Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia) - correlations between clinical and morphological features

Summary Histomorphometry was performed on representative trephine biopsies of the bone marrow on admission of 50 patients (21 male, 29 female-age 67 years) with so-called primary osteomyelofibrosis/-sclerosis (OMF) not preceded by any other subtype of chronic myeloproliferative disorders. This study was firstly aimed at testing correlations between histological features (amount of haematopoiesis, cytological aspects of mega-karyocytes, density of reticulin and collagen fibres and degree of osteosclerosis) and laboratory data, as well as spleen size and duration of relevant prediagnostic symptoms. Secondly, we concentrated on a discrimination of OMF patients into two sub-groups according to bone marrow morphology and clinical variables. Statistical evaluation of histomorphometric variables and haematological findings disclosed that there was a progressive fibro-osteosclerotic process in the evolution of disease features. Increase in medullary fibrosis was significantly paralleled by an abnormal or pleomorphic megakaryopoiesis in the bone marrow: there was an increase in irregularity of perimeters for megakaryocytes and naked nuclei combined with smaller sizes of these elements including the nuclei. Additionally, there was a greater number of pycnotic bare nuclei. A number of morphometric features (density of fibres, degree of osteosclerosis, amount of haematopoiesis) were associated with corresponding clinical data (spleen size, length of preclinical history). By consideration of a set of basic histomorphometric variables our co-hort of 50 patients could be divided into an early hyperplastic subtype with no or minimal medullary reticulin and another group with conspicuous fibrotic and osteosclerotic alterations of the bone marrow. It was noticeable that we found no significant correlation between amount of haematopoiesis or marrow cellularity with splenomegaly. This result suggests that splenic haematopoiesis (myeloid metaplasia) may represent an autonomous or neoplastic process and not only compensation for a failing fibro-osteosclerotic bone marrow.Supported by a grant from the Deutsche Forschungsgemeinschaft (DFG-Th 390/1-1)     

Imaging spectrum in disseminated histoplasmosis: Case report and brief review

The clinical manifestations of chronic disseminated histoplasmosis are non-specific and resemble those of other chronic infections and malignancies. We report the radiographic, sonographic and contrast-enhanced CT appearances of histoplasmosis in an adult male with non-insulin dependent diabetes mellitus, who was HIV negative and presented with weight loss and pyrexia. Imaging studies simulated tuberculosis with mediastinal lymphadenopathy, bilateral fibrotic lung lesions, hepatomegaly and bilateral hypoattenuating adrenal enlargement, without clinical or laboratory evidence of hypoadrenalism. Computed tomography-guided fine-needle aspiration biopsy of adrenal glands revealed Histoplasma capsulatum. We report our experience to increase awareness of the imaging spectrum of disseminated histoplasmosis and its similarity to tuberculosis as, with increasing incidence of AIDS, the chances of these infections are likely to increase. Moreover, awareness of this entity is important because it is known that untreated disseminated histoplasmosis is fatal.     

Protease inhibitors in patients with chronic obstructive pulmonary disease: the alpha-antitrypsin heterozygote controversy.

A group of 163 patients with chronic obstructive pulmonary disease, from the pulmonary service of a large urban hospital, were evaluated for their protease inhibitor (Pi) type by starch gel and crossed immunoelectrophoresis, for serum concentrations of alpha1-antitrypsin and alpha1-antichymotrypsin, and for pulmonary function. Of the patients with emphysema, 17.8% were of Pi type Z; 50% of these were less than 45 years of age, compared to 13% of those of Pi type M. Of all patients with chronic obstructive pulmonary disease, 4.9% were of Pi type Z; 4.9% of patients were of Pi type MZ (heterozygotes) compared with 1.9% of the control population. There was an increased incidence of chronic obstructive pulmonary disease in persons of Pi type MZ, but no increase in persons of Pi type MS. Concentrations of both alpha1-antitrypsin and alpha1-antichymotrypsin were increased and were correlated. No patient had a deficiency of alpha1-antichymotrypsin.     

Autologous protein solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti‐inflammatory cytokines and anabolic growth factors

The objective of this clinical study was to test if blood from osteoarthritis (OA) patients (n = 105) could be processed by a device system to form an autologous protein solution (APS) with preferentially increased concentrations of anti‐inflammatory cytokines compared to inflammatory cytokines. To address this objective, APS was prepared from patients exhibiting radiographic evidence of knee OA. Patient metrics were collected including: demographic information, medical history, medication records, and Knee Injury and Osteoarthritis Outcome Score (KOOS) surveys. Cytokine and growth factor concentrations in whole blood and APS were measured using enzyme‐linked immunosorbent assays. Statistical analyses were used to identify relationships between OA patient metrics and cytokines. The results of this study indicated that anti‐inflammatory cytokines were preferentially increased compared to inflammatory cytokines in APS from 98% of OA patients. APS contained high concentrations of anti‐inflammatory proteins including 39,000 ± 20,000 pg/ml IL‐1ra, 21,000 ± 5,000 pg/ml sIL‐1RII, 2,100 ± 570 pg/ml sTNF‐RI, and 4,200 ± 1,500 pg/ml sTNF‐RII. Analysis of the 82 patient metrics indicated that no single patient metric was strongly correlated (R² > 0.7) with the key cytokine concentrations in APS. Therefore, APS can be prepared from a broad range of OA patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1349–1355, 2014.     

Covered self-expanding stent treatment for anastomotic leakage: outcomes in esophagogastric and esophagojejunal anastomoses

Background

Anastomotic leakage of esophagogastric and esophagojejunal anastomoses is a severe complication after esophagectomy and gastrectomy associated with a high mortality. We conducted this non-randomized observational study to evaluate the outcomes and clinical effectiveness of covered self-expanding stents (CSESs) in treating esophageal anastomotic leakage.

Methods

From 2002 to 2013, consecutive patients with anastomotic leakage after esophagogastrostomy or esophagojejunostomy who received CSESs were analyzed concerning leakage characteristics, leakage sealing rate, success and failure rates of CSES treatment, stent-related complications, and mortality.

Results

In 35 patients, anastomotic leakage originating from 5 cervical esophagogastrostomies, 6 thoracic esophagogastrostomies, 12 mediastinal esophagojejunostomies and 12 abdominal esophagojejunostomies were treated with 48 CSESs (16 fully CSES, 32 partially CSES). Of 35 patients, 24 received one stent, 9 received two consecutive stents, and 2 received three consecutive stents. Stent-related complications occurred in 71 % of patients (25/35). The most frequent complications were leakage persistence (44 %) and stent dislocation (19 %). Sealing of the anastomotic leakage was achieved in 24 (69 %) patients after a median (range) stenting time of 19 (1–78) days. Sealing rates differed significantly with 20 % (cervical esophagogastrostomies), 50 % (thoracic esophagogastrostomies), 92 % (mediastinal esophagojejunostomies) and 67 % (abdominal esophagojejunostomies) of patients (p = 0.023). Moreover, clinical success rates differed among these groups (60 vs. 67 vs. 92 vs. 58 %; p = 0.247). Clinical failure of stent treatment was more likely to be recognized in early postoperative leakage (median postoperative day 3 vs. 8; p = 0.098) compared with successful treatment, whereas no difference for clinical success rates was found comparing leakage ≤10 versus >10 mm (68 vs. 64 %; p = 0.479).

Conclusion

CSESs are an effective treatment for anastomotic leakage in patients with esophagogastrostomies and esophagojejunostomies. Best results can be achieved in patients with anastomotic leakages following mediastinal esophagojejunostomy, and in leakages occurring after the very early postoperative phase.     

Small intestinal submucosa for reinforcement of colonic anastomosis

Background  Different materials have been evaluated for anastomotic reinforcement to prevent gastrointestinal anastomotic leakage. In this experimental study, small intestinal submucosa (SIS) was tested as a sealing for stapled colonic anastomosis in a porcine model. The aims of this study were to determine the macroscopic and microscopic outcomes and to evaluate the safety and feasibility of applying SIS for anastomotic sealing. Materials and methods  Circular stapled anastomoses were performed in 18 pigs. Standard anastomosis in the control group (n = 8) was compared to an SIS-sealed anastomosis in the study group (n = 10). After 30 days, anastomotic segments were examined for macroscopic and microscopic regeneration and their resistance to mechanical stress. Furthermore, animal survival and clinical course were evaluated. Results  None of the animals developed anastomotic leakage, intraabdominal abscess, or peritonitis. Shrinkage of SIS was evident in nine of ten animals. Encapsulation and displacement of the SIS patches were seen in two animals. Quantity of anastomotic granulation tissue and rate of complete mucosal coverage of anastomotic line were increased in SIS-sealed anastomoses without reaching significance. Moreover, no significant differences were found in the rate of survival of the animals, anastomotic stricture formation, intraabdominal adhesions, anastomotic bursting pressure, and microscopic healing parameters of the anastomosis between stapled colonic standard anastomosis and anastomosis protected by SIS. Conclusion  The results of this study indicate a safe use of SIS for anastomotic reinforcement in a porcine model. Adverse effects like strictures, increased adhesions, and anastomotic abscesses were absent. Promoting effects on colonic wound healing by SIS were microscopically evident. The results argue for a careful clinical evaluation in humans.