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.     

Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R²: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.     

Rewarming and cardiac surgery: a review

Patients undergoing cardiac surgery are mildly hypothermic by the completion of the surgical procedure. They need to return to a normothermic state if enzymatic functions are to proceed in their normal manner. The body can produce heat by elevating metabolic rate or by activating the shivering mechanism. Metabolic rate peaks shortly after separation of the patient from cardiopulmonary bypass, and therefore contributes to heat production. Because of the effects of neuromuscular blockage administered both during and after surgery; these patients may be unable to generate heat by shivering, and shivering is usually undesirable. This eliminates the major heat production mechanism available to the body. Therefore, heat must be transferred down its gradient by means of convection and conduction. External and internal methods accomplish these goals. External methods, which minimize additional heat loss, include the use of warming lights, elevation of room temperature, and the use of blankets. Internal methods, which transfer heat by convection, may be used to help actively reverse hypothermia. Such techniques include warmed inhalation gases and intravenous fluids, warmed nasogastric lavage fluid, and warmed peritoneal dialysis fluid for patients with end-stage renal failure with severe electrolyte disorders after surgery.     

An immunohistochemical investigation of diagnostic biopsy material taken from short and long term survivors with small cell lung cancer.

An immunohistochemical study has been carried out on fibre optic-biopsy specimens from patients with small cell lung cancer (SCLC) who had either died within 3 months, or who had survived more than 2 years. Long term survivors (LTS) were identified from completed clinical trials at major UK centres and were matched for age and sex within the trial with short term survivors (STS). The panel of immunohistochemical markers included those previously reported to be associated with prognosis, and reagents representative of both neuroendocrine and epithelial differentiation. A preliminary screen of 17 antibodies identified 11 as consistently reactive on paraffin-embedded material using streptavadin-biotin immunoperoxidase. Of 186 identified patients, 110 biopsy samples were retrieved. Of these, 70 gave sufficient material for analysis. All sections were scored by three observers without knowledge of the prognosis. The analysis failed to identify any antigen whose expression was correlated with prognosis. We conclude that, in fibre-optic biopsy specimens, immunohistochemical analysis does not add prognostic information in SCLC.     

Role of laparoscopy in identifying the clinical significance and cause of adhesions and chronic pelvic pain: a retrospective review at the Kiel School of Gynecological Endoscopy.

OBJECTIVES: We sought to define the role of laparoscopy in identifying the clinical significance, cause, and association between adhesions and chronic pelvic pain. METHODS: A retrospective chart review was conducted from October 2004 to July 2005, at the Kiel School of Gynecological Endoscopy, University Hospitals Schleswig-Holstein, Campus Kiel, Germany. Included in the study was the analysis of 462 laparoscopic procedures; 275 (59.5%) of the patients undergoing these procedures had pelvic or abdominal adhesions. Of these, 84 (30.5%) patients were admitted with the main complaint of chronic pelvic pain. Further evaluation and assessment of this group was carried out. RESULTS: Among those patients with adhesions, the second most frequent reason for admission was chronic pelvic pain (30.5%) (P<0.0005). In our study, adhesions were found in 79.2% (n=84) of patients (n=106) with chronic pelvic pain. These adhesions were thin-filmy (19.0%) or thick-fibrous (81.0%) adhesions containing blood vessels. Thick-fibrous adhesions were present in 50.0% of patients at multiple abdominopelvic sites (P<0.005). CONCLUSIONS: Thick-fibrous adhesions that extend beyond the pelvic sidewall can cause significant chronic abdominopelvic pain.     

Prospective evaluation of the effect on initial brain metastases from small cell lung cancer of platinum-etoposide based induction chemotherapy followed by an alternating multidrug regimen

BACKGROUND:: During the 1980s reports describing the effect of systemic chemotherapyon brain metastases from chemosensitive tumours emerged, includinga few retrospective reports on small cell lung cancer (SCLC)patients. DESIGN:: Previously untreated SCLC patients with no other malignancy,but in some cases with mixed histological subtype, who had symptomaticbrain metastases verified by contrast enhanced CT-scan, weretreated with a multidrug combination chemotherapy regimen andno cranial irradiation. Radiotherapy was optional at cranialrelapse or progression at the discretion of the physician incharge. The intracranial effect was evaluated by 4-weekly CT-scanand neurological examination, according to a standardized scoringsystem. END POINTS:: Intracranial response, duration of response, neurological score,terminal CNS status, and survival. RESULTS:: 21 patients were included, corresponding to 8.6% of consecutiveSCLC patients at our institution. 8 patients died before follow-upleaving 13 evaluable for response. In the former group, allpatients had WHO performance status of 3–4 compared to6/13 in the latter group. Of the 13 evaluable patients, 1 hadearly progression in the CNS and 1 had no change. 11 had CT-scanverified response, with a median duration of 135 days. Mostpatients, including all complete responders, had improvementin their neurological score. 6 out of 11 responders died withoutactive CNS disease. The crude median survival was 111 days,whereas the median survival(early deaths excluded) was 197 days. CONCLUSION:: Systemic combination chemotherapy was effective for palliationof initial brain involvement in the majority of patients ina small consecutive series. The role of consolidating cranialirradiation in responders should be assessed by a randomizedtrial. small cell carcinoma, brain metastases, chemotherapy