Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice.

Several molecules were shown to bind advanced glycation end products (AGEs) in vitro, but it is not known whether they all serve as AGE receptors and which functional role they play in vivo. We investigated the role of galectin-3, a multifunctional lectin with (anti)adhesive and growth-regulating properties, as an AGE receptor and its contribution to the development of diabetic glomerular disease, using a knockout mouse model. Galectin-3 knockout mice obtained by gene ablation and the corresponding wild-type mice were rendered diabetic with streptozotocin and killed 4 months later, together with age-matched nondiabetic controls. Despite a comparable degree of metabolic derangement, galectin-3-deficient mice developed accelerated glomerulopathy vs. the wild-type animals, as evidenced by the more pronounced increase in proteinuria, extracellular matrix gene expression, and mesangial expansion. This was associated with a more marked renal/glomerular AGE accumulation, indicating it was attributable to the lack of galectin-3 AGE receptor function. The galectin-3-deficient genotype was associated with reduced expression of receptors implicated in AGE removal (macrophage scavenger receptor A and AGE-R1) and increased expression of those mediating cell activation (RAGE and AGE-R2). These results show that the galectin-3-regulated AGE receptor pathway is operating in vivo and protects toward AGE-induced tissue injury in contrast to that through RAGE.

Pathogenesis of the glomerular abnormality in cyanotic congenital heart disease.

We present evidence of 2 distinct glomerular abnormalities in cyanotic congenital heart disease--vascular and nonvascular--each believed to reflect a distinct pathogenesis. Glomeruli from both kidneys were studied with light microscopy in 13 necropsied cyanotic patients and in 8 controls. The vascular study characterized hilar arteriolar dilatation, capillary diameter, glomerular diameter, and capillary engorgement with red blood cells. The nonvascular study characterized juxtaglomerular cellularity, mesangeal cellularity, mesangeal matrix, focal interstitial fibrosis, and megakaryocytic nuclei per cm2 of renal cortex. There was a significant increase in each of the above vascular and nonvascular items of interest relative to controls. Electron microscopy identified whole megakaryocytes with their cytoplasm in glomeruli. The vascular abnormality is believed to result from intraglomerular release of nitric oxide. The nonvascular abnormality is believed to result from platelet-derived growth factor and transforming growth factor-beta.

Role of galectin-3 as a receptor for advanced glycosylation end products.

The advanced glycosylation end product (AGE)-binding proteins identified so far include the components of the AGE-receptor complex p60, p90 and galectin-3, receptor for advanced glycosylation end products (RAGE), and the macrophage scavenger receptor types I and II. Galectin-3 interacts with beta-galactoside residues of several cell surface and matrix glycoproteins through the carbohydrate recognition domain and is also capable of peptide-peptide associations mediated by its N-terminus domain. These structural properties enable galectin-3 to exert multiple functions, including the modulation of cell adhesion, the control of cell cycle, and the mRNA splicing activity. Moreover, in macrophages, astrocytes, and endothelial cells, galectin-3 has been shown to exhibit a high-affinity binding for AGEs; the lack of a transmembrane anchor sequence or signal peptide suggests that it associates with other AGE-receptor components rather than playing an independent role as AGE-receptor. In tissues that are targets of diabetic vascular complications, such as the mesangium and the endothelium, galectin-3 is not expressed or only weakly expressed under basal conditions, at variance with p90 and p60 but becomes detectable with aging and is induced or up-regulated by the diabetic milieu, which only slightly affects the expression of p90 or p60. This (over)expression of galectin-3 may in turn modulate AGE-receptor-mediated events by modifying the function of the AGE-receptor complex, which could play a role in the pathogenesis of target tissue injury. Up-regulated galectin-3 expression may also exert direct effects on tissue remodeling, independently of AGE ligands, by virtue of its adhesive and growth regulating properties.

Pneumonectomy for chronic infection is a high-risk procedure.

BACKGROUND: The purpose of this study was to estimate operative risk, and to identify indicators of adverse prognosis, in patients undergoing pneumonectomy for chronic infection. METHODS: Twenty-five patients aged 41 +/- 15 years underwent pneumonectomy (three completions) for chronic infection: sequelae of tuberculosis, 15; cystic bronchiectasis, 9; and radiation pneumonitis, 1. Eight patients had aspergilloma (7 after tuberculosis, 1 with radiation pneumonitis). RESULTS: Operative mortality was 4%. Operative blood loss was estimated at 1,983 +/- 1,424 mL, ranging from 150 to 5,600 mL. A single patient required reexploration. Eight patients (32%) had empyema, and a further 3 (12%) had bronchopleural fistula; thoracoplasty was required for 10 (40%). Sequelae of tuberculosis heralded increased operative bleeding (t = 2.884; p < 0.005). Incidence of empyema or bronchopleural fistula was increased in patients with sequelae of tuberculosis (chi 2 = 3.896; p < 0.05), patients with aspergilloma (chi 2 = 4.588; p < 0.05), patients in whom the parenchymal cavities were entered (chi 2 = 11.5; p < 0.001), and those in whom blood loss was in excess of 1,000 mL (chi 2 = 4.911; p < 0.05). CONCLUSIONS: We conclude that pneumonectomy is a high-risk procedure, especially in patients with sequelae of tuberculosis.

Operative risk and prognostic factors of typical bronchial carcinoid tumors.

BACKGROUND: This study estimated operative risk and examined factors determining long-term survival after resection of typical carcinoid tumors. METHODS: From 1976 to 1996, 139 consecutive patients (66 male and 73 female patients with a mean age of 47 +/- 15 years) underwent thoracotomy for typical carcinoid tumor. The tumors were centrally located in 102 patients (73.4%). RESULTS: Radical resection was performed in 106 patients (7 pneumonectomies, 13 bilobectomies, and 86 lobectomies) and conservative resection in 33 (3 segmentectomies, 3 wedge resections, 20 sleeve lobectomies, and 7 sleeve bronchectomies). There were no postoperative deaths. Complications occurred in 19 patients (13.7%). The morbidity rate was not increased after bronchoplastic procedures (chi 2 = 0.033, not significant). Staging was pT1 in 107 patients (77.0%) and pT2 in 32 (23.0%); 13 patients (9.4%) had nodal metastases. Seventeen patients have died (12.2%), during follow-up, but only three deaths were related to the disease. The overall survival rate at 5, 10, and 15 years was estimated to be 92.4%, 88.3%, and 76.4%, respectively; estimated disease-free survival was 100% at 5 years and 91.4% at 10 and 15 years. Estimated survival of patients with lymph node metastasis was 100% at 5, 10, and 15 years. Univariate analysis failed to demonstrate any prognostic significance for sex, tumor size (T1 versus T2), tumor location (central versus peripheral), and type of resection. CONCLUSIONS: These data confirm an excellent prognosis after complete resection of typical carcinoid tumors, including those with lymph node metastases. Parenchyma-saving resections should be preferred.

Bronchopulmonary aspergilloma: a reappraisal.

BACKGROUND: Classically, most complications observed after operations for aspergilloma occurred in patients with sequelae of tuberculosis. Because the incidence of tuberculosis has declined over the past two decades, aspergilloma is expected to develop with increasing frequency in patients without previous tuberculosis. Therefore, our hypothesis was that operative outcome should have improved during the most recent years in comparison with our previous experience. METHODS: Operative outcome of 12 recently accrued patients was evaluated and compared with a historic control group of 55 patients, previously reported by the same center. RESULTS: As expected, only 17% of patients of the present series had a history of tuberculosis, compared with 57% in the former series. Postoperatively, there was no mortality. Major morbidity has decreased, although this difference is not statistically significant: bleeding decreased from 44% to 9% of patients; space problems decreased from 47% to 18%; and prolonged hospital stay (>30 days) decreased from 32% to 9%. CONCLUSIONS: Our results support a trend toward improved postoperative outcome of operations for aspergilloma owing to a decreased incidence of aspergilloma growing in tuberculous cavitations.

Long-term complications of extraperiosteal plombage.

BACKGROUND: As soon as complications due to migration of extraperiosteal plombage material had been documented, early removal became the rule. Some patients who have escaped this rule may still present with long-term complications. METHODS: Since 1980, 14 patients aged 54 +/- 10 years were admitted 28 +/- 11 years after collapse therapy. Eight presented with signs of infection, 4 with hemoptysis, and 2 with periscapular pain. Vascular erosion, suspected in 3 patients, was demonstrated with angiograms in 1. RESULTS: Ablation of the material was combined with excision of the devitalized ribs in 13 patients. Femorofemoral bypass was used in 2 patients for repair of an aortic erosion. Single ablation of subcutaneously migrated material was performed in a poor-risk patient. Operative bleeding was moderate except in 2 patients; 1 of them died intraoperatively during repair of an aortic erosion. A second patient died postoperatively with a massive pulmonary embolus on day 11. Infection was diagnosed in 8 patients (Mycobacterium tuberculosis, 4; and pyogens, 4). Operative outcome was satisfactory in all 12 operative survivors. A single patient presented with an infected apical space at 1 year and underwent complementary resection of the first rib. CONCLUSIONS: We recommend routine ablation of any residual plombage material whenever operative risk is acceptable because of the high incidence of spontaneous complications.

Acute myeloid leukemias M2 potentially misdiagnosed as M3 variant French-American-Britain (FAB) subtype: a transitional form?

From 1990 to 1994, 3 patients with de novo acute myeloid leukemia (AML) in whom light microscopy and cytochemistry suggested a FAB subtype M3 variant were observed at our Institute. Immunophenotype showed HLA-DR-, CD13+, CD33+, CD2+, CD9+; promyelocytic features were also detected by electron microscopy. However, leukemic cells lacked both translocation t(15;17) and RAR alpha/PML genes rearrangement. These cases were considered to be 'M2 atypical' subtypes and they contribute to point out how cytogenetics and molecular biology are mandatory for a correct diagnosis of acute promyelocytic leukemia (APL) particularly because therapy with all trans retinoic acid (ATRA) is now the best treatment for APL. Nevertheless these 3 cases indicate that the atypical M2 subtype may be confused with the M3v if only cytochemistry, immunophenotype and electron microscopy are used in the defining the FAB subtypes.

Renal involvement in feline immunodeficiency virus infection: p24 antigen detection, virus isolation and PCR analysis.

Renal alterations characterized morphologically by glomerular and tubulo-interstitial lesions and clinically by a heavy proteinuria and sometimes by renal failure are frequent in feline immunodeficiency virus (FIV) infected cats. To investigate the possible role of local FIV replication in the genesis of this renal damage, renal tissues of 15 consecutive naturally infected and five non-infected cats were examined for traces of the virus by immunohistochemistry, using a monoclonal anti-p24 antibody in a streptavidin-biotin peroxidase labeled system, cultivation and polymerase chain reaction (PCR). Tubular epithelial cells as well as scattered interstitial inflammatory and glomerular cells were positive for p24 antigen in 13 cats. Viral isolation was successful in seven cats, and FIV gag DNA and RNA sequences were detected in 14 and five cats, respectively. Control cats were constantly negative. Although not conclusive, these results suggest that a direct role of FIV in the induction of the renal damage observed in infected animals is possible.

Cervical bronchogenic cyst mimicking thyroid adenoma.

Bronchogenic cysts are congenital malformations of the foregut which are generally encountered within the mediastinum. We explored a patient presenting with a cystic, partially calcified tumor in a cervical and retrotracheal location. This lesion was interpreted as a thyroid adenoma preoperatively, but identified as a bronchogenic cyst at pathology.

Tricuspid valve vegetation in a child with periarteritis nodosa.

We report a case of a child who was first seen for acute renal failure and periarteritis nodosa. Angiography findings confirmed this diagnosis. Ultrasound scan revealed large tricuspid valve vegetation, as well as minute vegetation on the right ventricular wall. All vegetation disappeared after 12 months of immunosuppressive therapy. Serology findings for lupus were negative. All clinical and laboratory findings strongly support the hypothesis that this previously undescribed heart involvement is caused by PAN.

Solitary polypoid hamartoma of the oxyntic mucosa of the stomach.

A solitary pedunculated polyp of the oxyntic mucosa removed from a 66-year-old patient with atrophic gastritis and achlorhydria exhibited distinctive histological features consisting of submucosal, mostly oxyntic-type glands with a smooth muscular framework. Histochemical and immunohistochemical studies demonstrated that the glands were composed of well differentiated chief, parietal, and endocrine cells. Moreover, less frequent glands of the antro-pyloric type were also seen. The lesion was regarded as a previously unrecognized variety of gastric hamartoma.

Mucin-producing cells and endocrine cells of gallbladder epithelium in patients with uncomplicated cholelithiasis.

In this study we have investigated various morphofunctional features of gallbladder mucosa in patients with uncomplicated cholelithiasis. The histological changes, endocrine cell types and their distribution, and mucin-producing cells were characterized by immunocytochemistry and mucin histochemistry; moreover, we attempted to correlate these findings to the number and size of gallbladder stones and the type of bacteria present in the bile. Our results indicate that, despite similar clinical parameters, a wide range of histological changes can occur in the gallbladder mucosa of these patients. Moreover, the presence of certain endocrine and mucin-producing cell types in so-called "pyloric metaplasia" led us to hypothesize that this finding may be a trivial event in the gallbladder epithelium.

Silver staining of interphase nucleolar organizer regions in cytologic smears previously stained by the Papanicolaou and May-Grünwald-Giemsa techniques.

Malignant cells are known to display a distinctive argyrophilic nucleolar organizer region (Ag-NOR) protein distribution compared with distribution in their benign counterparts. In this study, Ag-NOR staining was applied to smears from reactive and malignant serous effusions. The smears were either unstained or had been previously stained with the Papanicolaou or May-Grünwald-Giemsa (MGG) technique. The purpose of this study was to assess the feasibility and usefulness of Ag-NOR staining in diagnostic cytopathology and to set up a procedure that could be used on prestained smears in retrospective studies. The one-step silver staining method was applied to prestained smears after a weak destaining step in trichloracetic acid and to unstained smears after a postfixation step in Carnoy's fluid. Positive results were observed on both destained and unstained preparations, MGG-stained smears showing a better visualization of the silver deposits than Papanicolaou-stained smears. Major differences in size, shape, and distribution patterns of the Ag-NOR-positive granules were observed between neoplastic and reactive cells. Furthermore, the mean number of silver-stained dots per cell was significantly higher in malignant cells (33.32 +/- 2.23) than in reactive mesothelial cells (9.71 +/- 0.66). These data indicate that this Ag-NOR technique can be profitably applied to prestained cytologic smears to assist in the diagnosis of malignancy and that the technique has the advantage that cellular morphology and silver staining can be evaluated on the same slide.

Ultrastructural histochemistry of mesotheliomas and adenocarcinomas in malignant effusions.

The results of electron microscopic examination of cytologic specimens from six cases of mesothelioma and 10 cases of metastatic carcinoma of different origins are presented. The formation of cell clusters in malignant effusions from the two neoplasms has been thoroughly investigated: in mesotheliomas, cells had longer, more slender microvilli than in carcinomas and more abundant bundles of intermediate filaments; the central cavity often seen in the clusters frequently contained collagen and showed basement membrane production. The application of periodic acid-silver methenamine (PASM) and phosphotungstic acid (PTA) demonstrated a peculiar ultrastructural difference in cell coat staining in the two tumor types: in mesotheliomas, PTA and PASM were consistently negative along the outer surface of the cell aggregates, while carcinomas displayed a positive reaction either on the outer surface or on both inner and outer surfaces of the clusters. The diagnostic significance of the above-mentioned difference between the two neoplasms will require further investigation in a larger number of cases.

Ultrastructural localization of sulphate glycoconjugates in the human glomerular capillary wall using the high iron diamine method.

The distribution of fixed anionic sites within glomerular capillary walls has been studied in man by applying two ultrastructural histochemical methods--the high iron diamine and dialysed colloidal iron methods--to tissue chopper sections and to isolated glomeruli obtained from surgical fragments of renal tissue. By using the high iron diamine method we have been able to demonstrate that in man, too, there are sulphate (possibly heparan sulphate proteoglycan) sites preferentially located in the lamina rara esterna of the basement membrane and in the cell coat of the urinary surface of podocytes. Non-sulphate (high iron diamine-negative, dialysed colloidal iron-positive) anionic sites have been identified not only in the glycocalyx of the epithelial and endothelial cells but also in the laminae rarae of the basement membranes, where they show a more extensive distribution pattern than sulphate sites. The proposed methods seem particularly suitable for the study of human renal tissue; they could, in fact, provide useful information about the behaviour of the various anionic components of the glomerular capillary wall in pathological conditions.

[Supraventricular arrhythmia after pneumonectomy. Apropos of 100 cases and review of the literature]. / Troubles du rythme supraventriculaire après pneumonectomie. A propos de 100 cas et d'une revue de la littérature.

Supraventricular arrhythmias are frequently observed in pneumonectomy surgery. We retrospectively studied a series of 100 consecutive patients undergoing pneumonectomy for cancer between 1994 and 1996. We found 24% of significant supraventricular arrhythmias, corresponding to atrial fibrillation in 75% of cases, occurring in 80% of cases until the third postoperative day. The only risk factor significantly associated with these arrhythmias was the patient's age. These arrhythmias are easily reduced, spontaneously in 25% of cases, and usually by amiodarone, alone or associated with digitalis alkaloids. While the mortality of the overall group was 12%, 8% of patients with arrythmia died. These deaths concerned patients whose arrythmias occurred after the fourth postoperative day in a context of a pulmonary infection.

[Predictive factors of recurrence in surgically treated rectal villous tumors. Therapeutic approach based on 184 cases]. / Les facteurs prédictifs de récidive des tumeurs villeuses rectales opérées. Attitude thérapeutique à propos de 184 cas.

The aim of this retrospective study on 184 operated cases was to propose a therapeutic management scheme for villous tumours of the rectum. Among the 184 operated patients, 167 (90,7%), mean age 65 years, were seen after a follow-up of 2 to 20 years. The tumour was most often localized in the rectal ampoula (141 cases) and was benign in 65 p. 100. Endoanal surgery was performed in 76 patients among whom recurrence was observed in 29.7%. Posterior exeresis (Kraske method) was performed in 52 cases with a recurrence rate of 31.9%). Finally, abdominoperineal amputation was performed 20 times, essentially for advanced stage tumours. Based on the statistical analysis of the recurrence factors for these different techniques, we have concluded that endoanal surgery predominates for benign tumours smaller than 5 cm situated at least 8 cm from the anus. Above the size of 5 cm, due to the major risk of tumourectomy, we believe rectal exeresis is the most rational treatment.

[Cystic dystrophy on an aberrant duodenal pancreas. Apropos of a case]. / Dystrophie kystique sur pancréas aberrant duodénal. A propos d'une observation.

Cystic dystrophy of the aberrant pancreas is a rare poorly understood condition which is difficult to diagnose and treat. The primary clinical signs are epigastralgia associated with poor general health and complications due to stenosis of the duodenum. Endoscopy gives the most information on tissue lesions and cystic formations in the duodenal mucosa. Although the condition is benign, and due to the lack of sufficient history in endoscopically treated cases, cystic dystrophy of the aberrant duodenal pancreas appears to require duodenopancreatectomy.

[Do pericardial strips (Peri-Strip) facilitate the follow-up after pulmonary surgery in emphysematous patients?]. / Les bandelettes de péricarde (Peri-Strip) facilitent-elles les suites après chirurgie pulmonaire chez le patient emphysémateux?

The aim of this study was to evaluate the contribution of bovine pericardial strips (Peri-Strip) to achieve aerostasis within emphysematous lungs. A preliminary evaluation included 15 patients (13 men and 2 women, mean age 57 years) with severe emphysema (mean FEV-1: 28.6 +/- 10.2% of predicted, mean RV: 18.4 +/- 41.3% of predicted). Two patients were on ventilator owing to acute respiratory failure. Indication for surgery was elective surgery for emphysema in 9 patients, emergency surgery for emphysema in 2, and resection for bronchogenic cancer in 4 patients. The various procedures included single aerostasis in 1, unilateral bullectomy in 6, bilateral volume reduction in 4, thoracoscopic wedge resection for peripheral cancer in 1 and lobectomy for cancer in 3 (2 of which underwent simultaneous bullectomy) Peri-Strip were used to buttress the staple lines at the base of bullae, on parenchymatous transsection lines, and on the borders of fissures. One patient who underwent emergency thoracotomy for single aerostasis died 8 days post-operatively due to multiple organ failure. Another patient developed pneumonia which resolved under treatment. Mean duration of air leaks was 5.6 days (0-21, median 8). Two patients required tube thoracotomy for residual effusions. Mean hospital stay was 17 days (6-53; median 16). We conclude that use of Peri-Strip offered a real benefit to 12 patients; no evidence of benefit was noted in 3 patients.