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Biomedical subjects

C Savage

Publications and source records attributed to C Savage.

At least 37 records · Page 2Linked to original sources

[Paraplegia episodes revealing tuberculous myelitis].

A 38 year-old woman, without previous medical history, presented, since 1993, several paraplegic fits carrying herself progressively through to a severe paraplegia. Diagnoses successively proposed were spinal cord compressions by slipped discs, spinal cord infarct and multiple sclerosis. In November 1998, the patient presented back pain and fever. Spinal cord magnetic resonance imaging (MRI) revealed a mildly enlarged dorsal cord with signal abnormalities. The lesions were isointense on T1-weighted images, hyperintense on T2-weighted images and showed a ringlike contrast enhancement. A lumbar puncture showed a trouble cerebrospinal fluid (CSF) with leucocytes 600/mm(3) (85 p.100 polynuclear), protein 6.7 g/l, glucose 0.26 g/l, chloride 109 mmol/l. The patient was first treated with parenteral unspecific antibiotherapy. Microbiological studies of blood and CSF were negative. CSF examination with polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis. Clinical (pain and fever) symptoms and CSF abnormalities decreased after antituberculous treatment. However, paraparesis remain severe. Spinal tuberculous localizations often lead to diagnostic and therapeutic errors. Improvement of spinal cord MRI sequences and using of PCR technics in CSF would contribute to reduce these difficulties.

Adult↗

Cyanide Chemistry in Comet Hale-Bopp (C/1995 O1).

Observations of comet Hale-Bopp (C/1995 O1) have been carried out near perihelion (1997 March) at millimeter wavelengths using the NRAO 12 m telescope. The J=1-->0, 2-->1, and 3-->2 lines of HCN at 88, 177, and 265 GHz were measured in the comet as well as the J=3-->2 lines of H13CN, HC15N, and HNC. The N=2-->1 transition of CN near 226 GHz was also detected, and an upper limit was obtained for the J=2-->1 line of HCNH+. From the measurements, column densities and production rates have been estimated. A column density ratio of [HCN]/[HNC] = 7+/-1 was observed near perihelion, while it was found that [HCN]/[HCNH+] greater, similar 1. The production rates at perihelion for HCN and CN were estimated to be Q(HCN) approximately 1x1028 s-1 and Q(CN) approximately 2.6x1027 s-1, respectively, resulting in a ratio of [HCN]/[CN] approximately 3. Consequently, HCN is sufficiently abundant to be the parent molecule of CN in Hale-Bopp, and HCNH+ could be a source of HNC. Finally, carbon and nitrogen isotope ratios of 12C/13C = 109+/-22 and 14N/15N = 330+/-98 were obtained from HCN measurements, in agreement with previous values obtained from J=4-->3 data. Such ratios suggest that comet Hale-Bopp formed coevally with the solar system.

Journal Article↗

[Diagnostic difficulties of transfusion incidents due to bacterial contamination: report of two cases].

The French hemovigilance system has recently underlined the relative frequency of transfusion-associated bacterial sepsis and the necessity to remain constantly aware of this eventuality. We describe the experience of a hematology unit over a 18-month period: 189 acute transfusion reactions were registered and bacterial cultures of the implicated cellular blood products realized in 82 of them. A positive result was obtained in two cases. For both cases, clinical symptoms of transfusion reaction were limited to a lasting fever, and a skin rash occurred in aplastic patients with preexisting signs of sepsis. The causal relationship between this contamination and the transfusion reaction is difficult to establish. Clinical manifestations justifying a bacterial inquiry must therefore be more precisely defined, particularly in multitransfused patients.

Adult↗

Molecular epidemiology of tuberculosis in the Nord Department of France during 1995.

In order to determine the current situation and to evaluate the human to human transmission of Mycobacterium tuberculosis in Northern France, the genetic polymorphism of strains was studied by using IS6110 fingerprint. One hundred and fifty-eight cases of bacteriologically confirmed tuberculosis were analyzed. One hundred and twenty-six patients (82%) were infected with genetically different isolates and 28 isolates (18%) were grouped into 14 clusters. No risk factors for recent Mycobacterium tuberculosis infections such as age, HIV status, immigrants, living in big cities were identified. This study shows that there was no major epidemic situation of tuberculosis in Northern France in 1995. Tuberculosis was characterized by a low proportion of HIV positive patients and a high proportion of elderly patients.

AIDS-Related Opportunistic Infections↗

Comparison of CHROMagar Salmonella medium and hektoen enteric agar for isolation of salmonellae from stool samples.

CHROMagar Salmonella (CAS), a new chromogenic medium, was retrospectively compared to Hektoen enteric agar (HEA) with 501 Salmonella stock isolates and was then prospectively compared to HEA for the detection and presumptive identification of Salmonella spp. with 508 stool samples before and after enrichment. All stock cultures (100%), including cultures of H2S-negative isolates, yielded typical mauve colonies on CAS, while 497 (99%) isolates produced typical lactose-negative, black-centered colonies on HEA. Following overnight incubation at 37 degreesC, a total of 20 Salmonella strains were isolated from the 508 clinical samples. Sensitivities for primary plating and after enrichment were 95% (19 isolates) and 100% (20 isolates), respectively, for CAS and 80% (16 isolates) and 100% (20 isolates), respectively, for HEA. The specificity of CAS (88.9%) was significantly higher than that of HEA (78.5%; P < 0.0001). On the basis of its good sensitivity and specificity, CAS medium can be recommended for use for primary plating when human stool samples are screened for Salmonella spp.

Agar↗

[Determination of the nosocomial origin of vancomycin-resistance strains of Enterococcus isolated from stool of patients in a hematology department].

Patients severely neutropenic, when hospitalized, occasionally receive selective digestive decontamination, and the risk of vancomycin-resistant strain selection is a drawback since glycopeptide resistance is often associated with betalactam and aminoglycosid resistance. Bacterial translocation can lead to multiresistant bacterial sepsis. Eighteen Enterococcus faecium strains were collected from patients hospitalized in the leukemia unit of the Universitary Hospital of Lille (CHRU, Pr Bauters) between October 1992 and July 1997 and were studied. Nosocomial acquisition or endogenous origin were investigated to choose well-adapted prevention. All the vancomycin-resistant strains were shown by Polymerase Chain Reaction having the van A gene. The clonality of these strains was investigated by Pulsed-Field-Gel-Electrophoresis after Sma I restriction. Pulsotype analysis showed variable homology (52%-100%). Our results do not show evidence of patient-to-patient E. faecium transmission and suggest vancomycin-resistant strains were independently selected by antibiotic therapy from individual fecal flora. Except when epidemic events or happen, this strain isolation is more related to antibiotic prescription than misuse of isolation techniques.

Adult↗

An agency-based representative payee program and improved community tenure of persons with mental illness.

OBJECTIVE: Representative payee programs help severely mentally ill individuals manage money from their Social Security payments to cover expenses for necessities and to avoid homelessness and rehospitalization. This study examined a representative payee program operated by a community mental health center to determine the criteria used by clinicians and ease managers to refer clients to the program and to learn whether participation in the program was associated with reductions in hospitalization. METHODS: The retrospective study included 56 individuals with severe mental illness who were enrolled in the representative payee program at Community Counseling Centers of Chicago for one year and who also had received services from the agency for at least one year before enrollment. Criteria used to refer clients to the representative payee program were determined through chart reviews. Data on state hospitalizations before and after enrollment were available for the entire sample; additional data on Medicaid-funded private hospitalizations were available for a subset of 33 clients. RESULTS: The most common criteria for enrollment in the representative payee program were comorbid substance abuse or dependence (49 percent), a history of homelessness (33 percent), and frequent hospitalizations (32 percent). During the year of participation in the representative payee program, the mean number of days spent in state hospitals decreased markedly compared with the year before enrollment, from 68 days to seven days. A similar reduction was noted in the number of days spent in state and private hospitals, from 97 days to 15 days. CONCLUSIONS: Findings from this pre- and postintervention retrospective study are tentative in the absence of a more rigorous design. However, the results suggest that the representative payee program is quite effective in reducing hospital stays.

Adult↗

Characteristics of persons with mental illness in a representative payee program.

This study compared the characteristics of 56 clients with severe mental illness in a community mental health agency's representative payeeship program with those of 54 clients who did not participate in the program. Based on data from a two-year period, participants in the representative payee program were characterized by disability or financial distress, indicated by a diagnosis of schizophrenia, homelessness, lack of rent money, and lack of financial skills; long-term dependence on income from Social Security and services provided by the mental health system, evidenced by receipt of Supplemental Security Income and frequent hospitalizations; and lack of financial independence, as reflected by inability to earn income from employment and lack of financial support from family.

Adult↗

Failure of intravenous antibiotic therapy of multiple temporal brain abscesses due to Propionibacterium acnes requiring temporal lobectomy.

Propionibacterium acnes is a common skin colonizer. Its involvement in brain abscesses is generally described as a complication of neurosurgical intervention. Propionibacterium acnes is susceptible to antibiotics used as treatment of anaerobic infections, except for the 5-nitroimidazoles. Surgical excision or drainage of a simple abscess combined with a long course of antibiotics is considered the treatment of choice. A case of a patient with multiple brain abscesses located in the right temporal lobe that occurred after the manipulation of an abscess of the right upper maxillary is reported. The patient did not improve despite a prolonged course of high-dose intravenous penicillin plus thiamphenicol and cure was finally obtained after the excision of the right temporal lobe. Culture of the purulent material and the shell of the abscesses yielded P. acnes which was sensitive to all the antibiotics administered to the patient up to the intervention. The temporal lobectomy was followed by a 6-month course of ofloxacin. One year after the intervention, the patient remained apyretic without any other abscess on cranial computed tomography scan.

Adult↗

Genetic and biochemical analysis of TGF beta signal transduction.

TGF beta-like ligands are involved in many different developmental processes that pattern a variety of tissues in invertebrates and vertebrates. In the last few years, rapid progress has been made toward elucidating the developmental roles of the TGF beta-like pathways and identifying the novel components involved in transducing their signals, particularly the newly discovered Smads. This rapid progress has been the result of a synergy between classical genetic approaches and biochemical approaches, and this combined approach is likely to propel future understanding of the signaling pathway used by TGF beta.

Animals↗

Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.

The dwarfin protein family has been genetically implicated in transforming growth factor beta (TGF-beta)-like signaling pathways in Drosophila and Caenorhabditis elegans. To investigate the role of these proteins in mammalian signaling pathways, we have isolated and studied two murine dwarfins, dwarfin-A and dwarfin-C. Using antibodies against dwarfin-A and dwarfin-C, we show that these two dwarfins and an immunogenically related protein, presumably also a dwarfin, are phosphorylated in a time- and dose-dependent manner in response to TGF-beta. Bone morphogenetic protein 2, a TGF-beta superfamily ligand, induces phosphorylation of only the related dwarfin protein. Thus, TGF-beta superfamily members may use overlapping yet distinct dwarfins to mediate their intracellular signals. Furthermore, transient overexpression of either dwarfin-A or dwarfin-C causes growth arrest, implicating the dwarfins in growth regulation. This work provides strong biochemical and preliminary functional evidence that dwarfin-A and dwarfin-C represent prototypic members of a family of mammalian proteins that may serve as mediators of signaling pathways for TGF-beta superfamily members.

Amino Acid Sequence↗

Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components.

Although transforming growth factor beta (TGF-beta) superfamily ligands play critical roles in diverse developmental processes, how cells transduce signals from these ligands is still poorly understood. Cell surface receptors for these ligands have been identified, but their cytoplasmic targets are unknown. We have identified three Caenorhabditis elegans genes, sma-2, sma-3, and sma-4, that have mutant phenotypes similar to those of the TGF-beta-like receptor gene daf-4, indicating that they are required for daf-4-mediated developmental processes. We show that sma-2 functions in the same cells as daf-4, consistent with a role in transducing signals from the receptor. These three genes define a protein family, the dwarfins, that includes the Mad gene product, which participates in the decapentaplegic TGF-beta-like pathway in Drosophila [Sekelsky, J. J., Newfeld, S. J., Raftery, L. A., Chartoff, E. H. & Gelbart, W. M. (1995) Genetics 139, 1347-1358]. The identification of homologous components of these pathways in distantly related organisms suggests that dwarfins may be universally required for TGF-beta-like signal transduction. In fact, we have isolated highly conserved dwarfins from vertebrates, indicating that these components are not idiosyncratic to invertebrates. These analyses suggest that dwarfins are conserved cytoplasmic signal transducers.

Amino Acid Sequence↗

Analysis of K-ras gene mutations in malignant and nonmalignant endobronchial tissue obtained by fiberoptic bronchoscopy.

Using polymerase chain reaction DNA amplification, we identified K-ras oncogene mutations in bronchial biopsies obtained from patients undergoing bronchoscopy for clinical indications. We hypothesized that these mutations would be found in a field encompassing malignant and nonmalignant tissues in patients with pulmonary carcinomas, and also possibly in tissue from some patients who smoked but did not have pulmonary malignancy. We found K-ras mutations in endobronchial biopsies from nine of 22 patients (41%) with carcinoma of the lung. In five of these patients, mutations were found in both malignant and nonmalignant specimens. In two instances, mutations were found only in the neoplastic tissue, and in two cases mutations were present only in the nonmalignant tissue. Furthermore, we identified two patients with K-ras mutations among seven patients in whom no clinical malignancy was apparent. Our data suggest that some oncogene activations may occur over a broad area in smokers with and without malignancy, and they imply that K-ras mutations may serve as surrogate markers for malignant potential.

Aged↗

Mutations in the Caenorhabditis elegans beta-tubulin gene mec-7: effects on microtubule assembly and stability and on tubulin autoregulation.

We have sequenced 45 mutations in mec-7, a beta-tubulin gene required for the production of 15-protofilament microtubules in the nematode Caenorhabditis elegans, and have correlated sequence alterations with mutant phenotypes. The expression patterns of most alleles have also been determined by in situ hybridization and immunocytochemistry. Most (12/16) complete loss-of-function alleles, which are recessive, result from nonsense mutations, insertions, or deletions; three others disrupt a putative GTP-binding domain. Three of the four loss-of-function, missense mutations result in elevated mec-7 message levels, suggesting a defect in tubulin autoregulation that may be attributable to a loss in the ability to form heterodimers. Most (8/9) mild alleles are caused by missense mutations. Two mild alleles appear to increase microtubule stability and lead to the elaboration of ectopic neuronal processes in mec-7-expressing cells. Most (15/23) mutations that cause severe dominant or semidominant phenotypes are clustered into three discrete domains; four others occur in putative GTP-binding regions. Many of these dominant mutations appear to completely disrupt microtubule assembly.

Alleles↗

[Buruli ulcer in a Zairian woman with HIV infection].

INTRODUCTION: Isolated cutaneous mycobacterial infection is exceptional in the acquired immunodeficiency syndrome (AIDS). We report a case of Buruli ulcer observed in a Zairan female infected with the human immunodeficiency virus (HIV). CASE REPORT: An HIV positive female patient was hospitalized for deep skin ulceration with detached and necrotic borders on the posterior aspect of the lower limb. Histological examination of a surgical biopsy showed numerous acid-fast bacilli identified as Mycobacterium ulcerans by thin layer gas chromatography. The clinical course was favourable with a three-drug antibiotic therapy replaced by rifampicin-clarithromycin after three months. The patient's immune status did not change for two years with a CD4 count of 500/mm3. The patient was negative for P24 antigen. DISCUSSION: While it is relatively easy to diagnose Buruli ulcers, identifying the causal bacteria is sometimes quite difficult requiring long culture periods. New techniques such as gas phase chromatography have been very useful in particularly low-count sub-cultures. Surgery remains the predominant therapy in endemic areas but antibiotic combinations are also effective. HIV-related immunosuppression did not change the clinical aspect of cutaneous mycobacteriosis in this patient whose immunological status was not modified.

Adult↗

Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis.

The continuing morbidity of patients with vasculitis, despite the improved prognosis with aggressive therapy, underlines the need for accurate disease assessment. We have devised a clinical index of disease activity, and evaluated its use in several forms of necrotizing vasculitis. The weighted score is based on symptoms and signs in nine separate organ systems. Disease features are only scored if they are attributable to active vasculitis. The Birmingham Vasculitis Activity Score (BVAS) was compared with two other published vasculitis activity scores, with the physician's global assessment (PGA), with outcome, and with serological markers of disease activity. In a cross-sectional study of 213 consecutive patients with different forms of vasculitis, all 107 vasculitis patients who were judged completely well on clinical assessment had a BVAS score of 0. Twenty-two patients with active vasculitis prior to treatment had a median score of 7.5 (range 4-30) and 69 with active disease on treatment had a median score of 10 (1-29). Of the 12 who died, median score immediately prior to death was 20.5 (9-30). In a serial prospective study, 30 cases had documented episodes of active disease. During periods of disease activity, the median BVAS values were significantly higher than in remission (15 [range 3-32] vs. 0 [0-2], p < 0.001); the same was true for CRP values (80 [9-361] vs. 13.5 [5-68], p < 0.001). This was not true for erythrocyte sedimentation rate (ESR), haemoglobin (Hb) or von Willebrand factor (VWF).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Isolation and characterization of mutations causing abnormal eversion of the vulva in Caenorhabditis elegans.

In Caenorhabditis elegans hermaphrodites, morphogenesis of the vulva culminates in a process called vulval eversion, whereby a passageway is made from the uterus through the vulva to the outside of the animal. We have screened for mutations causing abnormal eversion of the vulva (evl mutations) to identify new genes involved in vulval development, and found that evl mutants are relatively common after EMS mutagenesis. We also hoped to identify genes involved in lin-12-mediated cell fate decisions, since lin-12 null mutants have abnormally everted vulvae, but none of the 68 evl mutations recovered in our screen appeared to be good candidates for genes that function with lin-12. Initial genetic and phenotypic analysis of 30 evl mutations revealed that all affect the development of the uterus, but only some affect the vulval precursor cell lineages. We used laser ablation to show that the uterus and anchor cell are important for correct vulval eversion in wild type; the anchor cell is important early in the L3 stage, before the vulval cells have been generated, but not later, when vulval eversion occurs. We conclude that certain evl mutations may influence vulval eversion by primarily affecting the development of the somatic gonad, while others may affect processes required in the development of both structures.

Alleles↗