Patients with triangular fibrocartilage complex injuries and distal radioulnar joint instability have reduced rotational torque in the forearm.

UNLABELLED: A total of 20 patients scheduled for wrist arthroscopy, all with clinical signs of rupture to the triangular fibrocartilage complex and distal radioulnar joint instability, were tested pre-operatively by an independent observer for strength of forearm rotation. During surgery, the intra-articular pathology was documented by photography and also subsequently individually analysed by another independent hand surgeon. Arthroscopy revealed a type 1-B injury to the triangular fibrocartilage complex in 18 of 20 patients. Inter-rater reliability between the operating surgeon and the independent reviewer showed absolute agreement in all but one patient (95%) in terms of the injury to the triangular fibrocartilage complex and its classification. The average pre-operative torque strength was 71% of the strength of the non-injured contralateral side in pronation and supination. Distal radioulnar joint instability with an arthroscopically verified injury to the triangular fibrocartilage complex is associated with a significant loss of both pronation and supination torque. LEVEL OF EVIDENCE: Case series, Level IV.

Immunological profiling of haemodialysis patients and young healthy individuals with implications for clinical regulatory T cell sorting.

With the increasing interest in clinical trials with regulatory T cells (Tregs), immunological profiling of prospective target groups and standardized procedures for Treg isolation are needed. In this study, flow cytometry was used to assess peripheral blood lymphocyte profiles of young healthy individuals and patients undergoing haemodialysis treatment. Tregs obtained from the former may be used in haematopoietic stem cell transplantation and Tregs from the latter in the prevention of kidney transplant rejection. FOXP3 mRNA expression with accompanying isoform distribution was also assessed by the quantitative reverse transcriptase polymerase chain reaction. Flow-cytometric gating strategies were systematically analysed to optimize the isolation of Tregs. Our findings showed an overall similar immunological profile of both cohorts in spite of great differences in both age and health. Analysis of flow-cytometric gating techniques highlighted the importance of gating for both CD25high and CD127low expression in the isolation of FOXP3-positive cells. This study provides additional insight into the immunological profile of young healthy individuals and uraemic patients as well as in-depth analysis of flow-cytometric gating strategies for Treg isolation, supporting the development of Treg therapy using cells from healthy donors and uraemic patients.

"Building block picture" of the electronic structure of aqueous cysteine derived from resonant inelastic soft X-ray scattering.

The electronic structure of the amino acid L-cysteine in an aqueous environment was studied using resonant inelastic soft X-ray scattering (RIXS) in a 2D map representation and analyzed in the framework of a "building block" approach. The element selectivity of RIXS allows a local investigation of the electronic structure of the three functional groups of cysteine, namely, the carboxyl, amino, and thiol groups, by measuring at the O K, N K, and S L2,3 edges, respectively. Variation of the pH value allows an investigation of molecules with protonated and deprotonated functional groups, which can then be compared with simple reference molecules that represent the isolated functional groups. We find that such building blocks can provide an excellent description of X-ray emission spectroscopy (XES) and RIXS spectra, but only if all nearest-neighbor atoms are included. This finding is analogous to the building block principle commonly used in X-ray absorption spectroscopy. The building blocks show a distinct spectral character (fingerprint) and allow a comprehensive interpretation of the cysteine spectra. This simple approach opens the path to investigate the electronic structure of more complex biological molecules in aqueous solutions using XES and RIXS.

Patient-reported genitourinary dysfunction after laparoscopic and open rectal cancer surgery in a randomized trial (COLOR II).

BACKGROUND: This article reports on patient-reported sexual dysfunction and micturition symptoms following a randomized trial of laparoscopic and open surgery for rectal cancer. METHODS: Patients in the COLOR II randomized trial, comparing laparoscopic and open surgery for rectal cancer, completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR38 questionnaire before surgery, and after 4 weeks, 6, 12 and 24 months. Adjusted mean differences on a 100-point scale were calculated using changes from baseline value at the various time points in the domains of sexual functioning, sexual enjoyment, male and female sexual problems, and micturition symptoms. RESULTS: Of 617 randomized patients, 385 completed this phase of the trial. Their mean age was 67·1 years. Surgery caused an anticipated reduction in genitourinary function after 4 weeks, with no significant differences between laparoscopic and open approaches. An improvement in sexual dysfunction was seen in the first year, but some male sexual problems persisted. Before operation 64·5 per cent of men in the laparoscopic group and 55·6 per cent in the open group reported some degree of erectile dysfunction. This increased to 81·1 and 80·5 per cent respectively 4 weeks after surgery, and 76·3 versus 75·5 per cent at 12 months, with no significant differences between groups. Micturition symptoms were less affected than sexual function and gradually improved to preoperative levels by 6 months. Adjusting for confounders, including radiotherapy, did not change these results. CONCLUSION: Sexual dysfunction is common in patients with rectal cancer, and treatment (including surgery) increases the proportion of patients affected. A laparoscopic approach does not change this. REGISTRATION NUMBER: NCT00297791 (http://www.clinicaltrials.gov).

Distal radio-ulnar joint instability in children and adolescents after wrist trauma.

UNLABELLED: This study retrospectively evaluated the medical records and radiographs of patients younger than aged 25 that were referred for a second opinion due to ulnar-sided wrist pain and persistent distal radio-ulnar (DRU) joint instability. We identified 85 patients with a major wrist trauma before the age of 18. Median age at trauma was 14 years. Median time between trauma and diagnosis of DRUJ instability was 3 years. Sixty-seven patients (79%) had sustained a fracture at the initial trauma. The two most common skeletal injuries related to the DRUJ instability were Salter-Harris type II fractures (24%) and distal radius fractures (19%). In 19 patients (22%), the secondary DRUJ instability was caused by malunion or growth arrest. Eighteen patients (21%) had no fracture; in spite of this, they presented with subsequent symptomatic DRUJ instability. Fourteen of these 18 patients had a triangular fibrocartilage complex (TFCC) tear, confirmed by arthroscopy, open surgery, or magnetic resonance imaging. In conclusion, late DRUJ instability due to wrist fractures or isolated TFCC tears was found to be common in children and adolescents. LEVEL OF EVIDENCE: IV.

Health-related quality of life after laparoscopic and open surgery for rectal cancer in a randomized trial.

BACKGROUND: Previous studies comparing laparoscopic and open surgical techniques have reported improved health-related quality of life (HRQL). This analysis compared HRQL 12 months after laparoscopic versus open surgery for rectal cancer in a subset of a randomized trial. METHODS: The setting was a multicentre randomized trial (COLOR II) comparing laparoscopic and open surgery for rectal cancer. Involvement in the HRQL study of COLOR II was optional. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38, and EuroQol - 5D (EQ-5D™) before surgery, and 4 weeks, 6, 12 and 24 months after operation. Analysis was done according to the manual for each instrument. RESULTS: Of 617 patients in hospitals participating in the HRQL study of COLOR II, 385 were included. The HRQL deteriorated to moderate/severe degrees after surgery, gradually returning to preoperative values over time. Changes in EORTC QLQ-C30 and QLQ-CR38, and EQ-5D™ were not significantly different between the groups regarding global health score or any of the dimensions or symptoms at 4 weeks, 6 or 12 months after surgery. CONCLUSION: In contrast to previous studies in patients with colonic cancer, HRQL after rectal cancer surgery was not affected by surgical approach. REGISTRATION NUMBER: NCT00297791 (http://www.clinicaltrials.gov).

Dorsal scapholunate ligament injury: a classification of clinical forms.

The dorsal scapholunate (SL) ligament may disrupt in variety of ways. Each form of injury requires specific fixation. To investigate the incidence of each type of ligament failure, the records of 45 patients with adequate information, good quality pictures, or videos demonstrating injury characteristics were reviewed. Four types of SL injury were found: type 1 (lateral avulsion from the scaphoid) was the most frequent, present in 19 patients (42%); type 2 (medial avulsion from the lunate) was the least frequent, with 7 cases (16%); type 3 (mid-substance rupture) was found on 9 occasions (20%); and type 4 (partial rupture plus elongation) was observed on 10 occasions (22%). Based on our observations, we submit that an arthroscopically assisted SL capsuloplasty may not be possible in all cases, particularly not when the ligament has avulsed off the bone (60% of the cases), leaving no ligament remnant on one side. Most patients will require ligament reattachment techniques using transosseous sutures, bone anchors, or ligament reconstruction.

FluoroSpot Analysis of TLR-Activated Monocytes Reveals Several Distinct Cytokine-Secreting Subpopulations.

Monocytes have long been considered a heterogeneous group of cells both in terms of morphology and function. In humans, three distinct subsets have been described based on their differential expression of the cell surface markers CD14 and CD16. However, the relationship between these subsets and the production of cytokines has for the most part been based on ELISA measurements, making it difficult to draw conclusions as to their functional profile on the cellular level. In this study, we have investigated lipoteichoic acid (LTA)- and lipopolysaccharide (LPS)-induced cytokine secretion by monocytes using the FluoroSpot technique. This method measures the number of cytokine-secreting cells on the single-cell level and uses fluorescent detection, allowing for the simultaneous analysis of two cytokines from the same population of isolated cells. By this approach, human monocytes from healthy volunteers could be divided into several subgroups as IL-1ß, IL-6, TNF-α and MIP-1ß were secreted by larger populations of responding cells (25.9-39.2%) compared with the smaller populations of GM-CSF (9.1%), IL-10 (1.3%) and IL-12p40 (1.2%). Furthermore, when studying co-secretion in FluoroSpot, an intricate relationship between the monocytes secreting IL-1ß and/or IL-6 and those secreting TNF-α, MIP-1ß, GM-CSF, IL-10 and IL-12p40 was revealed. In this way, dissecting the secretion pattern of the monocytes in response to TLR-2 or TLR-4 stimulation, several subpopulations with distinct cytokine-secreting profiles could be identified.

Adipose zinc-α2-glycoprotein is a catabolic marker in cancer and noncancerous states.

OBJECTIVE: Zinc-α2-glycoprotein (ZAG) has been proposed as a tumour-derived cancer cachexia factor. However, ZAG is produced by some normal tissues, including white adipose tissue (WAT), and high serum ZAG levels are present in nonmalignant conditions. We determined whether human WAT contributes to serum ZAG levels and how serum and WAT-secreted ZAG levels correlate with catabolism in patients with cancer and in obese subjects undergoing a very low-calorie diet (VLCD) for 11 days. DESIGN/SUBJECTS: ZAG levels in serum and in conditioned medium from WAT/adipocytes were determined by enzyme-linked immunosorbent assay. ZAG release from WAT in vivo was determined in 10 healthy subjects. The correlation between ZAG and cachexia was studied in 34 patients with newly diagnosed gastrointestinal cancer. The impact of a VLCD on ZAG release and serum levels was assessed in 10 obese women. RESULTS: ZAG was released from abdominal WAT and adipocytes in vitro. However, the arteriovenous differences in vivo showed that there was no significant contribution of WAT to the circulating levels. WAT-secreted but not serum ZAG correlated positively with poor nutritional status but not with fat mass (or body mass index) in patients with gastrointestinal cancer. In obese subjects on a VLCD, ZAG secretion from WAT increased significantly whereas serum levels remained unaltered. CONCLUSIONS: ZAG is released from human WAT, but this tissue does not contribute significantly to the circulating levels. WAT-secreted ZAG correlates with nutritional status but not with fat mass in both cancer and nonmalignant conditions. Adipose ZAG is therefore a local factor activated primarily by the catabolic state per se.

Expression and secretion of the novel adipokine tartrate-resistant acid phosphatase from adipose tissues of obese and lean women.

OBJECTIVE: Tartrate-resistant acid phosphatase (TRAP) expressed by adipose tissue macrophages (ATMs) induces mice obesity and human adipocyte differentiation in vitro. This study aimed to investigate whether TRAP was secreted differently from human obese versus lean adipose tissues and to identify the cellular source of adipose tissue TRAP. DESIGN: Subcutaneous adipose tissues obtained from healthy subjects. Enzyme-linked immunosorbent assays (ELISAs) for total (5a+5b) and cleaved TRAP (5b) were used. TRAP secretion was determined in adipose tissue biopsies, and mRNA expression was studied in cell types isolated from the same. SUBJECTS: Results of 24 lean and 24 obese women (in vitro) and 8 subjects (in vivo) were compared. The main outcome measurements were TRAP expression and secretion in vitro and in vivo. RESULTS: In-house total TRAP ELISA showed high sensitivity and a coefficient of variance of 11%. Adipose secretion of total TRAP was linear in vitro with time and was evident in vivo. Total TRAP secretion in vitro was similar in lean and obese women expressed per unit weight of the adipose tissue but correlated positively with the number/size of adipocytes (P ≤ 0.01) and with adipose secretion of tumor necrosis factor-α and interleukin-6 (P<0.01). TRAP 5b was not secreted from the adipose tissue. ATMs displayed highest cellular expression of TRAP mRNA in adipose tissue cells derived from lean or obese women. CONCLUSIONS: TRAP is a novel human adipokine produced by macrophages and secreted from the subcutaneous adipose tissue in vivo and in vitro. Secretion is linked to the size and number of adipocytes, as well as to concomitant secretion of inflammatory mediators, suggesting that TRAP is involved in fat accumulation and adipose inflammation.

Differential expression of enteric neuroimmune-network in invasive and acute watery diarrhoea.

We aimed to evaluate the changes of nerve morphology and distribution of neurotransmitters and neuropeptides in the rectum of Shigella flexneri-infected patients and in the duodenum of Vibrio cholerae O1-infected patients. Nerve morphology was observed by transmission electron microscopy. Immunoreactivity of nerve growth factor (NGF), neurotransmitters and neuropeptides in tissues were studied by immunohistochemistry. Ultrastructural analysis of intestinal biopsy revealed persisting axons degeneration throughout the study period in all patients. Regeneration was already evident at the acute stage with marked increase at late convalescence. Both acute shigellosis and cholera were accompanied by increased expression of NGF and histamine and decreased expression of serotonin that was restored at convalescence. Immunoreactivity of vasoactive intestinal peptide (VIP) was increased during acute cholera, whereas in shigellosis VIP- and substance P-immunoreactive nerves appeared at early convalescence. Both shigellosis and cholera induced long-lasting degeneration of enteric neuronal axons, despite the presence of ongoing proliferation and regeneration processes. Neurotransmitters and neuropeptides may play differential roles in invasive and watery diarrhoea.

Gastrointestinal stromal tumour with a KIT exon 11 mutation presenting as a paratesticular mass.

Gastrointestinal stromal tumours (GISTs) are sarcomas arising in the gastrointestinal tract. They are characterised by a gain in function mutation of the KIT oncogene and the majority express the receptor tyrosine kinase KIT, which can be detected by the immunohistochemical stain CD117. Patients with a GIST present with symptoms such as abdominal pain or gastrointestinal bleeding, or may be asymptomatic. We describe the clinical history and pathological features of a patient with a GIST who presented with a paratesticular mass which, to our knowledge, has never previously been reported. With the development of new drugs to treat GISTs, the knowledge of the type of mutations may in the future prove helpful in determining optimal treatment strategies and prognosis.

Kinetics of plasma cytokines and chemokines during primary HIV-1 infection and after analytical treatment interruption.

BACKGROUND: There are strong theoretical arguments for initiating antiretroviral therapy (ART) during primary HIV-1 infection (PHI) to preserve HIV-1-specific T-cell responses and to decrease immune activation. METHODS: We assessed the degree of immune activation during PHI and after analytical treatment interruption (ATI) in plasma samples from 22 subjects by measuring 13 cytokines/chemokines with the Luminex system. Subjects initiated quadruple ART at PHI (the QUEST cohort) and were classified as responders or nonresponders according to their HIV-1 viral load (VL) 6 months post-ATI. RESULTS: During PHI, nonresponders had higher levels of HIV-1 RNA, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-10 and eotaxin than responders (P

Radiation doses in examination of lower third molars with computed tomography and conventional radiography.

OBJECTIVES: To measure organ doses and calculate effective doses for pre-operative radiographic examination of lower third molars with CT and conventional radiography (CR). METHODS: Measurements of organ doses were made on an anthropomorphic head phantom with lithium fluoride thermoluminescent dosemeters. The dosemeters were placed in regions corresponding to parotid and submandibular glands, mandibular bone, thyroid gland, skin, eye lenses and brain. The organ doses were used for the calculation of effective doses according to proposed International Commission on Radiological Protection 2005 guidelines. For the CT examination, a Siemens Somatom Plus 4 Volume Zoom was used and exposure factors were set to 120 kV and 100 mAs. For conventional radiographs, a Scanora unit was used and panoramic, posteroanterior, stereographic (scanogram) and conventional spiral tomographic views were exposed. RESULTS: The effective doses were 0.25 mSv, 0.060 mSv and 0.093 mSv for CT, CR without conventional tomography and CR with conventional spiral tomography, respectively. CONCLUSIONS: The effective dose is low when CT examination with exposure factors optimized for the examination of bone structures is performed. However, the dose is still about four times as high as for CR without tomography. CT should therefore not be a standard method for the examination of lower third molars. In cases where there is a close relationship between the tooth and the inferior alveolar nerve the advantages of true sectional imaging, such as CT, outweighs the higher effective dose and is recommended. Further reduction in the dose is feasible with further optimization of examination protocols and the development of newer techniques.

Adjuvant imatinib treatment improves recurrence-free survival in patients with high-risk gastrointestinal stromal tumours (GIST).

Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours (n=23) was compared with historic controls (n=48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies.

Unilateral mandibular condylar fractures: a 31-year follow-up of non-surgical treatment.

At the University Hospital of Malmö, Sweden, standardized trauma charts were used for registration of all jaw fractures from 1972 to 1976. During the year 2005 the aim was to interview all patients treated non-surgically for unilateral mandibular condylar fractures during this period. In total, 49 patients with unilateral condylar fractures were treated non-surgically in 1972-1976. Of these, 23 patients were available for follow-up, 17 were dead, 7 were not found and 2 did not answer letters or phone calls. The follow-up was a telephone interview according to a standardized questionnaire concerning occurrence of pain and headache, function of the jaw and joint sounds. Information from original records, radiographic reports and the standardized trauma charts revealed fracture site, type of fracture and intermaxillary fixation if any. Eighty-seven percent of the patients reported no pain from the jaws, 83% had no problems chewing and 91% reported no impact of the fracture on daily activities. Neck and shoulder symptoms were reported by 39% and back pain by 30%. The 31-year results of non-surgical treatment of unilateral non-dislocated and minor dislocated condylar fractures seem favourable concerning function, occurrence of pain and impact on daily life.

Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours.

BACKGROUND: The aim of this retrospective population-based study, which was conducted before the introduction of imatinib, was to evaluate the role of surgery in patients with gastrointestinal stromal tumours (GISTs) and clarify which subgroups might benefit from adjuvant treatment. METHODS: Two hundred and fifty-nine patients with clinically detected GISTs were studied. Univariate and multivariate analyses were performed to identify predictors for recurrent disease and survival. RESULTS: Thirty of 48 patients with high-risk GISTs and all of those with overtly malignant tumours developed recurrent tumour after complete (R0) resection. Thirty-four of 38 first recurrences occurred within 36 months of surgery. No recurrence was observed after 72 months. R0 resection, achieved in 48 (80 per cent) of 60 patients with high-risk tumours, was significantly associated with a decreased risk of death from tumour recurrence (P = 0.008). CONCLUSION: Completeness of surgical resection is an independent prognostic factor in patients with high-risk GISTs. A period of adjuvant treatment with imatinib is recommended in patients with high-risk or overtly malignant GISTs who have undergone R0 resection and have a tumour-free interval of less than 6 years.