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PubMed2000

[Laparoscopic splenectomy for hematologic diseases. Study of 275 cases. French Society of Laparoscopic Surgery].

AIM OF THE STUDY: To evaluate the results of laparoscopic splenectomy for hematologic diseases by a multicenter retrospective study. PATIENTS AND METHODS: Between 1991 and 1998, 275 patients (mean age: 40.4 years [18-93]) underwent splenectomy for idiopathic thrombocytopenic purpura (ITP) (n = 209, 76%), for hemolytic anemia (HA) (n = 37) including hereditary spherocytosis (n = 13) and auto-immune anemia (n = 24), lymphoma (n = 12), tumor (n = 6) and uncommon hematologic syndromes (n = 11). Laparoscopic splenectomy was attempted in every patient. The lateral approach was most commonly used with an anterior approach to the splenic hilar vessels, which were cut after hemostasis using a stapling gun; other techniques were also employed. RESULTS: The mean operating time was 165 minutes (45-360); it was shorter in the case of conversion (144 minutes) and became shorter with the operator's experience. Conversion was necessary in 55 patients (20%), due to hemorrhage in 2/3 of cases, related to splenic vessels (20 cases), short gastric vessels (9 cases), or injury of the spleen (8 cases). In ten cases (2%), conversion was necessary for extraction of the spleen. Conversion rate varied from 5.3 to 46.7%, depending on the surgical team. Univariate analysis of factors predisposing to conversion identified four causes: obesity; technique used to achieve hemostasis of the splenic hilar vessels; operator's experience; and presence of splenomegaly. An accessory spleen was found in 44 patients (16%). The weight of the spleen was more than 350 g in 43 patients (15.6%). There were no deaths. There were no significant complications in 236 patients (85.8%) and the mean hospital stay was 6.4 days. In comparison with patients who had a conversion, bowel function returned significantly earlier, use of analgesia was reduced and hospital stay was shorter. The overall morbidity rate was 13.8% (n = 38); morbidity rate was only 10.4% (n = 22) for laparoscopic splenectomy. In these 22 patients, the complications were: subphrenic collections (n = 5, 2.2%), abdominal wall infections (n = 5), thromboembolic events (n = 2), anemia (n = 2), pneumonia (n = 1), peptic ulcer (n = 1), bowel obstruction (n = 1), splenic vein thrombosis (n = 1). Re-operations were required in 4 patients (1.8%) because of hemorrhage, pancreatitis and bowel obstruction. Morbidity rate was significantly increased in the case of conversion (27%), obesity (20%), malignant disease (30%) and splenomegaly (21.8%). Forty-four patients (16%) received perioperative or postoperative blood transfusion and 23 (8.3%) received platelet transfusion. Mean time to return to normal activity was 21 days and was shorter in the absence of conversion (18.5 days versus 35 days). In patients with ITP, the mean platelet count was 240,000 after 3 months, and the failure rate was 8.3%. CONCLUSION: Laparoscopic splenectomy is a real alternative to conventional splenectomy for some hematologic diseases, particularly ITP and HA. The advantages are an uneventful postoperative course, a lower morbidity rate, a shorter hospital stay and an earlier return to normal activity. The limits of this technique are related to the operator's experience, the size of the spleen, the nature of the underlying disorders and patient characteristics, mainly obesity.

Adolescent↗
PubMed2000

Empirically based conversion factors for calculating couple-years of protection.

Couple-years of protection (CYP) is one of several commonly used indicators to assess international family planning efforts. It has been the subject of much debate, relating in part to the specific conversion factors used to translate the quantity of the respective contraceptive methods distributed to a single measure of protection. This article outlines a comprehensive effort to revisit those conversion factors based on the best available empirical evidence. In most instances, the analysis supports previously established standard conversion factors. However, there are two notable departures. Fewer condoms and spermicides are recommended for each CYP (120 vs. 150), primarily because coital frequency among condom users is lower than previously assumed. Furthermore, for sterilization, the authors recommend the use of country or region-specific conversion factors. Every program evaluation indicator has strengths and weaknesses, and the best program evaluation efforts use a variety of indicators. If CYP is used to evaluate programs, however, the authors believe that the conversion factors presented reflect the best available evidence.

Adolescent↗
PubMed2001

Phage conversion of Panton-Valentine leukocidin in Staphylococcus aureus: molecular analysis of a PVL-converting phage, phiSLT.

Staphylococcal Panton-Valentine leukocidin (PVL) is an important virulence factor, which causes leukocytolysis and tissue necrosis. Our previous report on the existence of the PVL genes (lukS-PV and lukF-PV) on the genome of prophage phiPVL in the Staphylococcus aureus strain V8 suggested the horizontal transmission of PVL genes by temperate bacteriophage among S. aureus (Kaneko, et al., 1998. Gene 215, 57-67). Here, we demonstrated the phage conversion of S. aureus leading to the production of PVL by discovery of a novel PVL-carrying phage, phiSLT (Staphylococcal Leukocytolytic Toxin) from a clinical isolate of S. aureus. phiSLT was able to lysogenize several clinical isolates of PVL-negative S. aureus strains as well as strain RN4220 at the conserved 29-bp sequence (attB) and all the lysogenized S. aureus strains had the ability to produce PVL. phiSLT had an elongated head of about 100x50 nm and a flexible tail of 400 nm long, that was quite different from phiPVL which had an isometric hexagonal head of about 60 nm diameter. The linear double-stranded phiSLT genome comprised 42,942 bp with 29-bp attachment core sequences and contained 62 open reading frames. Only 6.4 kbp region containing lysis cassette, PVL genes, attP, integrase, and orf204 of phiSLT was identical to that of phiPVL, while other regions were different from those of phiPVL. Thus, it can be concluded that PVL genes are carried by different temperate phages, which have the same attachment site.

Amino Acid Sequence↗
PubMed1994

Determination of resin cure using infrared analysis without an internal standard.

OBJECTIVES: The purpose of this study was to develop a methodology whereby the monomer conversion of dental restorative resins which contain no functional group acting as an internal standard can be easily determined using infrared spectroscopy. METHODS: Calibration solutions of MMA were made from which the quantification of weight percent methacrylate groups (CH2 = C(CH3)C = O) (termed WPMG) could be determined using infrared spectroscopy. The extent of resin cure using the WPMG method consisted of calculating the changes in WPMG pre- and post-cure. The extent of cure of a commercial unfilled bonding resin was calculated using infrared methods utilizing the internal aromatic standard, and also by means of WPMG. RESULTS: WPMG had an identical optical constant for a wide range of monomers: MMA, TEGDMA, EGDMA, HEMA: The extent of monomer conversion using both methods of analysis indicated statistically equivalent results: 75.2 +/- 1.0% using an internal standard, and 76.0 +/- 1.1% using WPMG. SIGNIFICANCE: The methods developed in this study using infrared spectroscopic methods facilitate the determination of cure of dental resins which do not have functional groups to serve as internal standards.

Analysis of Variance↗
PubMed1999

Intrachromosomal recombination between direct repeats in Penicillium chrysogenum: gene conversion and deletion events.

Recombination between direct repeats has been studied in Penicillium chrysogenum using strain TD7-88 (lys- py+), which contains two inactive copies of the lys2 gene separated by 4.5 kb of DNA (including the pyrG gene) in its genome. Gene conversion leading to products with the lys+ pyr+ phenotype was observed at a frequency of 1 in 3.2x10(3) viable spores. Two types of deletion events giving rise to lys+ pyr- and lys- pyr- phenotypes were obtained with different frequencies. Southern analysis revealed that gene conversion occurs mainly as a result of crossing over events that remove the BamHI frameshift mutation present in one of the repeats. In lys- pyr- recombinants, the deletion events do not affect the frameshift mutation in the BamHI site, while lys+ pyr- recombinants showed repair of the BamHI frameshift mutation and the genotype of the parental non-disrupted strain was restored. In summary, deletion events in P. chrysogenum tend to favor the restoration of the phenotype and genotype characteristic of the parental non-disrupted strain.

Chromosomes, Fungal↗
PubMed2004

Adjuvant chemotherapy and radiotherapy in non-small cell lung cancer.

Although surgical resection remains the best potentially curative treatment for non-small cell lung cancer (NSCLC), more than half the patients undergoing resection will eventually die of recurrent disease. Approximately two thirds of relapses occur outside the chest, indicating a potential role for adjuvant chemotherapy. Indeed, a meta-analysis has suggested an absolute survival benefit of 5% at 5 years with adjuvant cisplatin-based regimens. This finding has incited several large-scale randomized trials, the largest of which, the International Adjuvant Lung Trial, has confirmed a similar survival advantage. Conversely, a meta-analysis on postoperative radiotherapy has suggested a detrimental effect, especially for stage I and II patients, that is related most probably to a poor radiation technique. Its value for stage III remains controversial: the observed reduction in local failure did not translate into a survival benefit. In this article, the current status of adjuvant chemotherapy and radiotherapy are reviewed, and future prospects are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Neoplastic conversion of preneoplastic Syrian hamster cells: rate estimation by fluctuation analysis.

Analysis of the role of gene mutations in the multistep process of neoplastic transformation requires that the discrete steps in carcinogenesis first be dissected. Toward this end, we have isolated and characterized preneoplastic Syrian hamster cells which exhibit in vitro a trait highly correlated with neoplastic conversion in vivo. Previous findings (J. C. Barrett, Cancer Res. 40:91-94, 1980) indicate that spontaneous neoplastic transformation of Syrian hamster cells occurs in at least two steps. An intermediate stage, characterized by an aneuploid established cell line which has a propensity to become neoplastic spontaneously upon further growth in vitro, has been described. These preneoplastic cells differ from diploid early-passage Syrian hamster cells in becoming capable of anchorage-independent growth in semisolid agar, as well as becoming neoplastic in vivo when attached to a solid substrate. Evidence presented here demonstrates that anchorage-independent conversion in vitro is a reliable marker for neoplastic conversion in this cell system. Fluctuation analyses, patterned after those described by Luria and Delbruck for microbial genetics, demonstrate that anchorage-independent variants are generated randomly from clonally derived preneoplastic cells at the rate of 10(-8) to 10(-7) variants per cell per generation. These results establish a multistep stochastic process for transformation in vitro and indicate that conversion to anchorage independence may be necessary for Syrian hamster cells to become tumorigenic. The possible role of gene mutation in this step during neoplastic progression is discussed.

Aneuploidy↗
PubMed2005

One conversion of ventricular fibrillation is adequate for implantable cardioverter-defibrillator implant: an analysis from the Low Energy Safety Study (LESS).

OBJECTIVES: The purpose of this study was to analyze defibrillation conversion data from the Low Energy Safety Study (LESS) to determine how implant criteria that use fewer inductions of ventricular fibrillation (VF) correlate with outcome and, in particular, to assess the reliability of using a single VF induction and test shock at 14 J. BACKGROUND: A safety margin of 10 J has become standard for implantation of an implantable cardioverter-defibrillator (ICD), but the specifics and rigor of the implant test sequence are not standardized. METHODS: In LESS, 611 ICD recipients completed a rigorous VF induction test scheme that began at 14 J and continued until the energy that succeeded three times without a failure was determined (DFT++). The data were analyzed to determine how well the outcome of the first 14-J shock and various other combinations of first and/or second shocks predicted a rigorous gold standard of DFT++ < or =21 J (i.e., three successes at < or =21 J). RESULTS: The positive predictive accuracy for the 91% of patients in whom the first 14-J shock succeeded was virtually identical to the positive predictive accuracy for the commonly used criteria of two successes at < or =17 J (99.1% vs 99.0%, P = .69), and slightly higher than the positive predictive accuracy for two successes at < or =21 J (98.8%, P = .51). A single success at 17 J or 21 J had a somewhat lower positive predictive accuracy of 98.2% (P = .17). Eliminating VF induction testing would have resulted in a significantly lower positive predictive accuracy of 97.1% (P = .01). CONCLUSIONS: A single conversion success at 14 J on the first VF induction provides similar positive predictive accuracy as two successes at 17 J or 21 J. Using this criterion, 91% of patients meet implant criteria with a single induction of ventricular fibrillation.

Aged↗
PubMed2004

Gene conversion and GC-content evolution in mammalian Hsp70.

To investigate the mechanisms regulating the nucleotide usage in mammalian genes, we analyzed the sequences of three physically linked Hsp70 paralogs in human and mouse. We report that the sequences of HSPA1A and HSPA1B genes are almost identical, whereas the HSPA1L gene contains some regions very similar to HSPA1A/B and some regions with much higher divergence. Phylogenetic analysis reveals that gene conversion has homogenized the entire coding regions of HSPA1A/B and several fragments of HSPA1L. The regions undergoing conversion are all very GC rich, contrarily to the regions not subject to conversion. The pattern of nucleotide substitution in mammalian orthologs suggests that the mechanism increasing the GC content is still functioning. To test the possibility that the high GC content facilitates the expression of Hsp70 during heat-shock, we performed in vitro translation experiments. We failed to detect any effect of GC content on the translation efficiency at high temperatures. Taken together, our data strongly support the biased gene conversion hypothesis of GC-content evolution.

Animals↗
PubMed1998

A genetic defect resulting in mild low-renin hypertension.

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2) cause AME. Typical patients with AME have defective 11beta-HSD2 activity, as evidenced by an abnormal ratio of cortisol to cortisone metabolites and by an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. Recently, we have studied an unusual patient with mild low-renin hypertension and a homozygous mutation in the HSD11B2 gene. The patient came from an inbred Mennonite family, and though the mutation identified her as a patient with AME, she did not demonstrate the typical features of AME. Biochemical analysis in this patient revealed a moderately elevated cortisol to cortisone metabolite ratio. The conversion of cortisol to cortisone was 58% compared with 0-6% in typical patients with AME whereas the normal conversion is 90-95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous C-->T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L). The parents and sibs were heterozygous for this mutation. In vitro expression studies showed an increase in the Km (300 nM) over normal (54 nM). Because approximately 40% of patients with essential hypertension demonstrate low renin, we suggest that such patients should undergo genetic analysis of the HSD11B2 gene.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1991

Statistical analysis of bilingual speaker's speech for cross-language voice conversion.

The goal of cross-language voice conversion is to preserve the speech characteristics of one speaker when that speaker's speech is translated and used to synthesize speech in another language. In this paper, two preliminary studies, i.e., a statistical analysis of spectrum differences in different languages and the first attempt at a cross-language voice conversion, are reported. Speech uttered by a bilingual speaker is analyzed to examine spectrum difference between English and Japanese. Experimental results are (1) the codebook size for mixed speech from English and Japanese should be almost twice the codebook size of either English or Japanese; (2) although many code vectors occurred in both English and Japanese, some have a tendency to predominate in one language or the other; (3) code vectors that predominantly occurred in English are contained in the phonemes /r/, /ae/, /f/, /s/, and code vectors that predominantly occurred in Japanese are contained in /i/, /u/, /N/; and (4) judged from listening tests, listeners cannot reliably indicate the distinction between English speech decoded by a Japanese codebook and English speech decoded by an English codebook. A voice conversion algorithm based on codebook mapping was applied to cross-language voice conversion, and its performance was somewhat less effective than for voice conversion in the same language.

Algorithms↗
PubMed1991

3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase expression in rat and characterization of the testis isoform.

The isolation, cloning and expression of a DNA insert complementary to mRNA encoding rat testis 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta-HSD) is reported. The insert contains an open reading frame encoding a protein of 373 amino acids, which exhibits 73% and 78% identity to the cDNA encoding the human placental form at the amino acid and nucleotide levels respectively. Northern blot analysis of total RNA of rat tissues using as probe a specific radiolabeled cDNA insert encoding rat testis 3 beta-HSD demonstrated high levels of 1.6 kb mRNA species in ovary, adrenal and Leydig tumor, with lower but detectable message in testis and adult male liver, while the probe also hybridized to a 2.1 kb mRNA species in liver. The cDNA was inserted into a modified pCMV vector and expressed in COS-1 monkey kidney tumor cells. The expressed protein was similar in size to 3 beta-HSD present in H540 Leydig tumor cell homogenate and human placental microsomal 3 beta-HSD, as detected by immunoblot analysis, and catalyzed the conversion of pregnenolone to progesterone, 17 alpha-hydroxypregnenolone to 17 alpha-hydroxyprogesterone, and dehydroepiandrosterone to androstenedione. Transfected COS cell homogenates, supplemented with NAD+, but not NADP+, converted pregnenolone to progesterone and dehydroepiandrosterone to androstenedione with apparent Km values of 0.13 and 0.09 microM, respectively. Immunoblot analysis of various rat tissues using a polyclonal antibody directed against human placental 3 beta-HSD, in addition to immunoreactivity in the adrenal and testis, demonstrated immunoreactive 3 beta-HSD protein in adult male liver, but not in adult female or fetal liver. We conclude that while one gene product is highly expressed in testicular Leydig cells, and probably adrenal and ovary, accounting for their 3 beta-HSD content, a 3 beta-HSD is also expressed in liver in a sex-specific manner.

Amino Acid Sequence↗
PubMed2003

Effectiveness of amiodarone for conversion of atrial fibrillation to sinus rhythm: a meta-analysis.

BACKGROUND: Although clinicians sometimes choose amiodarone to convert atrial fibrillation (AF) to sinus rhythm, no current and comprehensive systematic review has summarized its effectiveness. OBJECTIVE: To review the effectiveness of amiodarone in converting AF to sinus rhythm over a 4-week period. METHODS: Two reviewers conducted a systematic search for randomized trials in databases, complemented by hand searches and contact with experts. Selected trials compared amiodarone with placebo, digoxin, or calcium channel blockers for conversion of AF to sinus rhythm. Reviewers evaluated the methodology and extracted data from each primary study. RESULTS: Twenty-one studies met eligibility criteria. Duration of AF proved to be a source of heterogeneity, leading to 2 analyses. The relative risk (RR) for achieving sinus rhythm was 4.33 (95% confidence interval [CI], 2.76-6.77) for trials with mean AF duration of greater than 48 hours and 1.40 (95% CI, 1.25-1.57) for those with AF of 48 hours or less. The risk differences for these 2 groups were 27% and 26%, respectively, yielding a number needed to treat of 4 for both groups. The low control event rate among trials with long duration of AF, compared with that of trials with a duration of 48 hours or less, explained the difference in the RR for conversion. We found that the size of the left atrium, presence of cardiovascular disease, and protocols of amiodarone administration did not influence the magnitude of effect. Serious adverse events were infrequent. CONCLUSIONS: Amiodarone is effective for converting AF to sinus rhythm in a wide range of patients. Although use of amiodarone is apparently safe, safety data are too scarce for definitive conclusions.

Amiodarone↗