Age as a prognostic factor in the malignant melanoma population

Background: The incidence of malignant melanoma is increasing faster than any other cancer, and the state of Florida has one of the highest incidence of melanoma in the United States. This increased incidence is thought to be due to the intense sunlight exposure and ultraviolet radiation exposure in the elderly population. With the increased emphasis on issues of aging, it is appropriate to study the role of age as a prognostic factor for malignant melanoma in the Florida population. Methods: A retrospective, computer-aided search identified 442 consecutively registered patients with malignant melanoma at the Cutaneous Oncology Program. All patients had stage 1 or 2 disease (cutaneous disease only) at diagnosis. Prognostic variables analyzed included the most powerful factors for stage 1 and 2 melanoma, tumor thickness, ulceration, and Clark level of invasion. Other prognostic variables included in the analysis were the clinical variables of sex and primary site (axial vs. extremity). The population was divided into patients 65 and >65 years of age. Results: Significant disease-free survival differences were encountered in the older population, with only 55% of the elderly population being disease free at 5 years compared with 65% for the younger population (p=0.0073). However, a greater percentage of patients with melanoma who were >65 years of age had ulcerated lesions (17.5% vs. 12.9%) and a greater percentage of thick lesions at diagnosis (67.2% vs. 62.7%). Both of these prognostic factors would bias the older population with a poorer survival. A stepwise regression analysis of the entire population was performed, treating age as a continuous variable. Surprisingly, increasing age along with tumor thickness were the only significant predictors for disease-free survival. After inclusion of these two prognostic variables, none of the other prognostic factors, including Clark level, ulceration, sex, and primary site, added to the prognostic model. Conclusions: From this analysis, it is apparent that geriatric patients with melanoma have a worse prognosis than a younger control population, even after the correction for the more commonly cited prognostic factors. This information should be used in mathematical modeling to identify high-risk populations who are candidates for perhaps more aggressive primary or adjuvant therapies.Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Microdissection and microcloning of chromosomal alterations in human breast cancer

Summary The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.Presented by Jeffrey M. Trent at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.     

Reexamination of hip biomechanics during unilateral stance

The Koch model, as initially proposed, is an incomplete representation of hip biomechanics during the unilateral support phase of midstance. The model proposed by this study includes the iliotibial band as a tension band lateral to the femoral shaft. During the unilateral support phase of gait, the iliotibial band creates compression loading laterally and medially throughout the femur distal to the greater trochanteric apophysis. Bench testing of cadaveric femora with and without protheses demonstrated the necessity of a total hip replacement femoral component to engage the proximal lateral femoral cortex as an additional area of support against subsidence. This model, byproviding a more complete and accurate depiction of hip biomechanics, creates a more valid basis for analysis of hip function.     

Incipient left ventricular rupture complicating anomalous left coronary artery

A 4-month-old girl presented with 2 weeks of symptoms and physical signs of heart failure. Echocardiography demonstrated marked left ventricular dilation, thinning of the myocardium with anterolateral akinesis, mitral regurgitation, a moderate pericardial collection, and an anomalous left coronary artery from the pulmonary artery. At operation there was a tense hemopericardium and a site of imminent rupture through a transmural anterior infarction. The anomalous artery was reimplanted in the ascending aorta, and an extensive infarct resection and ventricular repair performed. Support with a left ventricular assist device was required for 3 days, but the infant subsequently made a satisfactory recovery. Left ventricular rupture is a very rare complication of this lesion, but should be considered if there is evidence of a pericardial collection.     

Comparison of adenosine and remifentanil infusions as adjuvants to desflurane anesthesia

BACKGROUND: Because adenosine has been alleged to produce both anesthetic and analgesic sparing effects, a randomized, double-blinded study was designed to compare the perioperative effects of adenosine and remifentanil when administered as intravenous adjuvants during general anesthesia for major gynecologic procedures. METHODS: Thirty-two women were assigned randomly to one of two drug treatment groups. After premedication with 0.04 mg/kg intravenous midazolam, anesthesia was induced with 2 micro/kg intravenous fentanyl, 1.5 mg/kg intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with desflurane, 2%, and nitrous oxide, 65%, in oxygen. Before skin incision, an infusion of either remifentanil (0.02 microg x kg(-1) x min(-1)) or adenosine (25 microg x kg(-1) x min(-1)) was started and subsequently titrated to maintain systolic blood pressure, heart rate, or both within 10-15% of the preincision values. RESULTS: Adenosine and remifentanil infusions were effective anesthetic adjuvants during lower abdominal surgery. Use of adenosine (mean +/- SEM, 166+/-17 microg x kg(-1) x min(-1)) was associated with a significantly greater decrease in systolic blood pressure and higher heart rate values compared with remifentanil (mean +/- SEM, 0.2+/-0.03 microg kg(-1) x min(-1)). Total postoperative opioid analgesic use was 45% and 27% lower in the adenosine group at 0-2 h and 2-24 h after surgery, respectively. CONCLUSIONS: Adjunctive use of a variable-rate infusion of adenosine during desflurane-nitrous oxide anesthesia was associated with acceptable hemodynamic stability during the intraoperative period. Compared with remifentanil, intraoperative use of adenosine was associated with a decreased requirement for opioid analgesics during the first 24 h after operation.     

Bench surgery with autotransplantation for bilateral synchronous Wilms' tumor: a report of three cases

The surgical management of bilateral synchronous nephroblastoma remains controversial. The authors describe three cases treated using ex vivo tumor dissection followed by autotransplantation in an attempt to preserve functioning renal tissue. Two children are alive and tumor free with adequate renal function at 30 months and 3 years, respectively. One died from tumor recurrence with metastases 9 months after surgery. This technique is an acceptable alternative to bilateral nephrectomy followed by transplantation.     

The epidural blood patch. Resolving the controversies

PURPOSE: To review the literature regarding epidural blood patch (EBP) to generate conclusions relating to the controversial issues surrounding its application. SOURCE: A Medline search was made for relevant publications using keywords epidural blood patch, prophylactic epidural blood patch, dural puncture, and postdural puncture headache. Bibliographies of retrieved articles were hand-searched for relevant articles. Case series and comparative trials were emphasized in the analyses. These were culled and those deemed relevant were reviewed. PRINCIPAL FINDINGS: The majority of the literature consists of observational reports: there are few comparative studies. Headache most likely results from cerebrospinal fluid (CSF) loss leading to intracranial content shift and traction on pain sensitive structures; cerebrovascular alterations may be implicated. An EBP with 10-15 ml blood is indicated and effective therapy for severe headache after dural puncture. There is conflicting evidence regarding larger volume blood injections or delaying EBP for 24 hr or more after the diagnosis of postdural puncture headache (PDPH). Efficacy of EBP is related to a "patch effect" as well as transmission of increased epidural space pressure to the CSF space. Previous estimates of EBP efficacy were overgenerous; persistent symptomatic relief can be expected in 61-75% of patients with initial EBP. Patching with non-blood solutions, although initially effective, is associated with a high incidence of headache recurrence. Prophylactic injection of saline or blood decreases the incidence of severe headache after dural puncture. CONCLUSION: Blood-patching is an effective treatment of PDPH but further research is required regarding its mechanisms and prophylaxis.     

Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded. The response to a conditioning stimulus was compared to the response to a test stimulus delivered 500 ms later: the ratio of the test response to the conditioning response provided a measure of inhibitory gating. Auditory-evoked potentials were recorded at all sites. Overall, brainstem reticular nucleus neurons showed the greatest gating of local auditory-evoked potentials, while the auditory cortex showed the least. However, except for the auditory cortex, both gating and non-gating of the evoked response were recorded at various times in all brain regions. Gating of the hippocampal response was significantly correlated with gating in the medial septal nucleus and brainstem reticular nucleus, but not the auditory cortex. Single-unit neuron firing in response to the clicks was most pronounced in the brainstem reticular nucleus and the medial septal nucleus, while relatively few neurons responded in the CA3 region of the hippocampus and the auditory cortex. Taken together, these data support the hypothesis that inhibitory gating of the auditory-evoked response originates in the non-lemniscal pathway and not in cortical areas of the rat brain.     

Measuring developmental and functional status in children with disabilities

This study compared performance on the Functional Independence Measure for Children (WeeFIM), the Battelle Developmental Inventory Screening Test (BDIST), and the Vineland Adaptive Behavior Scales (VABS) in children with developmental disabilities. The three instruments were administered to 205 children with identified disabilities. All 205 children were tested using the WeeFIM instrument. The BDIST was administered to 101 children and the VABS to the remaining 104 children. Administration was counterbalanced and randomized across all three instruments. A proportional sampling plan was used to select the 205 children, who ranged in age from 11 to 87 months. A variety of medical diagnoses and levels of severity of motor, cognitive, and communication impairments were systematically included in the sample. Correlations (r) among subscales for all three instruments ranged from 0.42 to 0.92. Correlations for total scores ranged from 0.72 to 0.94. Analyses of potential moderator variables found no significant relation between age and severity of disability (r=0.05) or between socioeconomic status (SES) and severity of disability (r=0.21). Correlations with age were strongest for those subscale scores involving gross and fine motor skills. Correlations with SES and subscale scores ranged from 0.03 to 0.18. The three instruments provide important information regarding childhood performance in motor, self-care, communicative, cognitive, and social skills. The WeeFIM instrument requires less administration time and provides information directly relevant to evaluating functional outcomes for children with disabilities and their families.