Hypersensitivity of human lymphocytes to UV-B and solar irradiation.

T-lymphocytes from three normal human donors, irradiated with broad-spectrum UV-B (peak emission, 312 nm), are 20-fold more sensitive than fibroblasts from four normal donors in a clonogenic assay. We have compared the formation of thymine cyclobutane dimers and pyrimidine-(6-4)-pyrimidone photoproducts following irradiation by UV-C (254 nm) and UV-B and studied killing at doses giving equal dimer formation. UV-B killing of fibroblasts appears to be associated with dipyrimidine photoproduct formation, whereas UV-B killing of lymphocytes is mediated by nondimer damage. Strand breakage following UV-B irradiation measured using the "Comet" assay (single cell gel electrophoresis) reflects this nondimer damage and has kinetics consistent with excisable damage. Lymphocytes from three excision-deficient xeroderma pigmentosum donors show reduced strand breakage and increased killing following UV-B irradiation, compared with lymphocytes from normal donors. We therefore suggest that UV-B kills human lymphocytes by excisable nondimer damage and that xeroderma pigmentosum lymphocytes are defective in its repair. The putative nondimer damage does not appear to be associated with radical attack, and the strand breakage is not a manifestation of apoptosis. A 1-min exposure of human lymphocytes in vitro to natural sunlight is sufficient to produce damage measurable by the Comet assay.

The cancer-free phenotype in trichothiodystrophy is unrelated to its repair defect.

The DNA repair-deficient genetic disorders xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) can both result from mutations in the XPD gene, the sites of the mutations differing between the two disorders. The hallmarks of XP are multiple pigmentation changes in the skin and a greatly elevated frequency of skin cancers, characteristics that are not seen in TTD. XP-D and most TTD patients have reduced levels of DNA repair, but some recent reports have suggested that the repair deficiencies in TTD cells are milder than in XP-D cells. We reported recently that inhibition of intracellular adhesion molecule-1 (ICAM-1) expression by UVB irradiation was similar in normal and TTD cells but increased in XP-D cells, suggesting a correlation between ICAM-1 inhibition and cancer proneness. In the first part of the current work, we have extended these studies and found several other examples, including XP-G and Cockayne syndrome cells, in which increased ICAM-1 inhibition correlated with cancer proneness. However, we also discovered that a subset of TTD cells, in which arg112 in the NH2-terminal region of the XPD protein is mutated to histidine, had an ICAM-1 response similar to that of XP-D cells. In the second part of the work, we have shown that TTD cells with this specific NH2-terminal mutation are more sensitive to UV irradiation than other TTDs, most of which are mutated in the COOH-terminal region, and are indistinguishable from XP-D cells in cell killing, incision breaks, and repair of cyclobutane pyrimidine dimers. Because the clinical phenotypes of these patients do not obviously differ from those of TTDs with mutations at other sites, we conclude that the lack of skin abnormalities in TTD is independent of the defective cellular responses to UV. It is likely to result from a transcriptional defect, which prevents the skin abnormalities from being expressed.

Sustained angina relief 5 years after transmyocardial laser revascularization with a CO(2) laser.

BACKGROUND: Although transmyocardial laser revascularization (TMR) has provided symptomatic relief of angina over the short term, the long-term efficacy of the procedure is unknown. Angina symptoms as assessed independently by angina class and the Seattle Angina Questionnaire (SAQ) were prospectively collected up to 7 years after TMR. METHODS: Seventy-eight patients with severe angina not amenable to conventional revascularization were treated with a CO(2) laser. Their mean age was 61+/-10 years at the time of treatment. Preoperatively, 66% had unstable angina, 73% had had >/=1 myocardial infarction, 93% had undergone >/=1 CABG, 42% had >/=1 PTCA, 76% were in angina class IV, and 24% were in angina class III. Their average pre-TMR angina class was 3.7+/-0.4. RESULTS: After an average of 5 years (and up to 7 years) of follow-up, the average angina class was significantly improved to 1.6+/-1 (P=0.0001). This was unchanged from the 1.5+/-1 average angina class at 1 year postoperatively (P=NS). There was a marked redistribution according to angina class, with 81% of the patients in class II or better, and 17% of the patients had no angina 5 years after TMR. A decrease of >/=2 angina classes was considered significant, and by this criterion, 68% of the patients had successful long-term angina relief. The angina class results were further confirmed with the SAQ; 5-year SAQ scores revealed an average improvement of 170% over the baseline results. CONCLUSIONS: The long-term efficacy of TMR persists for >/=5 years. TMR with CO(2) laser as sole therapy for severe disabling angina provides significant long-term angina relief.

Tumor necrosis factor-alpha and interferon-gamma inhibit insulin secretion and cause DNA damage in unweaned-rat islets. Extent of nitric oxide involvement.

Nitric oxide has been implicated as one possible mediator of interleukin-1 beta (IL-1)-induced inhibition of insulin secretion and islet cell damage. The aim of this study was to define the effects of tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) on nitric oxide production, insulin secretion, and DNA damage in islets from unweaned rats. Treatment of islets with 0.5-500 U/ml of either TNF or IFN on their own inhibited glucose-stimulated insulin secretion in a dose-dependent manner (minimum effective dose 5 U/ml). In combination, the cytokines exerted a pronounced synergistic inhibitory effect on secretion and were equipotent at causing a significant and concentration-dependent increase in culture medium nitrite levels, islet cyclic GMP formation, and DNA damage. Used alone or in combination, TNF and IFN significantly enhanced the activity of inducible nitric oxide synthase as determined by measuring the conversion of 14C-labeled arginine to 14C-labeled citrulline and nitric oxide. Use of arginine-free medium, without or with NG-monomethyl-L-arginine, resulted in inhibition of nitrite formation by 5-1,000 U/ml IFN+TNF and partial restoration of the insulin secretory response to glucose. Treatment of rat islets with increasing doses of TNF+IFN (5, 50, and 500 U/ml) resulted in a progressive increase in DNA damage, as shown by the comet assay, which detects DNA strand breaks in individual islet cells. The DNA damage caused by an intermediate concentration (50 U/ml) of TNF+IFN was comparable to that generated by IL-1 when used at 20 U/ml. We conclude that TNF and IFN induce nitric oxide formation, which partially inhibits glucose-induced insulin secretion and causes significant DNA strand breakage, but that as cytokine concentrations increase, non-nitric-oxide-mediated events predominate.

Ultrasound diagnosis of pseudoaneurysm and contiguous ventricular septal defect complicating inferior myocardial infarction.

Two patients with recent inferior myocardial infarction were found by two-dimensional and Doppler echocardiography to have both an inferior wall pseudoaneurysm and a contiguous rupture of the posterior ventricular septum. The pseudoaneurysm was not suspected clinically in either patient. In one patient, a complex or dissecting septal rupture was visualized in detail. To our knowledge, the combined defect has not previously been diagnosed during life by noninvasive methods.

Effects of distant potentials on unipolar electrograms in an animal model utilizing the right ventricular isolation procedure.

The effects of distant potentials on local epicardial unipolar electrograms were examined utilizing a model that enabled both ventricles to be paced independently in five dogs. The right ventricular isolation procedure electrically isolates the right from the left ventricle. Right ventricular electrograms were separated into their local (right ventricular) and distant (left ventricular) components by altering the left-right ventricular pacing interval. Waveform configuration, peak to peak amplitude, magnitude of the slope and timing of the fastest downstroke were carefully evaluated at each electrode site, both with and without the presence of distant left ventricular potentials. Except for the timing of the fastest downstroke, all of these variables were significantly altered by distant potentials. Although the slope of the fastest downstroke was significantly affected by distant potentials, it remained a sensitive indicator of local versus distant activation. All electrograms of local right ventricular activation had a slope magnitude greater than 2.5 mV/2 ms whereas none of the right ventricular electrograms containing only distant left ventricular activity had a magnitude greater than 2.5 mV/2 ms. Computer-generated electrograms were calculated by digitally summing the recorded local right and distant left ventricular components. The simulated electrograms correlated well with the recorded electrograms during synchronous ventricular pacing. Thus, the configuration, amplitude and slope of unipolar electrodes were profoundly influenced by distant potentials. The timing of the fastest downstroke is largely independent of the effect of distant potentials and most closely represents local activation. The magnitude of the slope of the recorded electrogram accurately distinguishes local from distant activation.

Improvement in inducible ischemia during dobutamine stress echocardiography after transmyocardial laser revascularization in patients with refractory angina pectoris.

OBJECTIVES: The purpose of this ongoing study is to determine whether transmyocardial laser revascularization (TMLR) can lessen inducible ischemia and improve contractile reserve in patients with refractory angina pectoris. BACKGROUND: TMLR is an emerging surgical technique for the treatment of myocardial ischemia and angina pectoris not amenable to conventional percutaneous or surgical revascularization. Objective data documentating a reduction in ischemia during noninvasive stress testing after TMLR are rare. METHODS: Fifteen patients with severe coronary artery disease unsuitable for treatment with standard revascularization techniques were studied with dobutamine stress echocardiography (DSE) before TMLR. Of the 12 patients who underwent TMLR, DSE was repeated at 3 months postoperatively in 11 patients and at 6 months in 9 patients. Stress echocardiograms were analyzed for inducible ischemia, with calculation of the wall motion score index (WMSI). Heart rate and dobutamine dose achieved at peak stress were also assessed as indexes of stress tolerance. RESULTS: Compared with that before TMLR, wall motion at rest for all myocardial segments did not change significantly after TMLR, although there was a mild improvement in the WMSI of the lased myocardial regions ([mean +/- SD] 1.64 +/- 0.34 after vs. 1.78 +/- 0.34 before TMLR, p < 0.05). Overall WMSI at peak stress improved markedly after TMLR (1.70 +/- 0.30 after vs. 2.06 +/- 0.31 before TMLR, p < 0.002), with the improvement in WMSI limited to the lased segments only (1.47 +/- 0.31 after vs. 2.15 +/- 0.34 before TMLR, p < 0.0004). The improvement in WMSI with stress resulted primarily from a decrease in the percentage of ischemic segments (47% before vs. 23% after TMLR, p < 0.0008), with no change in the percentage of infarcted segments (23% before vs. 26% after TMLR). Heart rate (83 +/- 5 beats/min before vs. 102 +/- 21 beats/min after TMLR, p = 0.01) and dobutamine infusion rate (26 +/- 9 micrograms/kg body weight per min before vs. 34 +/- 9 micrograms/kg per min after TMLR) achieved at peak stress also increased postoperatively, consistent with improved stress tolerance. The reduction in ischemic wall motion abnormalities and improved stress tolerance persisted at 6 months, without evidence of further improvement or deterioration of function over time. CONCLUSIONS: TMLR performed in patients with refractory angina pectoris reduces ischemic wall motion abnormalities and improves stress-induced tolerance during dobutamine echocardiography. These beneficial effects persist up to 6 months postoperatively.

Perioperative morbidity and mortality after transmyocardial laser revascularization: incidence and risk factors for adverse events.

OBJECTIVES: The purpose of this study was to describe the incidence and spectrum of perioperative cardiac and noncardiac morbidity and mortality after transmyocardial laser revascularization (TMR) and to identify predictors of these adverse clinical events. BACKGROUND: Clinical studies have demonstrated the efficacy of TMR for relieving angina pectoris, although no study to date has specifically addressed the associated perioperative morbidity and mortality. METHODS: Between October 1995 and August 1997, 34 consecutive patients with end-stage coronary artery disease (CAD) underwent isolated TMR. The majority of patients (94%) had class III or IV angina pectoris, and two patients (6%) had unstable symptoms preoperatively. Patient records were reviewed for fatal and nonfatal adverse cardiac and noncardiac events. RESULTS: Perioperative death occurred in two patients (5.9%) due to cardiogenic shock complicating acute myocardial infarction. Perioperative cardiac morbidity occurred in 16 patients (47.1%); noncardiac morbidity was seen in 12 patients (35.3%). Preoperative unstable angina was the only variable predictive of perioperative death (p = 0.005). Cardiac (p = 0.005) and noncardiac (p < 0.001) morbidity rates were significantly higher for the initial 15 patients undergoing the procedure. Other predictors of perioperative complications included lack of postoperative treatment with a furosemide infusion (p < or = 0.04) and preoperative unstable angina (p = 0.05). CONCLUSIONS: Perioperative mortality in patients undergoing isolated TMR is low. Transmyocardial laser revascularization patients are at higher risk for adverse perioperative cardiac and noncardiac events, likely reflecting the lack of immediate benefit from the procedure in the setting of severe CAD. These patients merit vigilant surveillance for adverse events and aggressive medical management in the perioperative period.

Early postoperative changes in regional systolic and diastolic left ventricular function after transmyocardial laser revascularization: a comparison of holmium:YAG and CO2 lasers.

OBJECTIVES: The purpose of this study was to determine the short-term effects of transmyocardial laser revascularization (TMR) on regional left ventricular systolic and diastolic function, myocardial blood flow (MBF) and myocardial water content (MWC). BACKGROUND: Clinical studies of TMR have noted a significant incidence of cardiac complications in the early postoperative period. However, the early post-treatment effects of laser therapy on the myocardium and their potential contribution to postoperative cardiac morbidity are unknown. METHODS: Swine underwent holmium:yttrium-aluminum-garnet (holmium:YAG) (n = 12) or carbon dioxide (CO2) (n = 12) laser TMR. Regional systolic function for the lased and nonlased regions was quantitated using preload recruitable work area (PRWA) and regional diastolic function with the ventricular stiffness constant alpha. RESULTS: Preload recruitable work area was significantly decreased in the lased regions both 1 (59.8+/-13.0% of baseline, p = 0.02) and 6 h (64.2+/-9.4% of baseline, p = 0.02) after holmium:YAG TMR. This decreased PRWA was associated with a significant reduction in MBF to the lased regions (13.2% reduction at 1 h, p = 0.02; 18.4% decrease at 6 h post-TMR, p = 0.01). These changes were not seen after CO2 laser TMR. A significant increase in MWC (1.4+/-0.3% increase with holmium:YAG, p = 0.004; 1+/-0.2% increase with CO2, p = 0.002) and alpha (217.4+/-44.2% of baseline 6 h post-holmium:YAG TMR, p = 0.05; 206+/-36.7% of baseline 6 h post-CO2 TMR, p = 0.03) was seen after TMR with both lasers. CONCLUSIONS: In the early postoperative setting, impaired regional systolic function in association with regional ischemia is seen after TMR with a holmium:YAG laser. Both holmium:YAG and CO2 lasers are associated with increased MWC and impaired diastolic relaxation in the lased regions. These changes may explain the significant incidence of early postoperative cardiac morbidity. The impact of these findings on anginal relief and long-term outcome are not known.

Diagnosis and course of nephrogenic ascites.

Nephrogenic ascites is a complex diagnostic problem with poorly understood pathophysiology. Morbidity and eventual mortality from this ongoing problem are significant. The diagnosis of nephrogenic ascites must be established by exclusion. We report the cases of nine patients investigated between 1978 and 1985. Laparoscopy, which was utilized in all nine patients, led to a specific diagnosis in two. We believe that a vigorous diagnostic evaluation, including laparoscopy, is essential in patients with chronic renal failure who develop persistent ascites.

Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium.

OBJECTIVE: Transmyocardial laser revascularization (TMR) is emerging as a potential treatment option for patients with end-stage CAD, and adjuvant gene therapy may be helpful in further improving the results of the procedure. However, the effects of TMR on gene transfer are unknown. METHODS: Swine underwent left thoracotomy. TMR was performed to create five channels at 2-cm intervals in the anterolateral free wall of the left ventricle (LV) followed by injection of 1 x 10(9) plaque-forming units (pfu) of a replication-deficient adenovirus vector carrying the reporter gene beta-galactosidase (Ad.Pac beta-gal). An additional five direct injections of 1 x 10(9) pfu Ad.Pac beta-gal were made at 2-cm intervals in the posterolateral LV of each heart. Control animals underwent TMR alone/vehicle alone (n = 3) or empty virus alone/no treatment (n = 3) of the anterolateral/posterolateral LV, respectively. RESULTS: ELISA revealed significantly greater transgene expression in the direct Ad.Pac beta-gal injection versus TMR plus Ad.Pac beta-gal inject regions at both 3 (n = 6) (273.0 +/- 58.5 vs. 133.4 + 28.1 pg beta-gal/g protein, P = 0.02) and 7 days (n = 6) (180.0 + 59.9 vs. 56.7 + 18.1 pg beta-gal/g protein, P = 0.02) postoperatively. At 14 days postoperatively (n = 2), no transgene expression was detected in either region. No transgene expression was detected in any of the control regions at 3 days postoperatively. CD-18 staining revealed significantly greater inflammation in the TMR plus Ad.Pac beta-gal and TMR alone regions as compared to Ad.Pac beta-gal or vehicle (P < 0.001). CONCLUSIONS: Adenoviral-mediated gene transfer in conjunction with TMR is possible, although TMR appears to limit the degree of transgene expression attained as compared to direct intramyocardial injection alone, likely due to the greater immune response observed with the former. These findings may have important implications for therapeutic strategies aimed at combining TMR with gene therapy for CAD.

Ultraviolet-B-induced apoptosis and cytokine release in xeroderma pigmentosum keratinocytes.

We have assessed the ability of xeroderma pigmentosum and normal keratinocytes grown out from skin biopsies to undergo apoptosis after irradiation with ultraviolet B. Keratinocytes have been studied from xeroderma pigmentosum complementation groups A (three biopsies), C (three biopsies), D (one biopsy), xeroderma pigmentosum variant (two biopsies), and Cockayne syndrome (one biopsy). The three xeroderma pigmentosum group A and the xeroderma pigmentosum group D samples were at least six times more sensitive than normal cells to ultraviolet B-induced apoptosis. The xeroderma pigmentosum variant samples showed intermediate susceptibility. Xeroderma pigmentosum group C samples proved heterogeneous: one showed high sensitivity to apoptosis, whereas two showed near normal susceptibility. The Cockayne syndrome sample showed the high susceptibility of xeroderma pigmentosum groups A and D only at a higher fluence. These results suggest that the relationships between repair deficiency, apoptosis, and susceptibility to skin cancer are not straightforward. Ultraviolet B-induced skin cancer is also thought to be due in part to ultraviolet B-induced impairment of immune responses. The release of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha from cultured xeroderma pigmentosum keratinocytes tended to occur at lower fluences than in normals, but was less extensive, and was more readily inhibited at higher fluences of ultraviolet B.

Transient assay, by [3H]guanine incorporation of Escherichia coli xanthine-guanine phosphoribosyl transferase (GPT) in transfected human fibroblasts.

We have used [3H]guanine incorporation as a rapid and sensitive assay of xanthine-guanine phosphoribosyl transferase (GPT) activity in SV40 transformed human fibroblasts. The SV40 early promoter is more efficient than the Rous sarcoma virus long terminal repeat for transient expression of the gpt gene. The assay works well in a derivative of AT5BIVA which lacks hypoxanthine-guanine phosphoribosyl transferase (hprt-) and we show here how the assay has been adapted to work in the hprt+ AT5BIVA parent.

SV 40-transformed normal and DNA-repair-deficient human fibroblasts can be transfected with high frequency but retain only limited amounts of integrated DNA.

The ability of simian virus 40-transformed human fibroblasts to integrate and maintain transfected genomic DNA has been investigated in two normal and six DNA-repair-deficient human cell lines. These cell lines were transfected with DNA containing two selective markers (G418 and hygromycin (Hyg) resistance) separated by random pieces of human DNA of 0-40 kb in length. The transfection frequency for the selected (G418R) marker was between 2 x 10(-4) and 2 x 10(-3) for all cell lines, comparable to many other mammalian systems. About 50% of the G418R colonies were also initially resistant to Hyg. Analysis of the DNA from individual clones expanded for a further month revealed, however, that about one to three copies of the selected marker but only about 0.1 copy per cell of the unselected marker were maintained. Our results were broadly similar for all eight cell lines. Thus the amount of integrated DNA that is stably maintained in these cells is in general very small (less than 50 kb). This may provide an explanation for the difficulties encountered in many laboratories in attempts to correct the defect in DNA-repair-deficient human cells by transfection with genomic DNA. Our results also show that none of several defects in DNA repair has any obvious effect on either the transfection frequency or the amount of stably integrated foreign DNA.

Endogenous nitric oxide induced by interleukin-1 beta in rat islets of Langerhans and HIT-T15 cells causes significant DNA damage as measured by the 'comet' assay.

We have used the comet assay (single cell gel electrophoresis) to measure nitric oxide-induced DNA damage in rat islets of Langerhans and insulin-containing HIT-T15 cells. Damage was induced following treatment with the nitric oxide donor SIN-1, which also releases superoxide, but was not reduced by exogenous superoxide dismutase, suggesting that nitric oxide itself, rather than superoxide or peroxynitrite may be the active species. The DNA damaging effect of nitric oxide was easily detectable at the earliest time point tested (15 min). Damage also resulted following induction of nitric oxide synthase by the cytokine interleukin-1 beta in both islets and HIT-T15 cells and was prevented by replacing the substrate, arginine, with nitromonomethyl arginine. Thus intracellular levels of nitric oxide generated by interleukin-1 beta-induced nitric oxide synthase were sufficient to cause DNA damage in islet cells and HIT-T15 cells.

Hypersensitivity of ataxia-telangiectasia fibroblasts to a nitric oxide donor.

Ataxia-telangiectasia (A-T) is a human autosomal recessive disease characterised by immunodeficiency, extreme sensitivity to ionising radiation and progressive cerebellar ataxia. The defective gene has recently been cloned and is a member of the phosphatidylinositol 3-kinase family. We have investigated the possibility that the neurodegeneration in A-T might be induced by an endogenously formed mutagen causing radiation-like damage. Nitric oxide is known to be formed in the cerebellum and we present evidence that A-T fibroblasts are hypersensitive to killing by the nitric oxide donor S-nitrosoglutathione (GSNO), as are fibroblasts from a radiosensitive individual without ataxia. Killing was determined as loss of colony forming ability. GSNO induces dose-dependent DNA strand breakage, but to no greater extent in A-T fibroblasts. Breakdown of GSNO to nitrite and nitrate appears to occur to the same extent in both normal and A-T fibroblasts. Cell killing by GSNO appears to be associated in both types of cell with formation of nitrite, rather than nitrate, as the ultimate oxidation product of nitric oxide.

Predictors of outcome of tricuspid valve replacement in carcinoid heart disease.

The cardiac valvular surgical experience of patients in the Duke Carcinoid Database was reviewed to assess operative outcome. Of the 604 patients in the database, 19 patients with carcinoid heart disease were identified by cardiac catheterization or echocardiography, or both. Eight of these underwent tricuspid valve replacement surgery with bioprostheses (2 also had open pulmonic valvuloplasty). Compared with patients medically managed, surgically treated patients were similar with the exception that they had higher right atrial mean (17 +/- 6 vs 9 +/- 4 mm Hg, p = 0.03) and v-wave (27 +/- 6 vs 17 +/- 7 mm Hg, p = 0.04) pressures. Of the 8 surgical patients, 5 (63%) died within 30 days. Causes of death included tricuspid valve thrombosis, cerebral vascular accident, coagulopathy, renal failure, and intractable right heart failure. High comorbidity was present in all 8 patients. There was a weak trend (p = 0.17) toward lower Charlson comorbidity indexes in survivors (6.7 +/- 0.6) compared with nonsurvivors (7.6 +/- 0.9). Age was significantly lower (p = 0.036) in survivors (46 +/- 13 years) compared with nonsurvivors (69 +/- 4 years). Extended follow-up revealed 2 patients who survived beyond a decade. Review of 47 carcinoid valve replacement cases (Duke Carcinoid Database and 39 published cases) revealed a 30-day mortality of 56% for patients > 60 years of age, and 0% for those < or = 60 years of age (p < 0.0001). Although valve replacement surgery can afford prolonged palliation from carcinoid heart disease, it is associated with a significant mortality risk. Careful preoperative risk stratification by age and comorbidity may provide a means for optimal selection of surgical candidates.

Computer-assisted intraoperative mapping of the entire ventricular epicardium in the Wolff-Parkinson-White syndrome.

Intraoperative mapping with a hand-held, roving electrode requires a sustained rhythm lasting 5 to 10 minutes. To overcome this limitation, a computerized mapping system that records from 60 epicardial electrodes simultaneously was used to study 16 patients with Wolff-Parkinson-White syndrome. A sock containing 6 rows of electrodes arranged concentrically from base to apex was place over the ventricles. The total time from placing the sock to analyzing the most basal row of electrode recordings was 5 minutes. A 39 X 44-mm plaque containing 56 electrodes was than placed across the atrioventricular (AV) groove for detailed simultaneous mapping of the ventricle and atrium in the preexcited region identified from the most basal row of sock electrodes. During plaque placement and recording, the remaining sock recordings were analyzed and a complete isochronal epicardial map was drawn. The plaque recordings were then analyzed. This technique rapidly detects early activation at the AV groove as do other computer systems using only a band of electrodes around the AV groove. Also, complete epicardial mapping supplied important additional information. One patient with a posterior paraseptal accessory pathway had ventricular epicardial breakthrough below the strip recorded by the AV band. When more than 1 early activation site was present along the AV groove, complete maps allowed multiple pathways to be differentiated from normal activation fronts ascending from the bundle branches. Complete epicardial maps allowed the study of rapidly changing or short-lived electrical events including isolated premature impulses, initiation and termination of reciprocating tachycardia by pacing, entrainment and changing degrees of fusion created by pacing during reciprocating tachycardia, and ventricular responses during atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary tuberculosis in children.

A major change has occurred in the incidence and management of pulmonary tuberculosis in patients of all ages. This review emphasizes the effectiveness of drug therapy and the declining role of surgical management of pulmonary tuberculosis in children. Surgical intervention was necessary in only two of 140 children (1.4%) with proved tuberculosis, one for a large tuberculoma and the other for refractory involvement of the chest wall. The remaining 138 children were treated successfully with anti-tuberculous drugs. Pulmonary tuberculosis in children is primarily a medical disease and only rarely is surgical intervention indicated.

The role of bronchoplastic procedures in the surgical management of benign and malignant pulmonary lesions.

Conservative pulmonary resection is appropriate for the majority of patients with endobronchial neoplasms of low-grade malignant potential in the proximal airways and for a small but significant number of patients with carcinoma. A portion of the bronchus is removed, with or without lobectomy, as a sleeve resection and a primary bronchial reanastomosis is performed to preserve ventilatory function. Bronchoplastic techniques can also be used to repair traumatic airway injuries and benign strictures. The present series of bronchoplastic procedures consists of 28 patients undergoing operation with pathological diagnoses of carcinoma in 20, adenoma in six, hamartoma in one, and a post-traumatic laceration in one. There were minimal morbidity and no deaths. From 1947 to 1981 a total of 565 bronchoplastic procedures have been reported in the literature. Of these, 504 were sleeve resections for carcinoma. The remaining 61 bronchoplastic procedures were for either excision of endobronchial adenomas or repair of airway injuries of strictures. It appears that bronchoplastic procedures are the ideal surgical therapy for benign endobronchial lesions, tumors of low-grade malignant potential, such as adenomas, and for repair of airway injuries. This approach is also applicable to a select group of patients with carcinoma of th lung, and long-term survival periods comparable to those achieved by pneumonectomy can be demonstrated.