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Biomedical subjects

J C Noel

Publications and source records attributed to J C Noel.

At least 37 records · Page 2Linked to original sources

Classic Kaposi's sarcoma after multiple-partner heterosexual behavior in Central Africa.

We present a case of a possible sexual transmission of classic Kaposi's sarcoma. To our knowledge, this is the first report of such a case. We noted a long delay between the probable contaminant contact and onset of lesions, suggesting that human herpesvirus 8 has longer incubation periods in healthy individuals than in immunocompromised patients.

Africa, Central↗

Iron as a potential co-factor in the pathogenesis of Kaposi's sarcoma?

The role of iron in the pathogenesis of several tumours is being increasingly investigated. In particular, its involvement in the pathogenesis of Kaposi's sarcoma (KS) is suggested by the distribution of the endemic form of KS corresponding to continental rifts and associated iron-oxide-rich volcanic clays. We investigated in vitro to what extent iron supplementation or withdrawal could affect the growth of KS-derived cells, by analysing the effects of adding iron salts (iron chloride and ferric nitrilotriacetate) and/or reducing iron by iron chelators (desferrioxamine) on KS-derived cell cultures. The addition of iron salts strongly stimulated the growth of KS cells, as reflected by increase in thymidine incorporation and cell number. Conversely, desferrioxamine and deferiprone inhibited cell growth. The inhibitory effect of iron chelation was more pronounced on rapidly dividing basic fibroblast-growth-factor-stimulated cells. These results may point to a novel therapeutic approach to KS.

Carcinogens↗

Methotrexate induces apoptotic cell death in human keratinocytes.

The mechanism by which low doses of methotrexate act in psoriasis to restore a clinically normal skin is poorly understood. Apoptosis is a programmed cell death activated when cell removal is needed. The purpose of the present work was to examine using an organotypical model of keratinocyte culture, the possibility that low doses of methotrexate can induce apoptosis of keratinocytes. Epidermal explants were cultivated on dead deepidermized dermis under air-exposed conditions. After 10 days, methotrexate (10(-7) M) was added. After a further 5 days, one part of each culture was fixed and submitted to routine histology, DNA nick end labelling (TUNEL) to detect DNA fragmentation (a molecular marker of apoptotic cell death) and immunohistochemical detection of p53 (a protein involved in apoptosis induced by DNA-damaging agents). The other part of each culture was processed for electron microscopy. A significant proportion of keratinocytes (1%) were damaged and exhibited the morphological features of apoptotic cell death. Immunohistochemical overexpression of p53 was detected in the basal layer of the cultures treated with methotrexate. Low doses of methotrexate induce apoptosis. This mode of action could explain the reduction in epidermal hyperplasia during treatment of psoriasis with methotrexate.

Apoptosis↗

Percutaneous transperineal radiofrequency ablation of prostate tumour: safety, feasibility and pathological effects on human prostate cancer.

OBJECTIVE: To evaluate the safety of radiofrequency (RF) energy delivered interstitially in patients with prostate cancer scheduled for radical prostatectomy and to correlate the proposed theoretical lesion size with the pathological findings. PATIENTS AND METHODS: Radiofrequency interstitial tumour ablation (RITA) was performed in 15 patients with localized prostate cancer before radical surgery. RF energy was delivered to the prostate by active needle electrodes (monopolar or bipolar) placed transperineally under transrectal ultrasonography guidance. Needle electrodes were used with different configurations and in some cases were covered by retractable shields to vary the length and circumference of the thermal lesions created. In eight patients, the procedure was performed immediately before radical prostatectomy, in six RITA was performed under spinal anaesthesia 1 week before surgery and in one patient, no surgery was performed but the patient was followed by serial determinations of prostate specific antigen (PSA). At least two lesions were created in each prostate, including both capsule and peripheral zones. NADPH and haematoxylin & eosin (H&E) staining were used to assess the extent of the necrotic lesion in the radical prostatectomy specimen. RESULTS: The mean energy delivered was 10.5 kJ, with central temperatures reaching up to 105 degrees C during 12 min of ablation; rectal temperature remained at < 38 degrees C. There were no complications. Macroscopic examination showed well-demarcated lesions including the prostatic capsule, up to 2.2 x 1.5 x 4.5 cm. With monopolar energy, the observed lesion size was comparable to the predicted 2 x 2 x 2 cm lesion, while with bipolar energy, lesion size was related to interneedle distance and uncovered needle length. Microscopic examination showed clearly delineated lesions both with NADPH (in prostates immediately removed after surgery) and H&E (at 1 week after RITA) staining. The lesion size observed on pathological analysis correlated with the predicted lesion size. In one patient, no residual cancer was found in the specimen. In the patient whose entire prostate was targeted and followed by serial PSA measurements, the latter were undetectable at 3 months of follow-up. CONCLUSION: Transperineally delivered RF energy is capable of safely creating extensive coagulative necrotic lesions in prostate cancer tissue, in a reproducible and controlled manner. The results presented here provide basic information for the potential future application of this form of energy for localized prostate cancer.

Catheter Ablation↗

Overexpression of Bcl-2 in Kaposi's sarcoma-derived cells.

The pathogenesis of Kaposi's sarcoma (KS), a tumor of probable vascular origin, remains an enigma. It is still unclear whether KS is a true malignancy or whether it represents a reactive polyclonal process. Using both an immunohistochemical and an immunoblot approach, we found that cells derived from KS lesions express significant levels of Bcl-2, a protein known to prolong cellular viability and to antagonize apoptosis. Bcl-2 expression was found in AIDS-related KS-derived cells, as well as in cells derived from iatrogenic and sporadic KS, indicating that Bcl-2 upregulation may be important in the pathogenesis of KS regardless of its epidemiologic form. By contrast, fibroblasts and dermal microvascular endothelial, cells which are the probable vascular progenitors of KS cells, expressed low levels of Bcl-2. The expression of Bcl-2 in KS-derived cells was associated with a long-term survival in serum-deprived conditions, a situation that has been shown to induce apoptosis in various cell types. Incubation of fibroblasts or of dermal microvascular endothelial cells with KS cell-free supernatants did not enhance Bcl-2 expression, suggesting that Bcl-2 expression is not mediated by an agent released by KS cells. Analogously, KS supernatants failed to promote the viability of fibroblasts and of dermal microvascular endothelial cells cultured in serum-free conditions. Our findings suggest that the spindle cells derived from KS have a survival advantage and may adequately represent the tumor cells of KS.

Cell Survival↗

Carcinoma of the glans penis arising 20 years after lichen sclerosus.

Lichen sclerosis (LS) is an inflammatory disease of incompletely characterized pathogenesis. The relation between LS and carcinoma is well known in women, but in men it is still a matter of debate whether LS is a premalignant lesion or not. We describe a case of LS of the glans penis which occurred in 1976. Within the next 20 years, the patient developed carcinoma at this site.

Adult↗

Role of viral agents in the pathogenesis of Kaposi's sarcoma.

Several viruses have been detected, at various frequencies, in Kaposi's sarcoma (KS) tissues. The detection of human herpesvirus 8 (HHV-8) in all the epidemiological and histological forms of KS makes it the most attractive candidate causative agent to date. In this report, we discuss the possible explanations for the detection of genomic sequences of various viral agents in KS and the putative role of those viruses in the pathogenesis of the disease.

Herpesviridae Infections↗

Treatment of classical Kaposi's sarcoma with intralesional injections of cidofovir: report of a case.

The effect of intralesional injections of cidofovir, a nucleotide analog with potent in vitro activity against human herpesvirus 8 (HHV-8), was studied in vivo in an HIV-negative patient with classical Kaposi's sarcoma (KS). After five weekly injections of the drug, no clinical, histological, immunohistological, or virological changes could be detected in comparison with saline-injected lesions. These findings suggest that, once the KS tumor has developed, active viral replication is no longer involved in the pathogenesis of the disease. Alternative hypotheses are that HHV-8 replication in blood-borne cells may foster growth of spindle cells in the skin, or that blocking HHV-8 may not affect existing lesions but may prevent new lesions from developing.

Aged↗

[Cap polyposis: a rare syndrome].

We report a case of inflammatory cap polyposis of the colon, a rare syndrome, affecting the rectosigmoid. It was observed in a context of mucous diarrhea. Endoscopic and radiological features consisted of elevated and umbilicated nodular lesions. Histology revealed polypoid lesions containing elongated crypts with superficial abrasions, covered by inflammatory and fibrinoid material. Etiopathogenesis of this new syndrome is unknown.

Colon, Sigmoid↗

Radiofrequency interstitial tumor ablation (RITA) is a possible new modality for treatment of renal cancer: ex vivo and in vivo experience.

Small renal tumors are increasingly diagnosed and are frequently treated by nephron-sparing surgery. Tumors can be ablated by radiofrequency (RF) energy, which allows the operator to create very localized necrotic lesions. Radiofrequency interstitial tumor ablation (RITA) has been used in human kidneys in an ex vivo experiment to assess the necrotic lesions produced in a model close to physiologic conditions and then in three patients with localized renal cancer prior to radical nephrectomy. In the ex vivo model, four freshly removed kidneys were treated. Bipolar RF energy was delivered by a generator connected to two needles introduced parallel to each other into the renal parenchyma. A thermocouple was inserted between the two active electrodes. The renal artery at physiologic conditions was maintained at a constant temperature of perfusion of 37 degrees C by a computer-assisted Hot-line monitor. Two lesions were produced in each pole of each kidney including the cortex and the medulla. In an initial human study focusing on safety, feasibility, and pathology, three patients were treated by RITA with bipolar and monopolar energy. One patient with a peripheral 2-cm upper-pole tumor was treated percutaneously under ultrasound guidance with local anesthesia only 1 week prior to surgery. The other patients, with 3- and 5-cm tumors, were treated during surgery under general anesthesia just before nephrectomy. Ex vivo, the maximum temperature at the active needles ranged from 84 degrees C to 130 degrees C with 10 to 14 W applied during 10 to 14 minutes. Lesions were on average 2.2 x 3 x 2.5 cm.3 Microscopic examination showed stromal edema with intensive pyknosis. No damage was seen to adjacent untreated tissue. In the in vivo procedure, tolerance of RTA as an anesthesia-free procedure was excellent. The size of the observed lesions was comparable to the forecast size depending on the needle deployment. No side effects were noted, and no adjacent structures were affected by the RF ablation. These preliminary studies demonstrate the ability of RITA to produce localized extensive necrosis in kidney parenchyma and tumors safely under local anesthesia. Further studies could evaluate this new minimally invasive treatment in small kidney tumors considered for nephron-sparing surgery.

Aged↗