Rickettsial disease: An underestimated cause of posterior uveitis.

Rickettsioses are worldwide distributed infectious disease caused by intracellular small Gram-negative bacteria transmitted to humans by the bite of contaminated arthropods, such as ticks. Systemic disease typically consists of a triad of high fever, headache, and skin rash. It usually has a self-limited course, but severe, life-threatening complications can sometimes occur. It may be clinically difficult to differentiate rickettsial diseases from other febrile illnesses. Rickettsial infection has been largely underestimated as a cause of infectious uveitis for long decades in the past. Conversely, recent data show that ocular involvement is much more common than previously thought, with retinitis, retinal vasculitis, and neuroretinitis being the most typical and frequent findings. Early clinical diagnosis of rickettsial disease, while awaiting laboratory test results, is essential for prompt initiation of appropriate antibiotic treatment to prevent systemic and ocular morbidity. The prevention remains the mainstay of rickettsial infection control.

Increasing use of radical prostatectomy for locally advanced prostate cancer in the USA and Germany: a comparative population-based study.

BACKGROUND: Current guidelines do not recommend a preferred treatment modality for locally advanced prostate cancer. The aim of the study was to compare treatment patterns found in the USA and Germany and to analyze possible trends over time. METHODS: We compared 'Surveillance Epidemiology and End Results' (SEER) data (USA) with reports from four German federal epidemiological cancer registries (Eastern Germany, Bavaria, Rhineland-Palatinate, Schleswig-Holstein), both from 2004 to 2012. We defined locally advanced prostate cancer as clinical stage T3 or T4. Exclusion criteria were metastatic disease and age over 79 years. RESULTS: We identified 9127 (USA) and 11 051 (Germany) patients with locally advanced prostate cancer. The share was 2.1% in the USA compared with 6.0% in Germany (P<0.001). In the United States, the utilization of radiotherapy (RT) and radical prostatectomy (RP) was comparably high with 42.0% (RT) and 42.8% (RP). In Germany, the major treatment option was RP with 36.7% followed by RT with 22.1%. During the study period, the use of RP increased in both countries (USA P=0.001 and Germany P=0.003), whereas RT numbers declined (USA P=0.003 and Germany P=0.002). The share of adjuvant RT (aRT) was similar in both countries (USA 21.7% vs Germany 20.7%). CONCLUSION: We found distinctive differences in treating locally advanced prostate cancer between USA and Germany, but similar trends over time. In the last decade, a growing number of patients underwent RP as a possible first step within a multimodal concept.

Structured assessment of current mental state in clinical practice: an international study of the reliability and validity of the Current Psychiatric State interview, CPS-50.

OBJECTIVE: To develop a reliable standardized assessment of psychiatric symptoms for use in clinical practice. METHOD: A 50-item interview, the Current Psychiatric State 50 (CPS-50), was used to assess 237 patients with a range of psychiatric diagnoses. Ratings were made by interviewers after a 2-day training. Comparisons of inter-rater reliability on each item and on eight clinical subscales were made across four international centres and between psychiatrists and non-psychiatrists. A principal components analysis was used to validate these clinical scales. RESULTS: Acceptable inter-rater reliability (intra-class coefficient > 0.80) was found for 46 of the 50 items, and for all eight subscales. There was no difference between centres or between psychiatrists and non-psychiatrists. The principal components analysis factors were similar to the clinical scales. CONCLUSION: The CPS-50 is a reliable standardized assessment of current mental status that can be used in clinical practice by all mental health professionals after brief training.

Radiologic diagnosis and management of complications related to central venous access.

Central venous access is an important aspect of medical treatment. There are different designs of access devices for different purposes. In essence, they can be classified as short- and long-term devices. Insertion procedures vary for different devices. There is a risk for both acute and delayed complications. Radiology plays a central role both in placement and in device management. Image-guided insertion increases technical success and reduces the rate of acute complications. The diagnostic approach to long-term complications includes radiography, fluoroscopy, CT, and ultrasound. Treatment by interventional procedures is possible for a number of these conditions. These interventions increase device lifespan and reduce the number of necessary reinsertions.

Procera AllCeram laminates: a clinical report.

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.

Combination of phenylbutyrate and 13-cis retinoic acid inhibits prostate tumor growth and angiogenesis.

Differentiation-inducing agents, such as retinoids and short-chain fatty acids, have an inhibitory effect on tumor cell proliferation and tumor growth in preclinical studies. Clinical trials involving these compounds as single agents have been suboptimal in terms of clinical benefit. Our study evaluated the combination of phenylbutyrate (PB) and 13-cis retinoic acid (CRA) as a differentiation and antiangiogenesis strategy for prostate cancer. On the basis of previous evidence, common signal transduction pathways and possible modulation of retinoid receptors and retinoid response elements by PB could be responsible for such activities. We assessed the effect of the combination of PB and CRA on human and rodent prostate carcinoma cell lines. The combination of PB and CRA inhibited cell proliferation and increased apoptosis in vitro in an additive fashion as compared with single agents (P < 0.014). Prostate tumor cells treated with both PB and CRA revealed an increased expression of a subtype of retinoic acid receptor (retinoic acid receptor-beta), suggesting a molecular mechanism for the biological additive effect. The combination of PB and CRA also inhibited prostate tumor growth in vivo (up to 82-92%) as compared with single agents (P < 0.025). Histological examination of tumor xenografts revealed decreased in vivo tumor cell proliferation, an increased apoptosis rate, and a reduced microvessel density in the animals treated with combined drugs, suggesting an antiangiogenesis effect of this combination. Thus, endothelial cell treatment with both PB and CRA resulted in reduced in vitro cell proliferation. In vivo testing using the Matrigel angiogenesis assay showed an additive inhibitory effect in the animals treated with a combination of PB + CRA (P < 0.004 versus single agents). In summary, this study showed an additive inhibitory effect of combination of differentiation agents PB and CRA on prostate tumor growth through a direct effect on both tumor and endothelial cells.

[Clinical characteristics of patients with tardive dyskinesias]. / Klinische Charakteristika von Patienten mit tardiven Dyskinesien.

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.

Long-term culture of murine epidermal keratinocytes.

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.

Prognostic significance of CT contrast enhancement within histological subgroups of intracranial glioma.

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.

Survival, prognostic factors, and therapeutic efficacy in low-grade glioma: a retrospective study in 379 patients.

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.

Harlequin ichthyosis keratinocytes in lifted culture differentiate poorly by morphologic and biochemical criteria.

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.

Protein phosphatase activity in human keratinocytes cultured from normal epidermis and epidermis from patients with harlequin ichthyosis.

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.

Effect of postoperative intravenous loop diuretic on renal function after major surgery.

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.

[Prognosis in primary tumors of the central nervous system. A patient material from the Norwegian Radium Hospital 1960-94]. / Prognosen ved primaere svulster i sentralnervesystemet. Det Norske Radiumhospitals pasientmateriale 1980-94.

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.

Clinical stage I and II Hodgkin's disease: long-term results of therapy without laparotomy. Experience at one institution.

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.

Prognostic variables and results of salvage treatment in Hodgkin's disease.

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.

Isometric muscle strength and muscular endurance in normal persons aged between 17 and 70 years.

Isometric muscle strength was measured in 63 women and 65 men, randomly selected, aged 17-70 years, using Penny & Giles' hand-held dynamometer. Eight muscle groups as well as the hand grip strength were tested bilaterally. The muscular endurance was measured as time to exhaustion in the abductors of the shoulder and the flexors of the hip. Reference values for muscle strength and muscular endurance are given in the age groups 17-18, 20-29, 30-39, 40-49, 50-59 and 60-70 years of age. The mean strength of females was about 65-70% of that of the men, but when the results were related to weight, the differences almost disappeared. Both men and women seem to have the greatest muscle strength at the age of about 17-18. The strength is rather constant up to the age of about 40 years, after which a discrete decline is seen up to about 60, from where the decline is more obvious. Muscular endurance showed great variability between individuals. However, no decrease in endurance was seen in older ages. For both sexes, lower reference limits of endurance, with the methods used, for arm abductors are suggested as being 3 minutes and for hip flexors, 90 seconds.

Global variations in the geoid/topography admittance of venus.

Global representations of geoid height and topography are used to map variations in the geoid/topography ratio (admittance) of Venus. The admittance values are permissive of two mutually exclusive models for convection-driven topography. In the first, compressive highland plateaus are expressions of present mantle downwelling, broad volcanic rises are expressions of mantle upwelling, and lowlands overlie regions with no substantial vertical motion in the mantle. In the second, compressive highland plateaus are remnants of an earlier regime of high crustal strain, and most other long-wavelength topographic variations arise from normal convective tractions at the base of the lithosphere.

Magnetic resonance imaging and 67gallium scan in mediastinal malignant lymphoma: a prospective pilot study.

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.