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Biomedical subjects

K E Wells

Publications and source records attributed to K E Wells.

50 records · Page 3Linked to original sources

Etiology and prognosis of local recurrence in malignant melanoma of the skin.

All patients with stage I and stage II malignant melanoma of the skin were analyzed for stage; time of local, regional, or systemic recurrence, or two or more of these events; presence or absence of ulceration of the primary tumor; thickness of the primary tumor; level of invasion according to Clark; and margins of resection. Local recurrence had a significant negative impact on the long-term survival of patients. Our data revealed that local recurrence had the same poor prognostic effect as regional or systemic recurrence, or both. Factors significant in predicting local recurrence included the primary tumor characteristics of ulceration of the primary tumor and thickness of the primary tumor. Margins of resection and level of invasion were not noted significant in predicting local recurrence.

Florida↗

The concept of lymph node dissections in patients with malignant melanoma.

Therapeutic lymph node dissections in patients with grossly palpable metastatic melanoma are performed to control regional disease, to salvage a small percentage of patients, and to obtain staging information. Patients with malignant melanoma may undergo elective lymph node dissections, when the basin is clinically negative, for three reasons. There is some evidence based on large retrospective studies that survival is increased in patients with intermediate thickness melanoma if elective lymph node dissections are performed as part of the initial treatment of the primary melanoma. Second, in a small percentage of patients, a previous elective lymph node dissection may have helped control disease in the regional lymphatics, so that more extensive procedures, including amputations, are not necessary. Another important reason is to obtain staging and prognostic information for the patient because most adjuvant protocols are based on the presence or absence of disease in the regional basin. During a 3-year period, 115 patients have undergone a regional nodal dissection at the Moffitt Cancer Center and James Haley VA Hospital as part of their surgical treatment. With a follow-up of 3 years, patients with 1 node positive do significantly better than those with more than 1 node positive in their dissection (p = 0.06). The percentage of nodes positive is also important. Those patients who have less than 10% of their nodes involved with metastatic melanoma have a better survival than those patients whose percentage is greater than 10% (p = 0.07).

Adolescent↗

Isolated limb perfusion for recurrent melanoma of the extremity.

Recent reports in the literature suggest that hyperthermic isolated limb perfusion (HILP) may be effective in preventing local recurrence in patients with deeply invasive melanoma or in patients with recurrent disease confined to the extremity. It has been used in the past as an adjuvant treatment after resection of the primary melanoma or recurrence, or as a therapeutic measure if all the disease on the extremity cannot be resected. A prospective, nonrandomized trial of 16 patients with melanoma with recurrent disease confined to the extremity underwent HILP. The protocol involved the wide local excision of all recurrent disease when possible, elective or therapeutic node dissection when indicated, and HILP using cisplatin. In 11 patients in whom all recurrent disease could be resected and the HILP was considered prophylactic, only 1 patient's disease has recurred in the perfusion circuit. Before the perfusion, the 11 patients had a total of 19 local or intransit recurrences. Of the 5 patients in whom all recurrent disease could not be resected, disease persisted in 4 patients. When compared with a concurrent control population of patients with extremity melanoma who had a local recurrence and were not perfused, the patients with melanoma who underwent HILP had a significant prolongation of disease-free survival (p less than 0.05), but a similar actuarial survival. In this study, we demonstrate that HILP can prevent local regional recurrences in patients with metastatic melanoma who are at high risk for further recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Arm↗

The evaluation of putative tumor markers for malignant melanoma.

Biomarkers have long held out the promise that malignancies might be diagnosed early and that patients could be monitored more confidently during their clinical course to more reliably predict recurrence and the effect of therapy. Reliable tumor markers have been described for colon carcinoma, hepatomas, and other tumors, but no reliable marker has been identified to monitor the course of malignant melanoma. Recently, the plasma level of lipid-bound sialic acid (LASA-P) has been described as reflecting an alteration in the surface membrane of cancer cells. An attempt was made to correlate the LASA-P level, along with the serum level of neuron-specific enolase, a glycolytic enzyme specific to cells of neuroectoderm origin including melanocytes, with clinical disease activity with a follow-up to at least 2 years. Two hundred seventy patients had blood samples drawn at various times during their clinical course for assay of LASA-P and neuron-specific enolase. Eighty of the patients (30%) sampled developed a recurrence sometime during their clinical course, whereas another 10 patients had active disease noted at diagnosis with evaluative tumor markers. The sensitivity and specificity of neuron-specific enolase was 27% and 77%, respectively, and cannot be recommended as a marker for melanoma. LASA-P showed a sensitivity of 65%, with 55 patients recurring and having active disease with abnormally high markers and 35 patients recurring or having active disease with normal markers. Specificity of the LASA-P test was 76%. When recurrence was associated with elevated LASA-P levels, the elevated level preceded recurrence by a median of 9.3 months. LASA-P may be a useful marker to follow patients with malignant melanoma.

Biomarkers↗

Adjuvant chemotherapy in malignant melanoma using dacarbazine, carmustine, cisplatin, and tamoxifen: a University of South Florida and H. Lee Moffitt Melanoma Center Study.

A prospective, nonrandomized trial was performed of the four-drug chemotherapy protocol consisting of dacarbazine, carmustine, cisplatin, and tamoxifen citrate given to high-risk patients for recurrence of melanoma after local regional treatment. The treated patients were consecutively registered and 6 patients who did not elect to be treated served as the control population. Criteria for inclusion in the trial were the presence of four or more lymph nodes positive for metastatic melanoma on regional modal dissection, the presence of metastatic disease in second station lymph node areas such as the iliac basin, greater than 5 cm in maximal diameter tumor burden in the nodal basin, and patients who had resected stage 4 (systemic metastases) disease with clear margins and were rendered free of disease. Actuarial survival curves for the treated group and the control subjects were similar (p = 0.91). There was a definite trend toward an increased disease-free survival for the group receiving adjuvant chemotherapy (p = 0.09). The mean disease-free survival for the control population was 200 days and for the treated group, 600 days. The study suggests a therapeutic benefit for adjuvant chemotherapy treatment of patients with metastatic melanoma who have been rendered free of disease but are at high risk for recurrence.

Adult↗

Treatment of stage IV malignant melanoma with dacarbazine, carmustine, cisplatin, and tamoxifen regimens: a University of South Florida and H. Lee Moffitt Melanoma Center Study.

Fourteen consecutive patients with stage IV metastatic melanoma with measurable disease were treated between January 1989 and August 1990 with combination chemotherapy. The chemotherapy regimen (DBPT) included dacarbazine (DTIC) 200 mg/m2/i.v. on days 1 through 3, carmustine (BCNU) 150 mg/m2/i.v. on day 1, cisplatin 25 mg/m2/i.v. on days 1 through 3, and tamoxifen citrate 10 mg p.o. twice daily. This cycle was repeated every 4 weeks. BCNU was given every other cycle. A total of six cycles of chemotherapy were delivered. Patients were then restaged to assess the response. Six concurrent patients during the study period did not elect to undergo chemotherapeutic approach and served as control subjects. When evaluated at 300 days of follow-up, 4 patients had response (3 complete response and 1 partial response), 3 had stable disease, and 7 showed progression. At 300 days of evaluation after chemotherapy, survival appeared significantly increased between treated and nontreated groups, that is, 48% in the chemotherapy group versus 27% in the control group (p = 0.03). Actuarial survival was significantly increased between those who responded to chemotherapy versus the nonresponders. At 300 days follow-up, survival was at 83% in the responders and 22% in nonresponders (p = 0.0002). This study shows that in stage IV disease, systemic chemotherapy appears to make a difference in survival. Attempts to discover better chemotherapy regimens to improve response in patients with stage IV malignant melanoma should continue to be rewarded.

Adult↗

Metastatic melanoma with an unknown primary.

An infrequent initial presentation for malignant melanoma is the diagnosis of metastatic disease without a history of an obvious primary lesion. Confusion exists in the literature concerning the workup, treatment, and prognosis of the unknown primary melanoma. A retrospective, computer-aided chart review of 580 consecutively registered patients with melanoma at the University Treatment Center (Tampa, FL), identified 18 patients with an unknown primary presentation. There were 10 males and 8 females with a mean age of 38.4 years. Ninety-four percent of the patients were diagnosed with metastatic disease in a nodal basin, whereas 1 patient had a resected isolated lung mass as the initial presentation. In the patients who presented after having a biopsy of a single positive node for diagnosis, more disease was recovered in the nodal basin with a formal node dissection in 59% of the patients. Actuarial survival curves were constructed for the group with unknown primary melanoma. As a control population, survival curves were constructed of the subpopulation of patients with melanoma who had a known primary and had stage III (regional nodal disease) at diagnosis. There was no difference in survival between those with known and unknown primary melanoma (p = 0.96).

Adolescent↗

The current management and prognosis of acral lentiginous melanoma.

A computer-aided retrospective analysis was performed on 359 patients with stage I and II melanoma at the time of diagnosis (disease confined to the primary melanoma), at the University of South Florida (Tampa, FL). Eighteen patients were identified with primary melanoma in acral locations, most being acral lentiginous melanoma. A comparison of actuarial survival curves of patients with melanoma in four different locations (acral, head and neck, trunk, and other extremity site) was performed. The patients with melanoma in acral locations did not have a statistically different actuarial survival than those with primary melanoma in other sites. When actuarial disease-free survival curves were constructed, however, acral primary melanoma had a shorter interval to recurrence than those located on the trunk or other extremity sites. Differences between actuarial disease-free survival for the head and neck and for acral primary sites were not significant. To identify prognostic factors responsible for the decreased disease-free survival of the acral lentiginous population, a regression analysis was performed. Three prognostic factors were analyzed for stage I and II melanoma, including Breslow tumor thickness, ulceration of the primary lesion, and primary site location. In the univariate analysis, with each prognostic factor acting independently, tumor thickness (p less than 0.01) and ulceration (p = 0.02) were significant variables influencing the disease-free interval. Primary site did not, however, add prognostic information to the model (p = 0.54). A stepwise multivariate analysis confirmed this finding.

Female↗

Human dystrophin gene transfer: production and expression of a functional recombinant DNA-based gene.

The identification and cloning of the gene responsible for Duchenne muscular dystrophy (DMD) and characterization of the protein product of the gene, dystrophin, has led to major advances in diagnostic and genetic counselling procedures for this inherited disorder. Due to its high mutation rate, however, individuals affected by DMD will continue to arise in large proportion by de novo mutations, and the search for direct therapies remains a high priority. In this respect direct genetic correction of dystrophin deficiency via grafting of healthy myoblast stem cells or direct introduction of functional DNA into diseased muscle tissue have both been proposed as potential therapeutic approaches. We describe here, the first example of the engineering and cloning of a synthetic gene encoding recombinant human dystrophin and its stable transfer to and expression in mammalian cells. This DMD gene construction represents a primary step towards evaluating direct DNA-mediated gene transfer as a potential treatment for this debilitating disorder.

3T3 Cells↗

Schistosoma mansoni: eggshell formation is regulated by pH and calcium.

The protein precursors of the schistosome eggshell are synthesized and packaged into secretory vesicles in the vitelline cells. These vesicles appear to contain an emulsion of eggshell precursor material. Evidence is presented to show that these secretory vesicles are acidic as in other systems and that this acidity stabilizes the emulsion and prevents the eggshell cross-linking reactions from occurring. Alkalinizing treatments trigger eggshell formation within the secretory vesicles as shown by (1) the induction of autofluorescence and (2) by electron microscopy which shows that the eggshell precursors have aggregated within the secretory vesicles into spherical particles bearing microspines. These aggregates formed in the secretory vesicles were isolated and shown to have the same protease resistance and amino acid composition as authentic eggshell. The calcium ionophore A23187 induces scattered autofluorescence in intact female worms which electron micrographs show to be due to exocytosis of eggshell material. Based on these observations we propose a model for the formation of schistosome eggshell and suggest that it may apply to all trematodes in which the eggshell precursors are present as stable emulsions in the secretory vesicles of the vitelline cells.

Ammonium Chloride↗

Yersinia enterocolitica infection complicated by intestinal perforation.

Yersinia enterocolitica causes primarily ileocolitis in human beings, and is manifested by abdominal pain, diarrhea, and fever. Usually, it is a self-limiting disease. Local or systemic complications are rare. A 71-year-old man with Y enterocolitica colitis complicated by perforation and abscess formation is described. This complication is very rare, and the four other cases that have been reported in the literature are reviewed.

Aged↗

Recognition and treatment of arterial insufficiency from cafergot.

Cafergot is a combination of ergotamine tartrate and caffeine and may cause symptoms of peripheral vascular insufficiency. Iatrogenic ergotism should be suspected in any patient exhibiting ischemic symptoms while receiving this medication. Progression to fulminant necrosis and gangrene can occur. Two cases are presented and the management reviewed. This effect of ergotamine tartrate and caffeine may be an idiosyncratic hypersensitivity reaction with therapeutic doses or may result from excessive medication. Iatrogenic ergotism occurs most often in women in their mid-thirties with migraine syndrome. By alpha-adrenergic agonism, as well as by possible interactions with prostaglandins, calcium, and serotonin, ergotamine causes vasoconstriction of both arteries and veins. The angiographic pattern of spasm, collateral formation, and intravascular thrombi is typical. Treatment of ergotism depends on the severity of the symptoms and the possibility of gangrene. Discontinuation of ergotamine, cigarette smoking, and caffeine may be all that is necessary in most patients. Nitroprusside is the drug of choice in the treatment of acute vascular insufficiency from ergotism, but in a less urgent situation, prazosin has also been effective. Intra-arterial balloon dilatation has also been helpful. Other forms of therapy have been supportive and the results inconsistent. Cafergot should be used with extreme caution in patients with renal or hepatic failure, peripheral vascular disease, or pregnancy. Relative contraindications include hypertension, ischemic heart disease, and Raynaud's phenomenon.

Adult↗

Ossifying ameloblastoma in a horse.

The features of an ossifying ameloblastoma in a 5-year-old gelding are described. The tumour developed in the angle of the right mandible and microscopically consisted of multiple follicles and islands of epithelial tissue adjacent to which were trabeculae of bone, osteoid and compact collagenous tissue.

Animals↗

Analysis of the major metabolite of delta 9-tetrahydrocannabinol in urine II. A HPLC procedure.

A high performance liquid chromatographic (HPLC) procedure was developed for the analysis of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine. Hydrolyzed urine samples were cleaned up using Bond-Elut columns. 11-Nor-cannabinol-9-carboxylic acid was used as internal standard. The analysis was carried out using a C8 reversed-phase column with acetonitrile:50 mM phosphoric acid (65:35) as the solvent. Detection was done by ultraviolet detector at 214 nm. The minimum detectable level of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid was 25 ng/mL.

Chromatography, High Pressure Liquid↗