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Biomedical subjects

R Heller

Publications and source records attributed to R Heller.

At least 109 records · Page 6Linked to original sources
PubMed1995

The role of selective lymphadenectomy in the management of patients with malignant melanoma.

BACKGROUND: A novel surgical technique based on selective lymphadenectomy was used to stage 132 patients with intermediate and thick cutaneous malignant melanoma. Preoperative and intraoperative lymph node mapping techniques were used to ascertain regional lymph node basins at risk for metastasis, and to identify the first node(s) the afferent lymphatics encounter in the basin, defined as the "sentinel" node(s). It has been shown that the histology of the sentinel node reflects the histology of the rest of the nodal bain, and according to preliminary studies using this technique, the likelihood of bypassing the sentinel node(s) to "higher" level nodes is less than 2%. Epidemiologic studies indicate that the long-term survival of patients with melanomas of intermediate thickness or greater is significantly compromised if regional lymph nodes are involved. Yet, the utility of performing lymph node dissections for the purposes of staging only is controversial, not only because of the morbidity and expense of the procedure, but the lack of proven survival benefit. OBJECTIVE: In the present study, we performed preoperative and intraoperative lymphatic mapping, harvested clinically normal sentinel nodes, and examined them for micrometastasis by light microscopy. Both conventional stains and immunocytochemistry for S-100 protein and HMB-45 antibodies were performed, and only those patients with documented micrometastasis received complete lymph node dissections. RESULTS: The sentinel node(s) was identified in each of the patients. Micrometastatic disease was detected in 31 (23%) of the patients by selective lymphadenectomy, and the sentinel node(s) was the only node involved in 83% of the cases upon subsequent complete nodal dissection. CONCLUSION: Our preliminary results suggest that selective lymphadenectomy following lymphatic mapping is an effective procedure for staging melanoma patients with lesions of intermediate thickness or greater. Our results indicate that sentinel lymph nodes may be successfully identified and harvested in the majority of patients, and that they may be examined for the first evidence of micrometastasis without the need of a complete nodal dissection. Information as to whether micrometastases are present in the sentinel node would be valuable in staging patients, and identifying candidates for complete nodal dissections. We are participating in a National Cancer Institute-sponsored multicenter trial to ascertain whether this surgical approach can impact on the recurrence rate and survival of patients with stage 1 and 2 melanoma.

Adolescent↗
PubMed1995

Accurate Nodal Staging of Malignant Melanoma.

The incidence of malignant melanoma is increasing at a faster pace than that of any other cancer in the United States. It is estimated that people born in the year 2000 will have a 1:75 risk of developing melanoma sometime during his or her lifetime. Stimulated by novel lymphatic mapping techniques, the surgical care of the melanoma patient is evolving toward more conservative resections that can provide the same staging information but without the added morbidity of more radical surgeries. This approach promises to yield positive results in the age of health care reform, outcome measurements, and cost:benefit considerations.

Journal Article↗
PubMed1995

Treatment of cutaneous nodules using electrochemotherapy.

The ability to increase the amount of chemotherapeutic agents absorbed by tumor cells can be accomplished using electrochemotherapy. A preclinical study demonstrated the potential of this treatment; therefore, a clinical trial was initiated to determine if it would be effective in cutaneous and subcutaneous malignancies. Three melanoma, one adenocarcinoma and two basal cell carcinoma patients were treated. Each received a 10 unit/m2 dose of bleomycin intravenously. Eight 99 microseconds pulses at an amplitude of 1.3 kV/cm were administered directly to the tumors approximately 10-12 minutes after initiating the bleomycin injection and following the injection of 1% lidocaine solution around the treatment site. Two of three melanoma patients have responded positively to the treatment. Both basal cell carcinoma patients responded. The patient with adenocarcinoma responded as well. All patients tolerated the treatment well with no residual effects from the electric pulses. Although conclusions cannot be made, the results thus far are very encouraging.

Animals↗
PubMed1995

The identification and mapping of melanoma regional nodal metastases: minimally invasive surgery for the diagnosis of nodal metastases.

The most controversial part of melanoma surgical care involves the role of elective lymph node dissection (ELND). Whereas proponents cite retrospective studies demonstrating the ability to control regional metastases and more accurate staging, opponents cite the unnecessary morbidity of a complete node dissection for the majority of patients. The technology of sentinel node mapping and selective lymphadenectomy, defined as the identification and removal of the first node into which the primary melanoma drains, may revolutionize melanoma care. If the sentinel node is negative, then theoretically the remainder of the nodes should also be negative (no "skip" metastases), and a complete lymphadenectomy would not be required to control occult nodal disease. The location of the sentinel node may be variable in the lymphatic basin. Ideally, the surgeon needs a map of the position of the sentinel node in reference to the other nodes in the basin in order to do the procedure under local anesthesia with small incisions. In this way, patients are subjected to minimal morbidity and the procedure can be performed as an out-patient. Twenty-nine patients with clinically negative nodes and melanomas greater than 0.76 mm in thickness were judged to be candidates for ELND. Preoperative lymphoscintigraphy in two planes was used to mark the sentinel node, and the patients were taken to the operating room for intraoperative lymphatic mapping and sentinel node biopsy followed by complete dissection.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1994

Detection and quantitation of cell-cell electrofusion products by flow cytometry.

A cytometric method for detecting and quantitating hybrid cells that resulted from cell-cell electrofusion was developed. Cells from two different lines and two vital fluorescent dyes were used in conjunction with a flow cytometer to demonstrate the method. Each dye was used to stain one cell type prior to electrofusion. Hybrid cells exhibited dual fluorescence while unfused cells retained their single fluorescence. Flow cytometry was used to detect dual fluorescing hybrid cells that resulted from electrofusion. Fluorescent microscopy was used to confirm that 92% of the cytometrically detected cells were hybrids. Flow cytometry was also used to quantitatively show differences in hybrid yields for samples fused using different electrical conditions. These results demonstrate that the method can be used for detection and quantitation of electrofusion products. The methodologies presented are not specific to the cell types used; they can be adapted for use with other cell types.

Animals↗
PubMed1994

Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice.

Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumably Apoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus.

Animals↗
PubMed1994

Cystic lung disease in Down syndrome.

It is well known that Down syndrome (DS) affects multiple organ systems, including cardiovascular, gastrointestinal, hematological, and musculoskeletal. Involvement of the lungs by a characteristic form of subpleural cystic disease is well described in the pathology literature. The imaging characteristics of changes caused by this disease have not been previously described in detail in the radiology literature, possibly because they are not well appreciated on plain chest radiographs. We present a child with DS in whom extensive cystic lung disease was discovered incidentally at CT, and review the current literature regarding the pathogenesis of cystic pulmonary abnormalities in children with DS.

Cysts↗
PubMed1994

Mechanically facilitated cell-cell electrofusion.

Apparatus and methods were developed to enable mechanically facilitated cell-cell electrofusion to be performed. The apparatus and methods mechanically place cells in contact before fusion. The key component of this fusion system was a newly developed fusion chamber. The chamber was composed of two functionally identical electrodes that were housed in a multi-layer structure. The layers functioned as support for the electrodes. They also allowed adjustment of the distance between opposing electrode faces. The electrodes were constructed in a manner that allowed cells to be deposited, by vacuum, onto each face. Electrode faces were positioned at a predetermined distance from each other to mechanically force cell-cell contact between the deposited cells. Fusion was induced by delivering direct current pulses to the juxtaposed cells. Fusion products were detected and quantitated by flow cytometry. Details of the chamber design and a protocol for using the fusion chamber are given. Mechanically facilitated cell-cell electrofusion was demonstrated by using the chamber to produce fusion products from like fusion partners. The practical applicability of the chamber was demonstrated by fusing unlike cell types. Mechanically facilitated cell-cell electrofusion is not specific to the cells used in this study; the chamber can be adapted for use with other cell types.

Animals↗
PubMed1994

The orderly progression of melanoma nodal metastases.

OBJECTIVE: The aim of this study was to determine the order of melanoma nodal metastases. SUMMARY BACKGROUND DATA: Most solid tumors are thought to demonstrate a random nodal metastatic pattern. The incidence of skip nodal metastases precluded the use of sampling procedures of first station nodal basins to achieve adequate pathological staging. Malignant melanoma may be different from other malignancies in that the cutaneous lymphatic flow is better defined and can be mapped accurately. The concept of an orderly progression of nodal metastases is radically different than what is thought to occur in the natural history of metastases from most other solid malignancies. METHODS: The investigators performed preoperative and intraoperative mapping of the cutaneous lymphatics from the primary melanoma in an attempt to identify the "sentinel" lymph node in the regional basin. All patients had primary melanomas with tumor thicknesses > 0.76 mm and were considered candidates for elective lymph node dissection. The sentinel lymph node was harvested and submitted separately to pathology, followed by a complete node dissection. The null hypothesis tested was whether nodal metastases from malignant melanoma occurred in equal proportions among sentinel and nonsentinel nodes. RESULTS: Forty-two patients met the criteria of the protocol based on prognostic factors of their primary melanoma. Thirty-four patients had histologically negative sentinel nodes, with the rest of the nodes in the basin also being negative. Thus, there were no skip metastases documented. Eight patients had positive sentinel nodes, with seven of the eight having the sentinel node as the only site of disease. In these seven patients, the frequency of sentinel nodal metastases was 92%, whereas none of the higher nodes had documented metastatic disease. Nodal involvement was compared between the sentinel and nonsentinel nodal groups, based on the binomial distribution. Under the null hypothesis of equality in distribution of nodal metastases, the probability that all seven unpaired observations would demonstrate that involvement of the sentinel node is 0.008. CONCLUSIONS: The data presented demonstrate that nodal metastases from cutaneous melanoma are not random events. The sentinel lymph nodes in the lymphatic basins can be mapped and identified individually, and they have been shown to contain the first evidence of melanoma metastases. This information can be used to revolutionize melanoma care so that only those patients with evidence of nodal metastatic disease are subjected to the morbidity and expense of a complete node dissection. Because sentinel node histology accurately reflects the histology of the remainder of the lymphatic basin, information gained from the sentinel node biopsy can be used as a prognostic factor for melanoma. These findings demonstrate effective pathologic staging, no decrease in standards of care, and a reduction of morbidity with a less aggressive, rational surgical approach.

Adolescent↗
PubMed1994

Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma.

BACKGROUND: The presence or absence of lymph node metastases in patients with malignant melanoma is the most powerful prognostic factor for predicting survival. If regional nodal metastases are found, the 5-year survival for the patient decreases approximately 50%. If the presence or absence of regional nodal metastases will determine which patients receive formal dissections or which patients enter adjuvant trials, then a technique is needed to accurately screen lymph node samples for occult disease. Routine histopathologic examination routinely underestimates the number of patients with metastases. This study was initiated to develop a highly sensitive clinically applicable method to detect micrometastases by examining lymph nodes for the presence of tyrosinase messenger RNA (mRNA). The hypothesis was that if mRNA for tyrosinase is found in the lymph node preparation, that finding is good evidence that metastatic melanoma cells are present. METHODS: The assay is accomplished using the combination of reverse transcription and double-round polymerase chain reaction (RT-PCR). The amplified samples are examined on a 2% agarose gel and tyrosinase cDNA is seen as a 207 base pair fragment. Lymph node preparations from 29 patients who were clinically stage I and II and undergoing elective node dissections were analyzed both by standard pathologic staining and RT-PCR. RESULTS: Eleven of 29 lymph node (38%) samples from 29 patients with intermediate thickness melanoma were pathologically positive. Nineteen of the 29 lymph node preparations (66%) were RT-PCR-positive, and these included all of the pathologically positive samples, so that the false-negative rate was 0. In a spiking experiment, one SK-Mel-28 melanoma cell in a background of one million normal lymphocytes could be detected, thus indicating the sensitivity of this method. In addition, analysis by restriction enzyme mapping showed that the amplified 207-bp PCR product produced is part of the tyrosinase gene sequence. CONCLUSION: The RT-PCR method is an extremely sensitive, reproducible, and efficient technique for the identification of micrometastases in patients with melanoma and could be widely applicable. If clinical correlation is obtained, staging of the melanoma patient becomes more accurate, and treatment becomes more standardized and rational, because all those patients who have evidence of nodal disease can be identified so that they may benefit from more extensive surgery (formal node dissections) or adjuvant therapies. Based on these results, RT-PCR could be a powerful tool to detect micrometastatic melanoma.

Humans↗
PubMed1994

Histoplasmosis during childhood.

To define the clinical presentation of histoplasmosis among hospitalized children, we reviewed the charts of patients treated for histoplasmosis at Vanderbilt University Children's Hospital during the years 1968 through 1988. Thirty-five patients with histoplasmosis diagnosed by culture, pathologic examination, or serologic testing were identified, including 29 patients (83%) with pulmonary/mediastinal infection, 5 (14%) with disseminated disease, and 1 (3%) with primary cutaneous histoplasmosis. The most common symptoms included fever, present in 26 patients (74%), and cough, present in 20 (57%). Of 26 patients with fever, 18 (69%) had fever of > 2 weeks' duration and 7 (27%) had temperatures > or = 40.5 degrees C (> or = 105 degrees F). Abnormal physical findings were few, but 19 patients (54%) had wheezing. Chest radiographs were obtained in all cases except one; 31 (91%) showed abnormalities, including adenopathy in 25 cases (74%) and infiltrates in 19 (56%). Histoplasmin skin tests were positive for 22 (96%) of the 23 patients tested. No cases of classic disseminated histoplasmosis of infancy were identified. Histoplasmosis should be considered in the differential diagnosis when children living in endemic areas are evaluated for persistent fever, cough, and/or wheezing, particularly if adenopathy is seen on the chest radiograph.

Adult↗
PubMed1994

The new manager.

Explore the source record for details and available documents.

Administrative Personnel↗
PubMed1993

S35b, a new phenylsulfonylfuroxan compound, inhibits thrombin-induced synthesis of platelet-activating factor and prostacyclin in human endothelial cells.

Endothelial cells (EC) produce platelet activating factor (PAF) and prostacyclin (PGI2) in response to inflammatory agents such as thrombin. Upon cell stimulation a calcium-dependent phospholipase A2 (PLA2) is activated which hydrolyzes a membrane phospholipid to yield 1-0-alkyl-2-lyso-sn-glycero-3-phospho-choline (lyso-PAF) and free arachidonic acid. Lyso-PAF is in turn converted into PAF by a specific acetyltransferase and arachidonic acid is metabolized via cyclic endoperoxides to PGI2. In the present study we report that S35b (4-methyl-3-phenylsulfonylfuroxan), a new phenyl-sulfonylfuroxan compound with potent antiaggregatory effect, inhibits thrombin-induced PAF synthesis and acetyltransferase activation as well as PGI2 production in human umbilical vein endothelial cells (HUVEC) in a concentration-dependent way. Additionally, we show that S35b stimulates the production of cyclic GMP (cGMP) in HUVEC in a concentration- and time-dependent manner. At high concentration, S35b potentiates the cAMP increase induced by iloprost or forskolin without having a significant influence on cAMP level itself. Potentiation of cAMP increase during agonist-induced EC stimulation seems not to be important for the effect of S35b on cellular function as the compound is active in inhibiting PAF production when endothelial cells are pretreated with indomethacin to block PGI2 synthesis. The increase of cGMP evoked by S35b may account for the effect on endothelial cell function.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Cytogenetics of Askin's tumour. Case report and review of the literature.

The eleventh cytogenetically analyzed Askin's tumour, diagnosed in a two-year-old girl, is reported. Chromosomal analysis revealed a pseudodiploid karyotype of tumour cells with translocations of t(11;22)(q24;q12) and der(4)t(2;4)(q24;q35). The observed t(11;22)(q24;q12) is not only a unique characteristic of all cytogenetically analyzed Askin's tumours but it also occurs in 92-100% of peripheral neuroepithelioma and of Ewing's sarcoma, irrespective of its osseous or extraosseous localization. This genetical similarity further supports a nosological concept according to which Askin's tumour, Ewing's sarcoma and peripheral neuroepithelioma represent phenotypic variations of the same tumour, namely the peripheral primitive neuroectodermal tumour.

Child, Preschool↗
PubMed1993

Causes of hospital-acquired septicaemia--a case control study.

Hospital-acquired septicaemia is common and an important cause of morbidity and expense. Few studies have explored its cause by comparing features of people who do and do not develop septicaemia--the aim of this study. All blood cultures were monitored over one year in a 400-bed tertiary care hospital where special care is taken with intravenous cannulae to prevent septicaemia. Cases had at least one positive blood culture taken at least 48 h after admission. The nearest two patients in the same ward were controls, and information was abstracted on all three from the hospital records by a research nurse. There were 84 cases during the 12 months (3.8 per 1000 admissions) and 167 controls. Univariate odds ratios (95% CI) were 5.57 (2.06-15.95) with the presence of a central venous line, 3.40 (1.16-16.40) with total parenteral nutrition, 2.41 (1.30-4.32) with blood transfusion, 2.10 (1.16-4.56) with immunosuppressive disease, 2.06 (1.02-4.44) with the presence of a urinary catheter and 0.32 (0.17-0.69) with recent surgery. Conditional logistic regression identified a central venous line and blood transfusion to be independent risk factors for septicaemia, odds ratios (and 95% CI) being 5.14 (1.74-15.23) and 2.74 (1.28-5.88), respectively, while recent surgery and antibiotic prophylaxis were independently 'protective' at 0.31 (0.12-0.79) and 0.38 (0.16-0.90), respectively. Thus, in a hospital where great care has been taken to avoid septicaemia, especially by attention to intravenous cannulae, there were only two independent risk factors for the development of hospital-acquired septicaemia--a central venous line and blood transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗