Search

A bispecific antibody (BsAb) targeting the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) pathways represents a novel approach to overcome resistance to targeted therapies in patients with nonsmall cell lung cancer. In this study, we sequentially screened a panel of BsAbs in a combinatorial approach to select the optimal bispecific molecule. The BsAbs were derived from different EGFR and MET parental monoclonal antibodies. Initially, molecules were screened for EGFR and MET binding on tumor cell lines and lack of agonistic activity toward MET. Hits were identified and further screened based on their potential to induce untoward cell proliferation and crossphosphorylation of EGFR by MET via receptor colocalization in the absence of ligand. After the final step, we selected the EGFR and MET arms for the lead BsAb and added low fucose Fc engineering to generate amivantamab (JNJ-61186372). The crystal structure of the anti-MET Fab of amivantamab bound to MET was solved, and the interaction between the two molecules in atomic details was elucidated. Amivantamab antagonized the hepatocyte growth factor (HGF)-induced signaling by binding to MET Sema domain and thereby blocking HGF beta-chain-Sema engagement. The amivantamab EGFR epitope was mapped to EGFR domain III and residues K443, K465, I467, and S468. Furthermore, amivantamab showed superior antitumor activity over small molecule EGFR and MET inhibitors in the HCC827-HGF in vivo model. Based on its unique mode of action, amivantamab may provide benefit to patients with malignancies associated with aberrant EGFR and MET signaling.

Purpose The primary study objective was to describe the incidence of osteochondral damage (OD) in our cohort of patients with patellar instability (PI). The secondary objective was to assess for associations between patient demographic characteristics, duration of PI, and quantitative radiographic measurements of anatomic risk factors for PI and OD in this cohort. Methods A retrospective chart review identified patients treated for PI at a tertiary referral center between 2013 and 2018. Patients were evaluated for osteochondral injury with either magnetic resonance imaging if treated nonoperatively or operative reports if treated surgically. The Caton-Deschamps ratio, proximal tibial tubercle–to–trochlear groove (pTT-TG) distance, distal tibial tubercle–to–trochlear groove (dTT-TG) distance, lateral trochlear inclination (LTI) angle, lateral patellar inclination (LPI) angle, and sulcus angle were calculated from magnetic resonance imaging scans. Trochlear dysplasia is an important risk factor for PI that can be reliability quantified by the pTT-TG distance, dTT-TG distance, LTI angle, sulcus angle, and LPI angle. Demographic data including age at first instability event, sex, body mass index, symptom duration, and number of dislocations were documented. Results A total of 125 knees in 118 patients (average age, 13.9 ± 3.4 years; 48% female patients) with PI were identified. Within this cohort, 67% were treated surgically and 53% had OD. No association was identified between osteochondral injury and age, sex, body mass index, symptom duration, LTI angle, LPI angle, dTT-TG distance, pTT-TG distance, or number of dislocations. An increased sulcus angle (more dysplasia) showed a statistically significant association with osteochondral pathology (P = .021), and higher sulcus angles were statistically significantly associated with acute osteochondral fracture compared with chondral injury (P = .001). Conclusions Using quantitative analysis of trochlear dysplasia, this study identified a significant association between trochlear dysplasia (sulcus angle) and the incidence of OD in our cohort of patients with PI. The frequency of dislocation or subluxation and patient demographic characteristics were not significantly associated with OD. Level of Evidence Level III, retrospective prognostic study.

Summary Objective Patients with obesity are at risk for chronic kidney disease. The aim is to characterize the spectrum of kidney disease in these patients, which may be related to obesity, termed obesity-related glomerulopathy (ORG), or may have other diseases secondary to associated or unassociated medical conditions. Methods Native kidney biopsies from 2000 to 2012 were retrospectively reviewed from all patients with body mass index >30kg/m 2 . Glomerular diameter was measured using a standard micrometer and clinicopathologic characteristics were analyzed. Results 4% (287) of all biopsies were obtained from patients with obesity (mean: weight 122kg, BMI 40.4±7.35kg/m 2 ) for proteinuria in 93% and renal insufficiency in 53%. Frequent associated factors were abnormal glucose metabolism (31%), hypertension (60%), and obstructive sleep apnea (9%). Typical lesions of ORG were seen in 41% of cases and additional diseases in the rest. Glomerulomegaly, glomerular diameter >180μm, was present in 84% of cases (mean 224μm) vs normal size in 11% (mean 157μm), but was not increased with higher magnitude of obesity. Proteinuria was highest in patients with idiopathic FSGS (mean 8g/24h) and immune complex diseases (mean 7.4g/24h) and was mainly subnephrotic in obesity-related FSGS and tubulo-interstitial diseases. Creatinine levels were highest in tubulointerstitial diseases (mean 8.4mg/dL) and progressive diabetic nephropathy (mean 2.5mg/dL). Conclusions Diverse kidney pathology superimposed on ORG is present in patients with obesity with varied clinical renal disease, some of which may be amenable for therapy. Kidney biopsy will assist in delineating these lesions for appropriate management and prognosis.

Little is known about the genotypic make-up of HIV-1 DNA genomes during the earliest stages of HIV-1 infection. Here, we use near-full-length, single genome next-generation sequencing to longitudinally genotype and quantify subtype C HIV-1 DNA in four women identified during acute HIV-1 infection in Durban, South Africa, through twice-weekly screening of high-risk participants. In contrast to chronically HIV-1-infected patients, we found that at the earliest phases of infection in these four participants, the majority of viral DNA genomes are intact, lack APOBEC-3G/F-associated hypermutations, have limited genome truncations, and over one year show little indication of cytotoxic T cell-driven immune selections. Viral sequence divergence during acute infection is predominantly fueled by single-base substitutions and is limited by treatment initiation during the earliest stages of disease. Our observations provide rare longitudinal insights of HIV-1 DNA sequence profiles during the first year of infection to inform future HIV cure research., The dynamics of HIV-1 DNA sequences early after HIV-1 transmission remains poorly characterized. Here, the authors perform a longitudinal evaluation of HIV-1 DNA sequences in subtype C-infected individuals during acute infection, providing a landscape of the nature and evolution of the very early viral genome.

Healthy aging has been associated with a global reduction in white matter integrity, which is thought to reflect cognitive decline. The present study aimed to investigate this reduction over a broad range of the life span, using diffusion tensor imaging analyzed with conditional inference random forest modeling (CForest). This approach is sensitive to subtle and potentially nonlinear effects over the age continuum and was used to characterize the progression of decline in greater detail than has been possible in the past. Data were collected from 45 healthy individuals ranging in age from 19 to 67 years. Fractional anisotropy (FA) was estimated using probabilistic tractography for a number of major tracts across the brain. Age coincided with a nonlinear decrease in FA, with onset beginning at ∼30 years of age and the steepest declines occurring later in life. However, several tracts showed a transient increase before this decline. The progression of decline varied by tract, with steeper but later decline occurring in more anterior tracts. Finally, strongly right-handed individuals demonstrated relatively preserved FA until more than a decade following the onset of decline of others. These results demonstrate that using a novel, nonparametric analysis approach, previously reported reductions in FA with healthy aging were confirmed, while at the same time, new insight was provided into the onset and progression of decline, with evidence suggesting increases in integrity continuing into adulthood.

It has been well documented that IQ scores calculated using Canadian norms are generally 2-5 points lower than those calculated using American norms on the Wechsler IQ scales. However, recent findings have demonstrated that the difference may be significantly larger for individuals with certain demographic characteristics, and this has prompted discussion about the appropriateness of using the Canadian normative system with a clinical population in Canada. This study compared the interpretive effects of applying the American and Canadian normative systems in a clinical sample. We used a multivariate analysis of variance (ANOVA) to calculate differences between IQ and Index scores in a clinical sample, and mixed model ANOVAs to assess the pattern of differences across age and ability level. As expected, Full Scale IQ scores calculated using Canadian norms were systematically lower than those calculated using American norms, but differences were significantly larger for individuals classified as having extremely low or borderline intellectual functioning when compared with those who scored in the average range. Implications of clinically different conclusions for up to 52.8% of patients based on these discrepancies highlight a unique dilemma facing Canadian clinicians, and underscore the need for caution when choosing a normative system with which to interpret WAIS-IV results in the context of a neuropsychological test battery in Canada. Based on these findings, we offer guidelines for best practice for Canadian clinicians when interpreting data from neuropsychological test batteries that include different normative systems, and suggestions to assist with future test development.

Summary Monitoring of triglycerides for patients on isotretinoin is practised primarily to avoid hypertriglyceridaemia-associated pancreatitis. The aim of this study was to describe clinically the published cases of hypertriglyceride-associated pancreatitis. A comprehensive search strategy using MEDLINE, Embase and grey literature was conducted (1960 to January 2016) to identify all case reports of isotretinoin-associated pancreatitis and all relevant studies of isotretinoin and triglycerides for any indication (≥ 20 patients). Terms related to isotretinoin, triglycerides and pancreatitis were searched with all available synonyms. Any studies that used isotretinoin and mentioned triglycerides or pancreatitis were searched in full text, where available, for cases of pancreatitis. Studies from all countries and published in any language were included, but Korean and Turkish studies could not be analysed. Two authors independently reviewed the publications to determine eligibility, and for data extraction. In total, 125 papers fulfilled the inclusion criteria and were searched for cases of pancreatitis. Eleven papers with 25 cases of pancreatitis associated with isotretinoin were identified; four of these cases were likely due to hypertriglyceridaemia. Three patients had elevated baseline triglycerides, but no monitoring. Pancreatitis occurred 6 and 7 weeks, and 6 months after initiation of therapy. For the fourth patient who was treated for glioblastoma and died, no detailed clinical information was available. Idiosyncratic pancreatitis associated with isotretinoin is the most frequent pancreatitis on isotretinoin, and patients should be warned about it. Hypertriglyceride-associated pancreatitis is an exceedingly rare adverse event of isotretinoin therapy. Our data cannot give a frequency or risk for either adverse event. Based on the clinical information of the patients available, we conclude that for patients without elevated baseline triglycerides, or risk thereof, monitoring of triglycerides during therapy is of little value.

The unexpected observation of a hyperglycemic effect of some tricycle-based delta opioid receptor (DOR) agonists led to a series of studies to better understand the finding. Single administration of two novel tricyclic DOR agonists dose dependently elevated rat plasma glucose levels; 4-week toxicology studies confirmed the hyperglycemic finding and further revealed pancreatic β-cell hypertrophy, including vacuole formation, as well as bone dysplasia and Harderian gland degeneration with regeneration. Similar diabetogenic effects were observed in dog. A review of the literature on the antiserotonergic and antihistaminergic drug cyproheptadine (CPH) and its metabolites revealed shared structural features as well as similar hyperglycemic effects to the present series of DOR agonists. To further evaluate these effects, we established an assay measuring insulin levels in the rat pancreatic β-cell-derived RINm5F cell line, extensively used to study CPH and its metabolites. Like CPH, the initial DOR agonists studied reduced RINm5F cell insulin levels in a concentration-dependent manner. Importantly, compound DOR potency did not correlate with the insulin-reducing potency. Furthermore, the RINm5F cell insulin results correlated with the diabetogenic effect of the compounds in a 5-day mouse study. The RINm5F cell insulin assay enabled the identification of aryl-aryl-amine DOR agonists that lacked an insulin-reducing effect and did not elevate blood glucose in repeated dosing studies conducted over a suprapharmacologic dose range. Thus, not only did the RINm5F cell assay open a path for the further discovery of DOR agonists lacking diabetogenic potential but also it established a reliable, economical, and high-throughput screen for such potential, regardless of chemotype or target pharmacology. The present findings also suggest a mechanistic link between the toxicity observed here and that underlying Wolcott-Rallison Syndrome.

Objective To evaluate the causes and results of conversion to open repair after aortic aneurysm endovascular treatment (EVAR). Design Retrospective study of open conversion after EVAR was performed in eight French academic centres. Primary conversion (PC) within 30 days after EVAR and secondary conversions (SC) were analysed separately. Result Between 1997 and 2007, open conversions were performed in 34 patients (most often in high-risk patients): 14 PC and 20 SC. Two main causes of PC were unfavourable iliac artery anatomy and renal artery coverage. In hospital mortality was 21%. SC occurred at a median of 44 months after primary EVAR. Nine were urgent cases for rupture or infection and 11 elective for aneurysm growth, infection or thrombosis. Early mortality was similar after emergent or elective SC (25%). Conclusion Open conversion, and, in particular, PC and urgent SC, was associated with a poor outcome. According to the literature, mortality after elective SC is low but remains high in high-risk patients.

Non–small cell lung cancers (NSCLC) with activating EGFR mutations become resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M) and/or activation of the cMet pathway. We engineered a bispecific EGFR-cMet antibody (JNJ-61186372) with multiple mechanisms of action to inhibit primary/secondary EGFR mutations and the cMet pathway. JNJ-61186372 blocked ligand-induced phosphorylation of EGFR and cMet and inhibited phospho-ERK and phospho-AKT more potently than the combination of single receptor–binding antibodies. In NSCLC tumor models driven by EGFR and/or cMet, JNJ-61186372 treatment resulted in tumor regression through inhibition of signaling/receptor downmodulation and Fc-driven effector interactions. Complete and durable regression of human lung xenograft tumors was observed with the combination of JNJ-61186372 and a third-generation EGFR TKI. Interestingly, treatment of cynomolgus monkeys with JNJ-61186372 resulted in no major toxicities, including absence of skin rash observed with other EGFR-directed agents. These results highlight the differentiated potential of JNJ-61186372 to inhibit the spectrum of mutations driving EGFR TKI resistance in NSCLC. Cancer Res; 76(13); 3942–53. ©2016 AACR.

Diabetes is the leading cause of end stage renal disease (ESRD) in the United States, representing 44% of incident cases [1]. In this study, serum and peripheral blood collected from diabetic patients in five stages of chronic kidney disease (CKD), as defined by glomerular filtration rate (GFR), were compared to healthy (non-CKD) subjects.Serum samples were analyzed for 39 inflammatory or immune mediator protein levels and peripheral blood samples were analyzed for expression of 35 gene transcripts.In serum, MCP-1, FGF-2, VEGF, and EGF levels were elevated above controls at all stages of DN. Five mediator levels, GM-CSF, IL-1α, IL-1RA, IL-6, and MIP1β increased with disease progression until stage 4-5, at which point a decrease was observed paralleling a loss of functional renal mass that occurs in late stage CKD. Five mediator levels: GRO, IFNγ, MDC, Eotaxin, and G-CSF significantly differed from controls at one or more stages without apparent correlation with disease stage. Only a single mediator, sIL2RA, exhibited a linear increase with disease severity consistent with declining GFR. In peripheral blood, the transcript level of seven mediators, ICAM1, TNF-α, TGF-β, IL-8, IL17RA, IFNγ, and MYD88 were significantly elevated at all disease stages as compared to control.Statistically significant differences in protein and transcripts levels between diseased and control can be detected in serum and peripheral blood utilizing high content profiling. These changes occur as early as stage 1-2 before a significant decline in renal function.

We examined the self-reported use of reading, study, and learning strategies in university students with a history of reading difficulties (HRD; n = 77) and with no history of reading difficulties (NRD; n = 295). We examined both between-groups differences in strategy use and strategy use as a predictive measure of academic success. Participants completed online questionnaires regarding reading history and strategy use. GPA and frequency of use of academic support services were also obtained for all students. University students with HRD reported a different profile of strategy use than their NRD peers, and self-reported strategy use was differentially predictive of GPA for students with HRD and NRD. For students with HRD, the use of metacognitive reading strategies and the use of study aids predicted academic success. Implications for university student services providers are discussed.

Multiple skin cylindromas are of autosomal dominant transmission and may be associated with spiradenoma and trichoepithelioma. This condition is known as Brooke-Spiegler syndrome. The aim of this study is to compare surgical and laser treatment for these lesions.Five patients from a single family (two male and three female) consulted at the dermatology department for the treatment of multiple cylindromas of the scalp. The female patients presented a more severe form that had developed into "turban tumour". All patients were initially treated by surgery. Two had undergone multiple surgical excisions alone while the others had been treated with CO2 laser. One of the female patients treated with surgery had undergone complete excision of the scalp covered by total skin graft. The three patients treated with CO2 laser were completely satisfied with their therapy, which enabled a larger number of lesions to be treated at each session. They underwent one session every three months under local anaesthesia.CO2 laser constitutes an alternative to surgery in the treatment of multiple skin cylindroma. It gives excellent cosmetic result with excellent safety and a high degree of satisfaction among treated patients. It should be proposed for patients refusing surgery or where the number of lesions enables first-line use of this approach to be envisaged.

Tako-Tsubo syndrome is a reversible left ventricular myocardial dysfunction. There are few publications on its evolution and the purpose of this study is to describe the medium-term outcome of patients who presented this pathology.This retrospective study included 70 patients presenting with Tako-Tsubo syndrome who were referred to Haut-Lévèque hospital between November 2003 and January 2012. The parameters included in follow-up were: number of cardiovascular events, recurrence, electrocardiographic and echocardiographic evolution.Sixty-eight patients had a mean follow-up of 4.8±2.4 years. The survival rate was 92%, 39 patients (57%) showed no cardiovascular symptoms, 12 (18%) had one or more new episodes of chest pain and 4 (6%) had stage II dyspnoea on the NYHA classification scale. One patient had a recurrence 6.5 years later, triggered by the same stress as the first instance. Forty-five patients (64%) had ECGs which evolved in the early days to diffuse T-wave inversion. In the medium term, 32 (54%) patients had a normal ECG, 19 (32%) had inverted T-waves in precordial leads and 2 (3%) had Q-waves. In terms of echocardiography, left ventricular ejection fraction was normal in all with variable delays. Four patients continued to have apical hypokinesia.This study shows that the medium-term outlook is favourable in terms of cardiovascular mortality and that recurrence is rare. It highlights, however, the persistence of electrocardiographic and echocardiographic abnormalities.

Background. Collapsing glomerulopathy (CG) represents severe podocyte injury with massive proteinuria, rapid progression and relative resistance to therapy. It is associated with multiple etiologies, including obliterative arteriopathy in transplants. However, its association with diabetic nephropathy (DN) has not been reported. Methods. Renal biopsies performed in diabetic patients for either increasing proteinuria or deteriorating renal function, or both, were retrospectively reviewed. The clinicopathologic features and immunohistochemical staining of podocytes were analyzed. Results. Of 534 patients with DN, 26 human immunodeficiency virus (HIV)-negative patients were found to have CG superimposed on DN (5% DN cases). At the time of biopsy, their mean serum creatinine was 3.8 mg/dL and proteinuria was 9.8 g/24 h. Renal biopsy showed CG in 2–30% (mean 16% of glomeruli), with segmental (2%) and global (33%) glomerulosclerosis. DN classification was Class IV-12, III-8, IIb-4 and IIa-2. Vascular sclerosis was moderate (44%) and severe (56%). Extensive arteriolar hyalinosis with >50% luminal stenosis was seen in 85% of cases. Markers of podocyte differentiation were lost, consistent with other types of CG. Cytokeratin was focally positive in 70% and VEGF overexpressed in 43%. Follow-up on 17 patients: 13 developed end-stage renal disease (ESRD) in 7 months from the time of biopsy. The development to ESRD in these patients was more rapid than diabetic controls without CG (P=0.005). The remaining four, 5–24 months follow-up, had an increase in creatinine with stable proteinuria. Conclusions. CG contributes to an increased level or new onset of proteinuria in DN which may be intractable. CG in DN with advanced vascular hyalinosis is presumably due to ischemic podocyte injury and is of prognostic significance.

Neonatal exposure to diethylstilbestrol (DES) causes permanent alterations in female reproductive tract gene expression, infertility, and uterine cancer in mice. To determine whether epigenetic mechanisms could explain these phenotypes, we first tested whether DES altered uterine expression of chromatin-modifying proteins. DES treatment significantly reduced expression of methylcytosine dioxygenase TET oncogene family, member 1 (TET1) on postnatal day 5; this decrease was correlated with a subtle decrease in DNA 5-hydroxymethylcytosine in adults. There were also significant reductions in histone methyltransferase enhancer of zeste homolog 2 (EZH2), histone lysine acetyltransferase 2A (KAT2A), and histone deacetylases HDAC1, HDAC2, and HDAC3. Uterine chromatin immunoprecipitation was used to analyze the locus-specific association of modified histones with 2 genes, lactoferrin (Ltf) and sine oculis homeobox 1 (Six1), which are permanently upregulated in adults after neonatal DES treatment. Three histone modifications associated with active transcription, histone H3 lysine 9 acetylation (H3K9ac), H3 lysine 4 trimethylation (H3K4me3), and H4 lysine 5 acetylation (H4K5ac) were enriched at specific Ltf promoter regions after DES treatment, but this enrichment was not maintained in adults. H3K9ac, H4K5ac, and H3K4me3 were enriched at Six1 exon 1 immediately after neonatal DES treatment. As adults, DES-treated mice had greater differences in H4K5ac and H3K4me3 occupancy at Six1 exon 1 and new differences in these histone marks at an upstream region. These findings indicate that neonatal DES exposure temporarily alters expression of multiple chromatin-modifying proteins and persistently alters epigenetic marks in the adult uterus at the Six1 locus, suggesting a mechanism for developmental exposures leading to altered reproductive function and increased cancer risk.

This article reviews new mammography technologies resulting from advances in digital detectors and processing techniques. Most are just starting to be commercialized or are in the clinical trial phase. The results of clinical trials with the new 2D techniques (contrast-enhanced techniques or stereotactic techniques) show they are useful for diagnosing cancer. However, the greater complexity of the image acquisition process suggests that their use will be limited to particular cases such as inconclusive lesions or women with high risk for developing breast cancer. Among the 3D technologies (breast tomography and breast tomosynthesis), only breast tomosynthesis has been implemented in clinical practice, so it is the only technique for which it is possible to know the sensitivity, specificity, and radiation dose delivered. This article describes the principles underlying the way breast tomosynthesis works and the techniques used for image acquisition and reconstruction. It also summarizes the main results obtained in clinical studies, which generally show that breast tomosynthesis increases the breast cancer detection rate while decreasing the recall rate and number of biopsies taken. The protocol for breast tomosynthesis approved by the Food and Drug Administration (USA) consists of two conventional mammography projections for each breast and two tomosynthesis projections for each breast. This means multiplying the risks of inducing cancer and death associated with 2D mammography by a factor between 2 and 3 (2.6-3.3 and 0.7-0.9 per 100,000 women exposed when 50 years old, respectively). The protocol for breast tomosynthesis examinations is one of the aspects that is essential to determine when including tomosynthesis in screening programs and routine breast imaging.

To assess the relationship between renal Doppler parameters and renal cortical fibrosis in lupus nephritis (LN), we retrospectively reviewed 24 patients with LN underwent both renal color Doppler sonography and renal biopsy. The angle-corrected Doppler parameters, including peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) at the main and interlobar renal arteries were measured. The Doppler parameters and PSV and EDV ratios of the interlobar artery to main renal artery were compared with histopathologic analysis of the kidney biopsy specimen. On the basis of renal cortical fibrosis, the 24 cases of LN were divided into two groups: mild (6%-25%) renal cortex fibrosis (n = 13) and moderate (26%-50%) renal cortex fibrosis (n = 11). An independent-samples two tailed t test was used to statistically analyze the differences in PSV, EDV and RI between the two groups. Receiver operating characteristic was analyzed for assessing the accuracy of interlobar artery PSV and EDV in predicting moderate renal cortical fibrosis. In our result, both PSV and EDV in moderate renal cortex fibrosis were lower than that in mild renal cortex fibrosis. There were statistically significant differences in PSV and EDV at the interlobar artery, EDV and RI at the main renal artery, and PSV and EDV ratios of the interlobar artery to main renal artery between the two groups (all p 0.05). The area under receiver operating characteristic curves of PSV and EDV for predicting26% renal cortical fibrosis was 0.96 and 0.90, respectively. The optimal cutoff values for differentiating26% renal cortical fibrosis from those25% were PSV 30 cm/s (sensitivity = 0.92; specificity = 1) and EDV 13 cm/s (sensitivity = 0.77; specificity = 1). Therefore, the values of PSV and EDV at the interlobar artery can potentially be used as hemodynamic indicators of renal cortical fibrosis, which may non-invasively assist in monitoring the progression of renal cortical fibrosis in LN, especially in patients with contraindications to renal biopsy.

Enhancements to memory are associated with enhanced neural structures that support those capabilities. A great deal of work has examined this relationship in the context of natural variation in spatial memory capability and hippocampal (Hp) structure. Most studies have focused on volumetric and neuron measures, but have seldom examined the role of glial cells. Once considered involved only in supportive functions associated with neurons, the importance of glial cells in cognitive processes, including memory, is gaining more attention. Building upon our previous study on the relationship between the brain, memory, and environmental severity in food-caching birds, we compared the total number of Hp glial cells in wild-sampled and in lab-reared (common garden) black-capped chickadees (Poecile atricapillus) originating from two different environmental extremes. We found that birds from more harsh climate tended to have significantly more Hp glial cells than those from more mild climate and that lab-reared chickadees had significantly fewer Hp glial cells compared to the wild-sampled birds. These results suggest that population differences in glial numbers may be controlled, at least in part, by heritable mechanisms, but glial numbers appear to be additionally regulated by an individual's environment. The pattern of Hp glial cell abundance among our treatment groups closely followed that of the Hp volume, suggesting that Hp glial cell number may be associated with the Hp volume. Unlike Hp neurons, however, the number of Hp glial cells may be, at least in part, affected by an individual's experiences and environment.

Heparin is commonly administered during hemodialysis to prevent clotting in the extracorporeal circuit. The authors' unit instituted a change in heparin type and preparation procedure based on patient safety and potential cost savings. Fifty patient charts were reviewed to determine whether the change affected specific patient outcomes. Economic impact measures included drug, supply, and labor costs. No changes in hemodialysis efficacy or rates of adverse events were observed. Annual cost savings were estimated to be $81,627 USD.

THE advent of the cervical os smear (1) for the diagnosis of uterine cancer has led to extensive comparative studies of the vaginal and cervical methods in this laboratory. Cervical smears have been found to contain a larger concentration of cancer cells in positive cases. It has also been observed that almost invariably a greater concentration of the estrogenic cornified cells is found in the cervical smear than in the vaginal smear. This observation has prompted a study of the cornification counts of smears from the cervix compared with those from the vagina in 125 patients. The cases were chosen at random from our files of patients who had had both vaginal and cervical smears taken at the same time. Patients with cancer and those patients who showed total absence of estrogen, e.g., normal senile patients or castrates, were excluded. The smears covered all stages of the menstrual cycle and a large variety of age groups. It was found that 88.8 per cent of the cases showed the cervical cornification count...

From December 1971 to December 1989, 62 patients (pts) 42 males, 20 females, mean age 66 years (yr) 6 months (mth) (range 52-80) were operated upon for post-infarction ventricular septal defect (VSD), (anterior 34, inferior 28). Eight pts (13%), group (G) 1 presented with cardiogenic shock, 19 pts (30.5%), G2 with severe congestive heart failure (CHF); 31 pts (50%), G3 were stable with mild CHF and 4 pts (6.5%), G4 without CHF. Preoperative intra-aortic balloon pumping (IABP) was used in 49 pts (79%). One transplanted pt was excluded from this study. The VSD was closed from 1 day (d) to 5 mth (mean 13 d) after its occurrence. Hospital death (HD) occurred in 23 pts (37.7% +/- 6%). Of 44 incremental risk factors (RF) for HD studied, the preoperative status (PS) was the most significant (P less than 0.01). G1: 87% +/- 12%, G2: 42% +/- 12%, G3: 25.8% +/- 8%, G4: 0%. [table: see text] Non-survivors had a shorter mean delay between VSD occurrence and surgery than survivors: 5.6 +/- 3.7 d vs 18.2 +/- 30 d (P less than 0.05), but this delay was correlated to PS. The follow-up of the 38 early survivors ranges from 2 mth to 14 yr (mean 3 yr, 11 mth); 11 pts died between 45 d and 14 yr. No RF was identified for premature late death. HD included, the actuarial survival rate at 1, 5, 10 yr is: 57% (+/- 7%), 44% (+/- 8%), 30% (+/- 10%), respectively.

Congenital isolated atrio-ventricular block (CAVB) is a rare pathology, and its management is still rather poorly described through international literature. Within the service of pediatric cardiology leaded by Pr Choussat and Dr Jimenez (Cardiologic Hospital Haut-Lévêque of Bordeaux), we collected from 1980 to 2003, 30 isolated congenital CAVB, constituting the purpose of this retrospective study. Average follow-up is 14 +/- 8.8 years. None death occurred. CAVB are discovered at an average age of 4.8 years old; 6 cases were diagnosed in utero, half of them were associated with maternal lupus. Twenty patients on 30 were fitted with stimulator at an average age of 8.7 +/- 6.9 years old, due to symptoms or bradycardy. Epicardic fitting in VVI mode represents 65% of first approaches, it is followed by endocavitary way for 81% of cases. Cardiac stimulation does not prevent from dilated cardiomyopathy. Among 30 patients 10 were not fitted with stimulator, half of them presents chronotrop insufficiency during effort. As a conclusion, our patients show a good long-term vital prognosis; although CAVB discovered in utero lead to worse prognosis for children.

Arterial endofibrosis is a recently discovered artery disease that is specific to endurance athletes. Cycling is the sport that has shown the greatest number of cases. The endofibrosis is located most frequently in the external iliac artery, but other locations must also be sought. Thigh pain during supramaximal exercise and patient questioning provide strong indications. The diagnosis is confirmed when there is concordance of exercise-induced symptoms, a positive exercise test result and discrete arteriographic characteristics. Treatment is based on folate supplements and standardised surgery carried out by an experienced surgical team.

To compare the effects of caudal epidural xylazine versus saline on tolerance of paravertebral nerve block and flank surgery and on post-operative pain in heifers used for a veterinary student training laboratory.Randomized controlled prospective study.Fourteen one-year-old, nongravid, healthy Holstein heifers, weighing 360 +/- 5 kg.Xylazine (0.05 mg kg(-1)) or 0.9% saline (5 mL) was injected using a caudal epidural technique to seven heifers undergoing a flank surgery. Nerve block of the right paravertebral fossa was performed using equal parts of lidocaine 2% and bupivacaine 0.5%. Heart and respiratory rates, rectal temperature, rumination frequency, and appetite were recorded before and at 4, 8, and 24 hours after surgery. Scores were recorded for: tolerance of local anesthesia injections (pre-operatively), sedation, ataxia and distress (intraoperatively, every 30 minutes), and pain (4, 8, and 24 hours post-operatively).The animals reaction to local anesthetic injection was judged to be less in the xylazine group by both an experienced observer (p0.001) and student surgeons (p0.01). The xylazine group required less local anesthetic (82.9 +/- 13.8 mL) versus the saline group (108.4 +/- 19.6 mL, p=0.035). Intraoperatively, xylazine heifers were more sedated at all times (p-values from0.001 to 0.017), were more ataxic for the first 1.5 hours (p-values from0.001 to 0.026), and lower in distress at all times (p-values from0.001 to 0.007). No difference in post-operative pain or physiologic variables was found, except immediately post-operatively, rectal temperature was higher in the xylazine group (39.5 +/- 0.3 degrees C) than in the saline group (38.6 +/- 0.2 degrees C, p0.001).Compared with epidural saline, caudal epidural xylazine reduced distress of anesthetic injection and surgical manipulation in heifers and an improvement in animal well-being was apparent. This effect may have been as a result of sedation. Pre-operative epidural xylazine did not appear to improve post-surgical analgesia in our study.

In this study, 9 cases of tachycardia-induced cardiomyopathy have been reported, with a 7-year follow-up period. The patient population consisted of 5 males and 4 females with a mean age of 41 +/- 18 years (range: 10-70 years). It was difficult to determine the onset of the arrhythmia, due to its frequently asymptomatic course until such time as cardiac insufficiency became apparent (this was the case in 7 patients, while 2 subjects had palpitations). Four cases of AV intranodal reentry tachycardia (3 with an accessory pathway), 2 cases of atrial fibrillation, 1 case of auricular flutter, 1 case of atrial tachycardia and 1 case of ventricular tachycardia were observed. Disappearance of the symptomatology following restoration of sinus rhythm was accompanied by echocardiographically-determined normalization of systolic function on average 5 +/- 4 months post-arrhythmia (range: 1-12 months). Left-ventricular end-diastolic volumes decreased from 60 +/- 5 mm to 51 +/- 4 mm (P0.01), and end-systolic volumes from 50 +/- 7 mm to 35 +/- 4 mm (P0.001), while the left ventricular shortening fraction increased from 17 +/- 5% to 33 +/- 4% (P0.0001). In the differential diagnosis for primary dilated cardiomyopathy, tachycardia-induced cardiomyopathy appears very similar to the former, and only an adequate period of follow-up after the restoration of sinus rhythm can confirm the diagnosis.

Eighty-three patients underwent colectomy and ileorectal anastomosis for Crohn's disease of the large bowel. There were two postoperative deaths and seven anastomotic leaks. Fifty-two patients retained a functioning anastomosis with a mean follow-up of 8 years. Forty had an excellent or good functional result. The cumulative proportion of patients with a functioning ileorectal anastomosis was 77 and 63 per cent at 5 and 10 years respectively. Patients presenting with perforating Crohn's disease had a significantly increased risk of failure of the anastomosis. Perianal Crohn's disease following ileorectal anastomosis was significantly related to the need to defunction or excise the rectum.

Repair of post infarction ventricular septal defect (VSD) is still a challenging procedure with a high risk of recurrence of the VSD and subsequent mortality. The aim of this retrospective study was to assess if technical change in the surgical procedure was followed by an improvement in recurrence of the VSD and operative results.This retrospective study from 1971 to 2001 included 85 patients operated on early (15 days) after the occurrence of a post infarction VSD. Double patch technique was introduced in 1986. A total of 44 variables were studied by a uni- and multivariate analysis.Hospital death occurred in 36 patients. Significant factors for hospital mortality included: preoperative and evolution of the clinical status, right ventricular function and type of repair (one or two patches). Moreover, no recurrence was observed in patients repaired with the double patch technique (P=0.09). None of the studied variables were significant for long term survival. Concomitant CABG was not associated with higher hospital mortality and long-term survival rate was similar in patients with or without concomitant CABG.The use of the double patch technique and glue by avoiding recurrence of the VSD played a role in the reduction of the hospital mortality. This technique has to be recommended in the early repair of post infarction VSD. Concomitant CABG can be done safely to control the added risk of an associated coronary artery lesion.

The aim of this retrospective study was to report a series of nine aneurysms of the hepatic arteries, including real aneurysms (n = 4), pseudoaneurysms (n = 3) and false aneurysms (n = 2) observed from 1987 to 1999.There were 7 men and 2 women (mean age: 58 years). In 3 cases, the aneurysm was asymptomatic and detected by sonography; in 4 cases it was revealed by rupture with a severe hemorrhage and in 2 cases by cholestasis. The aneurysm was located on right (n = 3), proper and common (n = 3), proper (n = 2), and common (n = 1) hepatic arteries. The aneurysm was associated with hepatocellular carcinoma (n = 1), carcinoma of the head of the pancreas (n = 1) and liver metastases (n = 1).Eight patients were operated and one of them was operated three times. Hepatic arterial blood supply was restored in 6 patients with simple suture (n = 1), Goretex graft (n = 2), allograft (n = 2) and autologous vein (n = 1), with one failure which required liver retransplantation. Only one of the three attempts of embolization was successful. One patient with surgical contraindications died from hemobilia after embolization failure. During follow-up, there was one thrombosis of the common hepatic artery which had been excluded and two late deaths: one from rupture of a false aneurysm after bypass with an allograft and one by terminal progression of the cancer. The other 6 patients were alive at the time of this study.Clinical characteristics and therapeutic indications of hepatic arterial aneurysm are variable. Management is usually surgical, while embolization is reserved for special circumstances. Restoration of the hepatic arterial blood supply is necessary in aneurysms located on the proper hepatic artery.

Left atrial myxoma is considered to be exceptionally rare in the elderly. The authors observed and reported on 19 cases occurring in patients over 75 years of age out of a series of 100 myxomas diagnosed between 1962 and 1997, in 12 women and 7 men (mean age: 80 years, range 75 to 89 years). In 3 cases, the myxomas were chance findings at echocardiography but the 16 symptomatic patients (85%) had left ventricular failure (47%), positional symptoms (25%), pyrexia and poor general health (17%) or systemic embolism (17%). The location of the myxoma was the left atrium in all cases, with mitral valve obstruction in 13 of the 19 cases. Eighteen tumours were attached to the interatrial septum and one to the atrial surface of the anterior mitral leaflet. Calcifications were observed in 5 patients. Surgical ablation of the tumour was performed in 15 of the 19 patients. The post-operative course was usually uncomplicated: one patient died of a cerebral haemorrhage. Four patients did not undergo surgery because of patient refusal in 3 cases and major associated morbidity in the other case. These cases were included in the study because the tumours had all the characteristics of myxomas. Though the discovery of a myxoma remains a classical surgical emergency, the presence of quiescent, non-obstructive, well circumscribed and calcified myxomas with a low risk of obstruction and of embolism in elderly high risk patients may be exceptions to this traditional dogma.

Vascular injuries during orthopaedic hip surgery are rare. However, they must always be feared because they threaten life and limb. We present 11 vascular injuries observed over a 12-year period. Seven women and 4 men, treated by elective surgery, presented 14 vascular injuries (6 arterial, 5 venous and 3 prosthetic vascular graft). Four injuries occurred during revision procedures. They were all operated as an emergency for ischaemic syndrome (6 cases) and/or haemorrhage (7 cases). Four patients (37%) died and 4 developed sequelae, various directly attributable to the vascular injury. In the light of these cases, we tried to determine the various mechanisms of the injury and the orthopedic and vascular risk factors. Preoperative detection and well defined therapeutic rules are very important for the prevention of these severe vascular accidents.

We report a case of granulomatous peritonitis which occurred following laparoscopic exeresis of a dermoid cyst of the ovary performed together with medically induced abortion. The peritoneal cavity was contaminated when the cyst ruptured during the procedure emptying sebum and hairs in the peritoneum. Abondant washing with aspiration of all the visible particles was done with a 5 mm canula. The diagnosis of granulomatous peritonitis was suggested with the development of persistant fever, degradation of the patient's general health, moderate abdominal pain and a nodular image at echography located on the operated ovary. The nodule was found to be an inflammatory granuloma on a foreign body. Two second-look laparotomies, one transrectal and the other via the xypho-pubian route, were required 1 month after the initial operation for complete cure. The diagnosis was confirmed on the pathology report.

Two types of congenital heart disease are observed in adults: those discovered during childhood which may or may not have been operated, depending on their degree of severity and the surgical possibilities; those discovered during adulthood, which represent approximately 500 new cases per year and which raise particular problems: the extensive assessment which must be performed, the therapeutic solution adapted to particular situations, contraception, pregnancy, prophylaxis of endocarditis, sports or work. It is often difficult to decide to operate. Interventional catheterization represents an elegant solution in congenital heart disease in adults.

We have described an original technique of eversion carotid endarterectomy which has been performed in two series of patients. In the first series the patients were operated on in Angers. They were 65 carotid stenosis in 56 patients with a mean follow-up of 27 months (18-36 months). In the later series, the patients were operated on in Lyon. They were 51 carotid stenosis in 43 patients with a follow-up from 1 to 24 months. The two series were comparable in term of symptoms and grade of stenosis as determined by duplex-scan and arteriography. The technique which has been previously described is safe and presents a lot of advantages over classical endarterectomy or vein graft. We observed no postoperative neurological deficit and no postoperative thrombosis. Two residual stenosis (1.7%) were measured at 30% but they did show any impairment during two years of follow up in the first series. Eversion endarterectomy of internal artery is a safe and deficient alternative to others techniques in the surgical treatment of atherosclerosis stenosis of internal carotid artery.

This case report demonstrates the value of transoesophageal echocardiography (TOE) in comparison with transthoracic echocardiography as it allows a better view of the thoracic aorta, the auricles, the interauricular septum and the cardiac valves, especially in the intubated and ventilated patients. A 84-year-old woman was admitted to the ICU for hypoxia after carotid-subclavian bypass surgery for acute ischaemia of the left upper limb. The TOE showed a dilated right heart and a patent foramen ovale, compatible with pulmonary embolism as well as two thrombi in the aortic arch. The patient died on the 8th postoperative day from refractory hypoxia. the autopsy confirmed the pulmonary embolism and the intraaortic thrombi. It is concluded that TOE, readily feasible is indicated in case of hypoxia, shock and systemic embolism without cause immediately recognizable, especially in ventilated patients.

Vascular accidents during celioscopy are rare but potentially serious. Arterial injuries usually involve the aortic bifurcation and are generally recognized and treated as emergencies. In the present case, a transfixing wound of the right common iliac artery provoked by a trocar during gynecological celioscopy in a 36 year old woman was diagnosed secondarily, the posterior orifice being unrecognized during laparotomy to control hemorrhage. A false iliac artery aneurysm was detected 2 months later when she presented signs of a compressive retroperitoneal hematoma confirmed by arteriography and scan images. The common iliac artery was ligatured through a right retroperitoneal approach with extra-anatomical revascularization by a crossed iliofemoral venous shunt. The postoperative course was uncomplicated apart from a right cruralgia sequela. Immediate circumferential dissection for treatment of aortic bifurcation injuries is recommended, to avoid missing a transfixing wound, and to allow direct restoration usually by simple suture. In contrast, secondary treatment is complex, raises problems of arterial reconstruction, and cannot always prevent functional sequelae.

Modified subcutaneous mastectomy was described by one of us in 1968; its approach, the dissection of the gland, plastic reconstruction of shape and volume are completely different from the subcutaneous mastectomy performed by plastic surgeons. 3 different time periods were studied to explain clearly evolution in the technic and indications. During many years retrospective studies made it possible to build a procedure according to the new diagnostic means for infraclinical breast cancer and to the constant improving prosthetic material. Therefore our indications for modified subcutaneous mastectomy are as following: suspicious mastopathies are the best indications with a performing choice of the radiologic images which require histologic control some evolutive or evoluated mastopathies some small infiltrating tumors developing in a highly dystrophic glandular surrounding. The numerous in situ cancers accompanying them argue for this choice. some big phyllod tumors or phyllod's recurrences.

The potential thrombotic risk of mitral valve prolapse may, in certain circumstances, require preventive treatment. This study was aimed at determining whether the presence of angina in patients with mitral valve prolapse and healthy coronary vessels was accompanied by a high-risk thrombogenic profile. Forty two patients (19 women and 23 men) with anginal chest pain and angiographically normal coronary vessels were divided into two populations according to the presence (18 patients) or absence (24 patients) of mitral valve prolapse (MVP) shown by angiography. Before angiography, all patients underwent laboratory studies to detect any possible abnormality of plasma coagulation and of prothrombotic physiological fibrinolysis. Study of subgroups, according to sex and/or the presence of MVP, revealed no significant difference in the profile of laboratory parameters. Thus the presence of angiographic MVP in symptomatic patients free of atherosclerosis is not associated with the existence of any particular thrombotic profile and, theoretically, does not require preventive anti-thrombotic treatment.

The study of 44 patients treated with intra-arterial fibrinolysis is reported. All these patients had an impending subacute ischemia of the lower limbs, a major complication of atheromatous disease. The criteria for patient selection were clinical, hemodynamic and radiological. The procedure of the treatment associating Urokinase, Heparin and Naphthidrofluril are defined, as well as its follow-up. The results have been evaluated according to the clinical and radiological improvement. 2 patients died when the treatment ceased and 10 were amputated, ie 27% of failures. The fibrinolytic treatment allowed identifying the patients who might quickly receive an additional treatment. In our experience, this treatment seems to improve the prognosis of impending subacute ischemia.

The diagnostic value of combined transthoracic (TTE) and transesophageal echocardiography (TEE) was evaluated in 10 consecutive patients with acute dissecting aneurysm of the aorta and compared to aortography (10 cases) and computed tomography (7 cases). TEE seems to be highly superior to TTE because the intimal flap in always seen (versus 4 of the 10 TTEs) and the descending aorta and the entry site are better visualized. TEE is superior to X-ray computed tomography because it shows the direction of the flow in the false lumen (an advantage of a color Doppler), the entry site and aortic regurgitation. In spite of false-positives (1/10), TEE seems to be at least as good as aortography, the most reliable, but highly invasive, technique available. Thus, transesophageal echocardiography, performed at the patient's bedside, appears to be a promising non-invasive tool for diagnosing suspected dissecting aneurysms of the aorta.

114 patients aged over 75 underwent surgery for aneurysm of the infra-renal abdominal aorta in the University Teaching Hospitals in Nantes and Angers between 1979 and 1988. A retrospective study of these patients was performed to evaluate the immediate and long-term results. The mean age of the patients was 79 (+/- 4) years, the oldest being 94. 70% were men. Half of the patients underwent emergency or semi-emergency surgery (52 cases). Cardiovascular factors (in particular coronary insufficiency in 17% of cases) were the most common risk factors. In all cases grafting after laying open the aneurysm was performed, with an aorto-aortic graft in 32% of patients, an aorto-iliac graft in 37% or an aorto-bifemoral graft in 27% of patients. Combined intestinal revascularisation was performed in 10% of case either involving the inferior mesenteric artery or at least one internal iliac artery; renal revascularisation was performed in 3.5% of cases. 75% of patients underwent simple grafting. The mean duration of hospitalisation was 14 days (+/- 6), including a mean period of 7 days in ICU. 36 patients (31%) died in the first post-operative month. The mortality rate in patients who underwent emergency surgery for a complication of the aneurysm (essentially rupture) was 61% versus 6' for elective surgery. 96% of the patients who survived the first post-operative month were independent at the end of the study or at the time of their death.(ABSTRACT TRUNCATED AT 250 WORDS)

Injuries of the popliteal region remain a serious problem as far as the outcome is concerned. The role and the risks of revascularization have yet to be properly evaluated. It's always difficult to decide on a major amputation. A retrospective study was applied to 37 cases referred to the CHRU d'Angers, between 1976 and 1987. We were then able to establish a prognostic scale with 120 ischaemia, the contusion, the clinical context and the open wound. The scale is used before any decision and allows us to decide whether revascularization or amputation have to be performed. In this series, 2 patients (5%) eventually died; 11 (33%) underwent a major amputation and 24 (65%) were successfully revascularized. The results are analyzed in relation to the prognostic scale and the literature.

A series of thirty consecutive epithelial ovarian cancer patients were reviewed after long-term follow-up (more than 5 y) since their second-look operation (SLO). All patients had advanced tumors (stages IIb-IV). Primary chemotherapy consisted of a cisplatin-associated regimen. For all patients adjuvant treatment had been planned after completion of the SLO. Mean follow-up after SLO was 68 months (47-103 months). Tumor status at SLO divided the patients in 2 subgroups: Group A = 13 patients (43%), with no evidence of histologically proved disease at time of operation (NED); Group B = 17 patients (57%), with macroscopic persistence of tumor. Survival was significantly better in the first group than in the second (77% at 5 yr vs less than 25%). Recurrence rate in the NED group was 7.7% (1 recurrence at 32 months). Eight of 17 patients with gross tumor at SLO underwent satisfactory resection. However, recurrence rate was high (75%) and survival rate was low (25% at 5 yrs). This result was not significantly better than that of patients with no optimal resection at SLO (9 patients, survival 22%). Second effort resection at SLO does not seem to be beneficial in these patients after partial failure of initial chemotherapy with cisplatin. The usefulness of systematic second look operations is discussed. Controlled randomized trials should be made to determine the exact role of SLO in ovarian cancer treatment.

The study was carried out on patients with intermittent claudication (Fon taine's stage II). The arterial and atheromatous origin of the disease was con firmed and localized by angiography or Doppler velocimetry examination. One hundred eighty-six patients were selected initially. Their pain-free walk ing distance on a treadmill (at a speed of 3 km/hour and an inclination of 10%) had to be 150-300 m. During the first month all patients received 3 placebo tablets daily. At the end of this run-in period (D-30; D 0) and after checking walking distance stability (allowed variation: ±20% between the two measurements) the patients were included in the study. One hundred fifty-four patients were se lected and 118 remained during the whole study. The study was designed as a double-blind, using two parallel randomly selected groups. Sixty-four patients received for six months Naftidrofuryl (3 × 200 mg tablets daily with meals); 54 patients received placebo under the same conditions. Dur ing this period, clinical and paraclinical examinations were carried out every quarter (D 90 and D 180). After checking the initial homogeneity of the Naftidrofuryl and placebo- groups, the comparison between groups indicates a significant improvement in Naftidrofuryl group after 3 and 6 months of treatment. At the end of the study the observed differences in walking distance with Naftidrofuryl are approxi mately twice the difference in the reference group (D 90: p < 0.05; D 180: p < 0.02). The results of this study indicate that Naftidrofuryl is an efficient pharmacological tool for treatment of patients with chronic arterial disease (Fontaine's stage II).

The isolated azygos continuation of the inferior vena cave is a very rare variation of this organ. It is accompanied by the absence of the retrohepatic segment of the vena cava with two new observations, the literature is revised and the origin discussed.

Over the last two years, 15 patients have undergone revascularization surgery to a total of 17 distal extremities at the level of or distal to the last phalangeal joint. Operations were performed by three surgeons trained in microsurgical techniques, making the series a homogeneous one. Results were analyzed using Tamai and Nakamura's scores. Determinant factors, social and economic costs and effects on occupation are emphasized. The mean success rate of 65% is influenced by the total or partial nature of the section, its localization to the thumb or long fingers and the mechanism of section. The good functional results obtained were due to distal forms of amputation, recognized despite the technical difficulties as being an indication of choice for this reimplantation surgery. All patients in this group were able to return to work, with or without adaptation, within a variable lapse of time.

Sub-crural bypass operations on a single leg artery were analysed retrospectively with a follow-up period ranging from six months to eight years. The vitality of the limb was threatened in the majority of cases (91/96). Whenever possible (79/96) the internal saphenous vein was used as a graft, preferably by the in situ technique. Mortality was 6%. Morbidity with the exception of thromboses was 14.5%. Patency by actuarial analysis was 71.6% at 5 years and 65.8% beyond. The majority of thromboses occurred during the first few months and led, in the majority of cases, to amputation. Secondary thromboses were better tolerated. The influence of various parameters was studied: clinical stage, peroperative flowmeter results, material used, technique, associated procedure (sympathectomy), implantation site and permeable vessel.