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A man with four endocardial pacemaker leads and two vegetations (1.5 cm and 1 cm) underwent successful percutaneous laser-assisted lead extraction. Although this procedure was complicated by embolization to a left pulmonary arterial branch, the patient recovered without sequelae. This article reviews the literature on lead extraction associated with large vegetations.

Multiple endocardial countershocks applied during intraoperative endocardial implantable cardioverter-defibrillator testing for the purpose of defibrillation threshold determination resulted in detectable myocardial injury in 5 of 12 patients, as indicated by elevations in cardiac troponin I levels. This injury was not associated with acute changes on the surface electrocardiogram.

In a series of 14 patients undergoing transseptal catheterization for ablation of left-sided accessory pathways, hydrogen appearance time was used to detect left-to-right shunting after removal of the catheter. Six of the 12 patients who had no evidence of shunt before catheterization had evidence of shunting after the procedure.

Introduction: Ventricular tachycardia is commonly seen in patients following surgical repair for tetralogy of Fallot. The technique of ablation for this arrhythmia is not well defined., Methods and Results: In two patients with ventricular tachycardia following surgical repair of tetralogy of Fallot, the traditional indicators for a site for ventricular tachycardia ablation did not yield cure. Based on careful mapping, the circuit was found to involve the isthmus between the outflow tract patch and the tricuspid annulus; linear radiofrequency lesions across this isthmus resulted in cure of ventricular tachycardia. Not only was the tachycardia no longer inducible, but bidirectional block at the line of ablation confirmed interruption of the reentrant circuit., Conclusion: A linear radiofrequency lesion was effective in eliminating ventricular tachycardia in both patients. The demonstration of bidirectional block confirms a cure independent of inducibility of ventricular tachycardia.

In summary, this study reports 2 important findings: (1) AV nodal modification using the conservative protocol we describe reduces long-term success for ventricular rate control during atrial fibrillation but eliminates the incidence of permanent AV block; (2) directed lesions that eliminate clinical AV nodal reentry slow ventricular response to acute atrial fibrillation but are not sufficient to control ventricular response of chronic atrial fibrillation. Further refinement of these techniques may allow an optimal balance between rate control and avoidance of permanent pacing.

The use of non-thoracotomy endocardial implantable defibrillators with pacing capabilities has increased substantially over the past 2 years. This report demonstrates that the pacing threshold increases in some patients after endocardial defibrillation, and substantiates the practice of using maximal pacing output after endocardial defibrillation.

Physiological requirements for mitochondrial respiration change during fetal and postnatal development of cardiac and skeletal muscle, particularly after the abrupt transition from the hypoxic fetal environment to the oxygen-rich milieu of the neonate. This study defines the pattern of expression of nuclear genes encoding the muscle-specific (H) and non-muscle-specific (L) isoforms of cytochrome oxidase (COX) subunit VIa during pre- and postnatal development of striated muscles in the mouse. In the early embryo, COX VIa-L was the predominant isoform expressed in all tissues. COX VIa-H mRNA was detectable as early as day 8 postcoitum (pc) in the heart, but not until gestational day 14 in skeletal myofibers of the tongue, diaphragm, and other skeletal muscles. At late fetal stages up until birth (days 16-18 pc), COX VIa-L and COX VIa-H were both expressed in striated myocytes, although the L form remained the dominant isoform. In postnatal animals, however, expression of COX VIa-H increased whereas COX VIa-L decreased in a reciprocal manner. Activation of the COX VIa-H gene also was observed during differentiation of nurine myogenic cells in culture and was followed by diminished expression of the COX VIa-L isoform in maturing myotubes, as in the intact animal. We conclude that regulation of nuclear genes encoding subunits of COX is a component of the developmental programs that govern cardiac and skeletal muscle differentiation and maturation in the mammalian fetus and neonate. COX VIa-L, the predominant isoform in all fetal tissues, is gradually replaced by the muscle-specific H isoform in both cardiac and skeletal muscles, although this transition is not complete until after birth.

Background: Cocaine and ethanol are often abused concomitantly, and this combination may be more lethal than either substance alone. Although previous studies showed that cocaine causes coronary arterial vasoconstriction, the combined effect of cocaine and ethanol on the coronary vasculature in humans is unknown. Thus, we assessed the effects of intranasal cocaine, intravenous ethanol, or a cocaine-ethanol combination on heart rate, systemic arterial pressure, and coronary arterial dimensions in humans., Methods: Thirty-four subjects with chest pain (27 men and seven women, aged 34 to 67 years) who were referred for catheterization received one of the following pharmacologic interventions: (1) intranasal (2 mL) and intravenous (5 mL/kg) saline (n = 8 [group A]); (2) intranasal cocaine (2 mg/kg) and intravenous saline (5 mL/kg) (n = 9 [group B]); (3) intranasal saline (2 mL) and intravenous 10% ethanol (5 mL/kg) (n = 9 [group C]); or (4) intranasal cocaine (2 mg/kg) and intravenous 10% ethanol (5 mL/kg) (n = 8 [group D]). Heart rate, systemic arterial pressure, left coronary arterial dimensions (by computer-assisted quantitative angiography), as well as blood cocaine, ethanol, and cocaine metabolite concentrations were measured before and 30, 60, and 90 minutes after initiation of the intravenous infusions., Results: No hemodynamic or angiographic changes were observed in the group A (saline) subjects. In the group B (cocaine) subjects, the heart rate-systolic arterial pressure product increased by 5% and 10% at 30 and 90 minutes, respectively, and coronary arterial diameter decreased by 14% at these times. In the group C (ethanol) subjects, no hemodynamic changes were noted, but coronary arterial diameters increased by 12%, 11%, and 12% at 30, 60, and 90 minutes, respectively. In the group D (cocaine-ethanol) patients, rate-pressure product increased by 17%, 10%, and 16%, and coronary arterial diameters increased by 7%, 12%, and 13%, at 30, 60, and 90 minutes, respectively., Conclusion: The combination of intranasal cocaine and intravenous ethanol causes an increase in the determinants of myocardial oxygen demand. However, it also causes a concomitant increase in epicardial coronary arterial diameter.

A class of oligonucleotides which binds to naturally-occurring duplex DNA sites at physiologic pH to form triple helical structures was used as transcription attenuators in an in vitro transcription assay. Oligonucleotides were designed to form triple helices with a purine-rich, double-stranded target by binding in the major groove in an orientation anti-parallel to the most purine-rich strand of the target. A 45 base-pair purine-rich region located within the gag gene of Friend Murine Leukemia Virus (FMLV) was used as the duplex target. The target DNA was inserted by molecular cloning downstream of either the bacterial T7- or T3 promoter. The sequence-specific interaction of the triple helix-forming oligonucleotide (TFO) with the FMLV target was confirmed by DNAse I footprint analysis. The affinity of the TFO, as measured by the equilibrium dissociation constant of the TFO for the duplex, was determined by band shift analysis. When a TFO was allowed to form a triple helix with the target duplex in well-defined buffer conditions before the transcription reaction, truncated transcripts of a predicted size were observed. Attenuation of transcription was observed only when buffer conditions favorable to triple helix formation were used. In addition, oligonucleotides containing a high percentage of guanosine residues were able to inhibit mRNA production of the bacterial T7 polymerase by a mechanism independent of transcription attenuation. The ability of an oligonucleotide-directed triple helical structure to slow down, or even completely stop, RNA chain elongation may expand the utility of triple helix technology in the area of gene regulation.

An oligonucleotide hybrid is described which possesses two triple helix forming oligonucleotides which have been connected by a flexible polymeric linker chain. As a prototype, binding of this class of oligonucleotide to duplex DNA has been studied using a segment of the HSV-1 D-glycoprotein promoter, which possesses a pair of 12bp target sites for stable triple helix formation, separated by a duplex spacer region which is one helical turn long. Band shift and footprinting analysis show that such hybrids can bind to both 12bp elements simultaneously, if flexible linkers are included which are longer than 20-25 rotatable bonds. Molecular modeling confirms that a flexible polymeric linker as short as 22 rotatable bonds is enough to link the two distant segments of triple helix, providing that the linker element travels a path which is external to the helix grooves and parallel to the long helix axis.

Oligonucleotides provide novel reagents for inhibition of gene expression because of their high affinity binding to specific nucleotide sequences. We describe a 38 base, single-stranded DNA that forms a triple helix or 'triplex' on progesterone response elements of a target gene. This triplex-forming oligonucleotide binds with a Kd = 100 nM at 37 degrees C and physiological pH, and blocks binding of progesterone receptors to the target. Furthermore, it completely inhibited progesterone receptor-dependent transcription in vitro. To approach in vivo conditions, triplex-forming oligonucleotides were tested in cell transfection studies. The derivation of the oligonucleotides with cholesterol enhanced their cellular uptake and nuclear concentration by at least four-fold. The cholesterol-derivatized triplex-forming oligonucleotide specifically inhibited transcription of the PRE-containing reporter gene in cells when applied to the medium at micromolar concentrations. This is the first demonstration of steroid-responsive gene inhibition by triplex formation and joins the growing body of evidence indicating that oligonucleotides have therapeutic potential.

We have mapped a site within exon 1 of the murine c-myc gene that forms a variety of complexes with nuclear proteins derived from the murine WEHI 231 B-lymphoma cell line in exponential growth that are altered following treatment with phorbol ester, when transcription of this gene is reduced [Levine, R.A., McCormack, J.E., Buckler, A.J. & Sonenshein, G.E. (1986). Mol. Cell Biol., 6, 4112-4116]. This site, located at +440 to +459 bp relative to the P1 promoter, contains an NK-kappa B-like binding element. The sequence of this element, AGGGAATTTTT, is unusual in that the stretch of pyrimidines is entirely T residues. Binding of NF-kappa B protein was demonstrated by oligonucleotide competition, induction of binding upon 70Z/3 pre-B- to B-cell differentiation, response to GTP in the binding reaction, reduction of binding upon addition of I kappa B protein and uv cross-linking analysis. Functional activity of this internal regulatory element (IRE) was demonstrated in transfection assays using chloramphenicol acetyl transferase (CAT) reporter constructs containing multimerized copies of the IRE driving a heterologous promoter. Mutation of the IRE within the context of the c-myc promoter prevented NF-kappa B-mediated induction of transcription of this oncogene. Thus additional NF-kappa B elements may be defined by this new sequence.

Interleukin 1 (IL-1) is a pluripotent cytokine involved in mediating a variety of physiological processes, including induction of cell proliferation upon wound healing. Treatment of quiescent FS-4 human dermal fibroblast cells with IL-1 activates c-myc gene transcription, and nuclear localization of NF-kappa B. Previously, we have noted that the murine c-myc gene contains two functional NF-kappa B sites located at -1101 to -1081 bp (upstream regulatory element [URE]) and +440 to +459 bp (internal regulatory element [IRE]) relative to the P1 promoter. Here we have demonstrated that IL-1 treatment induced binding of NF-kappa B-like proteins (p50/p65) to these c-myc elements. Heterologous promoter-CAT constructs driven by multiple copies of either the URE or IRE were IL-1 inducible when transfected into FS-4 cells. In contrast, constructs harboring elements with two G to C residue conversions, such that they were no longer able to bind NF-kappa B, were not responsive to IL-1. Mutation of these two base pairs at both NF-kappa B sites within a c-myc promoter/exon I-CAT construct, resulted in loss of inducibility with IL-1 upon transfection into quiescent FS-4 cells. Thus, IL-1 significantly induces c-myc expression through positive regulation by NF-kappa B, suggesting a role for this family of factors in activation of proliferation associated with wound healing.

Human T cell leukemia virus type 1 is the causative agent of adult T cell leukemia. The virus encodes a 40-kDa protein, tax, that is important for the immortalization of T cells. Expression of tax activates several cellular transcription factors, including NF kappa B. We have previously identified two functional NF kappa B binding sites within the murine c-myc gene: upstream regulatory element (URE) and internal regulatory element (IRE). Using transient cotransfection analysis of Jurkat or HeLa cells, we report that tax can transactivate chimeric TK-CAT constructs containing multiple copies of wild-type URE or IRE, but not constructs with mutated versions of these elements. Furthermore, tax induced transcriptional activity of murine and human c-myc promoter-CAT hybrid genes in Jurkat and HeLa cells. A mutated tax expression vector, which fails to activate NF kappa B, was unable to induce either murine or human c-myc-CAT or URE/IRE-TK-CAT constructs. Mutant c-myc gene-CAT constructs, in which the URE and IRE were mutated either singly or in combination by site directed mutagenesis, displayed significantly reduced CAT activation upon cotransfection with a tax expression vector. These results suggest that tax can transactivate the c-myc gene through NF kappa B. The tax-induced stimulation of this oncogene may play a role in T cell immortalization.

The effect on human immunodeficiency virus 1 (HIV-1) viral transcription and subsequent gene expression mediated by mixed purine-pyrimidine oligodeoxyribonucleotides (oligodeoxynucleotides) designed to form collinear DNA triplexes with purine-rich elements in the viral promoter was evaluated in intact mammalian cell lines (MT4 and U937). Oligonucleotides HIV31 (5'-GTTTTTGGGTGTTGTGGGTGTGTGTGGTTTG-3') and HIV38 (5'-TGGGTGGGGTGGGGTGGGGGGGTGTGGGGTGTGGGGTG-3') were designed to interact with the transcription initiation site (-16 to + 13) and nuclear factor Sp1 binding site (-81 to -44) of HIV-1, respectively. Oligonucleotides, synthesized with a 3' amine blocking group (5'-R-O-PO2-OCH (CHOH)-CH2-NH+3-3') to prevent degradation by cellular nucleases, were readily taken up by MT4 cells from the culture medium, achieving measured intranuclear concentrations higher than the medium in less than 2 h of incubation. The 3' amine modified oligonucleotides were recoverable from the cells after 24 h as greater than 90% intact material. Treatment of acutely infected MT4 cells with either HIV31 or HIV38 significantly inhibited viral-associated cytopathology and P24 antigen production (p less than 0.001). Additionally, inhibition of P24 antigen release, culture supernatant viral titer, and expression of the intact 9.2-kb HIV-1 mRNA was observed when the chronically infected promonocyte cell line, U937, was treated with 10 microM HIV38. Control oligonucleotides with similar base composition did not inhibit virus expression in either cell line. Furthermore, inhibition of viral expression was not due to alpha-interferon induction resulting from oligonucleotide treatment. Both HIV31 and HIV38 associate with their respective DNA target duplexes at micromolar concentrations, and a strong negative ellipticity near 210 nm, characteristic of DNA triplexes, was observed in the circular dichroism spectrum of either target-oligonucleotide complex. These observations suggest that oligonucleotides, designed to form nucleic acid triplexes with specific proviral target sequences, can selectively inhibit transcription of viral mRNA in intact cells and suppress accumulation of viral products.

Development of oligonucleotide derivatives as therapeutic agents requires an understanding of their pharmacokinetic behavior. The in vivo disposition and stability of a prototype of such compounds are reported here. The compound studied, a relatively G-rich 38 base 3' phosphopropyl amine oligonucleotide (TFO-1), was cleared from the circulation with a half-life of approximately 10 minutes, displaying distribution kinetics consistent with a two compartment model. TFO-1 was also readily absorbed into circulation from the peritoneal cavity. All tissues examined except brain accumulated the compound reaching concentrations calculated to be in the micromolar range. TFO-1 was found to be stable in circulation and in tissues in that a large fraction of intact material was detected 8 hours after injection, as assessed by gel electrophoresis. Approximately 20-30% of the injected dose was excreted in the urine over an 8 hour period. These results suggest that G-rich oligonucleotides, minimally modified at the 3' end, are relatively stable in vivo and have distribution kinetics favorable to use as therapeutic agents.

A class of triplex-forming oligodeoxyribonucleotides (TFOs) is described that can bind to naturally occurring sites in duplex DNA at physiological pH in the presence of magnesium. The data are consistent with a structure in which the TFO binds in the major groove of double-stranded DNA to form a three-stranded complex that is superficially similar to previously described triplexes. The distinguishing features of this class of triplex are that TFO binding apparently involves the formation of hydrogen-bonded G.GC and T.AT triplets and the TFO is bound antiparallel with respect to the more purine-rich strand of the underlying duplex. Triplex formation is described for targets in the promoter regions of three different genes: the human c-myc and epidermal growth factor receptor genes and the mouse insulin receptor gene. All three sites are relatively GC rich and have a high percentage of purine residues on one strand. DNase I footprinting shows that individual TFOs bind selectively to their target sites at pH 7.4-7.8 in the presence of millimolar concentrations of magnesium. Electrophoretic analysis of triplex formation indicates that specific TFOs bind to their target sites with apparent dissociation constants in the 10(-7)-10(-9) M range. Strand orientation of the bound TFOs was confirmed by attaching eosin or an iron-chelating group to one end of the TFO and monitoring the pattern of damage to the bound duplex DNA. Possible hydrogen-bonding patterns and triplex structures are discussed.

A synthetic 27-base-long oligodeoxyribonucleotide, termed PU1, has been shown to bind to duplex DNA to form a triplex at a single site within the human c-myc P1 promoter. PU1 has been administered to HeLa cells in culture to examine the feasibility of influencing transcription of the c-myc gene in vivo. It is shown that uptake of PU1 into the nucleus of HeLa cells is efficient and that the compound remains intact for at least 4 hr. In nuclei extracted from PU1-treated cells, inhibition of DNase I cleavage is detected within the c-myc P1 promoter at the target site for triplex formation. The inhibition is shown to be both site and oligodeoxyribonucleotide specific. After cellular uptake of PU1, it is shown that steady-state mRNA arising from the c-myc P1 initiation site is selectively reduced relative to total mRNA, relative to mRNA from the alternative c-myc P2 initiation site, and relative to mRNA derived from the beta-actin promoter. Significant mRNA repression is not seen upon treating cells with oligodeoxyribonucleotides that fail to bind to the P1 promoter target. Taken together, these data suggest that triplex formation can occur between an exogenous oligodeoxyribonucleotide and duplex DNA in the nucleus of treated cells.

The promoter region of the IL2R alpha gene 5' flanking sequence contains enhancer elements crucial for binding nuclear factors which upregulate transcription following T lymphocyte activation. A 3' exonuclease resistant oligonucleotide (3'A-IL28p, terminated by a free amine group at its 3' end) was designed to bind to the IL2R alpha promoter region from -273 to -246, forming a collinear triplex spanning the kappa B enhancer (-266 to -256) as well as most of the serum response element (CArG box, -251 to -244). The binding site specificity of this oligonucleotide was demonstrated in electrophoretic mobility shift assays and by inhibition of restriction endonuclease (HinfI) cleavage within the segment of the target DNA predicted to form a triplex with the oligonucleotide. Intact normal lymphocytes, preincubated for 2h with 3'A-IL28p, accumulated less IL2Ralpha mRNA relative to other mRNAs (c-myc, beta-actin, IL2R beta, IL-6) for up to 12h after PHA stimulation, than did lymphocytes treated with a control oligomer of similar composition but different sequence. Nuclear run-on studies demonstrated that the rate of IL2R alpha mRNA synthesis relative to c-myc and beta-actin was also selectively diminished by treatment with 3'A-IL28p. These experiments suggest that transcription of individual genes can be selectively modulated in living cells by sequence specific collinear triplex formation in regulatory enhancer sequences.

We have employed a variety of physical methods to study the equilibrium melting and temperature-dependent conformational dynamics of dA.dT tracts in fractionated synthetic DNA polymers and in well-defined fragments of kinetoplast DNA (kDNA). Using circular dichroism (CD), we have detected a temperature-dependent, "premelting" event in poly(dA).poly(dT) which exhibits a midpoint near 37 degrees C. Significantly, we also detect this CD "premelting" behavior in a fragment of kDNA. By contrast, we do not observe this "premelting" behavior in the temperature-dependent CD spectra of poly[d(AT)].poly[d(AT)], poly(dG).poly(dC), poly[d(GC)].poly[d(GC)], or calf thymus DNA. Thus, poly(dA).poly(dT) and kDNA exhibit a common CD-detected "premelting" event which is absent in the other duplex systems studied in this work. Furthermore, we find that the anomalous electrophoretic retardation of the kDNA fragments we have investigated disappears at temperatures above approximately 37 degrees C. We also observe that the rotational dynamics of poly(dA).poly(dT) and kDNA as assessed by singlet depletion anisotropy decay (SDAD) and electric birefringence decay (EBD) also display a discontinuity near 37 degrees C, which is not observed for the other duplex systems studied. Thus, in the aggregate, our static and dynamic measurements suggest that the homo dA.dT sequence element [common to both poly(dA).poly(dT) and kDNA] is capable of a temperature-dependent equilibrium between at least two helical states in a temperature range well below that required to induce global melting of the host duplex. We suggest that this "preglobal" melting event may correspond to the thermally induced "disruption" of "bent" DNA.

Cystosarcoma phyllodes of the breast appears to encompass a diverse group of tumors with variable clinical behaviors. Although the tumor can behave in a malignant fashion, metastases to the head and neck region are distinctly uncommon. A case is presented of a solitary metastasis to the mandible appearing 1 year after mastectomy and in the absence of widespread disease. The metastatic potential of this neoplasm is discussed and involvement of the head and neck region is reviewed.

The clinical and histologic features of five homosexual men with acquired immunodeficiency syndrome (AIDS) who developed extranodal non-Hodgkin's lymphomas of the head and neck region are presented. The primary sites of these malignant neoplasms include the larynx, palate, alveolar ridge, nasal vestibule, and skin overlying the mastoid tip. In all cases, the patients' lymphomas followed an aggressive clinical course with frequent central nervous system involvement. Although, to our knowledge, this is the first report of head and neck lymphomas in patients with AIDS, this malignant neoplasm has been demonstrated to occur at other anatomic sites in such patients with an incidence far greater than that found in the general population. A high index of suspicion for lymphomas and other unusual malignant neoplasms is required on the part of the otolaryngologist and head and neck surgeon when evaluating patients with AIDS.

Despite the use of strict morphologic criteria, some head and neck neoplasms remain classified as "poorly differentiated" or "undifferentiated." To circumvent this diagnostic quandary, newer techniques primarily based on immunocytochemistry are being utilized to study tumor specimens. These methods rely on the binding of specific antibodies to cellular antigens in order to better define the tumor according to cell type. We treated six patients in whom a definitive pathologic diagnosis could not be obtained without the use of immunohistologic stains. In each case, the definition of a specific tumor category altered patient management. The approach to the evaluation of patients with undifferentiated head and neck neoplasms is important. Close cooperation between the clinician and pathologist is necessary in such cases; this is assisted by a knowledge of the uses and limitations of the current diagnostic modalities being used, as well as proper tissue handling and processing.

Natural killer (NK) cells are a subpopulation of lymphocytes involved in host defense against tumor cells. Although a great deal of clinical research has focused on the role of NK cells in the blood of patients with cancer, very little has been done to determine what role they may play at the regional or lymph node level. One hundred seven lymph nodes from 22 patients with head and neck cancer and eight control patients were assayed for NK cell cytotoxicity against the human erythroleukemia cell line K562. Six of these nodes contained a discrete intracapsular focus of metastatic tumor. Lymphocytes from these focally positive nodes exhibited a significant depression of NK cell cytotoxicity compared with all other nodes. These data suggest that the presence of metastatic tumor inhibits NK cell function at the regional level in patients with head and neck squamous cell carcinoma.

Malignant salivary gland tumors of the base of the tongue are unusual lesions and optimal treatment has not been established. As a group, these tumors tend to be diagnosed at an advanced stage, and consequently carry a grave prognosis. Fourteen patients were treated at UCLA between 1954 and 1984. Twenty-three percent of the patients have survived longer than ten years, although only one patient is free of disease. Eight of 14 patients developed distant metastases. Salivary tumors in this location are difficult to completely excise and surgical margins are frequently positive. Treatment using a planned combined approach is advocated.

This study evaluated peripheral blood lymphocyte and lymph node lymphocyte natural killer (NK) cell activity in 22 patients with head and neck squamous cell carcinoma and eight patients undergoing surgery for nonmalignant conditions who served as controls. A novel mixed-model analysis of variance was used to analyze the results because of the inherent difficulties in data interpretation among heterogeneous groups when several concurrent variables impinge upon the results. The peripheral blood lymphocyte NK activity of cancer patients was significantly less than controls. In contrast, lytic activity from uninvolved draining lymph nodes of cancer patients was comparable to the activity of control nodes. However, if the node contained a small focus of metastatic tumor, NK activity was significantly diminished relative to uninvolved nodes from cancer patients or to control nodes. The mixed-model analysis of variance was particularly helpful in confirming this finding. Finally, NK lysis by tumor-infiltrating lymphocytes, purified from grossly metastatic nodes, was severely depressed. These data indicate that a spectrum of NK suppression exists in draining lymph nodes of head and neck squamous cell carcinoma patients, and that the level of activity depends upon the degree of nodal tumor involvement.

Total laryngectomy has traditionally been considered the optimal treatment for patients with advanced glottic carcinoma who present with a fixed true vocal cord. However, using whole-organ sectioning techniques, it has been demonstrated that vertical partial laryngectomy is a sound oncologic procedure for selected fixed vocal cord lesions. During the period 1969 to 1984, 27 patients who presented at UCLA with T3 glottic carcinoma were treated using vertical partial laryngectomy. Follow-up for these patients averaged 4.0 years. The absolute two-year disease-free survival rate for this group was 85% (23 of 27 patients), and the local cancer recurrence rate during a two-year postoperative interval was 11% (three of 27 patients). These encouraging results support the continued use of partial laryngeal surgery for a subgroup of patients with T3 glottic cancer. Successful patient selection requires a careful analysis of disease extent based on data obtained from physical examination, magnetic resonance imaging or computed tomographic scanning, and direct laryngoscopy.

Epstein-Barr virus-immortalized human lymphocytes were used to analyze the transition from the benign hyperproliferative to the malignant transformed state. Treatment with N-acetoxy-2-acetylaminofluorene, a potent frameshift mutagen, induced conversion of the Epstein-Barr virus immortalized lymphocytes into high-grade "immunoblastic lymphomas" on injection into athymic mice, whereas injection of the untreated, original cells did not. The tumor cells were all of the B-cell lineage as determined by the presence of surface immunoglobulins and antigens detected by B-cell specific antibodies to B1 and B4, and the absence of the T-cell-specific markers, 3A1 and LEU-1. The N-acetoxy-2-acetylaminofluorene-induced tumor lines displayed abnormal diploid to tetraploid karyotypes. The fewest chromosomal rearrangement, excluding tetraploidy, observed in these chemically induced lymphomas involved a deletion in chromosome 6, and additions on both chromosomes 16 and 4. Neither major rearrangements nor amplifications were found for K-ras, H-ras, N-ras, c-myc, Blym, and c-myb in these tumor lines.

p40, a mouse 1040-nucleotide cDNA clone encoding a form of phenobarbital-inducible cytochrome P-450b, was selected by probing a cDNA library derived from phenobarbital-treated DBA/2N mouse liver with a rat 1830-nucleotide cDNA probe complementary to P-450b mRNA. When rat and mouse liver poly(A)+-enriched total RNAs are probed with p40, control rat P-450b mRNA levels are at least three times as much as control mouse P-450b levels. A 15-fold increase in rat 19S mRNA and only a 3-fold increase in the corresponding mouse 19S mRNA are found following phenobarbital treatment. An intranuclear 4800-nucleotide mRNA precursor is also detectable during the induction process with phenobarbital. Clofibrate, a hypolipidemic drug, is a potent inducer of P-450. There is no cross-hybridization between clofibrate-induced mRNA and either mouse P-450b cDNA or mouse P1-450 cDNA clones. At the level of hybridization stringency used for the Northern analysis, there is no cross-hybridization between phenobarbital-induced mouse or rat P-450b and the P1-450 cDNA probe or between 3-methylcholanthrene-induced mouse or rat P1-450 and the P-450b cDNA probe. These data indicate that the induction process by clofibrate involves activation of P-450 gene(s) not present in the multigene families inducible by either phenobarbital or polycyclic aromatic compounds, i.e., at least three sets of P-450 genes operate independently of one another. Two previously reported cDNA clones of phenobarbital-inducible rat P-450, R17 (P- 450e ) and pcP- 450pb4 (P-450b), were compared with mouse p40.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute carotid artery rupture is frequently heralded by prodromal arterial bleeding. This warning signal provides the physician with a brief interval in which to hemodynamically stabilize a patient, electively occlude the carotid, and consequently improve the patient's chance of survival. For three years, we have employed an initial nonoperative approach to patients with impending carotid rupture. A trial of endovascular balloon occlusion followed by detachable balloon embolization of the carotid artery has been utilized. Patients unable to tolerate temporary occlusion underwent a vascular bypass procedure followed by embolization. Six patients have undergone this approach, and all had permanent cessation of bleeding. None died as a result of the procedures. One patient developed permanent neurologic deficits. Balloon embolization offers improved results over elective ligation and should be considered as an alternative treatment for patients in this dire predicament.