[Indocyanine green fluorescence to visualize the ureteric vascularization of kidney transplants: An exploratory study]. / Visualiser la vascularisation urétérale des transplants rénaux par fluorescence au vert d'indocyanine : étude exploratoire.

INTRODUCTION: Urinary complications after kidney transplantation are common and can compromise renal function. While they are mainly attributed to ischemic lesions of the ureter, there is no existing method to evaluate its vascularization during surgery. The aim of the study was to evaluate if indocyanine green, revealed by infra-red light andused to visualize tissue perfusion, could provide an appreciation of the ureter's vascularization during kidney transplantation. METHODS: This feasibility study was conducted over one month, on eleven consecutive kidney transplants. During transplantation, an injection of indocyanine green enabled the surgeon to visualize in real time with an infra-red camera the ureter fluorescence. Its intensity was reported on a qualitative and semi-quantitative scale. Occurrence of urinary complications such as stenosis or ureteral fistula were collected during 6 months. RESULTS: In all of the 11 cases (100%), the last centimeters of the ureters were not fluorescent. Three (27%) ureters were poorly or partiallly fluorescent. Out of these three cases, only one case of urinary fistula occurred, followed by ureteric stenosis. In the series, two fistulas (18%) and two ureteric stenoses (18%) occurred. No side effects were observed. The low number of events did not allow statistical analysis. CONCLUSION: Infra-red fluorescence of indocyanine green could be a simple and innovative way to appreciate the transplant's ureteric vascularization during kidney transplantation. It could help surgeons to identify the level of ureter section and to decide the anastomosis technique, in order to limit urinary complications. LEVEL OF EVIDENCE: 3.

Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer.

BACKGROUND: In breast cancer patients, about two thirds of the tumors are estrogen receptor (ER)-positive and one third are ER-negative. The molecular mechanisms leading to the ER-negative phenotype are poorly understood. Nearly all ER-negative and about 40% of ER-positive cancers are resistant to endocrine therapy. PURPOSE: In this study, we examined the entire coding region of the ER gene in ER-positive and ER-negative primary breast tumors to determine whether deletions/insertions or point mutations might account for the ER-negative phenotype. METHODS: We amplified exons 1 through 8 of the ER gene in 118 ER-positive and 70 ER-negative primary breast tumors and searched for mutations by single-strand conformation polymorphism analysis, denaturing gradient gel electrophoresis, and DNA sequencing. RESULTS: Both ER-negative and ER-positive tumors contained neutral polymorphisms in codons 10 [TCT-->TCC (Ser)], 87 [GCG-->GCC (Ala)], 243 [CGC-->CGT (Arg)], 325 [CCC-->CCG (Pro)], and 594 [ACA-->ACG (Thr)]. There was no correlation of any of the polymorphic alleles with the ER phenotype or other clinicopathologic parameters including tumor type, size, grade, or stage. However, the polymorphism in codon 325 showed a strong association with a family history of breast cancer (P = .0005). This association was observed both in premenopausal and postmenopausal patients. Despite extensive searching in exons 1 through 8, we found no deletions/insertions and only two missense mutations in codons 69 [AAC (Asn)-->AAG (Lys)] and 396 [ATG (Met)-->GTG (Val)] of the same ER-negative tumor. Thus, only 1% of the primary breast cancers had point mutations in the ER gene. CONCLUSIONS: In the majority of primary breast cancers, the ER-negative phenotype is not the result of mutations in the coding region of the ER gene, but is due to deficient ER expression at the transcriptional or post-transcriptional level. IMPLICATIONS: The correlation reported previously, as well as our current findings, suggest that further investigations are warranted to understand the possible linkage of the ER gene locus to hereditary breast cancer.

Microsatellite instability and loss of heterozygosity in breast cancer.

Microsatellite instability (MSI) has been described in colorectal and other cancers. The purpose of this study was to determine the presence of MSI in breast cancer and to correlate its occurrence with clinicopathological parameters. For microsatellite markers we examined mono-, di-, tri-, and tetranucleotide repeats that, due to their polymorphic nature, may also be used to investigate loss of heterozygosity. In 20 paired breast cancer-peripheral blood DNA samples we identified four tumors (20%) with somatic MSI. All four tumors were stage I or II, grade 1 or 2, and estrogen receptor positive. To study MSI in relation to tumor progression we also examined paired DNA samples from two ipsilateral and three contralateral breast cancers, as well as two matched tumor-metastatic lymph node specimens. None of these seven cases showed MSI, but two of the contralateral tumors revealed allelic loss of polymorphic repeats. These data suggest that MSI is an early event in mammary tumorigenesis while loss of heterozygosity may occur at a later stage.

Breast cancer and CYPIA1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans.

Genetically based differences in carcinogen metabolism have been related to polymorphisms of the cytochrome P450IA1 gene (CYPIA1) and the null genotypes of glutathione S-transferase classes mu and theta (GSTM1 and GSTT1). By PCR we examined the genotypes of CYPIA1, GSTM1, and GSTT1 in relation to breast cancer risk in Caucasian and African-American women. The study included 164 Caucasian and 59 African-American women with primary invasive breast cancer and age-matched female controls. Enzyme polymorphisms included in this study were the null deletions of GSTM1 and GSTT1 and the m1 (MspI), m2 (codon 462: isoleucine-->valine), m3 (MspI-AA), and m4 (codon 461: threonine-->asparagine) polymorphisms of CYPIA1. Contrary to previous reports by other investigators, none of the enzyme genotypes, individually or combined, appear to associate with an increased risk for breast cancer in Caucasian or African-American women. We also report that the recently described m4 allele occurs at a lower frequency in African-Americans than Caucasians and is not linked with breast cancer in either race. Thus, it is unlikely that polymorphisms of GSTM1, GSTT1, or CYPIA1 represent susceptibility factors for breast cancer in Caucasians or African-Americans.

High-mobility group (HMG) protein HMG-1 and TATA-binding protein-associated factor TAF(II)30 affect estrogen receptor-mediated transcriptional activation.

The estrogen receptor (ER) belongs to a family of ligand-inducible nuclear receptors that exert their effects by binding to cis-acting DNA elements in the regulatory region of target genes. The detailed mechanisms by which ER interacts with the estrogen response element (ERE) and affects transcription still remain to be elucidated. To study the ER-ERE interaction and transcription initiation, we employed purified recombinant ER expressed in both the baculovirus-Sf9 and his-tagged bacterial systems. The effect of high-mobility group (HMG) protein HMG-1 and purified recombinant TATA-binding protein-associated factor TAF(II)30 on ER-ERE binding and transcription initiation were assessed by electrophoretic mobility shift assay and in vitro transcription from an ERE-containing template (pERE2LovTATA), respectively. We find that purified, recombinant ER fails to bind to ERE in spite of high ligand-binding activity and electrophoretic and immunological properties identical to ER in MCF-7 breast cancer cells. HMG-1 interacts with ER and promotes ER-ERE binding in a concentration- and time-dependent manner. The effectiveness of HMG-1 to stimulate ER-ERE binding in the electrophoretic mobility shift assay depends on the sequence flanking the ERE consensus as well as the position of the latter in the oligonucleotide. We find that TAF(II)30 has no effect on ER-ERE binding either alone or in combination with ER and HMG-1. Although HMG-1 promotes ER-ERE binding, it fails to stimulate transcription initiation either in the presence or absence of hormone. In contrast, TAF(II)30, while not affecting ER-ERE binding, stimulates transcription initiation 20-fold in the presence of HMG-1. These results indicate that HMG-1 and TAF(II)30 act in sequence, the former acting to promote ER-ERE binding followed by the latter to stimulate transcription initiation.

Ryanodine and theophylline-induced depletion of energy stores in amphibian muscle.

The effects of high and low levels of ryanodine on theophylline-induced energy depletion were studied in isolated frog sartorius muscle. Whereas low concentrations of ryanodine (1-10 microM) did not change high energy phosphate contents (PE) after 60 min, high levels (100 microM) reduced resting energy contents by 60% after 60 min. Subcontracture levels of theophylline (2 mM), in the presence of high ryanodine, produced an 80% PE depletion, suggesting possible additive or synergistic effects of these two agents. In contrast to theophylline-induced depletion, neither the ryanodine-induced depletion nor the theophylline-plus-ryanodine-induced depletion of PE seemed sensitive to inhibition by 1 mM procaine. This suggests that there may be differences in the mechanisms whereby methylxanthines and ryanodine deplete energy stores and evoke contractures in amphibian skeletal muscle.

An ageing-associated decline in force production after repetitive contractions by rat skinned skeletal muscle fibres.

Chemically skinned muscle fibre segments were prepared from the extensor digitorum longus (EDL) and soleus muscles of young (5-6 months) and old (24-31 months) male Wistar rats. Muscle fibres were activated repetitively with a buffered calcium solution a total of 50 times, and the force resulting from each activation recorded. Both EDL and soleus fibres showed a substantial decline in maximum force over the series of 50 contractions. The decline in maximum force was significantly higher in old EDL and soleus fibres than in their young counterparts, indicating a difference between the contractile apparatus of skeletal muscle from young and old animals. Normalized tension, defined as force per muscle fibre cross-sectional area, was significantly lower in fibres from the old animals than from the young, giving further evidence of the existence of changes to the contractile apparatus with ageing.

[The perforation of the small intestine into the free peritoneum revealing Crohn disease]. / La perforation du grêle en péritoine libre révélatrice d'une maladie de Crohn.

A new case of Crohn's disease was discovered due to a perforation of the small bowel into the free peritoneum. We recall the epidemiological, clinical and pathogenic features of this rare incident. On the basis of the data in the literature, we propose a discussion of the surgical techniques used. Resection appears to be preferred Anastomosis is usually performed later except in exceptional selected cases.

[A case of pure unilobar Caroli disease]. / Un cas de maladie de Caroli pure, unilobaire.

We describe a new case of pure Caroli disease and review of the literature. Although often sporadic, this disease is usually considered an autosomal recessive hereditary disease. It is often either associated with another congenital hepatorenal fibrocystic disease or with extrahepatic bile duct dilatation. The clinical examination and laboratory tests are of not specific if congenital hepatic fibrosis or congenital cysts of the coleduct is lacking. Certain echographic and scan images are however very specific. Complications are related to intrahepatic stone formation and to superinfections. The long-term course appears to involve increased risk of cholangiocarcinoma. Treatment of the localized form includes priority resection. In diffuse disease, treatment may be more medical with antibiotics and sometimes bile solvents. In case of failure, transplantation may be entertained.

[Comparison of 2 chemosensitivity tests by grafting a polyoma tumor in the cheek pouch of syngeneic hamsters and under the renal capsule of syngeneic mice]. / Comparaison de deux tests de chimiosensibilité par greffe d'une tumeur polyome dans la poche jugale du hamster syngénique et sous la capsule rénale de la souris syngénique.

The immunocompetent subrenal capsule assay tumour graft is a good chemosensitivity test. We have compared it to immunocompetent white hamster cheek pouch tumour graft. These two assays are both easy to perform. Each has specific advantages and disadvantages. However the six days immunocompetent mouse subrenal capsule assay tumour graft is the most practicable and reproducible. The hamster cheek pouch assay would be used when mouse subrenal capsule assay would not be efficient for the molecules under study.

[Immunologic assessment and acoustic "stressing situation" in an experimental system BALB/c mice, the Tsc-3T3 tumor]. / Surveillance immunitaire et "situation stressante" acoustique dans le système expérimental souris BALB/c tumeur Tsc-3T3.

Previous results in Hamsters showed enhancement of tumor takes in animals exposed to acoustic aggression. Since this phenomenon could be due to immunodepression, we investigated whether this was the case in a better defined system of inbred BALB/c Mice. The results show that in these conditions, the tumor graft could not transgress a minor histocompatibility antigen nor decrease the protective effects of polyoma virus against tumor challenge and that all the immune tests investigated were unaltered.

Colonic perforation due to colonoscopy: a retrospective study of 48 cases.

BACKGROUND AND STUDY AIMS: The aim of this retrospective study was to analyze data on the treatment of 48 cases of colonic perforation, with a view to defining the criteria for choosing between medical and surgical treatment. PATIENTS AND METHODS: A questionnaire requesting information about complications of colonoscopy and their treatment was sent out to four hospital gastroenterological and surgical units. RESULTS: From January 1979 to December 1993, we reviewed the records of 48 cases of colonic perforation following colonoscopy (24 perforations occurred after diagnostic colonoscopy and 24 after therapeutic colonoscopy). Diagnosis of perforation was delayed in 42% of the patients, with a mean delay of two days (range 0.5-7 days). The treatment was surgical in 35 cases, including eight in which previous medical treatment had been unsuccessful. The perforation was in the sigmoid colon in 74% of the surgical population. Operations were carried out using two procedures, including colostomy, in the case of 20 patients (57%). Colostomy closure was performed in 12 patients (60%) with no mortalities. Surgical mortality occurred in five patients (14%), in four cases due to preexisting medical diseases. Medical treatment was attempted in 21 cases, and was successful in 13, mainly in cases in which perforation had occurred after therapeutic colonoscopy (12 patients). CONCLUSION: The choice of the right type of treatment for colonoscopic perforation seems to depend on the size of the lesion. Surgical treatment is appropriate when the perforation has occurred during diagnostic colonoscopy, since the lesion in this case is usually a large colonic laceration, whereas nonsurgical treatment seems to be justified after polypectomy, as long as there is rapid clinical improvement.

Hemodynamics and wall mechanics after stent placement in swine iliac arteries: comparative results from six stent designs.

PURPOSE: To compare the hemodynamics and wall mechanics of swine iliac arteries after placement of six types of stent. MATERIALS AND METHODS: Stents were placed in the iliac artery of 18 pigs (three pigs each underwent placement with one of six types of stent); 16 untreated pigs served as control animals. Iliac arterial hemodynamics and wall mechanics were measured 4 days after placement. RESULTS: Four stents (Palmaz-Schatz, Cordis, Warren, NJ; and Strecker, Cragg, and Symphony, Boston Scientific/Vascular, Natick, Mass) caused decreased pulsatile flow rate in the treated and contralateral iliac arteries; one (Memotherm; Bard, Covington, Ga) caused increased flow pulsatility; and one (Wallstent; Schneider, Plymouth, Minn) had no effect. No compliance mismatching was noted for the Cragg, Symphony, and Memotherm stents, whereas a decrease in compliance was noted for the Palmaz-Schatz, Strecker, and Wallstent designs. The Palmaz-Schatz and Strecker stents caused increased arterial wall rigidity, the Symphony and Wallstent designs had no effect, and the Memotherm and Cragg stents caused decreased wall rigidity. Stents made of stiff metal yielded different early results than did stents made of the less rigid nitinol. CONCLUSION: Soon after implantation, the six stent designs elicited varying changes in blood flow, arterial compliance, and arterial wall mechanics. Contralateral arterial flow also was affected.