to the infection, each apparently associated with a different combination of pathological symptoms and immunological reactions. The correlation between Th2-type immune reactions and the disease in the F2 mice was either absent, or it was limited to mice with specific genotypes at loci on chromosomes 10 and 17. This suggests that the resistance vs susceptibility is influenced by mechanisms additional to the postulated antagonistic effects of Th1 and Th2 responses, and that the host's genotype affects the development of leishmaniasis in a complex way.

Animals↗