Intraoperative radiotherapy in stage I and II lung cancer

Lung cancer is the leading cause of cancer deaths in both men and women in the United States. Treatment depends on the type and stage of lung cancer. For stage I and II cancer, surgery is usually the treatment of choice. Radiation therapy is used in patients who are considered poor risks for surgical resection. Intraoperative brachytherapy is an effective alternative to external irradiation in this group of patients. From 1958 to 1984, 55 patients with non-small-cell lung cancer were explored at Memorial Sloan Kettering Cancer Center and found to have surgical stage I or II tumors, which were considered to be unresectable mainly because of severe obstructive pulmonary disease precluding adequate resection. All these patients were treated with intraoperative brachytherapy at the time of the thoracotomy. Forty-four percent of these patients received in addition external irradiation, mainly to the mediastinum. The overall 5-year survival calculated by the Kaplan-Meier Method was 32%, and the local disease-free survival was 63%. Cox regression multivariant analysis demonstrated that there is a distinct subgroup with a better prognosis based on tumor site and patient's age--ie, patients who were younger than 58 years of age and had right-side lesions.     

Tuberculosis of the upper limb joints

Summary Seventy-four cases of tuberculosis of the upper limb joints (sterno-clavicular 1; shoulder 12; elbow 42; wrist 10 and fingers 9), treated by two of the authors, were reviewed. Eighty-seven percent presented at an advanced stage of destruction. The diagnosis was proved in 71 out of 74 cases. In most, the treatment was 6–12 months of chemotherapy, plaster immobilization (in order to prevent or correct deformity) and functional rehabilitation whenever possible. The sterno-clavicular and finger joints were not immobilized. Response to chemotherapy was favourable in 66 of the patients followed up. One relapse occurred at the 18th month.The affected shoulder joints healed with loss of movement, but were not painful. At the elbow, ten patients developed spontaneous bony fusion in the right-angle position, 27 had a useful range of motion and 19 had more than 70° of flexion-extension movement. One patient had an arthrodesis. At the wrist, two patients healed with painful stiffness and an arthrodesis was performed. All the finger lesions healed with painless stiffness which did not interfere much with function because rehabilitation had been started early. The authors believe that conservative management usually gives better results than arthrodesis or excision of the joint.

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Résumé Les auteurs rapportent les résultats de leur expérience dans 74 cas d'ostéo-arthrite tuberculeuse du membre supérieur: 1 sterno-claviculaire, 12 scapulo-humérales, 42 coudes, 10 poignets et 9 articulations des doigts, toutes traitées personnellement par les deux auteurs principaux. Sur le plan diagnostique, 87% des patients se présentaient à un stade de destruction avancée. Le diagnostic de certitude fut obtenu dans 71 cas sur 74. Dans la majorité des cas, le traitement a été standardisé: chimiothérapie de 6 à 12 mois, immobilisation plâtrée pour prévenir ou corriger les déformations, suivie de reéducation chaque fois que possible. Les lésions de la sterno-claviculaire et des doigts ne furent pas immobilisées. Les résultats ont été bons en ce qui concerne la chimiothérapie: 66 réponses favorables chez 66 patients suivis. Il y a eu une rechute au 18éme mois. Du point de vue orthopédique, les lésions scapulo-humérales ont guéri avec une raideur de l'épaule toujours importante mais indolore. Au niveau du coude, 10 patients évoluèrent vers la fusion osseuse précoce spontanée, qui se fit à 90° de flexion grâce à l'immobilisation plâtrée; 27 guérirent avec une conservation variable des mouvements du coude dans un secteur fonctionnel et 19 d'entre eux présentaient plus de 70° d'étendue de flexion; 1 patient fut arthrodésé. Au niveau du poignet, 2 patients guérirent avec une raideur douloureuse qui nécessita une arthrodèse. Les lésions des doigts guérirent avec une raideur plus ou moins marquée, bien compensée par la mobilité des autres articulations, conservée intacte par la reéducation. Les auteurs concluent à la meilleure qualité des résultats du traitement conservateur que des classiques interventions d'arthrodèse ou de résection articulaire.

     

Beyond C4d: Other Complement-Related Diagnostic Approaches to Antibody-Mediated Rejection

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor-independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody-mediated injury and T-cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.     

Thyrotrophin-Releasing Hormone Raises Cytosolic Free Calcium Concentration in Human Adenomatous Somatotrophs and Corticotrophs; Comparison with in vivo Responsiveness to Thyrotrophin-Releasing Hormone in Patients with Acromegaly or Cushing's Disease

The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca²⁺ concentration, [Ca²⁺)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca²⁺]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca²⁺ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca²⁺ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca²⁺]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca²⁺]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca²⁺]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca²⁺]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca²⁺]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca²⁺]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca²⁺]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca²]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide.     

Simian virus 40 in humans

Simian virus 40 (SV40) is a monkey virus that was administered to human populations by contaminated vaccines which were produced in SV40 naturally infected monkey cells.     

Immunoglobulin heavy chain Diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement.
DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences.
Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen.
The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.     

Changes in Neutrophil Oxidative Potential in Patients Undergoing Cardiopulmonary Bypass with Polypropylene Hollow Fiber Oxygenators

Neutrophil oxidative metabolism, C3d and beta 2 microglobulin levels, were assessed in nine consecutive patients undergoing cardiopulmonary bypass surgery with polypropylene hollow fiber oxygenators for open cardiac operations. Generation of oxygen free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and phorbol myristate acetate. A significant increase in light emission was detected by using both of the chemiluminescence stimulators. Moreover, a remarkable and significant increase in C3d levels was found already at 10 min. Conversely minimal changes in levels of beta 2 microglobulin were detected during cardiopulmonary bypass surgery. These data suggest that the impact of the patient blood with the foreign surface of cardiopulmonary bypass results in activation of phagocyte cells with increased potential in oxygen consumption. These effects could be partially complement-mediated.