SUPERFICIAL BLADDER TUMORS AND INCREASED REACTIVITY AGAINST MYCOBACTERIAL ANTIGENS BEFORE BACILLUS CALMETTE-GUERIN THERAPY

Purpose

The precise mechanism of action of bacillus Calmette-Guerin (BCG) in bladder cancer treatment remains poorly understood. Whether bladder tumor cells are destroyed by nonspecific mechanisms or targeted by specifically activated lymphocytes recognizing cognate antigens is unclear. To investigate a possible cross-reactivity between BCG and bladder cell tumors, we tested before BCG treatment the lymphoproliferation of peripheral blood lymphocytes against several mycobacterial antigens, including the secreted fibronectin binding antigen 85 complex from BCG (AG 85) in patients with superficial bladder tumors compared to control matched patients.

Materials and Methods

Using a whole blood assay, T cell response against purified protein derivative, BCG extract, whole BCG, purified AG 85, and the nonspecific mitogens pokeweed and phytohemagglutinin was investigated in 79 patients with superficial bladder tumors before BCG and in 39 control subjects without malignancy matched for age and sex. Neither group had a history of tuberculosis. Lymphoproliferation was measured with a tritiated thymidine uptake assay on day 7 of culture.

Results

Of the 79 patients with superficial transitional cell carcinoma, a significant lymphoproliferative response before BCG against PPD, BCG extract, whole BCG and AG 85 was observed in 65 (82.2%), 67 (84.81%), 30 (37.97%) and 49 (62.02%) patients, respectively. Of the 39 controls only 26 (64.1%), 23 (58.9%), 3 (7.7%) and 3 (7.7%) patients, respectively, had a significant lymphoproliferation against PPD, BCG extract, BCG and AG 85 (p >0.05, p = 0.004, p = 0.00001 and p = 0.00001, respectively). In terms of lymphoproliferative levels, patients with superficial transitional cell carcinoma also showed a significantly higher response against PPD (p = 0.000012), BCG extract (p = 0.000001), AG 85 (p = 0.000001), whole BCG (p = 0.00001) and pokeweed (p = 0.01) than controls but not against phytohemagglutinin.

Conclusions

Patients with superficial transitional cell carcinoma demonstrate an increased lymphoproliferation against mycobacterial antigens before BCG compared to control subjects. Although a nonspecific activation of the immune system cannot be excluded at this stage, our data may suggest the possible existence of bladder cancer antigens cross-reactive with mycobacterial antigens responsible for boosting precursor cells witnessing previous contacts with mycobacteria. The implication of these findings in the antitumoral mechanism of action of BCG are under investigation.     

IN VIVO PHOTOINDUCTION OF METALLOTHIONEIN IN HUMAN SKIN BY ULTRAVIOLET IRRADIATION

The aims of this study were to confirm and substantiate the in vivo cutaneous induction of metallothionein (MT) in human skin by UVR, which we have reported in brief previously, and to make a preliminary attempt to characterize the time course of this phenomenon. Buttock skin in 32 volunteers was irradiated with 2 MED of UVB and biopsies were taken at 24 h from matched non-irradiated and irradiated sites. In the kinetic study, skin biopsies from six volunteers were taken at 0, 2, 8, 24, and 48 h after 2 MED UVB irradiation. MT was immunolocalized in formalin-fixed, paraffin-embedded tissue with the monoclonal antibody E9 by an indirect immunoperoxidase method. Statistically significant differences between immunocytochemical scores were identified between non-irradiated (NI) and irradiated (I) skin within suprabasal keratinocytes (mean: NI=1·2, I=5·1; P =0·01), superficial dermal fibroblasts (mean: NI=2, I=43; P <0·001), mid-dermal fibroblasts (mean: NI=0, I=27; P<0·001), and deep dermal fibroblasts (mean: NI=0,1=11; P<0·001. In the kinetic study, no consistent rise in MT score with time was observed for the epidermal component. In dermal fibroblasts, however, the first statistically significant rise in immunocytochemically detectable MT was detected at 2 h and this was found to plateau beyond 8 h. These results confirm that ambient levels of UV irradiation are capable of inducing MT in human skin in vivo . Taken together with the relative rapidity of the response, this suggests a physiological photoprotective role for MT in human skin cells. The lack of a kinetic increase in epidermal MT may be due to high basal levels. Induction of MT in dermal fibroblasts may reflect the effects of a diffusible factor released from keratinocytes after UVR.     

Cutis Laxa (Generalized Elastolysis) A Report of Four Cases with Autopsy Findings

Four children with cutis laxa (generalized elastolysis) are reported. The first three cases were siblings from a Canadian Indian family and the fourth case was the only affected child in an American Black family. Loose and sagging skin folded over the face, neck and trunk, gave a premature senile appearance. Post-mortem examination was performed on the first three cases. The most common and serious visceral involvement was development of pulmonary emphysema. This was present in two autopsied cases and was demonstrated by chest X-ray in the fourth case. Other abnormalities included large inguinal and perineal hernia, rectal diverticulum and multiple diverticulae of the urinary bladder.     

Radiofrequency Catheter Ablation of Idiopathic Recurrent Ventricular Tachycardia with Right Bundle Branch Block, Left Axis Morphology

Idiopathic ventricular tachycardia with right bundle branch block and left axis deviation morphology is a well described clinical syndrome. Previous sludies have mapped the tachycordia focus to the inferior septal region at the base of the posterior papillary muscle of the left ventricle. We describe two typical cases in a 20-year' old man and 29-year-old woman in which the tachycardia focus was localized with endocardial mapping techniques. In both cases the ventricular tachycardia focus was ablated with application of radiofrequency current at the inferior septal region. There were no complications of the procedures. The patients remain asymptomatic over follow-up of 7 and 4 months, respectively.     

Variants of Preexcitation—Specialized Atriofascicular Pathways, Nodofascicular Pathways, and Fasciculoventricuiar Pathways:

Variants of Preexcitation. introduction: In the present report, the electrophysiiologic findings in patients with different types of variants of preeexcitwtion, i.e., atriofascicualr, nodofacicular, and fasciculoventricular fibers, and the results of radiofrequency catheter ablation using different target sites are described. Methods and Results: Twelve patients (mean age 36 ± 17 years) with variants of the preexcitation syndromes underwent electrophysiologic study and radiofrequency catheter ablation. The atrial origin of atriofascicular pathways remote from the normal AV node was assessed by application of late atrial extrastimuli that advanced (“reset”) the timing of the next QRS complex without anterograde penetration into the AV node. In patients with atriofacicular pathways, ablation of the accessory pathway or the retrograde fast AV node pathway was attempted. Ablation of the atriofascicular pathways was guided by a stimulus-delta wave interval mapping in the first live patients and by recording of atriofascicular pathway activation potentials in the next five patients. A nodofascicular pathway was suggested if VA dissociation occurred during tachycardia and if atrial extrastimuli failed to reset the tachycardia without anterograde penetration into the AV node. A fasciculoventricular connection was suggested if the proximal insertion of the accessory pathway was found to arise from the His bundle or bundle branches. The PR interval was expected within normal limits during sinus rhythm and the QRS complex to he slightly prolonged with a discrete slurring of the R wave, suggesting a small delta wave. Ten of the 12 patients had evidence for atriofascicular pathways and one patient each for a nodofascicular and fasciculoventricular pathway. In six patients, the atriofascicular pathways were successfully ablated, and in two patients, the retrograde fast AV node pathway. In one patient, a concealed right posteroseptal accessory AV pathway served as the retrograde limb and was successfully ablated. The nodofascicular pathway was shown to he a bystander during AV node reentrant tachycardia. After successful fast AV node pathway ablation resulting in marked PR prolongation, no preexcitation was present during sinus rhythm because of the proximal insertion of the nodofascicular pathway distal to the delay producing parts of the AV node. The proximal insertion of the fasciculoventricular pathway was suggested to arise distal to the AV node at the site of the penetrating AV bundle. The earliest ventricular activation at the His-bundle recording site indicated the ventricular insertion of this accessory connection into the ventricular summit. The fasciculoventricular connection gave rise to a fixed ventricular preexcitation and served as a bystander during orthodromic AV reentrant tachycardia incorporating a left-sided accessory AV pathway.