The Observable Movement Quality scale for patients with low back pain (OMQ-LBP): validity and reliability in a primary care setting of physical therapy.

BACKGROUND: The Observable Movement Quality scale for patients with low back pain (OMQ-LBP) is a newly developed measurement instrument for use in primary care settings of physical and exercise therapists to assess movement quality (MQ) of patients with low back pain (LBP). OBJECTIVE: This study aims to determine validity, reliability and feasibility of the OMQ-LBP. The OMQ-LBP consists of a standardized movement circuit (performed twice) consisting of five daily activities problematic for LBP patients, which are scored with an 11-item observation list. METHODS: Construct validity was determined by testing seven hypotheses on associations between constructs (n = 85 patients with LBP) and four hypotheses on known group differences (n = 85 patients with LBP and n = 63 healthy controls; n = 35 matched participant-patients having VAS-pain ≥ 20 mm during and/or after both circuits and healthy controls). Internal consistency was analyzed with Cronbach's alpha (n = 85 patients with LBP). For inter- and intra-rater reliability Intraclass Correlation Coefficient (ICC) values were examined (n = 14 therapists: seven primary care physical therapists and seven exercise therapists). Additionally, content validity and feasibility were determined using thematic analysis of a brief interview with participants, patients (n = 38) and therapists (n = 14). RESULTS: After Bonferroni correction 2/7 associations between constructs and 2/4 significant group differences were confirmed. Cronbach's alpha was 0,79. The ICC-values of interrater reliability of the OMQ-LBP total score and the duration score were 0.56 and 0.99 and intra-rater reliability 0.82 and 0,93, respectively. Thematic analysis revealed five themes. Three themes elucidate that both patients and therapists perceived the content of the OMQ-LBP as valid. The fourth theme exhibits that OMQ-LBP provides a clear and unambiguous language for MQ in patients with LBP. Theme 5 depicts that the OMQ-LBP seems feasible, but video recording is time-consuming. CONCLUSIONS: The OMQ-LBP is a promising standardized observational assessment of MQ during the five most problematic daily activities in patients with LBP. It is expected that uniform and objective description and evaluation of MQ add value to clinical reasoning and facilitate uniform communication with patients and colleagues.

Diagnosis of early pancreas graft failure via antibody-mediated rejection: single-center experience with 256 pancreas transplantations.

Early pancreas graft loss is usually attributed to technical failure while the possibility of antibody-mediated rejection (AMR) is generally overlooked. To investigate the role of AMR in early pancreas graft loss, we retrospectively assessed 256 patients with simultaneous pancreas-kidney transplantation (SPK) between 1985 and 2010 at our institute. We included 33 SPK patients who lost their pancreas graft <1 year after transplantation. AMR was diagnosed based on donor-specific antibodies, C4d and histology in 7 cases, 8 cases were suspicious for AMR and 18 pancreas graft losses were not due to AMR. Acute AMR occurred >1 month after transplantation in 6/7 cases, whereas all other causes typically led to loss <1 month after transplantation. Thrombotic lesions occurred equally among the 33 cases. In 12/18 concurrent kidney specimens, the diagnostic results paralleled those of the pancreas graft. All patients with acute AMR of the pancreas graft lost their renal grafts <1 year after transplantation. In the setting of a thrombotic event, histopathological analysis of early pancreas graft loss is advisable to rule out the possibility of AMR, particularly because a diagnosis of acute AMR has important consequences for renal graft outcomes.

Therapeutic potential of vasopressin V2 receptor antagonist in a mouse model for autosomal dominant polycystic kidney disease: optimal timing and dosing of the drug.

BACKGROUND: The renoprotective effect of vasopressin V2 receptor antagonist (V2RA) is currently being tested in a clinical trial in early autosomal dominant polycystic kidney disease (ADPKD). If efficacious, this warrants life-long treatment with V2RA, however, with associated side effects as polydipsia and polyuria. We questioned whether we could reduce the side effects without influencing the renoprotective effect by starting the treatment later in the disease or by lowering drug dosage. METHODS: To investigate this, we administered V2RA OPC-31260 at a high (0.1%) and low (0.05%) dose to a tamoxifen-inducible kidney epithelium-specific Pkd1-deletion mouse model starting treatment at Day 21 (early) or 42 (advanced). After 3 and 6 weeks of treatment, we monitored physiologic and potential renoprotective effects. RESULTS: Initiation of V2RA treatment at advanced stage of the disease lacked renoprotective effects and had less pronounced physiologic effects than early initiation. After 3 weeks on a high dose, cyst ratio and kidney weight were reduced versus untreated controls (18 versus 25%, P = 0.05, and 0.33 versus 0.45 g, P = 0.03, respectively). After 6 weeks of treatment, however, this did not reach significance anymore, even at a high dose (cyst ratio 24 versus 27%, P = 0.12, and kidney weight 0.55 versus 0.66 g, P = 0.38). CONCLUSIONS: Our results suggest that intervention with V2RA should be instituted early in ADPKD and that it might be necessary to further increase the dosage of this drug later in the disease to decrease cyst growth.

Pregnancy, chimerism and lupus nephritis: a multi-centre study.

Chimerism occurs twice as often in the kidneys of women with lupus nephritis as in normal kidneys and may be involved in the pathogenesis of systemic lupus erythematosus. Pregnancy is considered the most important source of chimerism, but the exact relationship between pregnancy, the persistence of chimeric cells and the development of systemic lupus erythematosus has not been investigated. Renal biopsies and clinical data from patients in the First Dutch Lupus Nephritis Study were used. Chimeric cells were identified by in-situ hybridization of the Y chromosome. A questionnaire was used to obtain detailed reproductive data including pregnancy history and miscarriages. Chimerism was found in 12 of 26 (46%) renal biopsies. Of the 12 chimeric women, 5 reported a pregnancy; of 14 women who were not chimeric, 8 reported a pregnancy. Chimeric women who had been pregnant reported significantly more pregnancies than non-chimeric women who had been pregnant (P=0.04). The median age of the youngest child was higher in chimeric women (19 years) than in non-chimeric women (6 years). Despite the attention given to pregnancy histories with respect to chimerism, this study shows that in patients with systemic lupus erythematosus, a clear-cut relationship is not apparent. A considerable number of chimeric women did not report a pregnancy: in these women, other sources of chimerism must be considered. Our data support the theory that only certain subsets of chimeric cells persist into the maternal circulation after pregnancy.

Treatment with mycophenolate mofetil attenuates the development of Heymann nephritis.

Active Heymann nephritis in the rat is a model of idiopathic membranous glomerulopathy in man. The autoimmune response is directed to gp330, a large epithelial glycoprotein that is expressed on the tubular and the glomerular epithelium. Characteristic of the disease is the presence of immune complexes and complement in the glomerulus and proteinuria. We studied the effect of a new xenobiotic immunosuppressive agent, mycophenolate mofetil, on active Heymann nephritis. Mycophenolate mofetil significantly reduced the production of autoantibodies against gp330 in rats with Heymann nephritis. Glomerular deposition of IgG was not significantly lower in the treated groups than in the untreated groups with active Heymann nephritis, as detected by immunofluorescence staining. Glomerular complement component C3, however, was significantly lower in the mycophenolate mofetil treated rats. Treatment did not completely prevent the disease, but the percentage of rats that developed proteinuria in the treated groups was significantly lower than in untreated Heymann rats. The results of this study show that mycophenolate mofetil influences the T-cell-mediated humoral autoimmune response in active Heymann nephritis and results in a decreased severity of the disease.

The decrease of liver LDL receptor mRNA during fasting is related to the decrease in serum T3.

UNLABELLED: Fasting is associated with a reduction in serum T3 and T4 and a rise of plasma LDL cholesterol. We hypothesized that an hypothyroid-like condition induced by fasting is responsible for the rise in LDL cholesterol. We therefore examined the relation between changes in thyroid hormone and cholesterol metabolism in rats fasted for 0, 8, 12, 24 or 48 h. Fasting resulted in a decrease of liver 5'-deiodinase mRNA from 8 h (to 50%, p < 0.05, n = 6), of serum T3 from 12 h and of serum T4 at 48 h; serum TSH remained unchanged. Furthermore, plasma LDL cholesterol increased from 24 h onwards preceded by a decrease of liver LDL receptor mRNA which in turn is related to serum T3 (r = 0.55, p < 0.05, n = 19). Adding T3 at a concentration such that normal T3 levels are maintained during 48 h fasting, prevents the decrease in the LDL receptor mRNA. Fasting did not change hepatic HMG CoA reductase mRNA but decreased cholesterol 7 alpha-hydroxylase mRNA, which however was not related to the decrease of serum T3. IN CONCLUSION: (1) Fasting induces a hypothyroid-like condition in which inhibition of hepatic conversion of T4 into T3 may be responsible for the decrease of serum T3. (2) Fasting induces an increase of plasma LDL cholesterol, apparently caused by a decrease of hepatic LDL receptor gene expression which is (partly) related to the fall in serum T3.

Induction of microhematuria by an IgA isotype switch variant of a monoclonal anti-Thy-1.1 antibody in the rat.

IgA nephropathy (IgAN) is a chronic form of glomerulonephritis (GN) characterized by the deposition in the glomerular mesangium of mainly IgA. An experimental form of mesangial proliferative GN can be induced in rats by either polyclonal or monoclonal antibodies against Thy-1.1, a glycoprotein present on the surface of MC. The IgG-mediated renal inflammation is complement dependent and associated with influx of platelets and monocytes. In the present study we switched an IgG2a anti-Thy-1.1 (ER4G) producing hybridoma to an IgA anti-Thy-1.1 (ER4A) producing clone and analyzed the effects of IgA anti-Thy-1.1 in rats. FPLC analysis by gel filtration revealed that the IgA produced by the hybridoma cells was mainly dimeric and polymeric. Infusion of rats with purified ER4A (1 mg/kg) resulted in the deposition of IgA in a mesangial pattern in the glomeruli, similar to that found with ER4G. While administration of ER4G resulted in proteinuria, no significant urinary protein excretion was found in rats treated with ER4A. However, significant microhematuria was observed in rats receiving either ER4A or ER4G. Furthermore, the administration of ER4A was not accompanied by activation of complement, and no significant influx of monocytes or polymorphonuclear leukocytes was observed in contrast to the rats receiving ER4G. We conclude that microhematuria is selectively induced in Wistar rats by mouse IgA anti-Thy-1.1 without detectable complement-mediated injury to MC. These studies may be of importance in understanding the mechanisms leading to IgAN in patients.

Epitope specificity of anti-gp330 autoantibodies determines the development of proteinuria in active Heymann nephritis.

In active Heymann nephritis, an experimental autoimmune disease in the rat, gp330 is regarded as the main antigenic target. Immunization with detergent-solubilized renal tubular epithelium (RTE-DOC) has been shown to be less nephritogenic than immunization with crude RTE. In this study immunization with either crude RTE or affinity-purified gp330 did, but immunization with RTE-DOC did not induce proteinuria. Both a possible aberrant subclass distribution of anti-gp330 autoantibodies and the involvement of additional nephritogenic autoantigens such as DPP IV (gp90) or laminin could be excluded. Circulating anti-gp330 autoantibody titers were significantly higher in RTE-DOC-immunized rats than in RTE-immunized animals. In contrast, significantly more antibodies were shown to bind in the glomeruli in the latter group. The time of onset of abnormal proteinuria was shown to be related to the recognition of a particular V8 protease-induced 250 kD fragment of gp330 in Western blots. This study shows that a particular fragment-specific subset of autoantibodies against gp330 is involved in the glomerular damage in Heymann nephritis.

57Co-bleomycin scintigraphy for the staging of lung cancer.

The value of Cobalt-57 bleomycin (57Co-BLM) scintigraphy in the detection of lymph node metastases in the hilum and mediastinum was investigated in 132 patients with peripherally located lung cancer. In one half of the patients with metastases, these were visualized. Specificity was 98%. These results were better than those obtained with chest radiography and conventional roentgen tomography. 57Co-BLM scintigraphy is routinely used in the staging of patients with lung cancer, obviating the need for mediastinoscopy.

Scintigraphy with 57Co-bleomycin in the detection of lung cancer. A review of 268 well-documented patients.

Over a 5-year period 57Co-bleomycin scintigraphy for tumor detection was performed with a large-field-of-view gamma camera. The scintigrams of 268 patients with lung cancer, with a benign lesion, or with no abnormality in the chest, were reviewed. A sensitivity of 96% was found. In a group of 193 patients in whom a preoperative pathologic diagnosis could not be obtained sensitivity was 95%, specificity was 87%. Correlation between tumor size and tumor-to-non-tumor ratio was established for squamous cell carcinoma, adenocarcinoma, and small cell anaplastic carcinoma. Adenocarcinomas were smaller and showed lower tumor-to-non-tumor ratios than other histologic types. In squamous cell carcinoma a possible correlation between tumor-to-non-tumor ratio and histologic differentiation was investigated, but could not be established. It is concluded that 57Co-bleomycin scintigraphy is helpful in the evaluation of patients with possible lung cancer in whom a preoperative pathologic diagnosis cannot be obtained.

Immunohistological findings in lip biopsy specimens from patients with Crohn's disease and healthy subjects.

Biopsies of apparently normal buccal mucosa were taken from 14 patients with Crohn's disease and 13 healthy controls who were matched for dental status. Most patients had an increased number of lymphocytes around vessels in the subepithelial tissue and two showed fibrosis with moderate atrophy of minor glands. Plasma cells which contained immunoglobulin, predominantly IgA, were only found around minor salivary glands in both patients and controls. Quantitative studies showed a significant increase in the number of cells containing IgA in patients compared with controls. No correlation was found between immunoglobulin pattern and disease activity, age, sex, or duration of Crohn's disease. A significant correlation was found between the activity of the disease, as defined by the Crohn's Disease Activity Index, and the number of plasma cells containing IgM.

57Co-bleomycin and 67Ga-citrate in detecting and staging lung cancer.

In the investigation of suspected lung cancer bleomycin labelled with cobalt-57 and gallium-67 labelled with citrate are currently used to detect the primary tumour and to establish the presence of metastases in the lung hilum and mediastinum. A comparative study of these radio-pharmaceuticals was performed in 63 patients with proved lung cancer. 57Co-bleomycin showed the primary tumour in 58 patients (92%) and 67 Ga-citrate in 34 (54%) (p less than 0.01). The average tumour-to-lung ratio was 3.4 with 57Co-bleomycin and 1.5 with 67Ga-citrate. Proved metastases in the hilum or the mediastinum were visualised with 57Co-bleomycin scintigraphy in 16 out of 18 patients (89%) and with 67 Ga-citrate scintigraphy in only eight (45%) (p less than 0.01). These results indicate that 57Co-bleomycin scintigraphy is more suitable for detecting and staging lung cancer than is 67Ga-citrate. 57Co-bleomycin is valuable in the detection of peripheral lesions, in which a pathological diagnosis is difficult to achieve, since a positive scintigram indicates malignancy. When 57Co-bleomycin scintigraphy suggests hilar or mediastinal metastases mediastinoscopy should be carried out; but when no metastases are apparent it is reasonable to proceed directly to thoracotomy without mediastinoscopy.

Long-term morphological and immunohistochemical observations on biopsy specimens of small intestine from children with gluten-sensitive enteropathy.

Jejunal biopsy specimens from nine Spanish children with gluten-sensitive enteropathy were studied with morphometric and immunohistochemical techniques in three stages of the diseases: the first biopsy was taken for diagnosis, when the child had a gluten-containing diet, the second after gluten withdrawal, and the third biopsy after gluten-provocation. The findings were compared with those in 10 healthy adults. The villous:crypt ratio and the length of the surface epithelium per stretched millimetre muscularis mucosae were decreased, whereas the number of interepithelial lymphocytes per millimetre surface epithelium was increased when the child had a gluten-containing diet. Although these parameters improved after withdrawal of gluten for at least seven months, they never reached the values of the healthy control group. With the indirect immunoperoxidase technique it was shown that the numbers of IgA-, IgG-, and IgM-containing cells, expressed per "mucosal tissue unit" of 4 micrometer thick and 1 mm wide, were significantly increased during the active phases of the disease. This increase was most striking for the IgM-containing cells. The most sensitive parameters for the histological diagnosis of gluten-sensitive enteropathy are the villous:crypt ratio or the length of the surface epithelium per millimetre muscularis mucosae, the number of interepithelial lymphocytes per millimetre surface epithelium, and the number of IgM-containing cells per millimetre muscularis mucosae.

Allergic proctitis, a clinical and immunopathological entity.

Patients with isolated ulcerative proctitis form a heterogeneous group. Some may develop ulcerative colitis, others have a limited, benign disease. Twelve patients with isolated proctitis with a mean course of seven years were studied. All patients had a typical clinical picture consisting of a mild and intermittent course of the disease with the presenting symptom of rectal blood loss. At endoscopic examination the inflammatory process was limited to the rectal and distal sigmoid colonic mucosa with a clear upper border beyond which the mucosa of the sigmoid colon was normal. Histologically the mucosal biopsy specimens of the affected rectum resembled those of ulcerative colitis. However, in contrast with proctitis on the base of ulcerative colitis or Crohn's disease, immunoperoxidase staining revealed a markedly increased number of IgE containing cells in the lamina propria of rectal mucosa biopsies. As an IgE-mediated immune mechanism was considered to play a role in this type of proctitis, eight of the 12 patients were treated with oral administration of disodium cromoglycate (DSCG). All patients were improved by the drug. The remaining four patients with mild proctitis did not require treatment. We concluded that, in patients with isolated proctitis on clinical and immunopathological criteria, a group can be separated which responds to DSCG, a condition for which we suggest the name 'allergic proctitis'.

Immunoglobulin containing cells in inflammatory bowel disease of the colon: a morphometric and immunohistochemical study.

Immunoglobulin containing cells in rectal and sigmoid colonic mucosa in endoscopically obtained biopsies from 10 patients with ulcerative colitis and 10 patients with Crohn's disease were studied, using an indirect immunoperoxidase technique. These findings were compared with the immunoglobulin containing cell number in colonic biopsies from 10 control patients with no evidence of colitis. In biopsies from the 20 patients with inflammatory bowel disease a marked increase in area of the lamina propria per millimetre mucosa length was found. In ulcerative colitis a marked increase in number of IgG containing cells was observed. In Crohn's disease the increase in IgG containing cell number is dependent on the degree of activity of inflammation. In quiescent of active Crohn's disease of the colon we found a significant increase of the IgM containing cells. The number of IgM containing cells per millimetre mucosa length will differentiate the pathology of Crohn's disease from ulcerative colitis.

Use of morphometry and immunohistochemistry of small intestinal biopsy specimens in the diagnosis of food allergy.

Eight babies with cow's milk protein intolerance and malabsorption, ages ranging from 2 weeks to 6 months, and five adult patients with a history of food allergy were studied. In the jejunal biopsies of the eight children with cow's milk protein intolerance we found partial villous atrophy with an increased number of interepithelial lymphocytes as determined by morphometric analysis. In the five adult patients no morphological changes of the jejunal mucosa were found. However, immunoperoxidase staining revealed a markedly increased number of IgE containing cells in the lamina propria of all jejunal biopsies studied. This proved to be specific for young and adult patients with food allergy. It is concluded that immunohistochemistry of jejunal biopsy specimens is of considerable value in the diagnosis of food allergy.