Les syndromes confusionnels du sujet âgé hospitalisé: polymorphisme sémiologique et évolutif. Étude prospective de 183 patients

Using explicit criteria contained in the DSM III R, we collected in a prospective cohort study clinical features, outcome and risk factors from two cohorts of delirium in hospitalized elderly patients: 138 hospitalized in geriatric department and 45 patients admitted to an acute and comprehensive care hospital. The clinical features were assessed using a quantitative scale (developed by Derouesné). Delirium was unrecognized or misdiagnosed by physicians in 34% of the cases. The onset was known only two thirds of cases. The incidence of hyperactive type, prolonged hospital stay, poor outcomes (persistent delirium leading up to dementia) were highest in subjects admitted in comprehensive hospital. The etiology of delirium is complex and multifactorial. An underlying cause was identified in 80% of patients. The length or the worsening of delirium was significantly higher in patients with psychiatric or dementia comorbidity (OR: 0.2; IC 95%: 0.1–0.5). The prognosis was better in patients without psychoactive medications (OR: 0.2; IC 95%: 0.1–0.4) or with metabolic abnormalities or acute diseases and disorders (OR: 3.3; IC 95%: 1.5–7.6). The predisposing factors to the development of dementia were prior use of psychoactive medications and signs of prior cognitive impairment. This article suggests delirium in elderly patients is associated with several outcomes. The prognosis should be improved at admission by specific scale and an evaluation of predisposing and precipitating factors.     

Macrophages can recognize and kill tumor cells bearing the membrane isoform of macrophage colony-stimulating factor

NBXFO hybridoma cells produced both the membrane and secreted isoforms of macrophage colony-stimulating factor (M-CSF). Murine bone marrow cells stimulated by the secreted form of M-CSF (sM-CSF) became Mac1+, Mac2+, Mac3+, and F4/80+ macrophages that inhibited the growth of NBXFO cells, but not L1210 or P815 tumor cells. In cytotoxicity studies, M- CSF activated macrophages and freshly isolated macrophages killed NBXFO cells in the presence of polymyxin B, eliminating the possibility that contaminating lipopolysaccharide (LPS) was responsible for the delivery of the cytotoxic signal. Retroviral-mediated transfection of T9 glioma cells with the gene for the membrane isoform of M-CSF (mM-CSF), but not for the secreted isoform of M-CSF, transferred the ability of macrophages to kill these transfected T9 cells in a mM-CSF dose- dependent manner. Macrophage-mediated killing of the mM-CSF transfected clone was blocked by using a 100-fold excess of recombinant M-CSF. Catalase, superoxide dismutase, and the nitric oxide inhibitor, N-omega- nitro-arginine methyl ester (NAME), did not effect macrophage cytotoxicity against the mM-CSF transfectant T9 clones. T9 parental cells when cultured in the presence of an equal number of the mM-CSF transfectant cells were not killed, indicating specific target cell cytotoxicity by the macrophages. Electron microscopy showed that macrophages were capable of phagocytosizing mM-CSF bearing T9 tumor cells and NBXFO hybridoma cells; this suggested a possible mechanism of this cytotoxicity. This study indicates that mM-CSF provides the necessary binding and triggering molecules through which macrophages can initiate direct tumor cell cytotoxicity.     

Germ cell defects and hematopoietic hypersensitivity to gamma- interferon in mice with a targeted disruption of the Fanconi anemia C gene

Fanconi anemia (FA) is an autosomal recessive chromosome instability syndrome characterized by progressive bone marrow (BM) failure, skeletal defects, and increased susceptibility to malignancy. FA cells are hypersensitive to DNA cross-linking agents, oxygen and have cell cycle abnormalities. To develop an animal model of the disease we generated mice homozygous for a targeted deletion of exon 9 of the murine FA complementation group C gene (fac). Mutant mice had normal neonatal viability and gross morphology, but their cells had the expected chromosome breakage and DNA cross-linker sensitivity. Surprisingly, male and female mutant mice had reduced numbers of germ cells and females had markedly impaired fertility. No anemia was detectable in the peripheral blood during the first year of life, but the colony forming capacity of marrow progenitor cells was abnormal in vitro in mutant mice. Progenitor cells from fac knock-out mice were hypersensitive to interferon gamma. This previously unrecognized phenotype may form the basis for BM failure in human FA.     

Intraductal papillary-mucinous tumors of the pancreas: Clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic

BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreatic ducts is increasingly recognized. This study investigated if clinical, imaging, or, histological features predicated outcome, formulated a treatment algorithm, and clarified relationships among IPMT, mucinous cystic neoplasms of the pancreas (MCN), and chronic pancreatitis. METHODS: The medical records, radiographs, and pathological specimens of 15 patients with IPMT (dilated main pancreatic duct or branch ducts with mucin overproduction) who were evaluated between October 1983 and January 1994 were reviewed. RESULTS: One patient had hepatic metastases. Fourteen underwent an operation (6 distal pancreatectomy, 4 total pancreatectomy, and 4 pancreaticoduodenectomy); all had dysplastic intraductal epithelium and chronic pancreatitis, whereas 3 had invasive adenocarcinoma. After a median of 25 months, 10 patients were alive; 3 of 4 with malignant and 2 of 11 with benign IPMT died (P < 0.05). Patients with or without carcinoma had similar clinical and radiographic features. A clinical diagnosis of chronic pancreatitis had been made in 9 patients with benign IMPT and in none with malignant IPMT (P < 0.05). CONCLUSIONS: IPMT is a dysplastic and likely precancerous lesion that is frequently diagnosed as chronic pancreatitis and is separate from MCN. Because it is not possible to distinguish noninvasive from invasive IPMT preoperatively, complete surgical excision of the dysplastic process is our treatment of choice whenever appropriate. (Gastroenterology 1996 Jun;110(6):1909-18)     

Biliary obstruction

Extrahepatic biliary obstruction resulted from chronic alcoholic pancreatitis in seven patients. All cases had a characteristic smooth symmetrical narrowing of the intrapancreatic portion of the common bile duct on retrograde cholangiography. Both medical and surgical therapy for their disorder is discussed.     

Functional characterization of thrombin Salakta: an abnormal thrombin derived from a human prothrombin variant

The genetic variant prothrombin Salakta has been described in a patient presenting with a normal level of prothrombin antigen but reduced prothrombin activity. Initial studies indicated that factor Xa- catalyzed cleavages proceed normally but lead to the production of a thrombin molecule with an altered enzymatic activity. To characterize the functional abnormality of thrombin Salakta more precisely, it was purified by chromatography on heparin-Sepharose and diethylaminoethyl- Sephadex. The purified variant does not differ from normal thrombin by size, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and is 93.1% +/- 7.6% active by titration with p- nitrophenyl-p'-guanidinobenzoate. Its activity, however, is altered to various extents toward the following substrates: H-D-phenylalanyl-L- pipecolyl-L-arginine paranitroanilide (S 2238), fibrinogen, factor V, protein C, and antithrombin III. The Michaelis constant (Km) of thrombin Salakta for S 2238 is higher (12.2 +/- 3.3 mumol/L) than normal (2.8 +/- 0.7 mumol/L), whereas the turnover number (Kcat) is normal (84.4 +/- 6.6 s-1 v 85.9 +/- 14.0 s-1 for normal thrombin). The interaction of thrombin Salakta with benzamidine is also altered as evidenced by an increased inhibition constant (Ki = 3.5 mmol/L v 0.28 mmol/L for normal thrombin). The inability of fibrinogen to act as a competitor in the inactivation of thrombin Salakta by diisopropylfluorophosphate clearly indicates that fibrinogen binding to the fibrinopeptide groove is drastically impaired. In contrast, interactions involving sites remote from the active site such as those with fibrin and thrombomodulin are only slightly impaired. These results indicate that thrombin Salakta exhibits a specific pattern of functional alterations different from those reported for other variants. The structural defect seems to affect essentially the primary substrate binding site and to a lesser extent recognition site(s) remote from the catalytic site such as those for fibrin and thrombomodulin.     

Vascular patterns in basal cell carcinoma

Background Dermoscopy has been proved to increase the diagnostic accuracy of basal cell carcinoma (BCC). Objective To characterize the type and frequency of vascular patterns in superficial and nodular BCCs. Methods We retrospectively analysed the dermoscopic images of 504 histopathologically proven BCCs. Results The most common vascular pattern was represented by arborizing vessels (306/504; 60.7%), which were significantly more frequent in nodular BCCs (nBCCs) compared with superficial BCCs (sBCCs), and in pigmented sBCCs vs. non‐pigmented sBCCs (P < 0.0001). Short fine telangectasias (SFTs) were found in 33.1% (167/504) of cases and were significantly more frequent in sBCCs compared with nBCCs (P < 0.0001). Hairpin vessels were detected in 52/504 (10.3%) BCCs. Minor vascular patterns included glomerular vessels (41/504; 8.1%), dotted (21/504; 4.2%), comma vessels (5/504; 1.0%) and polymorphous pattern (9/504; 1.8%). Conclusions Arborizing vessels are prototypic of nBCCs, whereas SFTs are characteristics of sBCCs. Differential diagnosis with squamous cell carcinoma or melanoma is mandatory when a polymorphous pattern is detected.     

Cimetidine reduces running-associated gastrointestinal bleeding

A prospective observational study was undertaken to compare the effect of cimetidine usage immediately before and during a 100-mile running race on the frequency of detectable gastrointestinal bleeding and to relate these data to the frequency and intensity of gastrointestinal symptoms and to training data collected from pre- and postrace questionnaires. Nine of 25 runners in the 1989 Old Dominion 100-mile Endurance Race took 800 mg of cimetidine 1 hr before the start and at 50 miles. Sixteen other runners acted as controls and were not different in age, gender, or training data. All runners also submitted three stool specimens from the week before the race and from the first three bowel movements after the race on standard Hemoccult cards. All runners were Hemoccult negative before the race. One of the 9 (11%) cimetidine runners and 14 of the 16 (87.5%) control runners were Hemoccult positive afterwards (P less than or equal to 0.05). Nausea and vomiting were less in those runners taking cimetidine (P less than or equal to 0.05). There was no difference in the race performance as related to the ability to finish or in the number of miles run during the race. This study may help to define the etiology of this common gastrointestinal bleeding in these ultradistance runners and may be useful in preventing some of the symptoms associated with long-distance running.     

Hypercholesterolemia promotes early renal dysfunction in apolipoprotein E-deficient mice

Background

Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function. Therefore, the aim of this study was to determine the effects of both hypercholesterolemia and aging on renal function in mice.

Methods

Male hypercholesterolemic apolipoprotein E-deficient mice (ApoE, n = 13) and age-matched C57BL/6 control mice (C57, n = 15) were studied at 2 (young) and 8 (adult) month-old. At each time point, animals were placed in metabolic cages for 24 hours to urine volume and urinary creatinine quantification. Blood samples were collected for serum cholesterol, urea and creatinine measurements. Glomerular filtration rate (GFR) was estimated through creatinine clearance determination. Mesangial expansion was evaluated by Periodic Acid Schiff staining, renal fibrosis was determined through Masson's trichrome staining and neuronal nitric oxide synthase (nNOS) expression in the kidney was performed by Western Blotting. To statistical analysis two-way ANOVA followed by Fisher's post hoc test was used.

Results

Total plasma cholesterol was increased about 5-fold in ApoE mice at both time points compared to C57 animals. At 2-month-old, GFR was already markedly reduced in ApoE compared to C57 mice (187 ± 28 vs 358 ± 92 μL/min, p < 0.05). Adult C57 (-77%) and ApoE (-50%) mice also presented a significant reduction of GFR. In addition, serum urea was significantly increased in young ApoE animals compared to C57 mice (11 ± 1.3 vs 7 ± 0.9 mmol/L, p < 0.01). A significant mesangial expansion was observed at 2-month old ApoE mice compared to C57 mice (35 ± 0.6 vs 30 ± 0.9%, respectively, p < 0.05), which was aggravated at 8-month old animals (40 ± 3 and 35 ± 3%, respectively). Tubulointersticial fibrosis was augmented at both young (17 ± 2%, p < 0.05) and adult (20 ± 1%, p < 0.05) ApoE mice compared to respective C57 age controls (8 ± 1 and 12 ± 2%, respectively). The expression of nNOS was markedly reduced in a time-dependent manner in both strains.

Conclusions

These data show that both hypercholesterolemia and aging contribute to the loss of renal function in mice.