Validation of computerized three-dimensional reconstruction of intravascular ultrasound: measurements of absolute luminal diameter and cross-sectional area in ex vivo human coronary arteries

Computer based 3-dimensional reconstruction transforms 2-dimensional intravascular ultrasound images into a longitudinal format facilitating analysis of luminal narrowing. To validate the accuracy of current software in measuring coronary artery diameter and cross-sectional area, in arteries with atherosclerosis, we performed 3-dimensional reconstruction in 10 human pathologic coronary arterial segments of 10-25mm length. Images were obtained using a 4.8 French catheter with pullback speed of 1mm/sec acquired at 3 frames/sec onto VHS tape. The data were digitized and intraluminal 3-dimensional reconstruction performed using a voxel-based program. Pathologic sections were obtained every 3mm, and dimensions were measured with a resolution of 0.01 mm. Maximum, minimum, and 3 other representative diameters were recorded by an observer blinded to the ultrasound diameters. Average histo-pathologic diameters were reported, and specimen cross-sectional area was then calculated. Results: In 53 sections, pathological diameters ranged from 1.4-4.5mm (mean 2.7 +/- 0.68mm) while 3-dimensional reconstructed diameters were 1.9 to 3.8mm (mean 2.6 +/- 0.54mm). Pathologic and ultrasound derived 3-dimensional reconstruction diameters had an excellent correlation (r=0.86, SEE=+/-0.36). Pathology and 3-dimensional reconstruction cross-sectional area also correlated closely (r=0.88, SEE=+/-1.50). Diameters less than 2.0mm were systematically overestimated and diameters greater than 3.5mm underestimated by 3-dimensional reconstruction. Most 3 dimensional reconstruction values were within +/- 10% of pathology, but diverged at each diameter extreme, approaching +/- 20%. Thus, computerized 3-dimensional reconstruction of ultrasound images shows excellent quantification of luminal size in the 2.0-3.5mm range, suggesting important investigative and clinical applications.     

The societal and organizational contexts of culturally sensitive mental health services: findings from an evaluation of bilingual/bicultural psychiatric programs

The Hispanic mental health literature focuses mostly on cultural and clinical issues. This paper argues that researchers and practitioners concerned with mental health services for Hispanics and other minority groups need to pay more attention to the societal and organizational contexts that facilitate or impede the development of effective culturally sensitive psychiatric programs. Utilizing data from an evaluation of three New York psychiatric programs for seriously mentally ill (SMI) Hispanic patients, the paper discusses societal and organizational factors that influenced the programs' development. Among societal forces were the significance of Hispanics as a voting bloc, the political organization of Hispanic mental health professionals, the philosophy of ethnic assimilation in American society, prevailing views about the place of cultural knowledge in psychiatric treatment, and fiscal crises, and the shortage of Hispanic mental health professionals. Among organizational factors, hospital administrative support and program leadership mediated the effects of societal forces upon the programs, while ethnic competition and lack of coordination between the program and other organizational units acted as barriers to the programs' development. The findings are relevant to any innovative mental health service in an organizational setting.     

Multiple sclerosis: basic concepts and hypothesis

Multiple sclerosis, an inflammatory disease of the central nervous system, is characterized by primary destruction of myelin. This review covers recent advances in neuropathology, immunogenetics, neuroimmunology, and neurovirology that have provided insights regarding its pathogenesis. Three hypotheses are discussed: (1) autoimmunity, (2) "bystander" demyelination, and (3) immune destruction of persistently infected oligodendrocytes. A paradigm for induction of primary demyelination is proposed in which immune cells recognize "foreign" antigens on the surface of oligodendrocytes in the context of major histocompatibility complex gene products. The final result of this scheme may be "dying-back gliopathy," the alteration being noted first in the most distal extension of the oligodendrocyte--that is, the myelin sheaths.     

Therapeutic criteria in hydrocephalic children

The xanthine, hypoxanthine, and total oxypurine levels were determined in the CSF of 28 hydrocephalic patients (age from newborn to 2 years) and 8 healthy controls using HPLC. The Evans' index, the mean weekly increase in cranial circumference, and the intracranial pressure were also measured. Of the hydrocephalic patients 13 were self-compensated and the other 15 had a shunt implanted during the course of the study. The mean xanthine, hypoxanthine, and total oxypurine levels in the normal children were 5.20, 5.94, and 11.29 mol/l, respectively. In the self-compensated hydrocephalics these levels were 5.17, 5.71, and 10.79 mol/l, respectively. In the noncompensated hydrocephalics, they were 9.90, 9.91, and 19.82 mol/l. The differences between the latter group and the first two are statistically significant (P<0.001). The mean Evans' index and the mean weakly increase in cranial circumference in the self-compensated hydrocephalics were 0.35 and 0.25 cm, respectively. In the noncompensated hydrocephalics, they were 0.55 and 0.95 cm. The differences between the two groups are statistically significant (P<0.001). Two weeks after implantation of shunts in the noncompensated cases, the mean xanthine, hypoxanthine, and total oxypurine levels fell to 4.22, 4.57, and 8.80 mol/l, respectively. These changes are statistically significant (P<0.001). We think that the two criteria (clinical and biochemical) are equally useful for the prediction of self-compensation in hydrocephalic children and that the oxypurine values after shunt implantation can be used to monitor progress in noncompensated cases.     

Years of potential life lost: application of an indicator for assessing premature mortality in Spain and Portugal

In this article, the authors present an analysis of causes of death in Spain and Portugal in 1984 based on a calculation of the "years of potential life lost" (YPLL) between the first and the 70th birthdays, the latter age corresponding approximately to the average life expectancy in both countries. This analysis of the YPLL led to a substantially different ranking of the main causes of death, based on what might be termed "premature mortality" compared with that obtained from more conventional mortality indices. According to this criterion, which is especially appropriate for the planning and evaluation of health interventions, the main causes of premature death (1-69 years) in the two countries of the Iberian peninsula are malignant tumours and, particularly in Portugal, violent deaths (especially motor-vehicle accidents, but also suicides). This is in contrast to the predominance of cardiovascular diseases indicated by other weightings of age-specific mortality rates. Portugal shows significantly worse YPLL rates than Spain not only for general mortality (45% higher than in Spain), but also for several major groups of causes. In Spain only malignant neoplasms, diabetes and chronic rheumatic heart diseases show higher specific mortality rates than in Portugal, based on traditional mortality indicators.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of a DIVA (Differentiating Infected from Vaccinated Animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian influenza

The present paper reports of the development and validation of a control strategy for avian influenza infections in poultry. The "DIVA" (Differentiating Infected from Vaccinated Animals) strategy is based on the use of an inactivated oil emulsion vaccine containing the same haemagglutinin (H) subtype as the challenge virus, but a different neuraminidase (N). The possibility of using the heterologous N subtype, to differentiate between vaccinated and naturally infected birds, was investigated through the development of an "ad hoc" serological test based on the detection of specific anti-N1 antibodies. This was achieved using a baculovirus expressing a recombinant N1 protein. The A/ck/Pakistan/H7N3 virus was used as a vaccine and birds were challenged with the HPAI A/ty/Italy/4580/V99/H7N1 strain. The homologous H group ensured a clinical protection of 93% regardless of the vaccination scheme used, and was able to prevent viraemia and muscle colonization in the clinically healthy challenged birds. However, it was not able to prevent viral shedding. The "ad hoc" serological assay was developed as an indirect immunofluorescence test, and was validated using 608 field sera, and showed an "almost perfect agreement" (Kappa value) with the HI test, with relative sensitivity and specificity values of 98.1 and 95.7, respectively. The results of the present investigation suggest that the "DIVA" control strategy may represent a tool for the control of avian influenza infections in poultry.     

Serum concentrations of oestradiol-17beta, progesterone, relaxin and chorionic gonadotrophin during blastocyst implantation in natural pregnancy cycle and in embryo transfer cycle in the rhesus monkey

The present study was undertaken to assess the temporal association between the profiles of serum concentrations of oestradiol-17beta, progesterone, chorionic gonadotrophin (CG) and relaxin in pregnancies established naturally, and after embryo transfer, as well as in failed pregnancies in rhesus monkeys. In naturally mated cycles (group 1) a conception rate of 75% was obtained. In group 1, the mean day of CG detection in serum was 11.5 +/- 1.9 day post-ovulation, and for relaxin, 9.0 +/- 2.5 day post-ovulation. In group 2, embryo transfer to synchronous, non-mated surrogate recipients was performed; seven embryo transfer cycles yielded three pregnancies which were allowed to continue to term and normal infants were delivered. In embryo transfer cycles the mean day of CG detection was 14.8 +/- 1.8 day post- ovulation, and for relaxin, 11.4 +/- 2.6 day post-ovulation. A delay of about 3 days was observed in the appearance in circulation of CG (P < 0.05) and also of relaxin (P < 0.05) between natural mated and embryo transfer conception cycles. Significant differences (P < 0.05 for progesterone and P < 0.03 for oestradiol) were obtained for the areas under the curves for progesterone and oestradiol between days 12 and 16 in conception cycles compared with failed pregnancies. These data provide the first observation of the normal hormonal signals associated with maternal recognition of transferred embryos during the peri- implantation period, and suggest that the use of such an experimental primate embryo transfer model may help to elucidate components of maternal and embryonic signal-response mechanisms during embryo implantation.      

Detection of human papillomavirus types 6 and 11 E4 gene products in condylomata acuminatum.

Polyclonal antiserum to an Escherichia coli-produced beta-galactosidase/E4 fusion protein of human papillomavirus type 6b (antiserum 256), and affinity purified HPV 11 anti-E4 antibodies were tested for reactivity in Western blots with bacterially expressed trpE/E4 fusion proteins of HPV types 6b, 11, 16, and 18. To further characterize the affinity purified anti-E4 antibodies, a dot-immunobinding assay was performed using overlapping synthetic HPV 11 E1E4 peptides as antigens. Protein extracts of condylomata acuminatum from 18 patients containing HPV type 6 or 11 DNA sequences were tested in Western blots using antiserum 256 or affinity purified HPV 11 anti-E4 antibodies. In the Western blots of the trpE proteins, antiserum 256 identified the HPV types 6b and 11 fusion proteins; the affinity purified HPV 11 anti-E4 antibodies identified only the HPV 11 fusion protein. In the dot-immunobinding assay, three HPV 11 peptides were recognized, each containing a shared 8 amino acid sequence that differs significantly from the corresponding sequences of HPV types 6b, 16, or 18. In the Western blots of protein extracts from 18 condylomata acuminatum samples shown to contain HPV types 6 or 11 DNA, putative E4 gene products were identified in six samples by antiserum 256. The affinity purified HPV 11 anti-E4 antibodies identified putative E4 gene products in one of these same six lesions, which was shown to contain HPV 11 sequences by the Southern blot method. All six samples containing E4 gene products were from women. Three of these women were pregnant, one had serum antibodies to the human immunodeficiency virus, and one was a renal transplant recipient receiving glucocorticoids.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparison of sensitivity for human cytomegalovirus of the polymerase chain reaction, traditional tube culture and shell vial assay by sequential dilutions of infected cell lines.

Although traditional tube culture (TTC) is still considered by many as the 'gold standard' for the laboratory diagnosis of human cytomegalovirus (HCMV), the shell vial assay (SVA) offers greater speed of detection. This technique utilizes immunofluorescence (IF) to detect early or immediate early nuclear antigens (IEA). The detection capabilities of these two tests were compared with the polymerase chain reaction (PCR), a technique that amplifies enzymatically selected DNA target sequences. Serial dilutions of crude culture harvests from 2 HCMV strains, Towne and a clinical urine isolate, were made up to 1:1 000,000. Ten-microliters aliquots of the original sample and each dilution were tested by PCR, TTC and SVA. For PCR, the nested-primer approach was used. Outer primers delimited a 721-bp sequence contained within the 2nd to 4th exons of the immediate-early protein. Inner nest primers delimited a 167-bp sequence in the third exon, detected by a 32P-labelled probe. The results show that: (1) control samples which contained all PCR reagents but no DNA were uniformly negative; (2) radiolabelled-probe detection (RPD) of PCR products is, on average, 100 x more sensitive than detection by ethidium bromide; (3) PCR is, on average, 100 x more sensitive than evaluation of cytopathic effect (CPE) in the TTC; (4) the predictive value of a negative SVA result is low compared to PCR.     

Early embryonic expression patterns of the mouse Flamingo and Prickle orthologues.

The Drosophila melanogaster proteins Flamingo and Prickle act in the planar cell polarity (PCP) pathway, which is required for acquisition of epithelial polarity in the wing, eye, and epidermis. In mammals, PCP signaling has been shown to regulate cell movements and polarity in a variety of tissues. Here, we show that the murine Flamingo orthologues Celsr1-3 and the Prickle orthologues Prickle1, Prickle2, and Testin have dynamic patterns of expression during pregastrulation and gastrulation stages. Celsr1 is expressed in the anterior visceral endoderm and nascent mesoderm, Celsr2 and Celsr3 mark the prospective neuroectoderm, Prickle1 is expressed in the primitive streak and mesoderm, Prickle2 in the node, and Testin in the anterior visceral endoderm, the extraembryonic ectoderm, primitive streak, and mesoderm. Analysis of a gene-trap mutation in Testin indicates that this gene is not required for embryogenesis; therefore, other Prickle homologues may compensate for its function during development.