Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.     

Digital movement analysis,a new objective method of measuring tardive dyskinesia and drug-induced parkinsonian tremor: acceptability,reliability and validity

Digital movment analysis (DMA) is a new instrumental approach to assessing oral tardive dyskinesia (TD) by means of digital image processing of a video signal, tracking five paper dots placed around the patient's mouth. A total of 40 schizophrenic patients, 30 with and 10 without TD, were examined twice (with a 3-month interval) with this new device. The patients were further examined with two TD rating scales: the St. Hans Rating Scale for extrapyramidal syndromes (SHRS) and the Abnormal Involuntary Movement Scale (AIMS).The schizophrenic patients accepted the instrumental assessment without any anxiety or resistance. The internal relibility of the apparatus was high, with correlation coefficients of 0.80–0.99. The DMA TD values correlated with the SHRS and AIMS scores with correlation coefficients of 0.48–0.73 indicating an acceptable, although not strong, concurrent validity. Fluctuations occurred from the first to the second examination independent of medication. For these fluctuations no correlation was found between DMA values and rating scores. Finally, the DMA device was able to detect perioral tremor as a sign of parkinsonism.It has been concluded that DMA is a useful supplement to classical TD rating, although further validity evaluation is warranted.     

Treatment of gingival lichen with free palatal grafts

BACKGROUND: Recalcitrant gingival erythematous lichen planus/lichenoid lesions comprise a considerable therapeutic problem. The objective of this study was to evaluate the therapeutic effect of grafting keratinized oral palatal mucosa to the sites of gingival lichen. METHODS: In 12 patients 20 grafts were transplanted to buccal gingival lesions. Mean age of the patients was 59.8 +/- 7.1 years (range 46-71 years). The mean observation time was 32 +/- 32.7 months (range 5-97 months). RESULTS: On a 4-point clinical grade scale (0-3), 12 (60%) transplants showed complete healing grade 3, six (30%) grade 2 and two (10%) grade 1. CONCLUSIONS: Using oral mucosal grafts from the palatal mucosa for the treatment of recalcitrant erythematous gingival lichen planus/lichenoid lesions seems to be a promising treatment modality.     

Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy.

BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients. METHODS: We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured. RESULTS: Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated. CONCLUSIONS: Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics.     

Do patient characteristics,disease, or treatment explain social inequality in survival from colorectal cancer?

This paper investigates the association between individually measured socioeconomic status (SES) and all-cause survival in colorectal cancer patients, and explores whether factors related to the patient, the disease, or the surgical treatment mediate the observed social gradient.     

Agenesis of permanent incisors in a mediaeval maxilla and mandible: aetiological aspects

A paleopathological maxilla and mandible with tooth agenesis were analyzed, focussing on the aetiology of the condition. The jaw material, derived from an adult mediaeval male, was examined by standard anthropological analyses, including radiography. In the maxilla there was agenesis of three permanent incisors and one premolar, and in the mandible of one permanent incisor and two permanent molars. Absence or marked reduction of the incisive foramen and the nasopalatine canal was found. The pattern of tooth agenesis was similar to the pattern observed in contemporary individuals, except for the agenesis of one permanent maxillary centreal insisor. It is suggested that the pronounced lack of the premaxillary area of the nasopalatine canals and the incisive foramen. As the condition can be ascribed to deviations in the prenatal developments, this investigation shows that embryological developmental patterns, which form the basis for the pattern of tooth agenesis, should be taken into account when evaluation dry bonde patholgy.     

Immunotherapy of tree pollen allergy with a modified alginate conjugated birch pollen extract compared to an aluminium adsorbed extract

The safety and efficacy of two birch pollen extracts, one chemically conjugated to alginate (Anjuvac) the other adsorbed to aluminium hydroxide (Alutard), were investigated in an open multicentre comparative study of 63 birch pollen allergic patients. Both extracts decreased the nasal symptoms during the birch pollen season. The changes in specific IgE and IgG were much the same in both treatment groups. The adverse reactions recorded were mild in both groups, but more frequent in the Anjuvac group, probably because of a more aggressive dose schedule though there were twice as many asthmatics in the Anjuvac group. The two investigated allergen extracts were useful alternatives for immunotherapy.     

TNF-alpha impairs peripheral tolerance towards beta-cells,and local costimulation by B7.1 enhances the effector function of diabetogenic T cells

Maintenance of peripheral tolerance and inactivation of autoreactive T cells is based on a delicate balance between pro-inflammatory and protective cytokines that is poorly understood. We have here addressed how the local expression of the inflammatory cytokine TNF-alpha can impair peripheral tolerance and lead to autoreactivity. After transplantation of pancreata that are immunogenic due to beta-cell expression of B7.1 and TNF-alpha, into thymectomized and euthymic syngeneic mice, we found that only euthymic mice rejected the grafts. This result suggests that under normal circumstances autoreactive T cells are functionally inactivated, and initiation of an autoreactive response requires de-novo generation of T cells. By contrast, thymectomized mice expressing TNF-alpha on the endogenous islets rejected the grafts, showing that expression of TNF-alpha prevents functional silencing of the autoreactive T cells. Thus, this study provides a mechanism by which TNF-alpha and possibly chronic inflammatory responses may promote autoimmune diseases. Furthermore, we have investigated whether B7.1 can enhance T cell responses of already activated T cells leading to islet rejection. By transplantation of wild-type and B7.1-expressing islets into overtly diabetic mice we found that only the wild-type islets could restore normoglycemia, suggesting that costimulation by B7.1 is required in the expansion or effector phase of the response.     

Somatic spectrum of cancer-associated single basepair substitutions in the TP53 gene is determined mainly by endogenous mechanisms of mutation and by selection

The spectrum of somatic TP53 single basepair substitutions detected in 955 cancers was compared with that of 2,224 different germline mutations in 279 different human genes (other than TP53), reported as the cause of inherited disease. This comparison reveals that, disregarding a relatively small subset (12%) of TP53 mutations that probably result from the action of exogenous mutagens, both the relative rates and the nearest-neighbor spectra of single basepair substitutions are similar in the two datasets. This spectral resemblance suggests that a substantial proportion of cancer-associated somatic TP53 mutations result from endogenous cellular mechanisms. The likelihood of clinical observation of a particular mutation type differs, however, between tumors and genetic diseases, when the chemical properties of the resulting amino acid substitutions are considered. Together with a sixfold higher observation likelihood for mutations at evolutionary conserved residues, this finding argues that selection is a critical factor in determining which TP53 mutations are found to be associated with human cancer. © 1995 Wiley-Liss, Inc.