Unifocal origin of advanced human epithelial ovarian cancers.

Ovarian cancers are often diagnosed at a late stage, after the cancer cells have spread to extraovarian sites. Failure to diagnose these tumors earlier may reflect the lack of symptoms and the need for a sensitive, reliable screening test. Alternatively, this can be explained by the hypothesis that some of the extraovarian tumor implants do not represent metastatic spread from the primary cancer but instead are multiple primary tumors developing simultaneously in the peritoneal epithelium. If this is the case, some patients with advanced ovarian cancer may never have had a stage I disease, making early detection theoretically impossible. In this study, we examined the mutational pattern of the p53 gene in 9 patients with epithelial ovarian cancers using tissue collected from different sites within the same patient. In all 9 cases, the mutational pattern of the p53 gene was identical in cancer cells from different sites within the same patient, strongly suggesting that these ovarian tumors were of unifocal origin and that cancer tissues collected from different sites are derived from a single origin.     

Selective elimination of mRNAs in vivo: complementary oligodeoxynucleotides promote RNA degradation by an RNase H-like activity.

Oligodeoxynucleotides lead to translation arrest of complementary mRNAs in the wheat germ translation system by a degradation of the mRNA. In an attempt to develop an effective reverse genetic approach in vivo, we demonstrate that injection of short (15- to 30-nucleotide) oligonucleotides into Xenopus oocytes leads to complete degradation of both injected and endogenous mRNAs by means of an RNase H-like activity.     

Incidence and Clinical Significance of Ventricular Late Potentials in Idiopathic Dilated Cardiomyopathy Compared to Coronary Artery Disease

Objective: This prospective study was designed to compare incidence and clinical significance of ventricular late potentials between patients with idiopathic dilated cardiomyopathy (IDC) and postinfarct patients (CAD) using exactly the same method of signal-averaged electrocardiography (SAECG) in both patient groups. Methods: Time-domain analysis of SAECG was performed in 120 consecutive patients with IDC, 120 patients with CAD, and 60 healthy controls. Ventricular late potentials were detected in 27 of 120 patients with IDC (23%) compared to 41 of 120 patients with CAD (34%; P < 0.05). Results: Ventricular late potentials were found in 2 of 60 controls (3%). During 15 ± 7 months follow-up, serious arrhythmic events occurred in 17 of 120 patients with IDC (14%) and in 13 of 120 patients with CAD (11%). The sensitivity of ventricular late potentials for future arrhythmic events was 35% for IDC compared to 77% for CAD (P < 0.05). The positive predictive value of late potentials detected by time-domain analysis was 22% for IDC versus 24% for CAD (P = ns). Conclusion: In this selected patient population with IDC and CAD, time-domain analysis of SAECG revealed a lower incidence of ventricular ate potentials in patients with IDC as compared to postinfarct patients. Whereas ventricular late potentials had a high sensitivity but a low positive predictive value for identification of postinfarct patients with serious arrhythmic events during follow-up, both sensitivity and positive predictive value of ventricular late potentials for future serious arrhythmic events were low in the setting of IDC.     

Urodynamic evaluation of ileal conduit function

Bilateral hydroureteronephrosis following ileal conduit urinary diversion is not uncommon. It may be owing to ureteroileal stenosis, stomal stenosis or a poorly compliant ileal conduit. The standard evaluation of stoma size, conduit residual urine and a loopogram often fail to allow determination of the cause of ureteral dilatation. In addition to these standard tests, we have used conduit urodynamics to study conduit function with a triple lumen urodynamic catheter to measure simultaneously conduit pressure proximal and distal to the fascia during filling under fluoroscopy. In 4 control patients with normal upper tracts who were studied with this technique conduit leak point pressures ranged from 5 to 20 cm. water pressure. Six patients with bilateral hydroureteronephrosis were studied to evaluate conduit function. We found abnormalities in 5 patients, including functional stomal stenosis in 2, an atonic loop in 1, segmental obstruction in 1 and a high pressure noncompliant distal segment in 1.     

Functional uncoupling of hemodynamic from neuronal response by inhibition of neuronal nitric oxide synthase.

The cerebrovascular coupling under neuronal nitric oxide synthase (nNOS) inhibition was investigated in alpha-chloralose anesthetized rats. Cerebral blood flow (CBF), cerebral blood volume (CBV), and blood oxygenation level dependent (BOLD) responses to electrical stimulation of the forepaw were measured before and after an intraperitoneal bolus of 7-nitroindazole (7-NI), an in vivo inhibitor of the neuronal isoform of nitric oxide synthase. Neuronal activity was measured by recording somatosensory-evoked potentials (SEPs) via intracranial electrodes. 7-Nitroindazole produced a significant attenuation of the activation-elicited CBF (P<10(-6)), CBV (P<10(-6)), and BOLD responses (P<10(-6)), without affecting the baseline perfusion level. The average DeltaCBF was nulled, while DeltaBOLD and DeltaCBV decreased to approximately 30% of their respective amplitudes before 7-NI administration. The average SEP amplitude decreased (P<10(-5)) to approximately 60% of its pretreatment value. These data describe a pharmacologically induced uncoupling between neuronal and hemodynamic responses to functional activation, and provide further support for the critical role of neuronally produced NO in the cerebrovascular coupling.     

Unusual mechanism of Chance fracture in an adolescent

Transverse fractures of the vertebral arch or Chance fractures are rare in children. The few cases described have been associated with lap-type seat belt use. The adolescent female reported sustained a transverse fracture of L2 from a fall. This is an unusual mechanism of injury producing a Chance-type fracture in an adolescent.     

Lifestyle factors in monozygotic and dizygotic twins

In examining genetic influences on biological variables using twins, it may be important to examine the distribution between and within twin pairs of demographic and lifestyle factors that may themselves affect the biological variable being studied. We explored the distribution of demographic and lifestyle factors that may affect blood lipid levels or ischaemic heart disease (IHD) risk among a sample of 106 monozygotic (MZ) and 94 like-sex dizygotic (DZ) twin pairs. In our sample, MZ twins were statistically significantly different from DZ twins only in marital status, cigarette smoking habits, and the ratio of polyunsaturated to saturated fat (P:S ratio) in their dietary intake. The latter variable was among many dietary variables examined (using 4-day weighed food diaries), and the size of the difference in intake was small. When comparisons were made of the similarities within twin pairs, we found members of MZ twin pairs to be statistically significantly closer than DZ twins in educational achievement, occupation, cigarette smoking, and exercise habits, and the number of days a week on which alcohol was consumed. These last three variables were consistently closer among twins with closer contact than among those with a smaller degree of current shared environment. For 12 of the 13 nutrients examined, the within-pair correlations were higher for MZ than for DZ twins, although our test for significant genetic variance showed statistical significance only for intake of complex carbohydrates. We conclude that MZ twins share demographic and lifestyle factors that might influence the risk of IHD and blood lipid levels to a greater degree than do DZ twins, although it is difficult to say if these similarities in lifestyle result from genetic influences or not. Nevertheless, ascribing differences between correlations in MZ and DZ twin pairs for lipid levels as being purely "genetic"--as implicit in conventional measures of heritability--is likely to overestimate the influence of genetic factors.     

Reevaluation of bacteriocinogeny in Neisseria gonorrhoeae.

Bacteriocin typing has been described previously and proposed for typing gonococci. A survey has been made of 150 strains of N. gonorrhoeae from various places to determine the feasibility of a gonocin typing system. All strains were found to produce an inhibitory substance which inhibited all strains of gonococci tested, one strain of Neisseria flavescens, two strains of Neisseria meningitidis, as well as the producing strain itself. The inhibitory activity was enhanced by supplementary glucose, reduced by supplementary serum, and unaffected by the addition of HEPES buffer, by the temperature of incubation, or by the exposure of potential producer strains to sublethal concentrations of mitomycin C. This nonspecific inhibitory activity differed from that of a putative bacteriocin produced by a strain of N. meningitidis, in that the latter inhibited most other meningococci but not the producer strain itself. Bacteriocinogeny has not yet been convincingly demonstrated in N. gonorrhoeae, and gonocin typing has not yet been shown to be feasible. Production of the nonspecific inhibitor may have obscured past attempts to demonstrate type-specific gonococcal bacteriocin.     

Protein expression of MMP-13, uPA, and PAI-1 in pseudocapsular and interface tissue around implants of loose artificial hip joints and in osteoarthritis

Matrix metalloproteinase 13 (MMP-13), urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor type-1 (PAI-1) have been reported to be involved in aseptic loosening of artificial hip joints. This study for the first time presents the protein levels of all of these factors in synovial-like interfaces between bone and prosthesis and in pseudocapsular tissues surrounding the artificial joint in patients with aseptic loosening (n=17) measured by ELISA. No differences were observed in the antigen expression of MMP-13, uPA, and PAI-1, comparing interface and pseudocapsular tissue. Also, no significant correlation between the protein expression of these factors and years from arthroplasty to revision or to type of fixation (cemented vs. cementless) was observed. As control, MMP-13, uPA, and PAI-1 antigen levels were also determined in the synovium of patients with osteoarthritis (n=10). Yet, the antigen levels of MMP-13, uPA, and PAI-1 in tissue specimens from patients with aseptic loosening of artificial hip joints were significantly higher compared to their expression in synovial capsular tissues obtained from patients with osteoarthritis. In conclusion, this study shows that elevated protein levels of uPA, PAI-1, and MMP-13 in periprosthetic pseudocapsular and interface tissues from patients after total hip replacement due to aseptic loosening seem not to be associated with the patient outcome.