Decreased collagen type I/III ratio in patients with recurring hernia after implantation of alloplastic prostheses

Background Abnormal collagen metabolism is suspected to play an important role in the pathogenesis of recurring inguinal and incisional hernias. Whereas alloplastic prostheses are nowadays routinely used, the quantity and quality of collagen formation after repair in humans has not been analysed in a large cohort.Method Seventy-eight prostheses (Prolene, Atrium, Marlex, Vypro, Mersilene, Gore-Tex) implanted for inguinal and incisional hernia repair were explanted because of recurrence, chronic pain or infection. The mean implantation period was 17.9±11.2 (range 0.5–48) months. Collagen formation was investigated quantitatively (collagen–protein ratio) and qualitatively (collagen type I/III ratio). Results were related to clinical data that included gender, age, implantation period, indication for implantation/explantation, type and location of prosthesis.Results Mean collagen–protein ratio was 45.3±8.5 g/mg, with significant differences between male (43.8±9.1 g/mg) and female tissue samples (48.1±6.8 g/mg, P=0.033). The mean collagen type I/III ratio of all samples investigated was 2.1±1.4. Samples explanted for recurring hernias exhibited a significantly decreased ratio (1.3±0.7, P<0.05) compared to samples explanted because of pain (3.4±1.2) or infection (2.9±1.6). Multivariate analysis excluded independent effects of age, gender, indication for implantation of prostheses, location and implantation period on collagen type I/III ratio.Conclusion The present study confirms the importance of a biological approach, next to technical aspects, to the understanding of the pathogenesis of recurrent hernia formation and underscores the presence of a disturbed scarring process. The composition of scar tissue with a lowered collagen type I/III ratio and, therefore, reduced tensile strength may be a major contribution to hernia recurrence.     

A case of glomerulopathy showing podocytic infolding in association with Sjögren’s syndrome and primary biliary cirrhosis

A 49-year-old man was admitted to our hospital with mild proteinuria. Prior to admission, he had been diagnosed as having Sjögren’s syndrome in association with primary biliary cirrhosis. Examination of a renal biopsy under light microscopy revealed diffuse and global mesangial cell proliferation and a spike and/or bubbling formation of the glomerular basement membrane (GBM), resembling membranoproliferative glomerulonephritis. In contrast, immunofluorescent studies showed marked immunoglobulin and complement depositions in the mesangial areas; however, only faint granular IgG and IgA deposition was observed along the GBM. Interestingly, electron microscopy revealed that a microtubular structure, derived from podocytes, was present in the GBM. We present a case of glomerulopathy showing podocytic infolding in association with Sjögren’s syndrome and primary biliary cirrhosis.     

Anaesthetic considerations in down’s syndrome: experience with 100 patients and a review of the literature

Down’s Syndrome (Trisomy 21, T21) occurs in approximately 0.15 percent of live births. In addition to the stigmata of the syndrome, other congenital defects are frequently found in these patients. Cardiac lesions are particularly prominent. To determine the complications associated with anaesthesia and surgery we examined the records of 100 consecutive patients (58 males, 42 females) who underwent surgery with general anaesthesia during a two year period, from March 1978-March 1980. In addition to the cardiac lesions, the low birth weight of Trisomy 21 infants, increased suceptibility to infections, atlanto-occipital dislocation, and reduced central nervous system catecholamine levels might be expected to result in an increased incidence of complications. This study of 100 patients with Trisomy 21 (T21) indicates that the incidence of complications is low. However, the anaesthetist must understand the pathophysiology of T21 in order to provide optimal anaesthetic care.     

Total knee arthroplasty in patients with inherited dwarfism – a report of five knee replacements in two patients with Morquio’s disease type A and one with spondylo-epiphyseal dysplasia

In Morquio’s disease and in hereditary spondylo-epiphyseal dysplasia of longer duration, malalignment, instability and unfavourable anatomy are generally the main surgical problems, but as these patients nowadays do not have a reduced life expectancy, it is worthwhile giving them a functional replacement for their severely deformed and painful knees. We report three patients with inherited dwarfism, in whom a replacement of the knee was performed. Received: 13 April 1999     

Serum extracellular secreted antagonists of the canonical Wnt/β-catenin signaling pathway in patients with Cushing’s syndrome

Summary

Patients with endogenous hypercortisolism have higher sclerostin, but do not differ in Dickkopf 1 (Dkk1) or secreted frizzled-related protein 1 (SFRP1) levels as compared to healthy control.

Introduction

Endogenous Cushing’s syndrome (CS), usually affecting young and otherwise healthy patients, is a good model to validate the effects of supraphysiological levels of glucocorticoids in humans. This study evaluates circulating levels of extracellular antagonists of the Wnt/β-catenin signaling pathway (sclerostin, Dkk1, SFRP1) in patients with CS versus healthy individuals.

Methods

Forty patients with clinically and biochemically evident CS and 40 sex-, age-, and body mass index-matched healthy subjects provided fasting serum samples for sclerostin, SFRP1 and Dkk1, along with bone turnover markers.

Results

Patients with CS had higher sclerostin levels (34.5 (30.3–37.1) pmol/L) versus healthy individuals (29.9 (24.3–36.8) pmol/L) (p?=?0.032). Differences in sclerostin were due to the lack of lower sclerostin values rather than an increase in protein levels above the upper limits of the healthy control. The odds of sclerostin levels being higher than 30 pmol/L were greater in patients with CS as compared with the odds in healthy subjects (odds ratio?=?3.81 95 % confidence interval 1.45–10.02) (p?=?0.01). It coexisted with suppressed bone formation and unchanged bone resorption markers. Dkk1, SFRP1 did not differ from the control group.

Conclusions

Of all the tested proteins (sclerostin, Dkk1, SFRP1), only sclerostin showed a significant difference when contrasting CS with healthy subjects. Hypercortisolism might prevent the down-regulation of sclerostin. Targeting sclerostin seems to be a promising therapeutic approach to treating osteoporosis in patients with CS.     

‘Long’ pressure reactivity index (L-PRx) as a measure of autoregulation correlates with outcome in traumatic brain injury patients

Background  

Cerebral autoregulation and, consequently, cerebrovascular pressure reactivity, can be disturbed after traumatic brain injury (TBI). Continuous monitoring of autoregulation has shown its clinical importance as an independent predictor of neurological outcome. The cerebral pressure reactivity index (PRx) reflects that changes in seconds of cerebrovascular reactivity have prognostic significance. Using an alternative algorithm similar to PRx, we investigate whether the utilization of lower-frequency changes of the order of minutes of mean arterial blood pressure (MAP) and intracranial pressure (ICP) could have a prognostic value in TBI patients.     

Comparison of the Performance of ‘Intubating LMA’ and ‘Cobra PLA’ as an aid to blind endotracheal tube insertion in patients scheduled for elective surgery under general anesthesia

ObjectiveSupraglottic airways (SGA) through which blind endotracheal intubation is made possible is an area of considerable interest. Our study aimed at comparing the Cobra Perilaryngeal Airway (CPLA) with the Intubating Laryngeal Mask Airway (ILMA) with regard to the performance of the former as a conduit for facilitating blind endotracheal intubation.MethodsAmerican Society of Anesthesiologists (ASA) I–II patients consenting to the study, with no predictors of difficult airway, scheduled for elective surgery were randomized into two groups of 30 each. Anesthesia was induced with fentanyl, propofol and vecuronium. CPLA was inserted in Group I and ILMA in Group II. Fibreoptic scoring of the laryngeal view was done through the SGA. Blind intubation through either CPLA or ILMA was then carried out with cuffed polyvinyl chloride (PVC) tube in Group I and ILMA-tracheal tube in Group II.ResultsDemographic and surgical data were comparable between the two groups. The success rate of intubation (87% through CPLA and 90% through ILMA) (p value 1), number of attempts made and the fibreoptic scores (p value 0.12) were comparable between the two groups. Insertion time was significantly longer in Group I as compared with Group II (9 s vs. 4 s; p value 0.004). Trauma and sore throat were more common in Group I (p value ?0.1, 0.19 respectively). Hemodynamic monitoring showed more tachycardia during CPLA insertion as compared with ILMA (p value 0.006).ConclusionWe conclude that CPLA can be used as an effective conduit for blind endotracheal intubation with cuffed PVC tube and has comparable efficacy in tracheal intubation as that with ILMA.     

Is morning urinary protein/creatinine ratio a reliable estimator of 24-hour proteinuria in patients with glomerulonephritis and different levels of renal function?

BACKGROUND: This cross-sectional study was conducted to determine whether a spot urine protein/creatinine ratio (UPr/UCr) provides accurate quantitation of 24-hr urinary protein excretion (24-hr Prot) in out-patients with primary glomerulonephritis (GN) and different renal function levels. METHODS: Patients were classified into three groups according to creatinine (Cr) clearance (ml/min) and into five categories according to morning UPr/UCr. Correlation between 24-hr Prot and UPr/UCr was calculated according to the three renal function levels. The Bland and Altman method was used to assess agreement between 24-hr Prot and UPr/UCr. Agreement limits were obtained calculating the mean difference between 24-hr Prot and morning UPr/UCr +/- 2SD. Sensitivity and specificity were determined for different renal function levels and UPr/UCr cut-off values. RESULTS: High correlation coefficients (r=0.91, 0.95 and 0.98) were observed in patients with normal, reduced and severely reduced renal function. Differences and variability between 24-hr Prot and UPr/UCr tended to increase with higher proteinuria levels, and this trend was observed for the three renal function levels. The best UPr/UCrcut-off values to detect abnormal or nephrotic proteinuria were, respectively, 0.3 and 2.6. CONCLUSIONS: Correlation and agreement between UPr/UCr and 24-hr Prot was good for all renal function levels, but demonstrated more marked differences as urinary protein excretion increased. Morning UPr/UCr had good sensitivity and specificity for the diagnosis of 24-hr Prot, even in patients with reduced renal function.     

The relation of prostate biopsy results and ratio of free to total PSA in patients with a total PSA between 4–20 ng/mL

Objective: In this study our aim was to investigate the efficacy of free tototal PSA ratio in discrimination of benign prostate hyperplasia andprostate cancer.Materials and methods: A total of 194 patients, 52 to 82 years old (mean66.06 ± 0.47 years) with PSA levels between 4 to 20 ng/mL wereincluded into this study. Each patient underwent sextant prostate biopsyunder transrectal ultrasound guidance. The patients were divided into twogroups as PSA 4–10 and 10–20 ng/mL. Patients with benign and malignresults were compared with respect to age, total PSA level, free PSA leveland free/total (f/t) PSA ratio.Results: Biopsies revealed prostate cancer in 16 of 130 patients (12.3%)with serum PSA 4–10 ng/mL and in 10 of 64 patients (15.6%) with serumPSA 10–20 ng/ml. In both PSA groups free PSA and f/t PSA levels werestatistically significant, where total PSA levels were not. In patients with4–20 ng/mL total PSA levels and a cut off level of < 0.18 for f/t PSA, thesensitivity, specificity and positive predictive value for prostate cancerwere 88.5%, 53.6% and 20.4% respectively.Conclusion: Higher levels of PSA suggest prostate cancer, but stilladditional parameters are needed for patients with PSA 4–20 ng/mL, suchas free PSA and f/t PSA. Although a cut off level of < 0.18 for f/t PSA seemsto be the most accurate one to discriminate benign and malign diseasesfurther studies on larger groups of patients are needed.     

Treatment of painful bladder syndrome/interstitial cystitis with botulinum toxin A: why isn’t it effective in all patients?

Botulinum toxin A (BTA) is currently used to treat a variety of painful disorders, including painful bladder syndrome/interstitial cystitis (PBS/IC). However, BTA is not consistently effective in all patients. This may be due to the disparity of causes of pain, but this may also relate to the processes by which BTA exerts anti-nociceptive effects. This review discusses mechanisms by which BTA may inhibit pain and studies of the use of BTA in PSB/IC patients. It is doubtful that any single treatment will effectively control pain in PBS/IC patients, and it is highly probable that multiple strategies will be required, both within individual patients and across the population of PBS/IC patients. The purpose of this review is to discuss those mechanisms by which BTA acts, with the intent that alternative strategies exploiting these mechanism, or work through alternative pathways, can be identified to more effectively treat pain in PBS/IC patients in the future.     

The role of free to total PSA ratio in prediction of extracapsular tumor extension and biochemical recurrence after radical prostatectomy in patients with PSA between 4 and 10?ng/ml

Objectives

The prognostic value of free to total PSA ratio (F/T PSA) in patients eligible for radical prostatectomy (RP) is controversial. The aim of the present study was to evaluate correlation of F/T PSA with tumor extracapsular extension (ECE) and biochemical recurrence (BR) at long-term follow-up.

Patient and methods

Clinical and pathological data were prospectively gathered from 200 patients treated with RP for clinically localized prostate cancer (PCa) and PSA between 4 and 10?ng/mL. Correlations of preoperative variables including F/T PSA with ECE and BR were evaluated with uni- and multivariate analysis. Adjunctive analyses evaluated the association of PSA F/T with other pathological results. The relationship between preoperative F/T PSA and BR was also assessed with Kaplan?CMeier survival analysis.

Results

Lower F/T PSA was significantly correlated with ECE (p?=?0.0063), higher GS (p?=?0.0054), and seminal vesicles involvement (p?=?0.0047). The F/T PSA value of 14% provided the greatest discrimination in predicting ECE. At multivariate analysis, F/T PSA did not achieve the statistical significance for predicting ECE independently. At a mean (median, range) follow-up of 52 (48, 14?C116) months, preoperative F/T PSA resulted significantly correlated with BR (p?=?0.001). At the Kaplan?CMeier survival analysis, the 5-year BR free survival rate resulted 89.3 and 68.9% in the group with F/T PSA?>14 and ??14?ng/mL, respectively (log rank p?=?0.0022). At Cox proportional hazard model, only ECE resulted an independent predictor of BR (R?=?2.646, p?=?0.037).

Conclusion

In patients with clinically localized PCa and PSA 4?C10?ng/ml, lower F/T PSA was significantly associated with ECE, other adverse pathologic features, and with BR at the long-term follow-up, but only ECE resulted an independent predictor of BR in our series.     

Phase I/II trial of subcutaneous interleukin-2, granulocyte-macrophage colony-stimulating factor and interferon-α in patients with metastatic renal cell carcinoma

Study Type – Therapy (individual cohort) Level of Evidence 2b

OBJECTIVE

? To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin‐2 (IL‐2), interferon‐α2b (IFN‐α) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).

PATIENTS AND METHODS

? Patients with metastatic renal cell carcinoma (RCC) received on a 3+3 trial design escalating doses of s.c. GM‐CSF, IL‐2 and IFN‐α. ? Dose‐limiting toxicities (DLTs) during the first 6‐week cycle were used to determine the MTD. ? A phase II trial was then initiated to determine clinical activity.

RESULTS

? A total of sixty patients were enrolled in the study (phase I = 31; phase II = 29). ? Two DLTs were observed (G3 nausea/vomiting and fatigue) and the MTD was determined to be GM‐CSF 5.0 µg/kg/day, IL‐2 9.0 mIU/m²/day and IFN‐α 5.0 mU/m²/day. ? Patients received a median (range) of four (one to 11) cycles of therapy. G3 adverse events were reported in 10 of 31 (32%) patients. ? The overall response rate was 20% (one complete response and 11 partial responses), including patients who were rendered free of disease with surgery. ? The median progression‐free survival and overall survival were 6.0 and 23.4 months, respectively.

CONCLUSIONS

? Immunotherapy with concurrent s.c. GM‐CSF, IL‐2 and IFN‐α is generally well tolerated. ? The overall response rate observed with this combination continues to show the efficacy of immunotherapy in a selected group of metastatic RCC patients.     

Diagnostic efficacy of free to total ratio of prostate-specific antigen and prostate-specific antigen velocity, singly and in combination, in detecting prostate cancer in patients with total serum prostate-specific antigen between 4 and 10 ng/ml

To assess the diagnostic efficacy of prostate-specific antigen (PSA)-related parameters, using a total of 226 patients with gray zone PSA who underwent prostate biopsy, various cutoff points of free to total ratio of PSA (f/t PSA) and PSA velocity (PSAV) were evaluated. Higher cutoff points of f/t PSA resulted in high sensitivity and negative predictive value (NPV): at f/t PSA <15%, sensitivity was 82.0% (41/50) and NPV 84.7% (50/59), and at f/t PSA <20%, 96.0% (48/50) and 92.3% (24/26). Lowering cutoff points also resulted in higher sensitivity and NPV: at PSAV ≥0.75 ng/ml per year, sensitivity was 71.4% (15/21) and NPV 82.4% (28/34), and at PSAV ≥0.40 ng/ml per year, 95.2% (20/21) and 95.2% (20/21). Further, among the patients with both of these parameters available, both sensitivity and NPV achieved 100% (10/10 and 7/7) when the indication for biopsy was determined as f/t PSA <15% or PSAV ≥0.40 ng/ml per year. Our results showed that unnecessary prostate biopsies could be more effectively avoided among patients with “gray zone PSA” by combination of f/t PSA and PSAV than single usage of these indexes.     

The relationship between the presence of autoantibodies,indicators of local and systemic inflammation,the serum concentration of B-cell activating factor (BAFF) and the intensity of salivary gland infiltration in patients with primary Sj?gren's syndrome – a preliminary study

Objectives

The aim of this study was to find markers related to activation of B cells, which show a correlation with the systemic inflammation markers – erythrocyte sedimentation rate and C-reactive protein and with the intensity of in situ inflammation.

Material and methods

Forty-one primary Sjögren''s syndrome (pSS) patients (33 female, 8 male) of the mean age 52.9 ±15 years were included. A group of 20 healthy volunteers was applied as a control. Erythrocyte sedimentation rate (ESR), concentration of gamma-globulins, C-reactive protein (CRP) and rheumatoid factor (RF) were measured by routine laboratory tests. Titres of antinuclear antibodies (ANAs) were determined by the indirect immunofluorescence method, while anti-SS-A/SS-B antibodies were detected by both the dot-blot method and an enzyme immunoassay. The concentrations of BAFF in sera were measured by sandwich ELISA. Biopsies of minor salivary glands were taken and the focus score (FS) was calculated. Correlations between quantitative variables were assessed using the Spearman correlation coefficient (r).

Results

Serum concentrations of BAFF was significantly higher in the pSS patients than in the control group. The study revealed a statistically significant correlation between ANAs titre and the FS (r = 0.421).Anti-SS-A/Ro and anti-SS-B/La antibodies positively correlated with ESR. There was also a positive correlation between the gamma globulin level and the titres of all tested autoantibodies.

Conclusions

The positive correlation between ANAs and FS confirms the importance of these autoantibodies in the local inflammatory process. The positive correlation between anti-SS-A/SS-B antibodies and ESR suggests involvement of these antibodies in generalization of the inflammatory response. In the pSS group serum concentrations of BAFF were statistically significantly higher than healthy volunteers. All presented results confirm the role of activity of B cells in the course of pSS.     

Probability of prostate cancer as a function of the percentage of free prostate-specific antigen in patients with a non-suspicious rectal examination and total prostate-specific antigen of 4–10 ng/ml

Our aim was to assess the usefulness of measuring the percentage of free prostate specific antigen (PSA) in serum in relation to reducing the number of prostate biopsies in men with benign prostate examinations and serum PSA levels between 4 and 10 ng/ml. The percentage of free PSA (Immulite) in serum was analyzed prospectively in 500 men, all of whom underwent ultrasound-guided sextant prostate biopsies. Cancer was detected in 21.4% (107/500) of the patients. Using a free PSA cutoff of 23% as a criterion for performing prostate biopsy would have detected 94.4% of cancers, avoided 18.8% of benign biopsies and yielded a positive predictive value of 25.3%. The percentage of free PSA increased with prostate volume. Mean total PSA and mean free percent PSA values increased as patient age increased, influencing the calculation of cutoff values, sensitivity and specificity. PSA density had a sensitivity and specificity not significantly different than the percentage of free PSA. Measurement of the percentage of free serum PSA improves the specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations.     

Comparison of symptoms, morphological, microbiological and urodynamic findings in patients with chronic prostatitis/pelvic pain syndrome. Is it possible to differentiate separate categories?

164 patients with prostatitic symptoms were evaluated by segmented urinalysis and culture and classified according to the National Institutes of Health classification system: 64 patients (38%) suffered from chronic bacterial prostatitis; 12 (7%) from inflammatory chronic pelvic pain syndrome, and 92 (55%) from non-inflammatory chronic pelvic pain syndrome. Transrectal ultrasound of the prostate, uroflowmetry and measurement of residual urine were also performed. Complaints were recorded using a questionnaire. Our studies revealed that leukocytes in expressed prostatic secretions could be detected in only 24 and 36% of patients with positive bacterial or chlamydial culture. Complaints, ultrasound and urodynamic findings were similar in the 3 groups. Therefore the differential diagnosis and therapy, based on the results of the 4-glass test and cultures as well as on transrectal ultrasound of the prostate, seem to be difficult.