Biomedical subjects
Publications and source records attributed to B Hager.
The use of Procera AllCeram laminates for patients with discolored teeth has been described. In our experience, these laminates are simple to use and provide possibilities for excellent esthetics.
UNLABELLED: Although there is a great number of studies on the relationship between tardive dyskinesia and patient characteristics, too often their validity is impaired by the lack of operationalized criteria for the description of patients and signs. Reliable phenotyping is of utmost importance for linking clinical data with data from methods in neurobiology or molecular genetics. 241 patients with the DSM IV diagnosis "schizophrenia" or "schizoaffective disorder" were examined with the instruments SADS-L, OPCRIT, BPRS and PANSS. Motor phenomena were analyzed on 2 separate days within 3 months with the scales TDRS, AIMS, SAS, BAS. Tardive dyskinesia was diagnosed following the research criteria of Schooler and Kane. Lifetime medication with neuroleptics and anticholinergic drugs was assessed quantitatively. RESULTS: 97 out of 233 patients (= 41.6%) displayed persistent tardive dyskinesia. In univariate analysis, significant associations were found between tardive dyskinesia and the following independent variables (higher values means greater risk): Age (p = 0.0001), years from onset of the disorder (p = 0.001), total length of stay in hospital (p = 0.001), PANSS (single scales and sum score) (p = 0.0001), total amount of neuroleptics expressed as CPZ equivalents (p = 0.004). Logistic regression analysis showed that only the variables "age" and "negative symptoms" expressed as score on the PANSS negative subscale showed an association with tardive dyskinesia that could not be explained by covariation with other variables. The same results were found when, instead of the dichotomous variable "tardive dyskinesia yes/no" the associations with the TDRS score were analyzed. Future research should aim to approach the neurobiological correlates of "age" and "negative symptoms" in relationship to tardive dyskinesia.
The production of transgenic and null mice with skin abnormalities makes it increasingly important to establish cultures of mouse epidermal keratinocytes for in vitro studies. This requires that each cell line be derived from a single mouse and that the cells be carried for multiple passages. Freezing the cells would also be advantageous by allowing comparison of keratinocytes from several mouse lines at the same time. Mouse keratinocytes, however, have been exceedingly difficult to grow as primary cultures, and subculturing these cells has been virtually impossible until now. We describe a gentle dissociation method and a highly supplemented fibroblast conditioned medium that allows us to grow and subculture total mouse keratinocytes for up to 19 subcultures, allowing an increase in cell number of greater than 10 logs. Epidermal keratinocytes from newborn mice were grown on collagen IV coated dishes in murine fibroblast conditioned medium with 0.06 mM calcium and added growth factors. The cells could be passaged, frozen as viable stocks, and induced to differentiate. Morphologically the cultured keratinocytes demonstrated a pattern characteristic of basal cells. Stratified cultures which made mouse keratin 1 and profilaggrin through passage 10 were induced by purging the monolayer cultures of growth factors, then adding medium with 0.15 mM calcium; expression of mouse keratin 1 and profilaggrin was lost by passage 15. The methods explained in detail here should be of great interest to investigators who are now trying to analyze skin phenotypes and expression of markers of epidermal differentiation of their transgenic or knockout mice.
UNLABELLED: We report the prognostic significance of tumor CT contrast enhancement within histological subgroups in 831 consecutive adult glioma patients of high-grade (n = 516) and low-grade (n = 315) histology. In the present report, a negative prognostic factor is associated with shortened survival. METHODS: Survival analysis including Kaplan-Meier plots, log-rank tests, Cox analysis, and Aalen's linear model as implemented in SPSS and S-PLUS. RESULTS: Sensitivity and specificity of contrast enhancement as a test for high-grade glioma was 0.87 and 0.79, respectively. Enhancement was a strong negative prognostic factor comparable to high-grade histology in the total patient population. Enhancement was also a negative prognostic factor within the subgroups adult high-grade (Grade 3-4), anaplastic (Grade 3), and low-grade (Grade 1-2) gliomas (p < 0.001). The prognostic implications of initial enhancement declined in high-grade patients surviving beyond 36 months. Tumor contrast enhancement or calcifications (in parentheses) were present in 96% (3.6%) of glioblastomas, in 87% (7.4%) of high-grade gliomas, in 56.5% of anaplastic gliomas, and in 21% (16.2%) of low-grade gliomas. Calcification was a positive prognostic factor within the high-grade group of patients (p < 0.0001). CONCLUSION: Enhancement was a major prognostic factor comparable to high-grade histology in this glioma patient population. Enhancement was a negative prognostic factor within each of the adult subgroups high-grade, anaplastic (grade 3), and low-grade gliomas. Enhancement was strongly associated with but not pathognomonic for high-grade histology.
Harlequin ichthyosis (HI) is a severe congenital ichthyosis in which massively thickened stratum corneum with abnormal barrier function often results in death of affected newborns. Survivors evolve into a severe nonbullous ichthyosiform erythroderma. Previously we have ascertained three biochemical phenotypes of HI, based on abnormal profilaggrin and K6 and K16 expression in epidermis. Submerged cultures of HI keratinocytes differentiated abnormally, but the three phenotypes were indistinguishable in vitro. We hypothesized that differentiation in submerged culture was insufficient to reflect in vivo biochemical abnormalities or that dermal components might be necessary for expression. To test these hypotheses HI keratinocytes and fibroblasts (n = 3) were grown on collagen gels at the air-medium interface in a cross-over design with normal keratinocytes and fibroblasts. Epithelia derived from lifted cultures were studied by light microscopy and immunocytochemistry and extracted for western blot analysis. In contrast to our prediction, lifted cultures of HI keratinocytes formed a poorly differentiated epithelium, and normal keratinocytes formed an epidermal-like tissue with expression of K1 and expression and processing of profilaggrin to filaggrin. In addition, the presence of HI fibroblasts consistently altered differentiation of both HI and normal keratinocytes, resulting in less complete morphologic differentiation. The findings suggest that both epithelial and mesenchymal elements of the skin from HI are affected but that the primary abnormality lies in the keratinocytes.
PURPOSE: We report survival, prognostic factors, and treatment efficacy in low-grade glioma. PATIENTS AND METHODS: A total of 379 patients with histologic intracranial low-grade glioma received post-operative radiotherapy (n = 361) and intraarterial carmustine (BCNU) chemotherapy (n = 153). Overall survival and prognostic factors were evaluated with the SPSS statistical program (SPSS Inc, Chicago, IL). RESULTS: Median survival (all patients) was 100 months (95% confidence interval [CI], B7 to 113); in age group 0 to 19 years (n = 41), 226 months; in age group 20 to 49 years (n = 263), 106 months; in age group 50 to 59 years (n = 49), 76 months; and for older patients (n = 26), 39 months. Projected survival at 10 and 15 years was 42% and 29%, respectively. Patient age, World Health Organization (WHO) performance status, tumor computed tomography (CT) contrast enhancement, mental changes, or initial corticosteroid dependency were significant independent prognostic factors (p < .05), while histologic subgroup, focal deficits, presence of seizures, prediagnostic symptom duration, tumor category, and tumor stage were not. Patients aged 20 to 49 years with no independent negative prognostic factors (n = 132) had a median survival time of 139 months versus 41 months in patients with two or more factors (n = 33). Patients who presented with symptoms of expansion (n = 97) survived longer when resected (P < .03); otherwise no survival benefit was associated with initial tumor resection compared with biopsy. Intraarterial chemotherapy and radiation doses more than 55 Gy were not associated with prolonged survival. Among 66 reoperated patients, 45% progressed to high-grade histology within 25 months. CONCLUSION: Prognosis in low-grade glioma following postoperative radiotherapy seems largely determined by the inherent biology of the glioma and patient age at diagnosis.
We investigated serine/threonine protein phosphatase (PP) activity and the expression of PP2A during growth and differentiation of epidermal keratinocytes in culture. Keratinocyte PP activity was strongly inhibited by calyculin A and okadaic acid, indicating that the activity was mainly due to PP2A and PP1. The phosphatase activity decreased to about 20% of the initial (day 1) level by the time of confluence and to about 10% at day 7 postconfluence. In contrast to activity, the level of expression of the PP2A catalytic subunit protein and the mRNA for the two isoforms increased slightly over the period of growth. Keratinocyte differentiation was shown by a significant increase in profilaggrin expression after confluence. Keratinocytes were also cultured from individuals affected with harlequin ichthyosis. This severe hyperkeratotic skin disorder has abnormal lipid structures and is blocked in the PP2A-dependent conversion of phosphorylated profilggrin to the non-phosphorylated filaggrin. The PP activity in harlequin cultures was lower than in normal cultures (about 20% of the subconfluent normal control value) and decreased even further in confluent cultures. In contrast, the level of expression of the PP2A catalytic subunit protein and mRNA for the two isoforms was similar to that of normal keratinocytes and increased with confluence. These results suggest that PP activity in keratinocytes is regulated in a post-translational manner; they also support the possibility of impaired or reduced function of PPs in harlequin ichthyosis.
We present the results of a retrospective survey of 1,218 patients treated at the Norwegian Radium Hospital during the years 1980-94 for primary tumours of the central nervous system. Median survival for patients with glioblastoma (n = 492) was 12 months, for patients with anaplastic astrocytoma (n = 83) 25 months, astrocytoma (n = 260) 95 months, oligodendroglioma (n = 85) 74 months, mixed glioma (n = 68) 65 months, and medulloblastoma (n = 53) 109 months. Median survival for patients with brain stem tumours (n = 37) was nine months, while 74% of patients with tumours in the pineal region (n = 38) survived for five years. The histology and localisation of the tumour, as well as age and functional status, are important prognostic factors for survival in patients with primary CNS tumours.
OBJECTIVE: To determine the effect on renal function of postoperative continuous, intravenous furosemide after major thoraco-abdominal or vascular surgery. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Intensive care unit of a referral hospital in Eastern Switzerland. METHODS: Furosemide (1 mg/h) or placebo was administered to 121 consecutive patients admitted to the intensive care unit after major abdominal, chest or vascular surgery and continued throughout the intensive care treatment period. Enrollment was performed during a 6 months period. No patient was excluded. Renal function was determined serially by measuring creatinine clearances and plasma creatinine concentrations. RESULTS: Postoperatively, creatinine clearance decreased significantly to 83% (furosemide) and to 81% (placebo group) of the initial value (p = 0.004). This decrease was not affected significantly by furosemide. Retrospective subgroup analysis using stepwise regression also did not show any differences between the groups. Hypokalemia was detected in 36 (furosemide) versus 19% of the blood sample (placebo, p = 0.006). CONCLUSIONS: Low-dose intravenous furosemide appears to offer no advantage over placebo in an unselected group of patients with moderate postoperative renal impairment. As no patients with acute renal failure necessitating dialysis were observed during the study period, the effect of furosemide in more severe postoperative renal impairment and the effects of higher doses of loop diuretics remain to be investigated.
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BACKGROUND: We concluded a program in which we administered radiotherapy only to clinical stages I and II Hodgkin's disease patients at standard risk, with the addition of 4 cycles of combination chemotherapy before radiotherapy for high-risk patients. PATIENTS AND METHODS: From 1980 to 1991, 313 patients with clinical stages I or II Hodgkin's disease underwent treatment in our hospital. Fifty percent of the patients in groups previously identified as being at high risk for relapse received 4 cycles of combination chemotherapy before radiotherapy. The remaining half of the patients received radiotherapy only. RESULTS: Low- and high-risk patients aged 15-59 years had, respectively, complete remission (CR) rates of 97% and 94%, 5-year survivals of 95% and 91%, and 5-year freedom from relapse (FFR) rates of 78% and 89%. Older low- and high-risk groups had CR rates of 97% and 93%, 5-year survivals of 60% and 56% and 5-year FFR of 77% and 93%, respectively. CONCLUSION: Here we present our favorable results after treating standard-risk patients with clinical stages I and II Hodgkin's disease with radiotherapy only. With the addition of chemotherapy, the rate of relapse in the high-risk patients was reduced below that of the standard-risk patients. Overall survival was the same for the high- and standard-risk patients.
Treatment results and prognostic variables were studied in 549 adult patients with Hodgkin's disease after first-line and salvage treatment. After first-line treatment, 479 out of 549 patients (87%) achieved complete remission (CR). During a mean observation time of 74 months, 99 patients (21%) relapsed. Sixty-nine patients (70% of relapsed patients) achieved a second CR. Variables predicting poor response (< CR) and shortened survival after first-line treatment were advanced disease, B-symptoms and age >60 years. In relapsing patients, age >60 years, relapse within 12 months and non-CR after relapse treatment predicted a poor prognosis, and none of these patients were alive after 10 years. Localized disease at diagnosis and relapse, and relapse later than 24 months predicted a good prognosis with 10-year survival after relapse of 68% and 57%, respectively. Patients with a second relapse had 5-year survival of 28% and 10-year survival of 14%. Based on the prognostic variables at first-line treatment and at relapse, selection of patients to more intensive treatment is discussed.
BACKGROUND: A residual mediastinal mass is common after treatment for bulky mediastinal lymphoma and represents a difficult diagnostic problem. PATIENTS AND METHODS: 19 patients with bulky mediastinal masses due to malignant lymphoma had computed tomography (CT), magnetic resonance imaging (MRI) and 67Gallium scan (67Ga) before treatment, after four cycles of chemotherapy, and two, six and twelve months after end of treatment. RESULTS: MRI and 67Ga showed active tumor in all patients before treatment. Twelve months after treatment full consistency was found between the results of the two techniques. During treatment and the first six months after treatment, the two techniques were not in accord in some patients, partly due to later normalization of MRI compared with 67Ga. CONCLUSION: Both MRI and 67Ga are useful in assessing tumor activity in lymphoma mediastinal masses.
Initial colonization of mutans streptococci in 36 crown margins of 21 patients was studied. Before cementation, salivary concentrations of mutans streptococci and Lactobacillus sp, microorganisms associated with dental caries, were determined. Within 1 week 25% of the selected crown margins in subjects with low salivary levels of mutans streptococci and 89% in subjects with high salivary levels were colonized. High salivary counts of lactobacilli seemed to reflect conditions that enhanced the risk of colonization of mutans streptococci. The results suggest that, before cementation of fixed prosthodontics, measures should be taken to control the salivary concentrations of these organisms to reduce the susceptibility to recurrent caries.
Survival was analyzed in 173 patients with malignant gliomas to study the importance of possible pretreatment prognostic factors. Seventy-nine of these patients received preirradiation intra-arterial chemotherapy with BCNU combined with vincristine intravenously and procarbazine orally; the others received only postoperative whole-brain irradiation. To judge by univariate and multivariate analyses the most important pretreatment prognostic factors were histology, corticosteroid dependency, pretreatment performance status and frontal lobe location of the tumors. Patients with anaplastic astrocytoma, not corticosteroid-dependent, with pretreatment performance status of 0-2 and with a frontal lobe location of the tumor seemed to benefit most from preirradiation chemotherapy.
Seventy-five patients harboring astrocytomas received 4 cycles of infra-ophthalmic carotid injections of BCNU, combined with vincristine intravenously and procarbazine orally. All of the patients thereafter, received radiation therapy. The five year survival was 73% for all patients. The age of the patients had no significant impact on survival. The treatment results were compared with the results of 57 patients with astrocytomas who were treated with surgery followed by radiation in the same period. These 57 patients had a 5 year survival of 45% with a five year survival in patients < or = 40 years and patients > 40 years of 70% and 22%, respectively (p < 0.05). In multivariate survival analysis of the BCNU group and radiation group together, treatment group and corticosteroid dependency were the only prognostic factors. No leukoencephalopathy was seen during the treatment or in the follow-up of the patients. We conclude that pre-radiation intra-arterial chemotherapy can be given without significant morbidity and produces an improvement in survival in patients older than 40 years.
Nineteen patients in an age group from 56-67 years (mean age 62.5 years) with histologically verified glioblastoma multiforme were treated with chemotherapy consisting of two cycles of oral CCNU, intravenous vincristine and oral procarbazine prior to radiation therapy. Ten of the patients had stable disease, monitored by CT scan and neurological examination, and received whole brain radiation. The median survival was 12 months. Nine patients who had progressive disease during chemotherapy did not receive radiation treatment and were put on palliative treatment with dexamethasone. This group had a median survival of 3 months. The median survival in all of the 19 patients who entered the study was 9 months which was comparable to the survival of 56 patients with glioblastoma multiforme who, in a retrospective study, received post-operative radiotherapy. The most important factor predicting survival was steroid-dependency after surgery.
Seventy-nine patients harboring recurrent brain tumors received four cycles of infraophthalmic carotid injections of 160 mg of carmustine. Two milligrams of intravenous vincristine and 50 mg of oral procarbazine was also administered three times daily for 1 week in conjunction with each BCNU treatment. The response rate was 60% with a median survival for patients with astrocytomas, anaplastic astrocytomas, and glioblastomas of 32, 20, and 6.5 months, respectively. The median survival of the responding patients was 20 months, and the survival at 30 months was 45%. The survival in patients not responding to treatment was 5 months, reflecting the natural history of the tumor. There have been no deaths related to the treatment procedure. No incidents of severe or permanent eye complications or leukoencephalopathy were observed. Based on multivariate survival analysis, only patients with a good performance status who are not steroid dependent are candidates for this treatment.