Leucine metabolism in patients with Cushing's syndrome before and after successful treatment

OBJECTIVE Results from studies on the effect of glucocor-ticosteroids on protein turnover in both rat and man have been conflicting. The aim of this study was to investigate the primary cause of muscle wasting in patients with Cushing's syndrome. DESIGN Studies of whole body 1-¹⁴C-leucine turnover in patients with Cushing's syndrome before and after successful treatment, and in control subjects. PATIENTS Eleven patients with Cushing's syndrome before and after (n= 5) treatment and 11 control subjects. MEASUREMENTS Whole body 1-¹⁴C-leucine turnover to determine leucine metabolic clearance rate, leucine production rate, leucine oxidation rate and leucine incorporation into protein. RESULTS Plasma leucine concentration (mean ± SEM 100 ± 6 μ mol/l), leucine metabolic clearance rate (9.97 ± 0.11 μ mol/min/kg), leucine turnover (0.98 ± 0.11 μ mol/min/kg) and leucine incorporation into protein (0.71 ± 0.09 μ mol/min/kg) were all significantly reduced in patients with Cushing's syndrome compared with control subjects (122 ± 6 μ mol/l, P < 0.05; 13.61 ± 1.27 μ mol/min/kg, P < 0.05; 1.65 ± 0.12 μ mol/min/kg, P < 0.05; 1.46 ± 0.10 μ mol/min/kg, P < 0.001, respectively). Leucine oxidation rate was similar in the patients with Cushing's syndrome and control subjects. When leucine metabolism was expressed in terms of lean body mass (LBM) in five patients with Cushing's syndrome and 11 control subjects, leucine MCR, leucine turnover and leucine oxidation were not significantly different in the two groups. However, leucine incorporation into protein was significantly reduced (P< 0.001) in the patients with Cushing's syndrome (1.07 ± 0.20 μ mol/min kg LBM) compared with control subjects (1.95 ± 0.11 μ mol/min/kg LBM). CONCLUSION We conclude from these studies that the muscle wasting associated with Cushing's syndrome is primarily due to a reduction in protein synthesis.     

The Significance and Clinical Factors Associated With a Subcentimeter Resection of Colorectal Liver Metastases

Background Prognosis after resection of colorectal liver metastases is influenced by various factors. A positive margin of resection (MOR) has been shown to adversely influence prognosis. Although a 1-cm MOR has been accepted as adequate, the data to support this guideline are sparse.Methods Our hepatobiliary database was queried for patients who underwent liver resection for colorectal metastases between January 1992 and July 2003. All patients were divided into three groups: MOR <.5 cm (group A), .5 to 1 cm (group B), and >1 cm (group C). Operative reports from each hepatic resection were analyzed to determine local factors that may have contributed to a subcentimeter MOR.Results A total of 112 patients (67 men and 45 women) underwent liver resection for colorectal metastases with negative margins. Fifty-three patients were in group A, 26 patients were in group B, and 33 patients were in group C. Group C demonstrated decreased local recurrence (LR; P = .003), distant recurrence (DR; P = .008), and disease-free recurrence (P = .002). A significant difference in the overall time to LR (P = .003), time to DR (P = .003), and disease-free survival (P = .002) was also demonstrated. Factors associated with a subcentimeter MOR included nonanatomical resection (P = .043), proximity to a major vessel (P = .003), and central location (P = .002).Conclusions A <1-cm resection for colorectal liver metastases is associated with increased LR and DR, as well as decreased disease-free survival. When a nonanatomical resection is performed, a MOR >1 cm should be attempted, because an adequate margin is often underestimated. Considerations should be made for extended resections when tumors are centrally located or near major vessels.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

Impact of the introduction of fee for service payments on types of minor surgical procedures undertaken by general practitioners: observational study

The 1990 general practitioners (GPs) contract introduced item of service payment for minor surgery, payable for six categories of procedure. Early review showed no substitution of cheaper procedures for more expensive treatments. Detailed payment data from six Health Authorities for the period 1993-2000 show an 11 per cent increase in claims, largely accounted for by the rise in cautery, incorporating cryotherapy. Cryotherapy is no more effective at treating warts than cheap commercially available products, but is quite profitable for GPs. This is yet another example of item of service payment distorting treatment priorities. The new GP contract, and the initiative to develop GPs with special interests in dermatology and minor surgery, will allow primary care trusts to develop minor surgery undertaken by appropriately skilled and experienced GPs, and which reflects the needs of the population.     

Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss

OBJECTIVE: To evaluate sperm chromosome aneuploidy and semen quality in 24 partners of women with unexplained recurrent pregnancy loss and to analyze the data in relation to sperm apoptosis data. METHODS: Semen quality parameters and sperm chromosome aneuploidy for chromosomes X, Y, 13, 18, and 21 were evaluated in the recurrent pregnancy loss patients, fertile controls, and a control group of men from the general population. RESULTS: The mean aneuploidy rate in the recurrent pregnancy loss group was 2.77 +/- 0.22, significantly higher (P <.005) than in either the general population (1.48 +/- 0.12) or in fertile (1.19 +/- 0.11) control groups. In the recurrent pregnancy loss patients, the percentage of aneuploid sperm was correlated to the percentage of apoptotic sperm (r =.62, P <.001). Normal morphology was diminished in the patient group, compared with the general population group (P <.01) and the donor group (P <.001). CONCLUSIONS: These data indicate that some recurrent pregnancy loss patients have a significant increase of sperm chromosome aneuploidy, apoptosis, and abnormal sperm morphology. This study demonstrates a new possible cause of recurrent pregnancy loss.     

Increased biliary fistulas after liver resection with the harmonic scalpel

The Harmonic Scalpel (HS) is frequently used for hepatic resection. Yet, no current study addresses its utility compared to conventional methods. We reviewed our experience with this device to determine if it decreased perioperative complications when compared to the traditional clamp crushing technique. One hundred forty-nine anatomic hepatic resections were performed at our institution from September 1992 to February 2002. Patients were divided into two groups based on the technique of resection: HS [53% (n = 79)] versus clamp crushing [47% (n = 70)]. Use of the HS was associated with a shorter mean operative time (357 +/- 15.0 vs. 404 +/- 19.1 min; p = 0.05) and a trend toward decreased blood loss (1211 +/- 125.5 vs. 1411 +/- 180.7 mL; P = NS) and transfusion requirements (2.6 +/- 0.5 vs. 1.7 +/- 0.3 units; P = 0.10). However, use of the HS was associated with a significant increase in biliary fistulas [24% (n = 19) vs. 7% (n = 5); P = 0.01]. Use of the Harmonic Scalpel was associated with decreased operative time and a trend toward decreased blood loss and transfusion requirements. Its use was also associated with a significant increase in the incidence of postoperative bile leaks, and, therefore, surgeons must be vigilant during liver parenchymal transection when using this device.