The American Orthopaedic Association's Own the Bone® database: a national quality improvement project for the treatment of bone health in fragility fracture patients.

The American Orthopaedic Association initiated the Own the Bone (OTB) quality improvement program in 2009. Herein we show that the data collected through this program is similar to that collected in other large studies. Thus, the OTB registry functions as an externally valid cohort for studying fragility fracture patients. INTRODUCTION: The American Orthopedic Association initiated the Own the Bone (OTB) quality improvement program in 2009 to improve secondary prevention of fragility fractures. In this study, we present a summary of the data collected by the OTB program and compare it to data from other large fragility fracture registries with an aim to externally validate the OTB registry. METHODS: The OTB registry contained 35,038 unique cases of fragility fracture as of September, 2016. We report the demographics, presenting fracture characteristics, past fracture history, and bone mineral density (BMD) data and compare these to data from large fragility fracture studies across the world. RESULTS: Seventy-three percent of the patients in the OTB registry were female, Caucasian, and post-menopausal. In 54.4% of cases, patients had a hip fracture; spine fractures were the second most common fracture type occurring in 11.1% of patients. Thirty-four percent of the patients had a past history of fragility fracture, and the most common sites were the spine and hip. The average femoral neck T-score was - 2.06. When compared to other studies, the OTB database showed similar findings with regard to patient age, gender, race, BMI, BMD profile, prior fracture history, and family history of fragility fractures. CONCLUSION: OTB is the first and largest multi-center voluntary fragility fracture registry in the USA. The data collected through the OTB program is comparable to that collected in international studies. Thus, the OTB registry functions as an externally valid cohort for further studies assessing the clinical characteristics, interventions, and outcomes achieved in patients who present with a fragility fracture in the USA.

EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines.

BACKGROUND: Allelic loss in chromosome 3p is one of the most frequent and earliest genetic events in lung carcinogenesis. We investigated if the loss of microRNA-128b, a microRNA located on chromosome 3p and a putative regulator of epidermal growth factor receptor (EGFR), correlated with response to targeted EGFR inhibition. Loss of microRNA-128b would be equivalent to losing a tumor suppressor gene because it would allow increased expression of EGFR. PATIENTS AND METHODS: We initially showed that microRNA-128b is a regulator of EGFR in non-small-cell lung cancer (NSCLC) cell lines. We tested microRNA-128b expression levels by quantitative RT-PCR, genomic copy number by quantitative PCR, and mutations in the mature microRNA-128b by sequencing. We determined whether microRNA-128b loss of heterozygosity (LOH) in 58 NSCLC patient samples correlated with response to gefitinib and evaluated EGFR expression and mutation status. RESULTS: We determined that microRNA-128b directly regulates EGFR. MicroRNA-128b LOH was frequent in tumor samples and correlated significantly with clinical response and survival following gefitinib. EGFR expression and mutation status did not correlate with survival outcome. CONCLUSION: Identifying microRNA regulators of oncogenes could have far-reaching implications for lung cancer patients including improving patient selection for targeted agents, development of novel therapeutics, or development as early biomarkers of disease.

Evaluation of the methods for enumerating coliform bacteria from water samples using precise reference standards.

AIMS: To use BioBall cultures as a precise reference standard to evaluate methods for enumeration of Escherichia coli and other coliform bacteria in water samples. METHODS AND RESULTS: Eight methods were evaluated including membrane filtration, standard plate count (pour and spread plate methods), defined substrate technology methods (Colilert and Colisure), the most probable number method and the Petrifilm disposable plate method. Escherichia coli and Enterobacter aerogenes BioBall cultures containing 30 organisms each were used. All tests were performed using 10 replicates. The mean recovery of both bacteria varied with the different methods employed. CONCLUSIONS: The best and most consistent results were obtained with Petrifilm and the pour plate method. Other methods either yielded a low recovery or showed significantly high variability between replicates. SIGNIFICANCE AND IMPACT OF THE STUDY: The BioBall is a very suitable quality control tool for evaluating the efficiency of methods for bacterial enumeration in water samples.

The relative importance of sexual reproduction versus clonal spread in an aridland bunchgrass.

Festuca idahoensis (Idaho fescue) is a perennial caespitose grass, common in semi-arid rangelands of the Intermountain West. To determine how individuals are recruited into a population, we studied two long-term monitoring plots that were established in 1937 at the Northern Great Basin Experimental Range in southeastern Oregon. The plots measured 3.05x3.05 m, and were located approximately 30 m apart. One plot was ungrazed, the other was subject to moderate levels of cattle grazing. The number of F. idahoensis plants in both plots increased ten-fold between 1937 and 1996, but whether this was due primarily to reproduction by seed or clonal fragmentation was unknown. In 1996, we mapped and sampled 160 plants of F. idahoensis. We used dominant inter-simple sequence repeat (ISSR) markers and codominant allozyme markers in order to identify genetic individuals and measure genetic diversity. Both plots were characterized by high levels of genetic and clonal diversity. When information from ISSRs, allozymes and sample location were combined, 126 genets were recognized, each consisting of one to four samples (ramets). By measuring the diameter of clones surrounding plants that were present in 1937, we estimated that clonal spread occurred at a rate of approximately 3.7 cm per decade, and thus was of secondary importance in the maintenance and increase of F. idahoensis stands. Sexual reproduction, rather than clonal fragmentation, accounted for most of the recruitment of new plants into these plots. The grazed plot had fewer ramets, genotypes, and clones than the ungrazed plot, but the ramets were significantly larger. Levels of genetic diversity did not differ in the grazed and ungrazed plots, but there was some evidence for a small, but significant level of genetic differentiation between the two. The results also indicate that F. idahoensis has the potential to be a long-lived species with some individuals persisting in excess of 60 years. This study demonstrates how long-term monitoring can be supplemented by genetic analysis to obtain detailed information on the population dynamics of plants. In the case of this community dominant species, this provides essential information for understanding succession and developing management and restoration strategies.

Management of primary cutaneous melanoma of the head and neck: The University of Colorado experience and a review of the literature.

BACKGROUND: While elective lymph node dissection (ELND), adjuvant radiation therapy and sentinel lymph node biopsy have all been advocated in the routine management of primary cutaneous melanoma arising in the head and neck, the optimal management has not been defined. METHODS: We have reviewed our experience of 273 patients with primary melanoma of the head and neck entered into a prospective database at the University of Colorado Health Sciences Center (UCHSC) from 1978 through 1998 and contrasted this with other reports in the literature. RESULTS: A total of 168 patients were identified that received their initial management at UCHSC and had no clinical evidence of distant disease. Only nine patients (5%) underwent ELND, and no patients received adjuvant radiation therapy. The local recurrence rate and 5-year melanoma specific survival, according to Breslow thickness, were similar to centers where adjuvant radiation therapy or ELND are routinely performed. Our preliminary experience and a review of the literature suggests that the technique of sentinel lymph node biopsy is an accurate and low risk procedure that provides valuable prognostic information useful in the further management of these patients. CONCLUSIONS: There is no clear indication that either ELND or adjuvant radiation therapy impacts on the outcome of patients with primary melanoma of the head and neck. Sentinel lymph node biopsy, in appropriate cases, is becoming the standard of care.

Nevi and melanoma: lessons from Turner's syndrome.

Females with Turner's syndrome (TS) have a markedly increased number of cutaneous nevi. While this is a well-recognized risk factor for cutaneous melanoma (CM), the incidence of this tumor in TS and the implications for our understanding of nevi and melanoma have not previously been considered. Here we report a case of an anorectal melanoma in a woman with TS and a review of the literature. Overall, there appears to be a lower than expected incidence of CM. Possible explanations are discussed and in particular the possible relationship between sex hormones and melanoma development as these girls fail to undergo normal pubertal development. Further study of this syndrome may provide important insights into the genetic factors involved in normal melanocyte and nevus development, the potential influence of sex hormones on melanoma development and the relationship between the presence of nevi and the risk of developing CM.

Positive tetracycline control of expression of p15INK4B from an Epstein-Barr autonomous plasmid in a human melanoma cell line.

Homozygous deletions in the region of chromosome 9p21 are frequent in human melanoma. Mutations in the p16INK4A cyclin-dependent kinase inhibitor (CDI) gene at this locus have implicated the product of this gene as a tumor suppressor. Less attention has been focused on the homologous, closely linked p15INK4B gene. To facilitate study of the phenotypic effects of restoring expression of the latter in aggressive melanoma cells lacking INK4 expression, we inserted the cDNA encoding p15INK4B into an autonomously maintained plasmid under positive tetracycline control ('TET ON' system). Similarly regulated luciferase and herpes thymidine kinase sequences were used as controls. We demonstrate that this system enabled efficient, and reasonably uniform, induction of p15INK4B expression in a human melanoma cell line exposed to the tetracycline derivative, doxycycline. Flow cytometry showed that this induction resulted in substantial accumulation of cells in the G0/G1 phase of the cell cycle. This system will facilitate detailed analysis of the cell cycle inhibitory mechanisms of this CDI in human melanoma cells.

Phylogenetics of Pinus (Pinaceae) based on nuclear ribosomal DNA internal transcribed spacer region sequences.

A 650-bp portion of the nuclear ribosomal DNA internal transcribed spacer region was sequenced in 47 species of Pinus, representing all recognized subsections of the genus, and 2 species of Picea and Cathaya as outgroups. Parsimony analyses of these length variable sequences were conducted using a manual alignment, 13 different automated alignments, elision of the automated alignments, and exclusion of all alignment ambiguous sites. High and moderately supported clades were consistently resolved across the different analyses, while poorly supported clades were inconsistently recovered. Comparison of the topologies highlights taxa of particularly problematic placement including Pinus nelsonii and P. aristata. Within subgenus Pinus, there is moderate support for the monophyly of a narrowly circumscribed subsect. Pinus (=subsect. Sylvestres) and strong support for a clade of North and Central American hard pines. The Himalayan P. roxburghii may be sister species to these "New World hard pines," which have two well-supported subgroups, subsect. Ponderosae and a clade of the remaining five subsections. The position of subsect. Contortae conflicts with its placement in a chloroplast DNA restriction site study. Within subgenus Strobus there is consistent support for the monophyly of a broadly circumscribed subsect. Strobi (including P. krempfii and a polyphyletic subsect. Cembrae) derived from a paraphyletic grade of the remaining soft pines. Relationships among subsects. Gerardianae, Cembroides, and Balfourianae are poorly resolved. Support for the monophyly of subgenus Pinus and subgenus Strobus is not consistently obtained.

Cardiac metastases from malignant melanoma.

BACKGROUND: Cardiac metastases are uncommon, with the exception of malignant melanoma. More cases of cardiac involvement are being diagnosed in association with the rising incidence and increasing survival of patients with melanoma. Surgical intervention may be an effective palliative measure and should be considered for selected patients who present with this problem. METHODS: In this article, the authors present clinical, laboratory, and imaging data from two patients with malignant melanoma who presented with cardiac metastases. A discussion of these patients is accompanied by a review of the current literature on this topic. RESULTS: Two females with known metastatic malignant melanoma presented with nonspecific pulmonary symptoms and were found to have intracardiac metastases involving the right heart. One patient underwent successful surgical removal of a large tumor mass, which resulted in relief of symptoms and prevention of imminent death from cardiac complications. Together with the literature review, these cases demonstrate the important clinical features of cardiac metastases from melanoma and define the best means of diagnosis as well as the potential benefits of surgical intervention. CONCLUSIONS: Cardiac involvement by malignant melanoma is now diagnosed with increasing frequency. A diagnosis can be made with relative ease, but clinical suspicion must precede it. Surgery may be useful to palliate symptoms and prevent death from cardiac complications.

Effects of oncostatin M and tamoxifen on human melanoma cells.

New agents are required in the treatment of malignant melanoma, to be used alone or in combination with established therapies. Oncostatin M (OSM), a member of the gp130 family of cytokines, has previously been shown to inhibit the growth of melanoma cell lines. Tamoxifen (TAM) is widely used in the treatment of melanoma, typically in combination with chemo- and/or immunotherapy. A component of the antitumour activity of TAM is via modulation of transforming growth factor-beta (TGF beta) which has previously been shown to be synergistic with OSM in vitro. To further investigate the clinical potential of OSM, alone and in combination with TAM, set concentrations of each were added to nine fresh and two well-established melanoma cell lines. The proliferation of seven of the 11 cell lines was inhibited by OSM, while two were unresponsive at the dose range tested. Of particular interest was the finding that the growth of two of the cell lines was significantly stimulated at low doses of OSM. The combination of OSM with TAM produced widely divergent results, most frequently resembling the effects of OSM alone. No synergism between the two was evident in any of the cell lines tested. Our results indicate that a combination of OSM and TAM in clinical trials needs further evaluation before it can be recommended. Furthermore, while OSM alone may be useful in the treatment of melanoma, this may be complicated by the possibility of stimulating tumour growth in some instances.

Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial.

BACKGROUND: A phase III, randomized, double-blind, multicenter trial of active specific immunotherapy (ASI) using vaccinia melanoma oncolysate (VMO) was performed in patients with stage III (American Joint Commission on Cancer) melanoma to determine the efficacy of VMO to increase the disease-free interval (DFI) or overall survival (OS) in these patients. Two interim analyses of data from this trial were performed in May 1994 and June 1995. Although the results from these analyses showed no statistically significant improvement in DFI or OS in all patients using VMO, two subsets-men aged 44-57 years with one to five positive nodes and all patients with clinical stage I and pathologic stage II disease-showed an overall survival advantage with VMO therapy. A final analysis of data from this trial was performed in May 1996 and is reported here. The design of future melanoma vaccine trials is discussed based on information learned from this first randomized, multicenter trial of ASI therapy. STUDY DESIGN: A polyvalent VMO was prepared using melanoma cells derived from four melanoma cell lines and vaccinia vaccine virus (V). Patients were accrued from 11 United States institutions and were randomized by the Statistical Center at the University of Alabama, Birmingham. Two hundred fifty patients were randomized to treatment with either VMO (1 U containing 2 mg of total protein derived from 5 x 10(6) melanoma cells and 10(5.6) 50% tissue culture infectious dose of vaccinia virus) or control V (1 U containing 10(5.4) 50% tissue culture infectious dose of vaccinia virus) once a week for 13 weeks and then once every 2 weeks for a total of 12 months, or until recurrence. Patient data were collected by the Statistical Center and analyzed as of May 1996 for DFI and OS using Wilcoxon test and log-rank analysis. RESULTS: Two hundred seventeen patients were found to be eligible according to the inclusion criteria. Data from these patients were analyzed for DFI and OS after a median followup of 46.3 months (50.2 months for VMO and 41.3 months for V). This final analysis showed no statistically significant increase in either DFI (p = 0.61) or OS (p = 0.79) of patients treated with VMO (n = 104) compared with V (n = 113). At 2-, 3-, and 5-year intervals, 47.8%, 43.8%, and 41.7% of patients treated with VMO were disease-free, respectively, compared with 51.2%, 44.8%, and 40.4% of patients treated with V. At the same intervals, 70.0%, 60.0%, and 48.6% of patients treated with VMO survived, compared with 65.4%, 55.6%, and 48.2% of patients treated with V. In a retrospective subset analysis, male patients aged 44-57 years (n = 20) with one to five positive nodes showed 18.9%, 26.82%, and 21.3% improvement in survival at 2-, 3-, and 5-year intervals, respectively, after treatment with VMO when compared with V (n = 18) (p = 0.046). CONCLUSIONS: This study was a randomized, multicenter, placebo-controlled evaluation of an active specific immunotherapeutic agent to increase the DFI or OS of patients with stage III melanoma in a surgical adjuvant setting. In this trial, ASI with VMO when compared with V showed no difference in either DFI or OS. In a retrospective subset analysis, however, a subset of men with one to five positive nodes, between the ages of 44 and 57 years, showed a survival advantage with VMO. This result suggests that one must include a detailed subset analysis in the design of future trials of ASI for patients with American Joint Commission on Cancer stage III melanoma. An appropriate control arm also must be included in ASI trials.

Clinical predictors of mandibular fractures.

To evaluate the diagnostic accuracy of clinical signs and symptoms of mandibular fracture, a prospective study of emergency department patients presenting with mandibular trauma was undertaken. Patients with airway compromise, who were edentulous, or could not cooperate with the physical examination were excluded. Over a 1-year period, 119 patients were studied. The presence of malocclusion, trismus, facial asymmetry, or a positive result on the tongue blade test (inability to grasp and hold a tongue blade between the teeth) was significantly associated with a mandibular fracture. Malocclusion and facial asymmetry were strong predictors of fracture, and a negative result on the tongue blade test was a strong predictor of nonfracture.

Human acquired naevi are clonal.

Naevi are nearly universal in humans, yet their cellular origin remains obscure. Understanding the cellular and molecular mechanisms involved in naevus development may be important in understanding the pathogenesis of malignant melanoma. This study aimed to discover whether human acquired naevi are premalignant by examining whether they are clonal. To determine clonality naevi were removed and separated into epithelial and naevus cell fractions and the DNA prepared and digested by a methylase-sensitive restriction enzyme. The highly polymorphic X-linked human androgen receptor (HUMARA) gene was then amplified by a polymerase chain reaction and examined by gel electrophoresis and autoradiography. In polyclonal cell populations both alleles are usually seen as two distinct bands, whilst clonal populations yield a single band. Using these techniques 35 junctional naevi, 11 compound naevi and one congenital naevus from 40 women were examined. Of these, 81% (37 out of 47) of the naevi were clonal, while all of the epithelial cell controls were polyclonal. These data are novel and have great importance for understanding the development of human acquired naevi and cutaneous malignant melanoma. Because monoclonality is a marker of neoplasia, or preneoplasia, our data support the hypothesis that common acquired naevi should be considered to be premalignant lesions, similar to colonic polyps. Such lesions may have undergone the first molecular step(s) in the development of cutaneous malignant melanoma. Understanding the events involved may lead to new methods of prevention and treatment.

Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial.

OBJECTIVE: The efficacy of vaccinia melanoma oncolysate (VMO) vaccine to increase overall survival and disease-free survival of patients with surgically resected International Union Against Cancer (UICC) stage II melanoma was studied in a phase III, randomized, multi-institutional trial. SUMMARY BACKGROUND DATA: Phase I and II trials with VMO showed minimal toxicity and clinical efficacy in patients with melanoma. In a recently completed phase III VMO trial, the first interim analysis performed in April 1994 showed an increasing trend in the survival of patients treated with VMO. The second interim analysis was performed in April 1995. METHODS: Patients with surgically resected stage II (UICC) melanoma were treated with VMO (N = 104) or placebo vaccinia vaccine virus (V) (N = 113) once a week for 13 weeks and then once every 2 weeks for a total of 12 months. Patients' clinical data were collected as of May 1995 and analyzed for survival. RESULTS: In this second interim analysis, the mean follow-up time is 42.28 months. No survival difference was observed between VMO and V treatments. However, in a retrospective subset analysis, a subset of males between the ages of 44 and 57 years and having one to five positive nodes (at 2-, 3-, and 5-year intervals, 13.6%, 15.9%, and 20.3% difference insurvival in favor of VMO [N = 20] when compared to V [N = 18] [p = 0.037]) and another subset of patients with clinical stage I (at 3- and 5-year intervals, 30% and 7% difference in survival in favor of VMO [N = 20] when compared to V [N = 23], [p = 0.05]) showed significant survival advantage with VMO. CONCLUSIONS: Although VMO vaccine therapy in surgical adjuvant setting did not produce a significant survival benefit to all patients with melanoma, patients from the above two subsets had significant survival benefit.

The use of pegorgotein in the treatment of frostbite.

Free oxygen radicals have been postulated to be an important mediator of injury in frostbite. A long-acting version of the endogenous scavenger enzyme, superoxide dismutase, has been created by conjugating it with polyethylene glycol (pegorgotein, formerly known as PEG-SOD). This study evaluated the efficacy of pegorgotein on frostbite tissue survival when administered prior to rewarming. In a prospective study, two groups of nine rabbits received a standardized frostbite injury using a modified Weatherley-White model. A control group received no pharmacologic therapy; the treatment group received 10,000 IU/kg pegorgotein intravenously immediately postinjury. Healing was followed until a clear line of demarcation was apparent (10 days). The percentage of viable ear surface remaining at the end of the study was measured and used to compare the effectiveness of treatment. Student's t-test was used to determine statistical significance. The study was designed to have an 80% ability to detect a 35% difference in tissue survival. No significant difference in frostbite injury (p = 0.967) was observed between the control and treatment groups. The treatment group showed a 9.3 +/- 15.5% tissue survival, whereas the control group had 9.6 +/- 14.5% tissue survival. These results indicate no significant treatment effect for pegorgotein on tissue survival in a rabbit frostbite injury model when administered immediately postinjury.

Deletion of the p53 gene in a patient with aggressive burn scar carcinoma.

BACKGROUND: Aggressive squamous cell carcinoma (SCC) is known to occur in scars that develop after a burn injury, especially in the underdeveloped areas of the world where care is lacking. Because most SCC are associated with abnormalities in tumor suppressor genes, particularly p53, we postulated that similar mechanisms may underlie the development of burn-associated SCC. METHODS: We analyzed tissue DNA from a patient who died from an aggressive SCC in a burn scar for evidence of p53 gene abnormalities by polymerase chain reaction and immunohistochemical staining for p53 protein. RESULTS: Using polymerase chain reaction, the p53 gene could not be detected in DNA from the patient's cancer. The p53 protein was also undetectable by immunohistochemical staining. CONCLUSION: These studies indicate that there was a homozygous deletion of the p53 gene in this burn-related carcinoma. Further studies of other patients may lead to new understanding of this cancer, explain in part the usual aggressive behavior, and lead to new methods of prevention and treatment.

Expression of the tumour suppressor genes p15 and p16 in malignant melanoma.

Recent evidence has suggested the presence of a malignant melanoma (MM)-related gene on human chromosome 9p21, the location of the putative tumour suppressor genes p15 and p16. DNA from patients with familial MM, from MM cell lines and sporadic MM cases has been examined for coding region and splice junction mutations of the p16 gene, but expression studies of both genes from the same cells have not been reported. We used the polymerase chain reaction to analyse p16 and p15 expression in 23 MM cell lines. Fourteen lines (61%) did not express either gene. Six (26%) expressed p16 and eight (35%) expressed p15. Expression patterns were concordant in most cases (83%), but one line (4%) expressed only p16 and three lines (13%) expressed only p15. These data suggest that loss of function of these genes, as judged by expression, may be higher than predicted by previous DNA-based studies. The lack of complete concordance between p15 and p16 expression implies that the genes are not functionally redundant and that loss of either gene may be important in the pathogenesis of MM.

Forced air speeds rewarming in accidental hypothermia.

STUDY OBJECTIVE: To compare the rates of rewarming of forced-air and passive insulation as a treatment for accidental hypothermia. METHODS: We carried out a prospective, randomized clinical trial in two urban, university-affiliated emergency departments. Our subjects were 16 adult hypothermia victims with core temperatures less than 32 degrees C. A convective cover inflated with air at about 43 degrees C (forced-air group) or cotton blankets (control group) were applied until the patient's core temperature reached 35 degrees C. Members of both groups were given IV fluids warmed to 38 degrees C and warmed, humidified oxygen at 40 degrees C by inhalation. RESULTS: The mean +/- SD initial temperature was 28.8 degrees +/- 2.5 degrees C (range, 25.5 degrees C to 31.9 degrees C) in the patients who underwent forced-air rewarming and 29.8 degrees +/- 1.5 degrees C (range, 28.2 degrees C to 31.9 degrees C) in those given blankets. Core temperature increased about 1 degree C/hour faster in patients treated with forced-air rewarming (about 2.4 degrees C/hour) than in patients given only cotton blankets (about 1.4 degrees C/hour, P = .01). Core-temperature afterdrop was detected in neither group. CONCLUSION: Forced air accelerated the rate of rewarming without producing apparent complications in hypothermic patients.

Melanoma: epidemiology, pathogenesis, and new modes of treatment.

The treatment of patients with advanced stage (stage III and IV) melanoma remains discouraging. Except for the study using tamoxifen, combination chemotherapy (cisplatin, DTIC, BCNU), plus biological therapy (IFN-alpha and/or IL-2), which achieved a 57% response rate, virtually any combination of agents or modalities yielded response rates of only 20% to 30%, and none are effective in central nervous system metastases. Durable clinical cures in patients with advanced-stage disease are extremely rare and can probably be attributed more to host defense mechanisms than iatrogenic intervention. The future in treatment then can only look promising to immunologists, molecular biologists, and clinicians striving to elucidate the biological mechanisms isolated patients have for destroying melanoma cells and incorporating those mechanisms into therapeutics for the remainder of melanoma victims.