Effects of hyaluronan on proteoglycan content of osteoarthritic chondrocytes in vitro.

PURPOSE: To investigate the effect of hyaluronic acid (HA) on proteoglycan (PG) concentration in alginate cultures of human osteoarthritic chondrocytes and to analyze whether HA exhibit anti-degradative effects in the presence of the cytokine IL-1beta. METHODS: Cartilage samples from ten patients with osteoarthritis of the knee were harvested and chondrocytes were cultivated in alginate beads. Four groups were cultured: control group with and without IL-1beta (500 pg/ml) and HA group (100 microg/ml) with and without IL-1beta (500 pg/ml). PG concentration was estimated by a dimethylmethylene blue assay. To assess cell proliferation, we measured DNA content fluorometrically. RESULTS: The proliferation rate (DNA) was unchanged in all culture groups. In the control-group PG/DNA (ng/ng) concentration was 27.1 +/- 7.2. Supplementation of the medium with HA decreased PG concentration to 25.3 +/- 6.9 (p < 0.05). After administration of IL-1beta PG/DNA concentration dropped to 23.1 +/- 6.0 (p < 0.01). By contrast HA treatment of IL-1beta stimulated chondrocytes did not further decrease PG concentration (23.9 +/- 6.1). In fact the negative effect of isolated HA application was inverted if HA was given with IL-1beta (p < 0.05). CONCLUSIONS: In osteoarthritic chondrocytes cultured phenotypically stable, HA could exhibit protective effects only in the presence of the degradative cytokine IL-1beta. Thus, the reported anti-inflammatory effects of HA to cartilage matrix seem to be more indirect by blocking degradative effects of cytokines to the matrix.     

Validation of the diagnostic value of NMP22 BladderChek test as a marker for bladder cancer by photodynamic diagnosis

OBJECTIVES: The aim of the present study was to validate the sensitivity and specificity of the new "point-of-care" NMP22 BladderChek test compared to photodynamic diagnosis (PDD). METHODS: Voided urine samples from 100 patients with suspicion of bladder cancer were collected to perform the NMP22 BladderChek test and voided urinary cytology. The nuclear matrix protein 22 (NMP22) levels were measured by a lateral flow immunochromatographic qualitative assay, using 10 U/ml as the cut-off value. Subsequently patients underwent PDD, using 5-aminolevulinic acid or hexyl-aminolevulinate; previous bladder washings for cytology were collected. Sensitivity and specificity of the NMP22 BladderChek test were compared with cytology and PDD. RESULTS: Forty of the 100 patients had urothelial malignancies (22 pTa, 4 pT1, 3 pT2, 9 carcinoma in situ, 2 pTx; 16 G1, 6 G2, 18 G3). The sensitivity was 65% for the NMP22 BladderChek test, 44% for voided cytology, 75% for washing cytology, and 93% for PDD. Specificity rates were 40%, 78%, 62%, and 43%, respectively. Positive predictive values were 0.42, 0.58, 0.53, and 0.52 and the negative predictive values 0.63, 0.68, 0.82, and 0.9, respectively. CONCLUSIONS: The results demonstrate that the NMP22 BladderChek is an easily applied test, giving diagnostic findings within 30 min. However, validated by the highly sensitive PDD, the NMP22 BladderChek test demonstrates poor specificity and sensitivity and, therefore, cannot be recommended for screening or surveillance in daily clinical routine use. Further studies with careful patient selection are necessary to identify the patient population that might benefit from the NMP22 BladderChek test.     

IGF-1 vs insulin: respective roles in modulating sodium transport via the PI-3 kinase/Sgk1 pathway in a cortical collecting duct cell line

Insulin and insulin-like growth factor 1 (IGF-1) may play a role in the regulation of sodium balance by increasing basal and aldosterone-stimulated transepithelial sodium transport in the aldosterone-sensitive distal nephron (ASDN). As insulin and IGF-1 are capable of binding to each other's receptor with a 50- to 100-fold lower affinity than to their cognate receptor, it is not clear which receptor mediates its respective sodium transport response in the ASDN. The aim of the present study was to characterize the IGF-1 regulation of Na(+) transport in the mCCD(cl1) cell line, a highly differentiated cell line which responds to physiological concentrations (K(1/2)=0.3 nM) of aldosterone. IGF-1 increased basal transepithelial Na(+) transport with a K(1/2) of 0.41+/-0.07 nM. Insulin dose-response curve was displaced to the right 50-fold, as compared to that of IGF-1 (K(1/2)=20.0+/-3.0 nM), indicating that it acts through the IGF type 1 receptor (IGF-1R). Co-stimulation with IGF-1 (0.3 nM) (or 30 nM insulin) and aldosterone (0.3 nM), either simultaneously or by pretreating the cells for 5 h with aldosterone, induced an additive response. The phosphatidylinositol-3' kinase (PI3-K) inhibitor LY294002 completely blocked IGF-1 and aldosterone induced and co-induced currents. As assessed by Western blotting, protein levels of the serum-, and glucocorticoid-induced kinase (Sgk1) were directly and proportionally related to the current induced by either or both IGF-1 and aldosterone, effects also blocked by the PI3-K inhibitor LY294002. IGF-1 could play an important physiological role in regulating basal sodium transport via the PI3-K/Sgk1 pathway in ASDN.     

Major tumor regression after paclitaxel and carboplatin polychemotherapy in a patient with advanced penile cancer

A 24-year-old man presented to our hospital twice with acute urinary retention in March 2002. Myelographic computed tomography demonstrated a posterior osteophyte. The preoperative urodynamic study indicated detrusor overactivity and detrusor sphincter dyssynergia 30 days after the first occurrence of urinary retention. During osteophyte resection and laminoplasty, the osteophyte, which was found to be fractured and to press on the cauda equina, was removed. The postoperative urodynamic study showed that detrusor overactivity remained and detrusor sphincter dyssynergia had disappeared. The patient was regularly followed up as an outpatient, and no dysuria had been noted by January 2003.     

The Lumbosacral Junction in Working German Shepherd Dogs – Neurological and Radiological Evaluation

The clinical and radiological incidence of lumbosacral (LS) disease was studied on 57 German Shepherd dogs (GSDs) used in active service. The study included a clinical history, a neurological examination, and plain radiographs of the caudal lumbar vertebrae. The neurological examinations revealed lower back pain and/or neural deficits in 21 dogs, of which 14 had a history of pain or pelvic gait abnormalities. Radiographic findings were spondylosis at L7–S1, degeneration of L7–S1 disc, LS malalignment, transitional LS vertebrae and/or primary spinal canal stenosis in 15 dogs with neurological abnormalities and/or back pain and in 18 dogs with no clinical signs. No correlation between the neurological and the radiographic findings were found. This study demonstrates that even prominent radiographic LS abnormalities are of minimal value in the evaluation of LS disease in the GSD.     

Significance of haemorrhagic lacunes on MRI in patients with hypertensive cerebrovascular disease and intracerebral haemorrhage

Our purpose was to determine the frequency and signifcance of haemorrhagic lacunes (HL) on MRI in patients with a history of, or at risk for intracerebral haemorrhage. We examined 72 patients with old spontaneous intracerebral haemorrhage (ICH) using T1-and T2-weighted spin-echo sequences. MRI studies of 137 consecutive patients with cerebrovascular disease but no known ICH were also reviewed. Both groups showed about the same degree of age-related white matter change and nonhaemorrhagic lacunar infarcts, whereas the ICH group had a higher frequency of HL (12/72 patients) than the non-ICH group (6/131 patients,p<0.01). These results correlate well with reported pathological findings. We conclude that haemorrhagic lacunes found on MRI studies of patients with cerebrovascular disease may suggest a higher risk of intracerebral haemorrhage.     

The ratio of plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury in patients undergoing liver transplantation

Background

Postoperative acute kidney injury (AKI) is associated with high morbidity and mortality after liver transplantation (OLT). Previous studies have shown the value of plasma neutrophil gelatinase-associated lipocalin (NGAL) taken 2 hours after reperfusion of the liver graft as an early marker predicting AKI. The study was performed to determine whether plasma NGAL concentrations obtained as early as 1 hour after reperfusion was predictive of AKI and whether the NGAL ratio was an early predictor for AKI in the first 48 hours after OLT.

Methods

Twenty-six liver transplant recipients donated plasma samples for NGAL determinations at induction (T1), at graft reperfusion (T3) as well as after 1 (T4) and hours 2 (T5), and at the end of the surgery (T7). AKI was defined at 48 hours after liver transplantation according to the acute kidney injury network criteria. Predictive ability was assessed using areas under the curve of receiver operator characteristic analyses.

Results

The area under the curve of the receiver operator characteristics curve of (plasma NGAL concentration at T4)/(plasma NGAL concentration at T1) to predict AKI was 0.717 at T5, 0.765 at T7, 0.714 at T8 (24 hours post-OLT), and 0.781 at T9 (48 hours post-OLT).

Conclusion

The plasma NGAL concentrations taken 1 hour after reperfusion of the liver graft seem to be predictive of AKI; the NGAL changing ratio may be an early predictor for AKI in the first 48 hours after OLT.     

Mini-open thoracoscopically assisted thoracotomy versus video-assisted thoracoscopic surgery for anterior release in thoracic scoliosis and kyphosis: a comparison of operative and radiographic results

BACKGROUND CONTEXT: Combining anterior release and interbody fusion with posterior instrumented fusion is an accepted treatment for severe rigid spinal deformity. Video-assisted thoracoscopic surgery (VATS) and mini-open thoracoscopically assisted thoracotomy (MOTA) are two minimally invasive approaches to the thoracic spine. Both reduce surgical trauma, improve cosmesis and provide effective exposure for release and fusion. Published data and the authors' surgical experience have demonstrated that both techniques are equivalent in degree of release to traditional open thoracotomy, but no comparison between these two minimally invasive alternatives has been published to our knowledge. PURPOSE: This study compared MOTA and VATS under the hypothesis that both result in similar corrections and comparable operative parameters when used in conjunction with posterior instrumented fusion. STUDY DESIGN/SETTING: Retrospective chart review of consecutive case series by two surgeons. PATIENT SAMPLE: Twenty-one (13 female, 8 male) patients underwent MOTA and 24 patients (17 female, 7 male) underwent VATS for anterior release, discectomy and fusion prior to posterior instrumented fusion. OUTCOME MEASURES: Outcomes were measured at a minimum of 1-year follow-up and included radiographic Cobb measurements and operative parameters. METHODS: The indications for surgery included rigid and severe scoliosis or thoracic kyphosis. Data collection included preoperative demographics, number of levels released, primary curve correction, operative time and blood loss. Data were normalized per number of levels released anteriorly. Statistical analysis of results was done using a two-sample t test assuming equal variances with two-tail p values less than .05. RESULTS: More anterior levels were operated on average in the VATS group (6.33 vs. 4.38 levels). Curve correction per anterior level released was similar in both groups (8.7 and 8.8 degrees/level for MOTA and VATS, respectively). There was a significant difference in operative time with MOTA averaging 131.7 minutes and VATS averaging 162.8 minutes. However, a comparison of the operative time per anterior level operated, approached statistical significance in favor of VATS (33.0 vs. 28.4 minutes, p=.08). There was no significant difference in estimated blood loss during the anterior portion of the surgeries. There was a trend toward decreased blood loss per operated level favoring VATS (68.4 vs. 38.9 cc, p=.09). CONCLUSIONS: Both approaches resulted in corrections that compare favorably with open thoracotomy. We suggest that a factor in choosing between these two minimally invasive techniques is the number of thoracic levels requiring release. For four levels or less, MOTA provides an excellent alternative to standard thoracotomy. For five or more levels, VATS provides for excellent exposure of additional levels with the advantages of less operative time and blood loss per operated level.     

Childhood exposure to environmental tobacco smoke and chronic respiratory symptoms in non-smoking adults: the Singapore Chinese Health Study

BACKGROUND: Childhood exposure to environmental tobacco smoke has been extensively associated with childhood respiratory illness; fewer studies have addressed the effects on adults. METHODS: Childhood environmental tobacco smoke exposure in relation to chronic cough, phlegm, and asthma diagnosis was studied in never smokers from a cohort of Singaporeans of Chinese ethnicity aged 45-74 years at enrollment from 1993 to 1998. From 1999 to 2004 subjects were interviewed regarding environmental tobacco smoke exposure before and after the age of 18 and the presence and duration of current symptoms of chronic cough and phlegm production and asthma diagnosis. RESULTS: Among 35,000 never smokers, fewer had smoking mothers (19%) than fathers (48%). Although few subjects currently lived (20%) or worked (4%) with smokers, 65% reported living with a daily smoker before the age of 18 years. Living with a smoker before the age of 18 increased the odds of chronic dry cough (149 cases, odds ratio 2.1, 95% CI 1.4 to 3.3) and, to a lesser extent, phlegm, after adjustment for age, sex, dialect group, and current and past exposure to smokers at home and at work after the age of 18. Associations strengthened with higher numbers of smokers in childhood. There was no association with asthma or chronic bronchitis. There was evidence to suggest a stronger association among subjects with a lower adult intake of fibre which has previously been found to be protective for respiratory symptoms. CONCLUSIONS: In this large study of non-smokers, living with a smoker in childhood was associated with chronic dry cough and phlegm in adulthood, independent of later exposures to environmental tobacco smoke.     

Inner choroidal ischaemia and CNV due to handheld laser-induced maculopathy: a case report and review

There has been a sharp rise of reported handheld laser-induced maculopathy (HLIM) cases over the past decade, a concerning trend that may continue due to unregulated online access to high power lasers. Though HLIM has distinct clinical features, not uncommonly it may masquerade as other retinal disorders. It is critical therefore to recognise the clinical and multimodal imaging characteristics of this important and potentially devastating condition. As HLIM patients are typically young, unique issues need to be considered, such as delayed presentation, difficult history, poor compliance and behavioural or psychiatric comorbidity. This article will review the clinical and diagnostic features of laser injury, with a special emphasis on the multimodal retinal findings. In addition, we present a unique case of HLIM, resembling the presentation of a placoid disease variant and illustrating choroidal ischaemia using advanced retinal imaging, that offers further insight into the mechanisms of laser injury and its complications. The issues addressed in this review aim to increase recognition of an increasingly important and trending condition with potentially profound visual complications.Subject terms: Retinal diseases, Paediatrics, Trauma