Treatment of renal angiomyolipoma: pooled analysis of individual patient data

Epididymal anomalies and patent processus vaginalis are frequently found in boys with cryptorchidism or hydrocele. We conducted this study to evaluate the association between epididymal anomalies and testicular location or patent processus vaginalis in boys with undescended testis or hydrocele. Children undergoing surgery with undescended testis (group A, 136 boys and 162 testes) or communicating hydrocele (group B, 93 boys and 96 testes) were included. Testicular locations and epididymal anomalies were investigated prospectively. An anomalous epididymis was defined as anomalies of epididymal fusion that consisted of loss of continuity between the testis, the epididymis, and the long looping epididymis. The epididymis was considered normal when a normal, firm attachment between the testis, the caput, and the cauda epididymis was present. The mean ages of groups A and B were 24.6 ± 19.7 (range, 8–52 months) and 31.4 ± 20.6 months (range, 10–59 months). The incidence of epididymal anomalies was significantly higher in group A than that in group B (65.4 % vs. 13.5 %, P < 0.001). The incidence of epididymal anomalies in boys with undescended testis was significantly different according to testis location. Epididymal anomalies were observed in 100 %, 91.4 %, and 39.3 % of cases when the testis was located in the abdomen, inguinal canal, and distal to the external inguinal ring, respectively (P < 0.001). We conclude that epididymal anomalies were more frequent in boys with undescended testis than in boys with hydrocele, and that these anomalies were more frequent when undescended testis was at a higher level. These results suggest that testicular location is associated with epididymal anomalies rather than patent processus vaginalis.     

Penile rehabilitation after radical prostatectomy: does it work?

Context

Erectile dysfunction (ED) represents one of the most common long-term side effects in patients with clinically localized prostate cancer (PCa) undergoing nerve-sparing radical prostatectomy (RP).

Objective

To analyze the role of penile rehabilitation in the recovery of erectile function (EF) after nerve-sparing RP.

Evidence synthesis

Penile rehabilitation is defined as the use of any intervention or combination with the goal not only to achieve erections sufficient for satisfactory sexual intercourses, but also to return EF to preoperative levels. The concept of rehabilitation is based on the implementation of protocols aimed at improving oxygenation, preserving endothelial structure, and preventing smooth muscle structural alterations. Nowadays, the most commonly adopted approaches for penile rehabilitation after nerve-sparing RP are represented by the administration of phosphodiesterase type-5 inhibitors (PDE5-Is), intracorporeal injection therapy, vacuum erection devices (VED), and the combination of these therapies. Several basic science studies support the rational for the adoption of penile rehabilitation protocols. Particularly, rehabilitation, set as early as possible, seems to be better than leaving the erectile tissues unassisted. On the other hand, results from solid prospective randomized trials finally assessing the long-term beneficial effects of PDE5-Is, intracavernosal injections, or VED on EF recovery after surgery are still lacking.

Conclusions

Although preclinical evidences support the rationale for penile rehabilitation after nerve-sparing RP, clinical studies reported conflicting results regarding its efficacy on long-term EF recovery. Nowadays, which is the optimal rehabilitation program still represents a matter of debate.     

Novel NOD2 haplotype strengthens the association between TLR4 Asp299gly and Crohn's disease in an Australian population

BACKGROUND: The first major Crohn's disease (CD) susceptibility gene, NOD2, implicates the innate intestinal immune system and other pattern recognition receptors in the pathogenesis of this chronic, debilitating disorder. These include the Toll-like receptors, specifically TLR4 and TLR5. A variant in the TLR4 gene (A299G) has demonstrated variable association with CD. We aimed to investigate the relationship between TLR4 A299G and TLR5 N392ST, and an Australian inflammatory bowel disease cohort, and to explore the strength of association between TLR4 A299G and CD using global meta-analysis. METHODS: Cases (CD = 619, ulcerative colitis = 300) and controls (n = 360) were genotyped for TLR4 A299G, TLR5 N392ST, and the 4 major NOD2 mutations. Data were interrogated for case-control analysis prior to and after stratification by NOD2 genotype. Genotype-phenotype relationships were also sought. Meta-analysis was conducted via RevMan. RESULTS: The TLR4 A299G variant allele showed a significant association with CD compared to controls (P = 0.04) and a novel NOD2 haplotype was identified which strengthened this (P = 0.003). Furthermore, we identified that TLR4 A299G was associated with CD limited to the colon (P = 0.02). In the presence of the novel NOD2 haplotype, TLR4 A299G was more strongly associated with colonic disease (P < 0.001) and nonstricturing disease (P = 0.009). A meta-analysis of 11 CD cohorts identified a 1.5-fold increase in risk for the variant TLR4 A299G allele (P < 0.00001). CONCLUSIONS: TLR 4 A299G appears to be a significant risk factor for CD, in particular colonic, nonstricturing disease. Furthermore, we identified a novel NOD2 haplotype that strengthens the relationship between TLR4 A299G and these phenotypes.     

Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis c virus genotype 1

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild <30%, or moderate-severe > or =30%. Thirty nondiabetic, nonobese blood donors served as controls. RBP4 levels were measured by a human competitive enzyme-linked immunosorbent assay kit (AdipoGen). Mean values of RBP4 were similar in NAFLD and CHC (35.3 +/- 9.3 microg/L versus 36.8 +/- 17.6; P = 0.47, respectively), and both were significantly higher than in controls (28.9 +/- 12.1; P = 0.02 and P = 0.01, respectively). RBP4 was higher in CHC patients with steatosis than in NAFLD (42.1 +/- 19.7 versus 35.2 +/- 9.3; P = 0.04). By linear regression, RBP4 was independently linked to steatosis only (P = 0.008) in CHC, and to elevated body mass index (P = 0.01) and low grading (P = 0.04) in NAFLD. By linear regression, steatosis was independently linked to homeostasis model assessment score (P = 0.03) and high RBP4 (P = 0.003) in CHC. By logistic regression, RBP4 was the only variable independently associated with moderate-severe steatosis in CHC (odds ratio, 1.045; 95% confidence interval, 1.020 to 1.070; P = 0.0004), whereas waist circumference was associated with moderate-severe steatosis in NAFLD (odds ratio, 1.095; 95% confidence interval, 1.007 to 1.192; P = 0.03). CONCLUSION: In nondiabetic, nonobese patients with genotype 1 CHC, serum RBP4 levels might be the expression of a virus-linked pathway to steatosis, largely unrelated to IR.     

Manganese superoxide dismutase activity and incidence of hepatocellular carcinoma in patients with Child-Pugh class A liver cirrhosis: a 7-year follow-up study.

AIMS: To evaluate possible modifications in the manganese superoxide dismutase (MnSOD) activity during neoplastic transformation of a cirrhotic liver and to find out whether its assessment may have predictive value to identify cirrhotic patients at a higher risk of hepatocellular carcinoma (HCC). METHODS: Seventy-one consecutive subjects with Child-Pugh class A liver cirrhosis were recruited. At the time of enrolment, HCC was diagnosed in 20 cirrhotic patients. The 51 cirrhotic patients without HCC were followed up for the occurrence of tumour by 6-monthly screening for 7 years. During follow-up, 16 patients developed HCC. Seventy healthy subjects formed the control group. MnSOD activity was assayed spectrophotometrically. RESULTS: Serum MnSOD activity was significantly lower in 70 healthy subjects compared with 51 cirrhotic patients and 20 cirrhotic patients with HCC. Cirrhotic patients who developed HCC during follow-up showed significantly higher values of MnSOD activity than HCC-free patients. The best cut-off of MnSOD activity was 0.40 U/ml. At this cut-off, chi2 analysis revealed that MnSOD activity was significantly different between the HCC-free cirrhotic patients and cirrhotic patients who developed HCC. CONCLUSION: The present findings suggest that during neoplastic transformation of cirrhotic liver, an increase in MnSOD activity may occur already during the precancerous phase, making this enzyme a probable malignancy-associated parameter.     

Low dose (1 microg) ACTH test in the evaluation of adrenal dysfunction in pre-clinical Addison's disease

OBJECTIVE: The presence of 21-hydroxylase autoantibodies (21OHAb) is a marker of adrenal autoimmunity and can be used to identify subjects with pre-clinical Addison's disease. The low-dose (1 microg) ACTH test (LDT) is more sensitive than the high-dose (250 microg) test (HDT) for the diagnosis of pituitary adrenal insufficiency, but no information is available on the use of a LDT in subjects with autoimmune adrenalitis and primary adrenal insufficiency. The aim of our study was to evaluate the clinical use of the LDT in the diagnosis of early adrenocortical dysfunction in patients with adrenal autoantibodies. DESIGN AND METHODS: Firstly, we evaluated the cortisol responses to both a LDT and a HDT in a group of 12 healthy volunteers. We then performed a LDT in 11 subjects positive for 21OHAb, but without clinical signs of Addison's disease identified by screening 920 patients with one or more organ-specific autoimmune diseases. In all cases, the LDT was followed by a sequential HDT which was used as a control test of the sensitivity and specificity of the LDT. RESULTS: In healthy subjects, the peak cortisol levels after the LDT were similar to those after the classical HDT. In 21OHAb-positive subjects, the LDT showed a pathological response in five out of 11 (45%) cases and the diagnostic concordance between the results of the LDT and those of the HDT was 100%. All the five cases with pathological LDT were also positive for adrenal cortex autoantibodies (ACA) and 4/5 had high levels of basal ACTH. One subject with pathological LDT developed clinical Addison's disease 4 months after the test had been performed. CONCLUSIONS: Our study demonstrates that the low dose ACTH test has a high diagnostic sensitivity and specificity for primary adrenal insufficiency and suggests that it can accurately identify subjects with pre-clinical adrenal dysfunction.     

Tyr-Ala-Hexarelin, a synthetic octapeptide, possesses the same endocrine activities of Hexarelin and GHRP-2 in humans

Hexarelin (HEX) and GHRP-2 are two synthetic hexapeptides, superanalogs of GHRP-6, belonging to GH secretagogue (GHS) family. GHS act via specific receptors at both the pituitary and the hypothalamic level to stimulate GH release both in animals and in humans. However, GHS also possess significant PRL- and ACTH/cortisol-releasing activity. Tyr-Ala-HEX as well as Tyr-Ala-GHRP-6 are, in turn, synthetic octapeptides generally used to perform binding studies because of their easy iodination. However, their endocrine activities have never been studied in humans. To clarify the endocrine activities of Tyr-Ala-HEX, in 7 young adult volunteers we compared the effects of the maximal effective dose of HEX (2.0 microg/kg i.v.) or GHRP-2 (2.0 microg/kg i.v.) with the same one of Tyr-Ala-HEX on GH, PRL, ACTH and cortisol levels. Basal GH, PRL, ACTH and cortisol levels in all testing sessions were similar. The administration of placebo did not modify hormonal levels. HEX and GHRP-2 administration induced the well known strong GH response (Cmax, mean+/-SE: 77.3+/-6.0 and 74.1+/-12.1 microg/l; AUC, mean+/-SE: 2596.7+/-251.1 and 2480.0+/-343.6 microg*min/l). These responses were similar to that induced by Tyr-Ala-HEX (63.7+/-18.5 microg/l; 1986.6+/-622.4 microg*min/l). Moreover, HEX, GHRP-2 and Tyr-Ala-HEX had the same significant stimulatory effect on PRL (14.9+/-2.5, 12.3+/-2.0 and 10.0+/-1.5 microg/l; 497.8+/-61.8, 480.4+/-66.9 and 415.8+/-58.5 microg*min/l), ACTH (48.0+/-10.1, 51.4+/-10.6 and 44.9+/-12.2 pg/ml; 1531.6+/-235.7, 1586.7+/-277.0 and 1338.1+/-164.5 pg*min/ml) and cortisol (179.9+/-10.0, 181.2+/-14.1 and 149.7+/-20.1 microg/l; 8465.0+/-406.6, 8689.2+/-788.1 and 6295.2+/-797.0 microg*min/l). Also the mean Tmax of the endocrine responses to HEX, GHRP-2 and Tyr-Ala-HEX were similar. In conclusion, the present results demonstrate that in humans Tyr-Ala-HEX is a GH secretagogue as potent as HEX and GHRP-2, two GHRP-6 superanalogs. Tyr-Ala-HEX also shares with HEX and GHRP-2 the same PRL- ACTH- and cortisol-releasing activity.     

Temporomandibular Disorders in Psoriasis Patients with and without Psoriatic Arthritis: An Observational Study

AIMS: Psoriasis is a chronic, remitting and relapsing inflammatory disorder, involving the skin, nails, scalp and mucous membranes, that impairs patients'' quality of life to varying degrees. Psoriatic arthritis is a chronic seronegative, inflammatory arthritis, usually preceded by psoriasis. Temporomandibular disorders is a generic term referred to clinical conditions involving the jaw muscles and temporomandibular joint. The aim of this study was to assess symptoms and signs of temporomandibular disorders in psoriasis patients with and without psoriatic arthritis.METHODS: The study group included 112 patients (56 men, 56 women; median age 49.7±12 years) with psoriasis, 25 of them were affected by psoriatic arthritis. A group of 112 subjects without psoriasis (56 men, 56 women; median age 47.7±17 years) served as controls. Signs and symptoms of temporomandibular disorders were evaluated according to the standardized Research Diagnostic Criteria for Temporomandibular Disorders. Psoriasis patients were subgrouped according to the presence/absence of psoriatic arthritis and by gender, to assess the prevalence of traditional symptoms and signs of temporomandibular disorders.RESULTS: Patients with psoriasis, and to an even greater extent those with psoriatic arthritis, were more frequently affected by symptoms and signs of temporomandibular disorders, including an internal temporomandibular joint opening derangement than healthy subjects. A statistically significant increase in symptoms of temporomandibular disorders, in opening derangement, bruxism and sounds of temporomandibular joint was found in patients with psoriatic arthritis as compared with psoriasis patients without arthritis and controls.CONCLUSIONS: psoriasis seems to play a role in temporomandibular joint disorders, causing an increase in orofacial pain and an altered chewing function.