Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function

Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25-44 years, mean 34; duration of diabetes 10-20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58 +/- 0.79 microV v. 7.34 +/- 1.12 microV; p less than 0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p less than 0.05) during ARI in AN patients.     

Differential Effects of Thalidomide on Angiogenesis and Tumor Growth in Mice

Thalidomide, clinically used as an antiinflammatory and antitumoral drug, inhibited sponge-induced angiogenesis when administered systemically (100 mg/kg^–1) in mice. However, it failed to inhibit solid Ehrlich tumor in the same mouse strain. We have used functional, biochemical and histological parameters to assess neovascularization and fibrovascular tissue infiltration of the mice sponge granuloma. The neovascularization growth as detected by development of blood flow and hemoglobin content extracted from the implants showed that thalidomide inhibited fibrovascular tissue formation by 40%. The functional and biochemical parameters correlated well with the histological study. Thalidomide had no inhibitory effect in the development of Ehrlich tumor. The detection of this selective action using the same animal strain bearing two different processes, supports the hypothesis that rather than species specificity, thalidomide is tissue specific. This approach may be used to identify the specificity of other therapeutic agents against distinct angiogenesis-dependent diseases.     

The gene encoding CD23 leukocyte antigen (FCE2) is located on human chromosome 19

Using Southern blot analysis of DNAs from human×rodent cell hybrids, we have mapped the CD23 leukocyte antigen gene (FCE2) to human chromosome 19.     

Pneumococcus observatory data in the Rhône-Alps region. Results from 1996

Throughout 1996, 22 hospital-based laboratories in the Rh?ne-Alpes region of France collected pneumococcal strains and used a standardized protocol to record the following data; patient age and sex; type of specimen; and determination of susceptibility to at least the following antibiotics: oxacillin 1 microgram and 5 micrograms, erythromycin (Ery), tetracycline (Tet), chloramphenicol (Chl), rifampin (Rmp), and loracarbef. For penicillin-nonsusceptible strains (PNSSs), which were identified based on results with oxacillin, MICs for penicillin G, amoxicillin (Amx), and cefotaxime (Ctx) were determined using the E Test, at the study site and agar dilution at the coordinating center. Of the 1153 strains, 65.5% were from adults and 31.8% from children; patient age was unknown in 2.7% of cases. PNSPs (MIC > 0.06 mg/l) contributed 32.9% of strains (I: 23.3%; R: 9.6%) and were more common in children (41.1%) than in adults (28.1%). The frequency of PNSSs varied across specimen types: 27.9% in blood cultures (305 strains), 15.6% in cerebrospinal fluid (32), 38.7% in protected bronchopulmonary specimens (31), 31.5% in unprotected bronchopulmonary specimens (434), 50.8% in acute otitis media (118), and 34.4% in other specimens (221). Among PNSSs, nonsusceptibility (I + R) to other antibiotics was variable: Ery, 62.1%; Tet, 41.5%; Chl, 40.4%; Rmp, 1.1%. Corresponding figures for the overall strain population were Ery, 33.3%; Tet, 22.7%; Chl, 22.8%; Rmp, 0.9%. In addition, 56.5% of PNSSs exhibited multiple drug resistance. Resistance to amoxicillin (MIC > 2 mg/l) was demonstrated for only 5 strains. No strains were resistant to loracarbef or cefotaxime. Serotypes of the 379 PNSSs were as follows: 23F, 26.6%; 14 (25.6%); 9V (18.2%), 6 (8.7%), 15 (5%), 19 (4.5%).     

The vigilance-promoting drug modafinil counteracts the reduction of tyrosine hydroxylase immunoreactivity and of dopamine stores in nigrostriatal dopamine neurons in the male rat after a partial transection of the dopamine pathway

We studied the ability of the vigilance-promoting drug modafinil to modulate the anterograde and retrograde changes in tyrosine hydroxylase (TH) immunoreactivity and in dopamine (DA) stores in the nigro-neostriatal DA neurons, following a partial hemitransection of this ascending DA system, using a combined morphometrical, biochemical and behavioural analysis. Modafinil was given daily i.p. in doses of 10–100 mg/kg, starting 15 min after the lesion, and the partially hemitransected rats were killed 2 weeks later. Changes in TH-immunoreactive nerve cell bodies and nerve terminals induced by the partial hemitransection were studied in the substantia nigra and neostriatum in combination with image analysis. The substantia nigra and neostriatum were also subjected to biochemical analysis of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Modafinil treatment dose-dependently (10–100 mg/kg) counteracted the hemitransection-induced disappearance of nigral TH-immunoreactive nerve cell body profiles and neostriatal TH-immunoreactive nerve terminal profiles. A 2-week treatment with 100 mg/kg of modafinil also counteracted the hemitransection-induced depletion of DA stores in the neostriatum and the ventral midbrain. Moreover, the repeated daily treatment with modafinil (100 mg/kg) protected against the hemitransection-induced disappearance of striatal 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and noradrenaline levels. Striatal DA function was analysed by studying apomorphine-induced (1 mg/kg, s.c.) ipsilateral rotational behaviour 4 and 11 days after the operation. A marked dose-dependent reduction of ipsilateral rotational behaviour was demonstrated after the daily modafinil treatment in the partially hemitransected rats. In another model involving unilateral nigral microinjections of 6-hydroxydopamine, acute (one single dose) modafinil (100 mg/kg) did not affect the contralateral rotational behaviour induced by apomorphine (0.05 mg/kg s.c.), when given 30 min before the apomorphine. Taken together, morphological, neurochemical and behavioural evidence has been obtained that anterograde and retrograde changes induced in the DA stores and TH immunoreactivity of the nigro-neostriatal DA neurons by a partial hemitransection are counteracted by modafinil in a dose dependent way with 100 mg/kg producing a significant protective action against impairment of DA transmission. The results of this study open up the possibility that modafinil may protect against the anterograde and retrograde degeneration of nigrostriatal DA neurons seen after mechanically induced injury.     

Cytologic analyses of spindle-cell lesions of the thorax and retroperitoneum

Thoracic and retroperitoneal spindle-cell lesions represent a diagnostic challenge in the evaluation of fine-needle aspiration (FNA) specimens. The challenge is due to the morphologic similarities and wide variety of different entities with spindle-cell morphology in these two sites. The purpose of this study was to identify criteria helpful in the classification and differential diagnosis of spindle-cell lesions in these two locations. A set of cytologic features was analyzed in 57 thoracic or retroperitoneal spindle-cell lesions. Our results show that pleomorphism and abundant single cells were parameters associated with high-grade tumors in univariate and multivariate analysis, while coarse chromatin pattern was significant only in a univariate analysis. The combination of absence of pleomorphism, rare single cells, tight cluster arrangement, fine chromatin pattern, and absence of macronucleoli was seen only in benign cases. Assessment of background material was helpful in the differential diagnosis and classification. Necrosis was only found in high-grade cases.     

Arbitrarily primed PCR, ribotyping, and plasmid pattern analysis applied to investigation of a nosocomial outbreak due to Enterobacter cloacae in a neonatal intensive care unit.

In December 1992, Enterobacter cloacae was isolated from the oropharynx and respiratory tract of six ventilated neonates hospitalized in the intensive care unit (ICU) of our hospital. To establish the spread of the outbreak, 41 strains of E. cloacae were analyzed for genotypic markers by three methods: plasmid profile analysis, ribotyping with EcoRI or PvuII endonuclease, and arbitrarily primed (AP) PCR. The tested strains included 12 isolates from the 6 epidemic cases, 4 isolates from the respiratory tract of 4 children hospitalized in other wards during the same period, 13 isolates from 12 children hospitalized in pediatric units before or after the outbreak, and 12 epidemiologically unrelated isolates. Ribotyping and AP PCR demonstrated that each of the last 12 strains exhibited distinct genomic patterns, as did each of the strains isolated from neonates hospitalized before or after the epidemic peak. Conversely, two clones of strains were found among the isolates recovered in December, with concordant results being obtained by the three typing methods: the first clone included seven strains from five ventilated children in the ICU and two children from another ward; another clone was shared by one neonate in the ICU and an infant from another ward. These results indicate that ribotyping and AP PCR-the latter applied, to our knowledge, for the first time to the genotypic analysis of E. cloacae--represent very discriminatory tools for the investigation of nosocomial outbreaks caused by this species.     

The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death.

Here we analyze limb development after the conditional inactivation of Fgf8 from the epiblast, using the previously described MORE (Mox2Cre) line. This line drives variable mosaic recombination of a floxed Fgf8 allele, resulting in a small proportion of AER cells that maintain Fgf8 expression. The phenotype of Mox2Cre;Fgf8 limbs is most similar to that of Msx2Cre;Fgf8 forelimbs, indicating that a small but durable expression of FGF8 is equivalent to an early normal, but transitory, expression. This functional equivalence likely relies on the subsequent Fgf4 upregulation that buffers the differences in the pattern of Fgf8 expression between the two conditional mutants. The molecular analysis of Mox2Cre;Fgf8 limbs shows that, despite Fgf4 upregulation, they develop under reduced FGF signaling. These limbs also exhibit an abnormal area of cell death at the anterior forelimb autopod, overlapping with an ectopic domain of Bmp7 expression, which can explain the abnormal morphogenesis of the anterior autopod.     

Monoclonal antibodies against Vibrio cholerae lipopolysaccharide.

A cell line producing monoclonal antibodies directed against the core region of Vibrio cholerae lipopolysaccharide has been established. These antibodies were inhibited by lipopolysaccharide preparations of both O-group 1 vibrios and some non-O-group 1 vibrios as detected in enzyme-linked immunosorbent assay-inhibition experiments. Coagglutination experiments with monoclonal and polyclonal antibodies adsorbed to protein A-carrying staphylococci were performed. All V. cholerae strains tested, regardless of serotype, were agglutinated when mixed with staphylococci coated with the monoclonal antibodies, whereas staphylococci coated with group-specific (O1) polyclonal antibodies only agglutinated with O-group 1 vibrios.     

Respiratory mortality among firefighters.

Although firefighters have been shown in some studies to suffer chronic respiratory morbidity from their occupational exposures, an increased risk for dying from non-malignant respiratory diseases has not been documented in any previous retrospective cohort mortality study. In order to assess the possibility that an unusually strong "healthy worker effect" among firefighters might mask this increased risk, a mortality analysis of firefighters was carried out in three cities in relation to the United States population and also to a comparison cohort of police officers. The firefighters were employed between 1945 and 1980 and experienced 886 deaths by 1 January 1984; compared with the United States population they had a significantly reduced risk of dying from all causes (SMR = 82, 95% confidence interval, 77-87), and from non-malignant circulatory diseases (SMR = 81, 95% confidence interval 73-89), but no significant difference in risk of non-malignant respiratory diseases (SMR = 88, 95% confidence interval 66-117). Compared with police, the firefighters experienced a trend toward improved mortality outcomes for all causes investigated (SMR = 82), but they had an excess of deaths from non-malignant respiratory diseases (SMR = 141). The results indicate that firefighters are probably at increased risk for dying from non-malignant respiratory diseases; this increased risk may have been missed in previous studies because of the limitations of using a general reference population.