Liver resection and cryotherapy for metastatic melanoma.

Previous studies suggest that surgical treatment of metastatic melanoma in carefully selected patients does improve survival. This paper assesses the survival of melanoma patients with hepatic metastases who underwent surgery in our unit. Fifteen (0.64%) patients had hepatic melanoma metastases. Seven patients underwent curative surgery. Surgical intervention included curative as well as palliative control of hepatic disease. Overall survival was calculated by the Kaplan-Meier method. Median survival for the 15 patients was 7 months. Median survival time in the curative surgical group and the palliative/nonsurgical group was 22 and 6 months, respectively. Patients with ocular primary, single lesions, and unilobar disease had a better outcome. Those who were selected and underwent surgery had a better overall survival compared with patients who are treated nonoperatively. Resection of hepatic melanoma metastases has a role in selected patients.

Is serum gentamicin level a good predictor of graft injury in intestinal transplantation?

INTRODUCTION: Following intestinal transplant (SBT), the early diagnosis and treatment of rejection is a major management aim. The diagnosis of rejection is based on histology of stomal biopsies. Oral gentamycin (2.5 mg/kg) was used for selective decontamination of the digestive system. Our hypothesis was that gentamycin might be absorbed in the presence of graft dysfunction. AIM: Our goal was to assess the correlation between serum gentamycin level and the health of the intestinal graft. SUBJECTS AND METHODS: Among 33 SBT performed from 1993 to 2005, serum gentamycin levels were performed once weekly or more often when there was a suspicion of rejection. All data were analyzed retrospectively. RESULTS: Adequate trough levels were achieved for only 23 patients, six of whom had histologically proven rejection and only one did not have a raised gentamycin content. Five patients with raised levels but no rejection included two with severe intestinal ischemia and three with bowel obstruction/ileus. Four of the five patients required laparotomies. CONCLUSION: We concluded that in our study raised serum gentamycin levels were a good predictor of rejection or significant injury to the graft.

Effect of Pilates exercises on postpartum maternal fatigue.

INTRODUCTION: Postpartum fatigue is a pervasive phenomenon and often affects mothers immediately after delivery. The present study aimed to assess the effect Pilates home exercises had on postpartum maternal fatigue. METHODS: A total of 80 women participated in our clinical trial study. The women were randomly divided into two groups - the intervention group (n = 40) and the control group (n = 40). In the intervention group, the women performed Pilates exercises five times a week (30 min per session) for eight consecutive weeks. The first session was conducted 72 hours after delivery. The control group did not receive any intervention. Each woman's level of fatigue was evaluated at hospital discharge (as a baseline), and at four and eight weeks after delivery, using the standard Multidimensional Fatigue Inventory (MFI-20) questionnaire and repeated measures analysis. RESULTS: During the eight weeks of follow-up, we found that the intervention group had lower mean MFI-20 scores than the control group with regard to general fatigue (7.80 ± 2.07 vs. 12.72 ± 1.79; p < 0.001), physical fatigue (7.12 ± 1.41 vs. 10.42 ± 2.02; p < 0.001), reduced activity (6.95 ± 1.35 vs. 11.27 ± 1.70; p < 0.001), reduced motivation (6.20 ± 1.01 vs. 9.80 ± 2.04; p < 0.001) and mental fatigue (6.85 ± 1.45 vs. 10.72 ± 1.98; p < 0.001). CONCLUSION: The present study's findings show that physical exercise can significantly reduce postpartum maternal fatigue in all subscales.

Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy.

To define molecular mechanisms of cardiac hypertrophy, genes whose expression was perturbed by any of four different transgenic mouse hypertrophy models [protein kinase C-epsilon activation peptide (PsiepsilonRACK), calsequestrin (CSQ), calcineurin (CN), and Galpha(q)] were compared by DNA microarray analyses using the approximately 8,800 genes present on the Incyte mouse GEM1. The total numbers of regulated genes (tens to hundreds) correlated with phenotypic severity of the model (Galpha(q) > CN > CSQ > PsiepsilonRACK), but demonstrated that no single gene was consistently upregulated. Of the three models exhibiting pathological hypertrophy, only atrial natriuretic peptide was consistently upregulated, suggesting that transcriptional alterations are highly specific to individual genetic causes of hypertrophy. However, hierarchical-tree and K-means clustering analyses revealed that subsets of the upregulated genes did exhibit coordinate regulatory patterns that were unique or overlapping across the different hypertrophy models. One striking set consisted of apoptotic genes uniquely regulated in the apoptosis-prone Galpha(q) model. Thus, rather than identifying a single common hypertrophic cardiomyopathy gene program, these data suggest that extensive groups of genes may be useful for the prediction of specific underlying genetic determinants and condition-specific therapeutic approaches.

In vitro and in vivo promoter analyses of the mouse phospholamban gene.

To determine the mechanisms responsible for regulation of the phospholamban (PLB) gene expression, a critical regulatory phosphoprotein in cardiac muscle, the mouse PLB gene was isolated and promoter analysis was performed in vitro and in vivo. The PLB gene consists of two exons separated by a single large intron. Deletion analysis revealed that a 7-kb 5' flanking fragment (including exon 1, the entire intron and part of exon 2) was necessary for maximal transcriptional activity in H9c2 and L6 cell lines. Interestingly, deletion of a 2.4-kb intronic region, which contained repetitive elements, caused a dramatic increase in CAT activity in both these cell lines. In vivo analysis indicated that the PLB fusion gene containing 7 kb of the 5'-flanking region was capable of cardiac specific gene expression in transgenic mice. Furthermore, these mice exhibited 3-fold higher levels of CAT activity in the ventricles compared with the atria, mimicking endogenous PLB mRNA expression. Our findings suggest that: (a) PLB gene expression may be regulated by the interplay of cis-acting regulatory elements located within the 5' flanking and intronic regions; and (b) the 7-kb upstream region is capable of directing cardiac-specific and compartment-specific expression in vivo.

Local control and survival in spinal cord compression from lymphoma and myeloma.

BACKGROUND: Between 1979 and 1989, 48 cases of extradural spinal cord and cauda equina compression in patients with lymphoma (24) and myeloma (24) received local radiation therapy for control of cord compression. Twenty five (52%) of the cases were treated by surgical decompression prior to irradiation. Thirty five (73%) of the cases received chemotherapy following the diagnosis of spinal cord compression. Post-treatment outcome was assessed at a minimum follow-up of 24 months to determine the significant clinical and treatment factors following irradiation. RESULTS: Seventeen (71%) of the lymphoma and 15 (63%) of the myeloma patients achieved local control, here defined as improvement to, or maintenance of ambulation with minimal or no assistance for 3 months from the start of radiotherapy. At a median follow-up of 30 (2-98) for the lymphoma and 10 (1-87) months for the myeloma patients, the results showed that survival following local radiation therapy for cord compression was independently influenced by the underlying disease type in favour of lymphoma compared to myeloma (P < 0.01). The median duration of local control and survival figures were 23 and 48 months for the lymphomas compared to 4.5 and 10 months for the myeloma cases. Survival was also independently influenced by preservation of sphincter function at initial presentation (P < 0.02) and the achievement of local control following treatment (P < 0.01). DISCUSSION: We conclude that while disease type independently impacts on outcome following treatment of spinal cord compression in lymphoma and myeloma, within both of these disease types the achievement of local control of spinal cord compression is an important management priority, for without local control survival may be adversely affected.

A new source of hepatocytes for transplantation.

INTRODUCTION: The most effective treatment for acute or chronic liver failure is orthotopic liver transplantation. Worldwide there is a shortage of organs for transplantation. This shortage has called for research into new treatments for management of patients with liver failure. One such treatment is hepatocyte transplantation. During liver resections considerable amounts of normal liver are unavoidably resected. We aim to harvest these hepatocytes and to filter the tumor cells from them to provide a source for transplantation. MATERIALS AND METHODS: After liver resection, the largest vessel at the resected liver edge was identified and cannulated. Seglen's two-stage technique of perfusing the liver with EDTA and collagenase was performed to harvest the hepatocytes. Ep-CAM Ags are consistently present on the surface of epithelial cells and in particular in colorectal cancer cells. Therefore, MOC31 antibodies (selective Abs for Ep-CAM) attached to magnetic beads were used to target the tumor cells. These tumor cells are selectively removed using a magnet. CEA staining was then used to ensure the hepatocyte collection was tumor cell free. Five million hepatocytes were rosetted with one million HT29 CRC cells to assess the immunomagnetic filtration technique. RESULTS: The hepatocyte harvesting resulted in 864,000 viable hepatocytes to be harvested per gram of liver. Histochemical staining using CEA demonstrated 75% of the HT29 cells in the hepatocyte collection were removed after one use of magnetic beads. CONCLUSION: We have demonstrated the successful initial stages of harvesting tumor-free hepatocytes from liver resected for malignancy.

Arterio-arterial prosthetic duct (AAD) as a vascular access in hemodialysis.

Vascular access (VA) is mainly a problem confronting patients undergoing hemodialysis (HD). In some cases, peripheral veins are damaged or thrombosed because of repeated vein punctures and subsequent thrombophlebitis or accompanying ailments like diabetes or other kinds of vasculitis, making the use of conventional VA methods unsuitable. In this study, we present our experience using a synthetic vascular graft as an arterio-arterial duct (AAD) in the upper arm of patients undergoing HD, in whom other procedures had failed. In this procedure, we used a synthetic vascular prosthesis of polytetrafluoroethylene(ePTFE) (Gore-Tex) or Vasculink as an AAD, subcutaneous in the media aspect of the upper arm. HD was performed for this duct. Twenty patients were selected in whom all other VA means had failed. Patient age ranged from 33-83 yrs. In two patients (12%), early graft thrombosis was the cause of failure. In the remaining 14 patients (87%), a suitable flow was established. In another two patients, after several dialysis sessions the duct stopped functioning. We believe the reason for this malfunction was too much pressure on the graft to control bleeding due to the inadequate training of the HD personnel. The remaining 12 patients (75%) used the duct for >6 months. With this method, because we used only the artery for placing the conduit, complications relating to the vein such as limb ischemia, edema and venous hypertension did not prevail. On the other hand, because the conduit is an accessory duct, should it have become thrombosed, arterial flow to the limb would be unhindered. Therefore, we believe when all other conventional VA methods have failed, AAD is a suitable technique.

Psychomotor effects of mixed organic solvents on rubber workers.

BACKGROUND: Exposure to organic solvents is common among workers. OBJECTIVE: To assess neurobehavioral effects of long-term exposure to organic solvents among rubber workers in Tehran, Iran. METHODS: Across-sectional study was conducted on 223 employees of a rubber industry. The participants completed a data collection sheet on their occupational and medical history, and demographic characteristics including age, work experience, education level; they performed 6 psychiatric tests on the neurobehavioral core test battery (NCTB) that measure simple reaction time, short-term memory (digit span, Benton), eye-hand coordination (Purdue pegboard, pursuit aiming), and perceptual speed (digit symbol). RESULTS: Workers exposed and not exposed to organic solvents had similar age and education distribution. The mean work experience of the exposed and non-exposed workers was 5.9 and 4.4 years, respectively. The exposed workers had a lower performance compared to non-exposed workers in all psychomotor tests. After controlling for the confounders by logistic regression analysis, it was found that exposure to organic solvents had a significant effect on the results of digit symbols, digit span, Benton, aiming, and simple reaction time tests. No significant effect was observed in pegboard test. CONCLUSION: Occupational exposure to organic solvent can induce subtle neurobehavioral changes among workers exposed to organic solvents; therefore, periodical evaluation of the central nervous system by objective psychomotor tests is recommended among those who are chronically exposed to organic solvents.

Safety and adequacy of percutaneous biopsies in pediatric orthotopic kidney transplantation.

BACKGROUND: The gold standard for investigating the cause of renal graft dysfunction is renal biopsy. However, as this procedure is invasive and has inherent risks, its safety must be established. OBJECTIVE: To determine the safety of percutaneous renal biopsy in pediatric orthotopic renal transplantation. METHODS: Percutaneous renal biopsies performed on pediatric orthotopic renal transplants in a single center between 1987 and 2010 were studied. Biopsy specimen adequacy and post-procedure complications were reviewed by prospectively collected data. RESULTS: A total of 54 ultrasound "real-time" guided biopsies in 25 patients were performed. Minimum specimen adequacy was achieved in 98% of biopsy specimens. No major complications were identified; 6% of patients developed minor complications-e.g., grade 3 macroscopic hematuria that did not require intervention. CONCLUSION: Percutaneous renal biopsies using "real-time" ultrasound guidance on pediatric orthotopic kidney transplants is safe.

Balancing the focus: art and music therapy for pain control and symptom management in hospice care.

Pain and symptom management are a major part of hospice care. Literature and direct experience suggest that pain can be resistant if psychological, emotional, or spiritual issues are not addressed. This article explains how art and music therapies can work in conjunction with traditional medical treatment of pain control in the hospice setting. The process of pain modulation through the use of art and music interventions is diagrammed and described. Brief clinical examples demonstrate the use of art and music therapies for pain reduction with a variety of hospice patients. Information regarding appropriate education and training necessary for art and music therapists to practice in their field is presented.

Coordinate regulation of SR Ca(2+)-ATPase and phospholamban expression in developing murine heart.

Phospholamban, the regulator of Ca(2+)-adenosinetriphosphatase (ATPase) activity in cardiac sarcoplasmic reticulum (SR), is an important determinant of basal myocardial performance. To determine whether phospholamban expression is developmentally regulated in the mouse and whether such regulation reflects alterations in Ca2+ pump activity, hearts from different stages of development were processed for molecular biological and biochemical studies. Both phospholamban and Ca(2+)-ATPase mRNAs were approximately 40% of adult (100%) levels at birth and gradually increased to approach adult levels by day 15 of development. These changes in transcript levels were indicative of changes at the protein level for both phospholamban and Ca(2+)-ATPase. Analysis of the initial rates of Ca2+ uptake demonstrated that over the course of development the upregulation of Ca(2+)-ATPase correlated with increases in the maximal rates of Ca2+ uptake and the constant apparent stoichiometric ratio of phospholamban to Ca(2+)-ATPase correlated with maintenance of a constant affinity of this enzyme for Ca2+ (0.25 +/- 0.03 microM Ca2+). Furthermore, targeted ablation of phospholamban in the mouse resulted in a much higher affinity of Ca2+ uptake for Ca2+ (0.10 +/- 0.02 microM Ca2+) than that observed in wild-type hearts, and this increased affinity was also maintained across different stages of postnatal development. These findings suggest that phospholamban is a major regulator of the affinity of Ca(2+)-ATPase for Ca2+, and coordinate regulation of the expression levels of these two SR proteins may be necessary for maintaining Ca2+ homeostasis in the developing mammalian heart.

Application of prognostic scoring systems in differentiated thyroid carcinoma.

BACKGROUND: Total thyroidectomy is widely practised in Australasia for papillary and follicular thyroid carcinoma. Data from large overseas series have demonstrated that patients with these cancers may be separated into risk groups based on clinicopathological prognostic factors. Furthermore, evidence suggests that low-risk patients may be safely treated with less than total thyroidectomy. The aim of the present paper was to determine what proportion of our patients with papillary and follicular thyroid cancer were in the low-risk group in order to select candidates for less aggressive treatment. METHODS: A prospectively documented series of 175 previously untreated patients with papillary and follicular thyroid carcinoma, treated principally by total thyroidectomy over a 10-year period, was divided into risk groups using the Mayo Clinic, Lahey Clinic and Memorial Hospital prognostic scoring systems. Complication rates for 103 patients treated by total thyroidectomy were also studied and reported. RESULTS: Women outnumbered men by 2.3:1. There were 128 papillary carcinomas (73%) and 47 follicular cancers (27%). These tumours were < 4 cm in diameter in 81% of patients, and 41% of patients were 40 years of age or younger. Low-risk patients accounted for 75, 81 and 45% of the study group, respectively, when the three prognostic scoring systems were applied to our patient population. The rates for recurrent laryngeal nerve palsy and permanent hypoparathyroidism for patients having total thyroidectomy were 1 and 1.9%, respectively. In the low-risk group there were no permanent complications. CONCLUSION: Most patients treated at Royal Prince Alfred Hospital during the past 10 years were low-risk patients who may have been eligible for less aggressive surgical treatment.

Evaluation of 250 free-flap reconstructions after resection of tumours of the head and neck.

BACKGROUND: Microvascular free-tissue transfer is now the primary method of reconstruction in many centres. The aim of this study was to evaluate the applications, complications and limitations of free-flap reconstruction in a series of patients with tumours of the head and neck. METHODS: This study reviewed prospectively accessioned computerized records in a dedicated head and neck database. Patients treated between 1987 and 1995 with a minimum of a 1-year follow-up were reviewed. There were 242 patients with a mean age of 58 years (172 men and 70 women). The most common tumour sites were oral cavity (42%), oropharynx (32%) and hypopharynx (11%). Mucosal squamous carcinoma accounted for 87% of primary cancers. RESULTS: Among the 250 free flaps, the radial forearm flap (205) and free jejunum (25) predominated. There were 21 episodes of vascular occlusion (8%), failure of 10 flaps (4%) and two patients died peri-operatively (0.8%). A second free flap was used in five of 10 cases of flap failure. The fistula rate was 4.4% among 203 patients at risk for this complication, which comprised four of 178 forearm flaps and five of 25 free jejunal grafts. Four of 16 jaw reconstructions failed. CONCLUSIONS: A 96% success rate was achieved using free-tissue transfer for head and neck reconstruction. The overall complication rate was low but jaw reconstruction and free jejunal grafts posed the greatest problems because of failure of radial bone and fistulas, respectively. The radial forearm septocutaneous flap was very reliable and remains our mainstay for oral reconstruction.

Structure and expression of the mouse cardiac calsequestrin gene.

Calsequestrin is a sarcoplasmic reticulum protein, which plays a predominant role in diastolic Ca2+-storage in the mammalian heart. The present study was designed to define the gene structure, developmental and tissue specific expression of the murine, cardiac isoform of calsequestrin. Two sets of genomic libraries (lambda phage and PAC) were screened using the mouse cardiac calsequestrin cDNA, and several overlapping clones were isolated. These clones were characterized using restriction enzyme digestion, Southern blotting and partial sequencing. The cardiac calsequestrin gene consists of 11 exons and its 5' flanking region is characterized by the presence of a TATA-like box, muscle specific promoter elements such as 7 E-boxes, 1 MEF-2, 1 MCBF and 1 Repeat (musS) motifs, as well as several muscle non-specific transcriptional elements (AP-2A, NRE1, NRE2, p53, Spel and TFI-IIA). Expression of the cardiac isoform of calsequestrin was first detected on day 11 pre-birth and approached adult levels by day 4 post-birth. Expression of cardiac calsequestrin was also detected in adult fast-twitch skeletal muscle, thyroid, testis and epididymis tissues. This genomic characterization of cardiac calsequestrin may form the basis for further evaluation of its regulatory role in Ca2+ homeostasis and contractility in the murine heart.

Phospholamban gene dosage effects in the mammalian heart.

Phospholamban ablation has been shown to result in significant increases in cardiac contractile parameters and loss of beta-adrenergic stimulation. To determine whether partial reduction in phospholamban levels is also associated with enhancement of cardiac performance and to further examine the sensitivity of the contractile system to alterations in phospholamban levels, hearts from wild-type, phospholamban-heterozygous, and phospholamban-deficient mice were studied in parallel at the subcellular, cellular, and organ levels. The phospholamban-heterozygous mice expressed reduced cardiac phospholamban mRNA and protein levels (40 +/- 5%) compared with wild type mice. The reduced phospholamban levels were associated with significant decreases in the EC50 of the sarcoplasmic reticulum Ca2+ pump for CA2+ and increases in the contractile parameters of isolated myocytes and beating hearts. The relative phospholamban levels among wild-type, phospholamban-heterozygous, and phospholamban-deficient mouse hearts correlated well with the (1) EC50 of the Ca(2+)-ATPase for Ca2+ in sarcoplasmic reticulum, (2) rates of relaxation and contraction in isolated cardiac myocytes, and (3) rates of relaxation and intact beating hearts. These findings suggest that physiological and pathological changes in the levels of phospholamban will result in parallel changes in sarcoplasmic reticulum function and cardiac contraction.

Superinhibition of sarcoplasmic reticulum function by phospholamban induces cardiac contractile failure.

To determine whether selective impairment of cardiac sarcoplasmic reticulum (SR) Ca(2+) transport may drive the progressive functional deterioration leading to heart failure, transgenic mice, overexpressing a phospholamban Val(49) --> Gly mutant (2-fold), which is a superinhibitor of SR Ca(2+)-ATPase affinity for Ca(2+), were generated, and their cardiac phenotype was examined longitudinally. At 3 months of age, the increased EC(50) level of SR Ca(2+) uptake for Ca(2+) (0.67 +/- 0.09 microm) resulted in significantly higher depression of cardiomyocyte rates of shortening (57%), relengthening (31%), and prolongation of the Ca(2+) signal decay time (165%) than overexpression (2-fold) of wild type phospholamban (68%, 64%, and 125%, respectively), compared with controls (100%). Echocardiography also revealed significantly depressed function and impaired beta-adrenergic responses in mutant hearts. The depressed contractile parameters were associated with left ventricular remodeling, recapitulation of fetal gene expression, and hypertrophy, which progressed to dilated cardiomyopathy with interstitial tissue fibrosis and death by 6 months in males. Females also had ventricular hypertrophy at 3 months but exhibited normal systolic function up to 12 months of age. These results suggest a causal relationship between defective SR Ca(2+) cycling and cardiac remodeling leading to heart failure, with a gender-dependent influence on the time course of these alterations.