Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy

PURPOSE: We characterize the consequences of androgen deprivation therapy on body composition in elderly men. MATERIALS AND METHODS: Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months. RESULTS: At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001). CONCLUSIONS: Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.     

C-reactive protein and interleukin-6 levels are related to renal function in predialytic chronic renal failure

BACKGROUND: Several studies have provided convincing evidence that in apparently healthy subjects elevated serum levels of plasma C-reactive protein (CRP) are associated with an increased risk of experiencing myocardial infarction and sudden cardiac death. It has been claimed that, in dialytic patients, the hepatic synthesis of this 'acute phase response' plasma protein is primarily induced by the macrophage-derived interleukin 6 (IL-6). Little information is available, however, regarding CRP and IL-6 plasma levels in pre-dialytic renal failure. METHODS: Plasma CRP by a modification of the laser nephelometry technique, IL-6 and serum albumin were determined in 103 chronic pre-dialytic patients (mean age 50 +/- 6.3 years; creatinine clearance (Cr.cl.) 36.3 +/- 23.1 ml/min). RESULTS: CRP was >5 mg/l (normal upper range) in 42% of the global population. CRP and IL-6 were significantly related (r = 0.35, p < 0.0004). CRP and IL-6 were related to renal function (CRP vs. Cr.cl., r = -0.56, p < 0.0001; IL-6 vs. Cr.cl., r = -0.55, p < 0.0001, Spearman correlation coefficient). When patients were divided in tertiles according to renal function, CRP median value resulted 7.9 mg/l (interquartile interval: 5-12) in the first tertile (Cr.cl. <18.5 ml/min), 4.0 mg/l (3-6) in the second tertile (Cr.cl. 18.5-45 ml/min) and 3.2 mg/l (2.7-4.0) in the last tertile (Cr.cl. >45 ml/min) (p < 0.0001). A negative correlation between CRP and S-albumin was also found (r = -0.52, p < 0.0001, Spearman correlation coefficient). CONCLUSIONS: IL-6 and CRP were increased and were inversely related to creatinine clearance in our population of 103 chronic predialytic patients. The possibility of a decreased renal clearance of CRP and/or cytokines as a cause of an activated acute-phase response is discussed. A negative correlation between CRP and S-albumin was found confirming the link between chronic inflammation and malnutrition in chronic renal patients.     

Glomerular cell replication and cell loss through apoptosis in experimental diabetes mellitus

AIM: To evaluate changes in the glomerular cell balance between replication and apoptosis in experimental diabetes mellitus (DM) in relation to morphometric data. METHODS: Adult Sprague-Dowley rats with streptozotocin-induced DM and controls of the same age and strain were sacrificed 4 and 8 weeks and 6 months after disease onset. Cell replication was demonstrated with MIB-5, and apoptosis with the terminal uridine nick end labeling technique. Glomerular size and glomerular cell population were estimated morphologically. RESULTS: Diabetic and control rats showed irrelevant MIB-5 positivity at all time points. Glomerular apoptosis was minimal in rats with 4 and 8 weeks of DM and in controls. Rats with 6 months of DM showed significantly higher glomerular apoptosis values than controls (2.49 +/- 0.25 vs. 0.65 +/- 0.16%; p < 0.001). The mean cell count per glomerular profile was significantly lower in these diabetic rats (64.02 +/- 1.93 vs. 78.27 +/- 0.99; p < 0.001), a change that correlated with that in apoptosis. The glomerular cell density was further decreased in diabetic rats because of the diabetic increase in mean glomerular volume (1.598 vs. 0.927 10(6) microm). CONCLUSIONS: Apoptosis is associated with loss of glomerular cells in rats with long-term, streptozotocin-induced DM and - to a considerably lower degree - in controls of the same age and strain. These changes could be relevant to glomerulosclerosis associated with long-term, streptozotocin-induced DM.     

alpha-Melanocyte-stimulating hormone protects the allograft in experimental heart transplantation

BACKGROUND: With the increasing need for organ transplantation and the use of "marginal" organs, novel approaches are sought to increase the efficiency and survival of transplanted tissue. We tested the idea that treatment with the anti-inflammatory peptide, alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous hormone that does not cause marked immunosuppression but does reduce reperfusion injury, may protect allografts and prolong their survival. METHODS: Donor cardiac grafts (Brown Norway) were transplanted heterotopically into the abdomen of recipient (Lewis) rats. Treatments consisted of intraperitoneal injections of Nle DPhe -alpha-MSH (NDP-alpha-MSH) or saline from the time of transplantation until sacrifice or spontaneous rejection. Allografts were removed on day 1, day 4, or at the time of rejection and examined for histopathology and expression of molecules prominent in reperfusion injury, transplant rejection, and apoptosis. RESULTS: NDP-alpha-MSH treatment caused a significant increase in allograft survival and a marked decrease in leukocyte infiltration. Expression of molecules such as endothelin 1, chemokines, and adhesion molecules, which are involved in allograft rejection, was significantly inhibited in NDP-alpha-MSH-treated rats. CONCLUSIONS: The results indicate that protection of the allograft from early injury with alpha-MSH can postpone rejection. Addition of this early protection with the peptide to usual treatment with immunosuppressive agents may, therefore, improve success of organ transplants.     

Hypospadias: incidence and effects on psychosexual development as evaluated with the Minnesota Multiphasic Personality Inventory test in a sample of 11,649 young Italian men

PURPOSE: We evaluated the incidence of hypospadias and its effects on psychosexual development in a sample of 11,649 young Italian males. Over the last 30 years only about 30 major publications have addressed these issues and the results of many studies have been contrasting. Some defects in methodology, such as low response rates, heterogeneity of age ranges and the choice of controls, have been the main limitations. Our study was designed to take these problems into account. MATERIALS AND METHODS: Forty-two hypospadic subjects and a random sample of 500 nonaffected males selected from the large sample of 11,649 young men (>90% of the 18-year-old males living in the Italian region of Tuscany) were screened by the Minnesota Multiphasic Personality Inventory (MMPI) test, psychological interview and clinical evaluation. RESULTS: The incidence of hypospadias in this representative group of Italian men is 3.6/1,000. No difference was noted in the percentage with altered MMPI compared with the control group. The age at surgical corrections and the number of operations are not related to an abnormal global psychological adjustment. Severity of disease influences a more negative genital appraisal and the number of operations is correlated only with more difficulty in initiating contact with the opposite sex. CONCLUSIONS: Surgery for hypospadias has to be strongly pursued in as many cases as possible. In addition, we strongly recommend following up all hypospadics, independently of the severity of their genital malformations, through adolescence to early adulthood, to ensure early detection of subjects with impaired psychological profiles.     

Aortic valve disease with severe ventricular dysfunction: stentless valve for better recovery

BACKGROUND: Stentless bioprostheses and homografts show better hemodynamic profiles compared with conventional stented bioprostheses and mechanical valves. Few data are available on stentless aortic valve implantation for patients with severe left ventricular dysfunction. The aim of this retrospective study was to assess the potential benefits of stentless aortic valve implantation for patients undergoing isolated aortic valve replacement with left ventricular ejection fraction < or = 35%. METHODS: From November 1988 through March 2000, 53 patients (45 men and 8 women, aged 64.2 +/- 15.2 years) with a LVEF < or = 35% (mean EF, 28.7 +/- 5.4%) underwent isolated, primary aortic valve replacement for chronic aortic valve disease. Twenty patients received stentless aortic valves and 33 patients received conventional stented bioprostheses and mechanical valves. Predictive factors for LVEF recovery at echocardiographic follow-up (36.2 +/- 32.1 months) were analyzed by simple and multiple regression analysis. RESULTS: There were no significant differences between groups in early and late mortality. Stentless aortic valve implantation required a longer aortic cross-clamp time (p = 0.037). The stentless aortic valve group showed a better LVEF recovery (p = 0.016). Stentless aortic valves had a larger indexed effective orifice area compared with conventional stented bioprostheses and mechanical valves (p < 0.0001). A smaller indexed effective orifice area (p = 0.0008), chronic obstructive pulmonary disease (p = 0.015), and implantation of a conventional stented bioprosthesis or mechanical valve (p = 0.016) were related to reduced LVEF recovery by univariate analysis. A larger indexed effective orifice area (p = 0.024) was an independent predictive factor for a better LVEF recovery by multivariate analysis. CONCLUSIONS: Stentless aortic valve implantation for patients with severe left ventricular dysfunction, even if technically more demanding, is a safe procedure that warrants a larger indexed effective orifice area leading to an enhanced LVEF recovery.     

Surgical technique of intraoperative radiotherapy in conservative treatment of limited-stage breast cancer

At the European Institute of Oncology, Milan, Italy, we have focused our interest on the use of intraoperative radiation therapy (IORT) in limited-stage breast cancer that is conservatively treated. A new technique to perform IORT was applied in 185 patients from July 1, 1999, to October 31, 2001. As the surgeon plays a crucial role in this procedure in selecting the patients, performing the breast resection, preparing the gland as a target to receive IORT, delivering the radiation directly to the mammary gland via a dedicated applicator, and, finally, reconstructing the breast, each phase of the surgical technique has been completely standardized and is described herein. The use of IORT in the conservative treatment of breast cancer could allow the course of external fractionated-dose radiation therapy to be completely avoided; IORT dramatically reduces radiation exposure of the skin, lung, and subcutaneous tissues and avoids the irradiation of the contralateral breast, which contributes to a very low incidence of radiation-induced sequelae. In our experience, IORT for limited-stage breast carcinoma is easy to perform and only briefly prolongs the duration of the surgical procedure.     

Non-recurrent inferior laryngeal nerve

Surgical damage to the inferior laryngeal nerve is one of the most feared complications of thyroid surgery. Prevention of surgical injuries requires systematic, early exposure of the inferior laryngeal nerve. A detailed knowledge of anatomical variations is necessary. Non-recurrent inferior laryngeal nerve is a rare anomaly on the right side and is exceptional on the left. Whereas the typical course of the inferior laryngeal nerve is due to the embryological development of the aortic arch and supra-aortic vessels, non-recurrence is associated with a vascular anomaly such as a right retro-oesophageal subclavian artery. The nervous anomaly on the left side is possible only with the occurrence of cardiac dextroposition (situs viscerum inversus) and a left retro-oesophageal subclavian artery. The situation is more dangerous when a non-recurrent branch of the inferior laryngeal nerve is associated with a recurrent branch. This anomaly does not appear to be associated with a vascular anomaly in all cases. The authors describe three cases of right non-recurrent inferior laryngeal nerve observed and one recent case of combined non-recurrent and recurrent nerve, highlighting the anatomical and surgical features of this anomaly.     

Resting energy expenditure in diabetic and nondiabetic patients with liver cirrhosis: relation with insulin sensitivity and effect of liver transplantation and immunosuppressive therapy

BACKGROUND: Hypermetabolism, insulin resistance, and diabetes are common in patients with liver cirrhosis. OBJECTIVE: We assessed whether diabetes and insulin resistance influence postabsorptive energy homeostasis in these patients and whether liver transplantation (LTx) and immunosuppressive drugs affect these relations. DESIGN: Twenty-six patients with liver cirrhosis (16 with and 10 without diabetes) were studied with an insulin clamp and indirect calorimetry. Eleven of these subjects were studied 9 mo after LTx to longitudinally assess its effects. To cross-sectionally explore a longer follow-up period, we studied 65 patients 6, 14, and 32 mo after LTx. Seven patients with chronic uveitis (receiving immunosuppressive therapy) and 20 healthy subjects served as control subjects. RESULTS: Diabetic and nondiabetic patients with cirrhosis had insulin resistance (S(I(clamp)); P < 0.03) and higher measured resting energy expenditure (REE) as a percentage of predicted REE than did healthy subjects (107.6 +/- 1.8% compared with 97.4 +/- 2.3%; P < 0.03), and these 2 alterations were associated (R(2) = 0.119, P = 0.0002). The longitudinal study showed an improvement in the 2 variables after LTx, but full restoration was not achieved. The cross-sectional analysis confirmed this observation in patients studied 6 mo (n = 28) after LTx. In patients studied 14 (n = 21) and 32 mo (n = 16) after LTx, S(I(clamp)) and measured REE as a percentage of predicted REE were not significantly different from those in control subjects. CONCLUSIONS: In patients with liver cirrhosis, higher-than-normal postabsorptive REE was associated with insulin resistance regardless of diabetes. This abnormality persisted in patients studied 6-9 mo after LTx but improved simultaneously with the improvement in insulin sensitivity thereafter.     

Investigation into the role of apolipoprotein B gene 8344C/T variant on plasma cholesterol levels by allele-specific PCR amplification

The 8344C/T polymorphism of the apoB gene was genotyped by an original modification of PCR allele-specific amplification consisting in a single amplification reaction double-primed by two opposite allele-specific oligonucleotides nested in a larger amplified fragment. This method was used to genotype 200 randomly selected healthy individuals (113 males, 87 females). The frequency of the rare allele in this random Italian population was 0.240, i.e. not far from the 0.282 frequency observed in hypocholesterolemic Norwegians and suggestive of a moderating effect on LDL levels of our population. However, we did not find any significant cholesterol-lowering effect of this polymorphism either by comparing the frequency of mutant alleles in the population stratified for its plasma lipoprotein levels or by studying the association between ApoB genotype and the different lipoproteins. In conclusion this ApoB polymorphism appeared to have a secondary role in LDL- and HDL-cholesterol variations of our population.