Isolated melanoma in the lung where there is no known primary site: metastatic disease or primary lung tumour?

Patients with no history of melanoma occasionally present with apparently metastatic melanoma in the lungs, but have no evidence of a primary melanoma. The aims of this study were to investigate the role of surgical resection in the treatment of such patients, and to examine the evidence for a diagnosis of primary pulmonary melanoma in each case. Patients with an unknown primary melanoma who presented with pulmonary disease and subsequently underwent surgical resection were identified from the Sydney Melanoma Unit database. Fifteen patients fulfilled the study criteria. Multiple lesions were present in four. Eight wedge resections and 10 lobectomies were performed. The patients' median survival was 32 months and the 5-year actuarial survival was 42%. This compares with the overall Sydney Melanoma Unit experience of lung resection for melanoma in 83 patients, where the median survival was 19 months and the 5-year survival was 22%. Resection of pulmonary disease in melanoma patients with an unknown primary lesion can result in long-term survival, and even apparent cure. It is possible that some of the patients in this series had primary melanoma of the lung, but this is impossible to prove.     

Doxorubicin and streptozotocin after failed biotherapy of neuroendocrine tumors

Background: Well-differentiated neuroendocrine tumors are treated primarily with somatostatin analogs and interferon-α. It is not clear what therapy should be applied after failed biotherapy. Our aim was to establish whether patients whose tumors rapidly progress under biotherapy may benefit from chemotherapy. Patients and Methods: In 10 patients with metastatic neuroendocrine tumors (4 foregut, 3 midgut, 1 retroperitoneal, and 2 of unknown origin) streptozotocin and doxorubicin were used as second-line or third-line therapy. Tumor response was assessed by computed tomography of the abdomen and thorax and measurement of tumor secretion products (serum chromogranin A, urinary 5-hydroxyindoleacetic acid). Results: Three patients showed a radiological response over a mean time of 30 mo (range: 7–67 mo). Median survival after initiation of chemotherapy was 50 mo in patients with a response and 8 mo in non-responders. Three patients developed major side effects (nephrotoxicity, diabetes, and encephalopathy). Conclusion: Streptozotocin and doxorubicin produce poor response rates in patients with progressive neuroendocrine tumors after failed biotherapy, but may prolong life in those patients who show a tumor response.     

Nucleotides and pronucleotides of 2,2-bis(hydroxymethyl)methylenecyclopropane analogues of purine nucleosides: synthesis and antiviral activity

Phenylmethylphosphor-L-alaninate pronucleotides 7a, 7b, 8a, and 8b, cyclic phosphates 10a and 10b, and phosphates 11a and 11b derived from 2,2-bis(hydroxymethyl)methylenecyclopropane analogues 1a, 1b, 2a, and 2b were synthesized and evaluated for their antiviral activity. An improved protocol for the synthesis of analogues 1a, 1b, 2a, and 2b is also described. Phosphate 11a was the most effective agent against human and murine cytomegalovirus (EC(50) 0.25-1.1 microM). The Z-pronucleotides 7a and 7b had EC(50) 3.6-25.2 and 3-18.4 microM, respectively. The EC(50) of cyclic phosphate 10a was 6.0-20 microM. The activity against Epstein-Barr (EBV) was assay-dependent. Pronucleotides 7a and 7b and phosphate 11a had EC(50) 2.3-3.4 microM against EBV/H-1, but 7b was cytotoxic (CC(50) 3.8 microM). Cyclic phosphate 10a was the only compound effective against EBV/Daudi (EC(50) 0.96 microM), but it was inactive in H-1 cells. Pronucleotide 7a was active against varicella zoster virus with EC(50) 6.3 and 7.3 microM, respectively, and hepatitis B virus (HBV, EC(50) 4.1 microM). Cyclic phosphate 10a was the most effective analogue against HBV (EC(50) 0.8 microM).     

Evaluation of a closed-loop muscle relaxation control system

Automatic muscle relaxation control may reduce anesthesiologists' workload freeing them for other patient care requirements. In this report we describe a muscle relaxation controller designed for routine clinical application using rocuronium and the train-of-four count. A muscle relaxation monitor (TOF Watch SX) was connected to a laptop computer running a controller algorithm program that communicates with a syringe pump to form a closed-loop muscle relaxation system. The control algorithm uses proportional-integral and lookup table components and is designed to avoid the usability restrictions of existing controllers. The controller is optimized using an objective method to avoid the uncertainties of 'hand-crafted' controller algorithms. Controller target was train-of-four count 1 or 2 and controller performance was evaluated in 15 patients. During 39 hours of closed-loop control, 96.1% of all twitches recorded were in the target range. Average rocuronium infusion rate was 0.36 mg.kg(-1).h(-1) (sd 0.18 mg.kg(-1).h(-1)). We show that the controller remains useful even in the presence of disturbances that can arise in routine clinical conditions. The muscle relaxation controller maintained the target train-of-four count values and may serve as a basis for the design of hardware and user interfaces for closed-loop muscle relaxation control in clinical conditions.     

Effects of premium discount on workers' compensation claims in agriculture in Finland

BACKGROUND: The objective of this study was to measure changes in injury claim rates after a premium discount program was implemented in the Finnish farmers' workers' compensation insurance. We focused on measures that could indicate whether the changes occurred in the true underlying injury rate, or only in claims reporting. METHODS: Monthly injury claim rates were constructed at seven disability duration levels from January 1990 to December 2003. We conducted interrupted time series analyses to measure changes in the injury claim rates after the premium discount was implemented on July 1, 1997. Three additional policy change indicators were included in the analyses. RESULTS: The overall injury claim rate decreased 10.2%. Decreases occurred at four severity levels (measured by compensated disability days): 0 days (16.3%), 1-6 days (14.1%), 7-13 days (19.5%), and 14-29 days (8.4%). No changes were observed at higher severity levels. Minor injuries had a seasonal pattern with higher rates in summer months while severe injuries did not have a seasonal pattern. CONCLUSIONS: The premium discount decreased the overall claim rate. Decreases were observed in all categories up to 29 disability days. This pattern suggests that under-reporting contributes to the decrease but may not be the only factor. The value of the premium discount is lower than the value of a lost-time claim, so there was no financial reason to under-report lost-time injuries. Under-reporting would be expected to be greatest in the 0 day category, but that was not the case. These observations suggest that in addition to under-reporting, the premium discount may also have some preventive effect.     

Additive and multiplicative covariate regression models for relative survival incorporating fractional polynomials for time-dependent effects

Relative survival is used to estimate patient survival excluding causes of death not related to the disease of interest. Rather than using cause of death information from death certificates, which is often poorly recorded, relative survival compares the observed survival to that expected in a matched group from the general population. Models for relative survival can be expressed on the hazard (mortality) rate scale as the sum of two components where the total mortality rate is the sum of the underlying baseline mortality rate and the excess mortality rate due to the disease of interest. Previous models for relative survival have assumed that covariate effects act multiplicatively and have thus provided relative effects of differences between groups using excess mortality rate ratios. In this paper we consider (i) the use of an additive covariate model, which provides estimates of the absolute difference in the excess mortality rate; and (ii) the use of fractional polynomials in relative survival models for the baseline excess mortality rate and time-dependent effects. The approaches are illustrated using data on 115 331 female breast cancer patients diagnosed between 1 January 1986 and 31 December 1990. The use of additive covariate relative survival models can be useful in situations when the excess mortality rate is zero or slightly less than zero and can provide useful information from a public health perspective. The use of fractional polynomials has advantages over the usual piecewise estimation by providing smooth estimates of the baseline excess mortality rate and time-dependent effects for both the multiplicative and additive covariate models. All models presented in this paper can be estimated within a generalized linear models framework and thus can be implemented using standard software.     

Thoracoscopic resection of intra- and extralobar pulmonary sequestration in the first 3 months of life

Background

Thoracoscopic techniques have gained increasing acceptance in pediatric surgery, but experience with newborns and small children is limited. To our knowledge, a series of minimally invasive resection of pulmonary sequestration in newborns has not yet been reported in the literature. We report on 5 patients with pulmonary sequestration thoracoscopically.

Methods

From November 2000 to November 2002, 5 patients underwent thoracoscopic resection of pulmonary sequestration. Ages ranged from 4 to 91 days. Two patients had postnatal pulmonary symptoms. Preoperative diagnosis was dubious in 4 children. There were 4 extralobar and 1 intralobar pulmonary sequestrations.

Results

Thoracoscopy was performed with 3-mm instruments and 3 to 5 ports. All procedures were completed successfully. The median duration of the operation was 95 minutes (range, 63-117 minutes), and visualization was excellent. Anomalous blood vessels were clipped and/or ligated. Four patients were extubated immediately after the operation, 1, the day after. The postoperative course was uneventful in all children. At follow-up after 14 months (mean; range, 10-19 months), all patients were free of symptoms and had normal chest x-rays.

Conclusion

Thoracoscopy is feasible for resection of intra- and extralobar pulmonary sequestrations during the first 3 months of life.     

Free fatty acids are associated with obesity, insulin resistance, and atherosclerosis in renal transplant recipients

BACKGROUND: Insulin resistance (IR) may be implicated in the pathogenesis of atherosclerosis in renal transplant recipients (RTRs) and be contributed to, in part, by free fatty acids (FFAs), produced in excess in centrally obese individuals. The aim of this study was to determine the prevalence of IR and the relationships between FFAs, central obesity, and atherosclerosis in a cohort of prevalent RTRs. METHODS: Observational data were collected on 85 RTRs (mean age 54 years; 49% male, 87% Caucasian). Fasting serum was analyzed for FFAs, glucose, and insulin; IR was calculated using the homeostasis model assessment (HOMA-IR) score. Vascular structure was assessed by carotid intima-media thickness (IMT) measurement. Linear regression analyses were performed to determine the factors associated with IR and atherosclerosis. RESULTS: IR occurred in 75% of RTRs, and FFA levels were independently associated with its occurrence (beta: -0.55, 95% CI: -1.02 to -0.07, P = 0.02). Other variables independently associated with IR were male sex, body mass index, central obesity, diabetes, systolic blood pressure and corticosteroid use. There was a significant correlation between FFA levels and IMT (r = 0.3, P=0.01). On multivariate analysis, IMT correlated with elevated FFA (beta: 0.07, 95% CI: 0.02-0.12, P = 0.007), diabetes mellitus (P = 0.05), older age (P < 0.002), and a body mass index >25 kg/m (P = 0.002). CONCLUSIONS: FFAs are associated with the development of IR and may be involved in the pathogenesis of atherosclerosis in RTRs. Additional studies are required to explore these associations further before considering whether an interventional trial aimed at lowering FFA would be a worthwhile undertaking.