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Biomedical subjects

P Rocmans

Publications and source records attributed to P Rocmans.

At least 19 recordsLinked to original sources

Pulmonary sequestration-like anomaly presenting as a spontaneously resolving mass.

A premature baby boy presented at birth with respiratory distress. A right lower lobe opacity was found on chest X-ray. Pulmonary sequestration was the diagnosis suggested by ultrasound. The size of the mass decreased on subsequent examinations. 4 months later X-rays and sonography failed to demonstrate any remaining mass. This case illustrates another example of involutive pathology and suggests that not all pulmonary sequestration-like anomalies should be operated on.

Bronchopulmonary Sequestration

Unlike thyrotropin, thyroid-stimulating antibodies do not activate phospholipase C in human thyroid slices.

The effects of thyroid-stimulating antibodies (TSAb) and of thyrotropin (TSH) were compared, on the generation of cyclic AMP and inositol phosphates (InsP), in human thyroid slices incubated in vitro, and on the Rapoport cyclic AMP bioassay. The TSAb positive sera were obtained from 19 patients with Graves' disease. In 14 experiments with the slices system, TSH significantly increased cyclic AMP accumulation (TSH, 0.03-10 mU/ml) as well as the cyclic AMP-independent inositol trisphosphate (InsP3) generation (TSH, 1-10 mU/ml). In the same 14 experiments, TSAb (0.10-28 mg/ml) enhanced cyclic AMP intracellular levels as expected while they did not induce any InsP accumulation. Even when TSAb increased cyclic AMP levels to the same or higher values as those obtained with TSH concentrations allowing InsP3 generation. TSAb were still unable to activate the phosphatidylinositol-Ca2+ cascade. The patterns of the response curves of TSAb and TSH on cyclic AMP accumulation were different, suggesting that different mechanisms may be involved. In addition, unlike TSH, TSAb were not able to stimulate H2O2 generation, which in human tissue mainly depends on the activation of the phosphatidylinositol-Ca2+ cascade. Immunoglobulins from six additional Graves' patients lacking measurable cyclic AMP-stimulating activity in both slices and cells systems did not activate phospholipase C either. In conclusion, our results show that TSAb do not share all the metabolic actions of TSH on human thyroid tissue. The data provide support for the concept that the pathogenesis of Graves' disease can be fully accounted for by the ability of TSAb to stimulate adenylate cyclase. This work also confirms that TSH activates the cyclic AMP and the phosphatidylinositol cascade by independent pathways in the human thyroid.

Adolescent

[NMR evaluation of neoplastic invasion of the pulmonary artery].

Bronchial tumors that invade the mediastinum are not necessarily inoperable. Whether surgery is possible depends, among other things, on the extent of pulmonary artery invasion. The authors have studied the value of cardiac-gated MRI and compared it with CT and venous DSA for staging tumor invasion. CT demonstrated the areas of contact between tumor and mediastinum. The MRI planes were transverse and also in the main axis of the pulmonary arteries. Twenty-one patients were studied and in 16 the findings could be checked during surgery. In all cases the findings on MRI were confirmed. In eight patients MRI provided more information than CT and DSA combined and thereby showed its superiority for evaluating arterial invasion.

Adenocarcinoma

The biochemistry of autonomous thyroid nodules: clues on the pathogenesis.

The "in vitro" characteristics of H2O2 generation, iodide, cAMP and PI metabolism, have been compared in tissues from autonomously functioning thyroid nodules and their quiescent counterpart to test the hypothesis that autonomy may result from constitutive activation of the tissue's TSH-IP's, or TSH-cAMP regulatory pathway. The enhanced iodide uptake is entirely due to increased transport capacity, the affinity of iodide transport and the fractional binding of iodide to protein remaining unchanged. The basal IP's accumulation is slightly higher in seven cases where it was studied but the response to TSH was markedly decreased. The cAMP-protein phosphorylation regulatory axis is not constitutively activated. Under TSH and forskolin stimulation, a 20K protein is not phosphorylated in nodular tissue as it is in its quiescent counterpart. The others, possible points of deviation in the cAMP cascade, studied in these tissues, i.e. basal cyclic AMP, desensitization to TSH, iodide inhibition, responses to other hormones or neurotransmitters were not systematically different in nodular tissue. The 20K protein, not phosphorylated in response to TSH in the nodules, could represent an absent negative controlling element. The absence of a 20K protein substrate of cAMP dependent protein kinases remains the most interesting clue about the mechanism of autonomy. We are now trying to purify and clone this protein.

Adenylyl Cyclases

[Long-term survival after surgery of solitary cerebral metastasis of lung cancer. Clinical case and review of the literature].

In cases of solitary brain metastasis of lung cancers other than small cell lung carcinoma, which has an even poorer prognosis, long-term patient survival over 1.2 years is rare. One case with a 12 year survival is presented. The authors review the other 18 cases with a minimum 5 year survival described in the literature. It is concluded that surgical aggressivity is justified in these cases.

Brain Neoplasms

[Aspergillus colonization of a pulmonary sequestration. Apropos of a case associated with erythema nodosum].

We describe a case of interlobar pulmonary sequestration diagnosed at thoracotomy in which there were a number of unusual features at presentation: an opacity with multiple cavities, positive aspergillus precipitins, erythema nodosum and a haemothorax complicating a trans-thoracic needle biopsy. Although it is unusual to find such a constellation of symptoms and signs they could be explained in a logical fashion.

Aspergillosis

Resection of lung metastases from sarcomas.

Between 1977 and 1987, 19 patients were candidates for resection of lung metastases from pretreated extrathoracic primary tumours. Primary tumours comprised 10 osteosarcomas, one Ewing sarcoma and eight soft tissue sarcomas. All 19 patients presented with metachronous metastases. Twenty-eight thoracotomies were performed in these 19 patients. Nine patients underwent multiple surgical explorations. All the metastases were removed by wedge resection. Seven out of 10 patients treated for osteosarcoma received pre- and postoperative chemotherapy, and three out of 10 postoperative chemotherapy only. The projected survival rate at 3 years is 33%. Seven out of 19 patients survived more than 2 years; four of them were free of disease at 33, 54, 56 and 137 months. Good prognosis appears to be long metastases-doubling time, metachronous metastases, small number of lung metastases, pathological evidence of tumour necrosis and/or fibrosis after chemotherapy and, of course, complete control of the primary tumour and no extrathoracic metastases.

Adolescent

[Neoplastic invasion of the pulmonary arteries. Evaluation by MRI. Preliminary experience].

Bronchial tumors invading the mediastinum are no longer systematically regarded as inoperable. Curative surgery has produced a significant survival rate and led to the adaptation of the TNM classification. The degree of invasion of the pulmonary artery is a criterion of operability. The authors are trying to assess the role of MRI with regard to CT and DSA for the measurement of invasion. Their study deals with the prospective assessment of ten patients. The MRI examinations have been carried out with a 0.5 and 1.5 T supraconductive magnet (Philips Gyroscan). Cardiac gating has been used for acquisition. The planes of section are axial, transverse or oblique along the greater axis of the pulmonary arteries. CT examinations in 9-mm thick sections with and IV contrast injection demonstrate the contact of the tumor with the mediastinum. The digital angiograms have been taken with an intravenous injection into a vein of the bend of the elbow or into a femoral vein. Six cases have been verified at surgery. In all cases, the invasion predicted with MRI proved to be correctly assessed. In three cases, MRI provides additional information to the combined findings of CT and DSA. MRI is a good complement for the preoperative assessment of patients with large tumors invading the mediastinum but for which curative surgery is indicated.

Bronchial Neoplasms

Phase II study of an intensive combination chemotherapy with cisplatin, adriamycin, etoposide and cyclophosphamide (CAVE) in small cell lung cancer.

One hundred and twelve patients with small cell lung cancer (SCLC) were treated with a combination (CAVE) of cisplatin (60 mg/m2 day 1), adriamycin (45 mg/m2 day 1), etoposide (80 mg/m2 days 1-2-3) and cyclophosphamide (1 g/m2 day 1) given every 4 weeks. A total of 10 courses were given. Response evaluation was initially evaluated after the first two courses of CAVE and repeated at least after treatment completion. This regimen was associated with severe hematological toxicity, mainly leucopenia; five toxic deaths related to sepsis were observed. One hundred and one patients were evaluable for response: 63 with limited disease and 49 with extensive disease. Overall complete and partial response rates after the first two courses of chemotherapy were 16% and 63% respectively but 14 late complete responses were documented, leading to a 30% total complete response rate; 38% in patients with limited disease and 19% in those with disseminated disease. Median overall survival was 46 weeks with a 17% 2 year survival. The only significant prognostic factor for survival was the type of response. There was no survival difference between 'early' and 'late' complete responders. Complete responders had a 75 week median survival time with a 34% 2 year survival. CAVE is thus an effective regimen for SCLC, but with a considerable toxicity.

Adult

Pathogenesis of autonomous thyroid nodules: in vitro study of iodine and adenosine 3',5'-monophosphate metabolism.

The in vitro characteristics of iodide and cAMP metabolism have been compared in tissues from autonomously functioning thyroid nodules and their quiescent counterpart to test the hypothesis that autonomy may result from constitutive activation of the tissue's TSH, cAMP, and protein phosphorylation regulatory axis, as in vivo nodular tissue took up more iodide. This effect was entirely due to increased transport capacity, the affinity of iodide transport, and the fractional binding of iodide to protein remaining unchanged. However, at high concentrations total iodide binding to protein was similar in quiescent and nodular tissue. In both tissues, this metabolic step was enhanced by phorbol esters and the ionophore A23187. As evaluated by autoradiography of two-dimensional gel protein electrophoregrams, no differences in the patterns of protein synthesis or phosphorylation between quiescent and nodular tissue were found. Basal cAMP levels were similar in quiescent and nodular tissue. The cAMP response to TSH was lower in nodular tissue, with no change in sensitivity or kinetics; both tissues responded to forskolin. No systematic suppression of iodide inhibition or abnormal responses to other hormones or neurotransmitters were found. Three proteins (24K-1, 24K-2, and 26K) were phosphorylated only in the presence of TSH or forskolin in both quiescent and nodular tissue. One protein substrate (20K) was phosphorylated in the presence of TSH in the quiescent, but not in the nodular, tissue. In conclusion, 1) slices from autonomous thyroid nodules reproduce the in vivo characteristics of the lesion and are, therefore, a suitable in vitro experimental model for biochemical studies; 2) taken together with data from transplantation experiments, the reproduction in vitro or its in vivo characteristics suggest an inherent defect in the nodule; 3) the homogeneity of biochemical findings within each nodule is compatible with the clonality of the lesion; 4) the autonomous nodule is a minimal deviation tumor; and 5) the characteristics of the TSH, cAMP, protein phosphorylation cascade are qualitatively normal, and autonomy does not result from constitutive activation of this system; and 6) a 20K protein, not phosphorylated in response to TSH in the nodule, could represent an absent negative controlling element.

Adult

Subrenal capsule assay for fresh human tumors in immunocompetent mice; an inappropriate technique for non-small cell lung cancer.

The subrenal capsule assay (SRA) seems to present some difficulties for the evaluation of the chemosensitivity of antineoplastic agents against fresh tumor xenografts. A study was therefore carried out to verify whether two different xenografts would behave in a similar way. Tumors such as melanoma provided adequate homogeneous material for this technique, while non-small cell lung carcinoma (NSCLC) were heterogeneous since the 1 mm3 specimen grafted under the renal capsule usually contained diffuse areas of necrosis and of infection. Furthermore, a large proportion of the grafted specimens, 257 out of 298, did not contain any tumor at all on microscopic examination even when they showed macroscopic growth. Added to these discrepancies, a random microscopic analysis of 180 adjacent fragments of NSCLC and melanomas demonstrated that the variability of heterogeneous tumors precludes any meaningful comparison between homologous tumor tissues designed to be grafted on treated and on control mice. The anti-inflammatory effect of chemotherapeutic drugs on the host's reaction to the graft is probably responsible for the differences between the macroscopic growth results observed in pieces grafted to both treated and control mice: however, it could not be simulated by hydrocortisone (HC) under our experimental conditions. This allows us to conclude that fresh tumors from NSCLC cannot be used in SRA.

Animals

Increased plasma motilin concentrations in small cell carcinoma of the lung.

Plasma samples from 21 patients with small cell carcinoma of the lung were screened for pancreatic polypeptide, somatostatin, motilin, and vasoactive intestinal polypeptide. One patient had severe impairment of both renal and liver function. In the 20 remaining subjects vasoactive intestinal polypeptide concentrations were normal, and only two patients had increased concentrations of somatostatin. Increases in pancreatic polypeptide were detected more commonly (7/20), but these may have been non-specific age related increases. The major finding was high concentrations of motilin (greater than 496 pg/ml) in 17 of 20 patients. Plasma motilin was subsequently assayed in 16 more patients with lung cancer, including 10 patients with non-small cell carcinoma of the lung. At concentrations over 900 pg/ml plasma motilin appears to be a tumour marker for small cell carcinoma of the lung with acceptable sensitivity (59%) and specificity (78%). The origin of increased plasma motilin in small cell carcinoma of the lung was investigated. Bombesin (gastrin releasing peptide), a peptide known to stimulate the release of motilin in man, was, as in previous studies, detected in tumour but not in plasma, except in one patient out of 21. Immunohistochemical studies failed to detect motilin antigen in biopsy samples. Motilin tumour content was found to be low in tumour tissue from three patients with small cell carcinoma of the lung who had appreciable hypermotilinaemia and from three patients with non-small cell carcinoma of the lung who had either normal or slightly raised plasma motilin concentrations. The stimulus to motilin secretion in patients with small cell carcinoma of the lung remains unclear.

Adult

[Polychemotherapy of undifferentiated small cell bronchial cancer. Long-term results].

Long-term results of 2 studies combining etoposide and adriamycin with cisplatin (CAV) or cyclophosphamide (AVE) in small cell lung cancer indicate a 2-year survival rate of 22% and 18% respectively. The complete response rate 2 years after the onset of chemotherapy was 8% (8/98) : 11% (4/36) with CAV and 5% (4/62) with AVE. Among these 8 patients, 2 had a late relapse and one died of an unrelated cause. The actual long-term survival rate was 6% with CAV and 5% with AVE.

Adult

A randomized study comparing a high and a standard dose of cisplatin in combination with etoposide in the treatment of advanced non-small-cell lung carcinoma.

We conducted a randomized trial comparing a high (120 mg/m2 day 1) v a standard (60 mg/m2 day 1) dose of cisplatin in combination with etoposide (120 mg/m2 days 3, 5, and 7) in advanced non-small-cell lung carcinoma (NSCLC). Two hundred forty-one patients were evaluable for survival and 207 for response. We obtained a 25% objective response rate in the standard-dose arm and 29% in the high-dose arm; this difference was not statistically significant. There was no significant improvement in the overall survival or survival of responders with the high-dose regimen. However, toxicity (mainly myelosuppression) was significantly increased in the patients receiving the higher dose of cisplatin. An analysis of prognostic factors showed that disease progression, loss of body weight, performance status, and prior therapy were predictive parameters of survival.

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