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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 19 recordsLinked to original sources
PubMed2006

Abnormal nitric oxide metabolism in systemic sclerosis: increased levels of nitrated proteins and asymmetric dimethylarginine.

OBJECTIVES: Endothelial dysfunction is a primary event in systemic sclerosis; however, the aetiology of events and the role of nitric oxide (NO) is still unclear. The aim of the present study is to investigate whether there are abnormalities in NO metabolism in plasma from patients with primary Raynaud's phenomenon (RP) and in the pathogenesis of systemic sclerosis (SSc): limited SSc (lSSc) and diffuse (dSSc). We also wanted to investigate the effect of factors within patients' SSc serum on NO metabolism in human microvascular endothelial cells (HMECs). METHODS: Plasma (n=89) or serum (n=80) was assayed for total nitrate and nitrite (NOx), nitration of proteins and the NO inhibitor asymmetric dimethylarginine (ADMA). HMECs were treated with patients' SSc serum and assayed for indicators of NO metabolism. RESULTS: Plasma NOx was elevated in patients with RP or lSSc (P<0.002), but not in patients with dSSc, compared with controls. Nitrated proteins in plasma, however, were found to be very high in dSSc patients (P<0.03), compared with RP, lSSc or controls. Patients with dSSc also showed increased levels of serum ADMA (P<0.05). The high level of nitrated proteins in dSSc was strongly associated with the severity and duration of dSSc disease. Skin biopsy sections from dSSc patients also showed enhanced nitrotyrosine staining compared with controls. In HMECs, pre-incubation with SSc serum impaired the activity of nitric oxide synthase (NOS) but not the expression of inducible or endothelial NOS. SSc serum also induced a reduction in intracellular cGMP synthesis, and NOx production in the cell culture medium, but was not associated with increased cell cytotoxicity. CONCLUSIONS: NO formation is increased in patients with primary RP or lSSc, but nitration of proteins and elevated ADMA is a particular feature of dSSc and may reflect abnormal NO regulation and/or contribute to endothelial dysfunction in SSc.

Adult↗
PubMed2006

Quality of in-hospital care for adults with acute bacterial meningitis: a national retrospective survey.

BACKGROUND: Most adults with bacterial meningitis and meningococcal septicaemia present to junior doctors who have limited experience of these conditions. In contrast to paediatric practice, data from industrialized countries with regard to current hospital management practice are lacking. AIM: To examine whether current practice meets recommended standards in hospital management of community-acquired bacterial meningitis and meningococcal septicaemia among adults. DESIGN: National audit of medical records. METHODS: We conducted a survey of all patients with acute bacterial meningitis and meningococcal septicaemia admitted to 18 randomly selected acute hospitals in England and Wales between 1 January 2000 and 31 December 2001. All stages of care, including pre-hospital management, initial hospital assessment, record keeping, and ongoing hospital and public health management, were assessed. RESULTS: We identified 212 cases of bacterial meningitis and meningococcal septicaemia; 190 cases remained in the final analysis. Clinical record keeping did not meet acceptable standards in 33% of cases. Parenteral antibiotics were given within 1 h of hospital arrival in 56% of cases, increasing to 79% among those with an initial differential diagnosis that included bacterial meningitis or meningococcal septicaemia. A full severity of illness assessment was made in 27%. The quality of clinical practice varied widely between hospitals. This was most pronounced in the timeliness of consultant review (p < 0.0005). DISCUSSION: The quality of adult clinical practice for bacterial meningitis and meningococcal septicaemia needs improvement. This study provides a tool for developing targeted interventions to improve quality of care and outcome among adults with life-threatening infections, both in the UK and in other countries.

Adolescent↗
PubMed2004

The Aristotle score: a complexity-adjusted method to evaluate surgical results.

OBJECTIVES: Quality control is difficult to achieve in Congenital Heart Surgery (CHS) because of the diversity of the procedures. It is particularly needed, considering the potential adverse outcomes associated with complex cases. The aim of this project was to develop a new method based on the complexity of the procedures. METHODS: The Aristotle project, involving a panel of expert surgeons, started in 1999 and included 50 pediatric surgeons from 23 countries, representing the EACTS, STS, ECHSA and CHSS. The complexity was based on the procedures as defined by the STS/EACTS International Nomenclature and was undertaken in two steps: the first step was establishing the Basic Score, which adjusts only the complexity of the procedures. It is based on three factors: the potential for mortality, the potential for morbidity and the anticipated technical difficulty. A questionnaire was completed by the 50 centers. The second step was the development of the Comprehensive Aristotle Score, which further adjusts the complexity according to the specific patient characteristics. It includes two categories of complexity factors, the procedure dependent and independent factors. After considering the relationship between complexity and performance, the Aristotle Committee is proposing that: Performance = Complexity x Outcome. RESULTS: The Aristotle score, allows precise scoring of the complexity for 145 CHS procedures. One interesting notion coming out of this study is that complexity is a constant value for a given patient regardless of the center where he is operated. The Aristotle complexity score was further applied to 26 centers reporting to the EACTS congenital database. A new display of centers is presented based on the comparison of hospital survival to complexity and to our proposed definition of performance. CONCLUSION: A complexity-adjusted method named the Aristotle Score, based on the complexity of the surgical procedures has been developed by an international group of experts. The Aristotle score, electronically available, was introduced in the EACTS and STS databases. A validation process evaluating its predictive value is being developed.

Cardiac Surgical Procedures↗
PubMed2004

Radiation-induced medulloblastoma in an adult: a functional imaging study.

We describe functional imaging findings using MRI, 1H-Magnetic resonance spectroscopy and positron emission tomography in a case of radiation-induced medulloblastoma following radiotherapy for pineal gland tumor. MRS showed a prominent choline peak; FDG, 11C-Met and 11C-Choline PET showed a minimal glucose, increased methionine and choline uptake.

Adult↗
PubMed2004

Clinical utility of 11C-flumazenil positron emission tomography in intractable temporal lobe epilepsy.

BACKGROUND: 11C-flumazenil (FMZ) positron emission tomography (PET) is a new entrant into the armamentarium for pre-surgical evaluation of patients with intractable temporal lobe epilepsy (TLE). AIMS: To analyze the clinical utility of FMZ PET to detect lesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to magnetic resonance imaging (MRI), 2-Deoxy-2 [18F] fluoro-D-glucose, (18F FDG) PET, electrophysiological findings and semiology of epilepsy in patients with intractable TLE. MATERIALS AND METHODS: Patients underwent a high resolution MRI, prolonged Video-EEG monitoring before 18F FDG and 11C FMZ PET studies. Regional cortical FMZ PET abnormalities were defined on co-registered PET images using an objective method based on definition of areas of abnormal asymmetry (asymmetry index {AI}>10%). SETTINGS AND DESIGN: Prospective. STATISTICAL ANALYSIS: Student's "t" test. RESULTS: Twenty patients (Mean age: 35.2 years [20-51]; M:F=12:8) completed the study. Mean age at seizure onset was 10.3 years (birth-38 years); mean duration, 23.9 years (6-50 years). Concordance with the MRI lesion was seen in 10 patients (nine with hippocampal sclerosis and one with tuberous sclerosis). In the other 10, with either normal or ambiguous MRI findings, FMZ and FDG uptake were abnormal in all, concordant with the electrophysiological localization of the epileptic foci. Remote FMZ PET abnormalities (n=18) were associated with early age of seizure onset (P=0.005) and long duration of epilepsy (P=0.01). CONCLUSIONS: FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.

Adult↗
PubMed2003

A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis.

OBJECTIVE: To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS. METHODS: A double-blind, placebo-controlled, multicenter randomized clinical trial was conducted. Participants with ALS (n = 296) were randomized (2:1) to receive topiramate (maximum tolerated dose up to 800 mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function as measured by the maximum voluntary isometric contraction (MVIC) strength of eight arm muscle groups. Secondary endpoints included safety and the rate of decline of forced vital capacity (FVC), grip strength, ALS functional rating scale (ALSFRS), and survival. RESULTS: Patients treated with topiramate showed a faster decrease in arm strength (33.3%) during 12 months (0.0997 vs 0.0748 unit decline/month, p = 0.012). Topiramate did not significantly alter the decline in FVC and ALSFRS or affect survival. Topiramate was associated with an increased frequency of anorexia, depression, diarrhea, ecchymosis, nausea, kidney calculus, paresthesia, taste perversion, thinking abnormalities, weight loss, and abnormal blood clotting (pulmonary embolism and deep venous thrombosis). CONCLUSIONS: At the dose studied, topiramate did not have a beneficial effect for patients with ALS. High-dose topiramate treatment was associated with a faster rate of decline in muscle strength as measured by MVIC and with an increased risk for several adverse events in patients with ALS. Given the lack of efficacy and large number of adverse effects, further studies of topiramate at a dose of 800 mg or maximum tolerated dose up to 800 mg/day are not warranted.

Adult↗
PubMed2003

A comparison of the whole-body and segmental methodologies of bioimpedance analysis.

Theory supports the use of a segmental methodology (SM) for bioimpedance analysis (BIA) of body water (BW). However, previous studies have generally failed to show a significant improvement when the SM is used in place of a whole-body methodology. A pilot study was conducted to compare the two methodologies in control and overweight subjects. BW of each subject was measured by D(2)O dilution and also estimated from BIA measurements. Bland and Altman analysis was used to compare the two values of BW. The SM resulted in a small but not significantly improved "limits of agreement" of measured and BIA estimated BW (approximately 0.3). This and the results of previous studies suggest that improvements in prediction of BW obtained from application of the SM may be intrinsically small and may not justify the additional effort in application.

Body Water↗
PubMed2003

Prediction of pathology and survival by FDG PET in gliomas.

OBJECTIVES: Despite being in use for nearly two decades, the utility of [18F]2-fluoro-2deoxy-D-glucose positron emission tomography (FDG PET) in the evaluation and treatment of brain tumors remains controversial. We retrospectively analyzed all patients with histologically proven gliomas, between the years 1990 and 2000, who underwent FDG PET studies at various stages of their treatment and who were followed till either death or for a minimum period of 1 year in an attempt to bring resolution to this controversy. METHODS: All PET scans prior to 1997 were acquired on an ECAT 951/31 scanner in 2D. Scans since 1997 were obtained on a Siemens HR+ scanner in 3D mode. The majority of FDG PET scans were co-registered with the magnetic resonance imaging (MRI) scans to aid in diagnosis and therapy. Based on independent visual inspection, two board certified nuclear medicine physicians graded the highest activity level of the tumor using the metabolic grading: 0 = no uptake; 1 = uptake less or equal to normal white matter; 2 = uptake greater than normal white matter and less than gray matter; 3 = uptake equal to or greater than gray mater. The measure of association of lambda (lambda) was used to measure the strength of predictive ability of FDG PET for pathological grading of the gliomas. The Cox proportional hazards regression model was used to assess the significance of grade of uptake on survival. RESULTS: A total of 331 patients were analyzed of which 137 had a PET scan prior to histological diagnosis and therapeutic intervention (mean age = 46.5 years; M:F = 1.7:1). Eighty six percent (143/166) of the patients with low uptake (metabolic scores 0,1) had low-grade gliomas (grade I,II) and 14% (23/166) high-grade gliomas (grade III,IV) on histologic examination. Ninety four percent (154/165) of the patients with high uptake (metabolic scores 2,3) on PET had high-grade gliomas and 7% (11/165) had low-grade gliomas on histologic examination. The grade of uptake had increasing significance on survival as the level increased from 'low' to 'high' (P = 0.0009). Ninety four percent (156/166) of the patients with low uptake survived for > 1 year (median survival of 28 months) and 19% survived for > 5 years. Only 29% (48/165) of patients with high uptake survived for > 1 year, (median survival of 11 months) and none survived for > 5 years. Irrespective of when the scan showed a high uptake of FDG, before or after intervention, the prognosis following that scan was poor. CONCLUSIONS: Our observations confirm the utility of FDG PET as a prognostic tool for the histological grading and survival in patients with gliomas and appears to more than complement pathological grading.

Adolescent↗
PubMed2003

Role of microbiological investigations in the management of non-perineal cutaneous abscesses.

BACKGROUND: Pus samples for microbiological examination are routinely sent after incision and drainage of abscesses. There is no evidence that microbiology reports influence treatment for non-perineal cutaneous abscesses. AIMS: This study assessed (1) how often the microbiology report is used to manage patients' treatment after incision and drainage of an abscess and (2) junior surgical trainees' opinions on sending pus for microbiological examination. METHOD: A retrospective analysis of the notes of all patients undergoing incision and drainage of abscesses from January 2001 to January 2002 was made. A telephone poll of junior surgical trainees was also undertaken. RESULTS: Most patients, 91%, had specimens referred for microbiology. Of these 43% yielded no growth. Staphylococcus aureus was the most common organism (55.9% of all positive cultures). Anaerobes were a frequent finding from axilla and groin abscesses. Mycobacterium tuberculosis was grown in two patients. Other less common organisms cultured were methicillin resistant S aureus (n=1) and Proteus sp (n=1). Follow up of microbiology reports was found to be inadequate. CONCLUSION: The bacteria present in non-perineal cutaneous abscesses are, for the most part, predictable. However, a significant number grow less common organisms. It is concluded that pus specimens should be sent routinely for culture and sensitivity and there should be further emphasis on following up microbiology reports by junior medical staff.

Abscess↗
PubMed2002

Autotransplantation for advanced lymphoma and Hodgkin's disease followed by post-transplant rituxan/GM-CSF or radiotherapy and consolidation chemotherapy.

Disease relapse occurs in 50% or more of patients who are autografted for relapsed or refractory lymphoma (NHL) or Hodgkin's disease (HD). The administration of non-cross-resistant therapies during the post-transplant phase could possibly control residual disease and delay or prevent its progression. To test this approach, 55 patients with relapsed/refractory or high-risk NHL or relapsed/refractory HD were enrolled in the following protocol: stem cell mobilization: cyclophosphamide (4.5 g/m(2)) + etoposide (2.0 g/m(2)) followed by GM-CSF or G-CSF; high-dose therapy: gemcitabine (1.0 g/m(2)) on day -5, BCNU (300 mg/m(2)) + gemcitabine (1.0 g/m(2)) on day -2, melphalan (140 mg/m(2)) on day -1, blood stem cell infusion on day 0; post-transplant immunotherapy (B cell NHL): rituxan (375 mg/m(2)) weekly for 4 weeks + GM-CSF (250 microg thrice weekly) (weeks 4-8); post-transplant involved-field radiotherapy (HD): 30-40 Gy to pre-transplant areas of disease (weeks 4-8); post-transplant consolidation chemotherapy (all patients): dexamethasone (40 mg daily)/cyclophosphamide (300 mg/m(2)/day)/etoposide (30 mg/m(2)/day)/cisplatin (15 mg/m(2)/day) by continuous intravenous infusion for 4 days + gemcitabine (1.0 g/m(2), day 3) (months 3 + 9) alternating with dexamethasone/paclitaxel (135 mg/m(2))/cisplatin (75 mg/m(2)) (months 6 + 12). Of the 33 patients with B cell lymphoma, 14 had primary refractory disease (42%), 12 had relapsed disease (36%) and seven had high-risk disease in first CR (21%). For the entire group, the 2-year Kaplan-Meier event-free survival (EFS) and overall survival (OS) were 30% and 35%, respectively, while six of 33 patients (18%) died before day 100 from transplant-related complications. The rituxan/GM-CSF phase was well-tolerated by the 26 patients who were treated and led to radiographic responses in seven patients; an eighth patient with a blastic variant of mantle-cell lymphoma had clearance of marrow involvement after rituxan/GM-CSF. Of the 22 patients with relapsed/refractory HD (21 patients) or high-risk T cell lymphoblastic lymphoma (one patient), the 2-year Kaplan-Meier EFS and OS were 70% and 85%, respectively, while two of 22 patients (9%) died before day 100 from transplant-related complications. Eight patients received involved field radiation and seven had radiographic responses within the treatment fields. A total of 72 courses of post-transplant consolidation chemotherapy were administered to 26 of the 55 total patients. Transient grade 3-4 myelosuppression was common and one patient died from neutropenic sepsis, but no patients required an infusion of backup stem cells. After adjustment for known prognostic factors, the EFS for the cohort of HD patients was significantly better than the EFS for an historical cohort of HD patients autografted after BEAC (BCNU/etoposide/cytarabine/cyclophosphamide) without consolidation chemotherapy (P = 0.015). In conclusion, post-transplant consolidation therapy is feasible and well-tolerated for patients autografted for aggressive NHL and HD and may be associated with improved progression-free survival particularly for patients with HD.

Adult↗
PubMed2002

International business travel: impact on families and travellers.

OBJECTIVES: Spouses and staff of the World Bank Group (WBG) were questioned about the impact of international business travel on families and travellers. Dependent variables were self reported stress, concern about the health of the traveller, and negative impact on the family. We hypothesised that several travel factors (independent variables) would be associated with these impacts. These travel factors had to do with the frequency, duration, and predictability of travel and its interference with family activities. METHODS: Survey forms were developed and distributed to all spouses of travelling staff as well as a small sample of operational staff. Kendall's tau b correlation coefficients of response frequencies were computed with the data from scaled items. Written responses to open ended questions were categorised. RESULTS: Response rates for spouses and staff were 24% and 36%, respectively. Half the spouse sample (n=533) and almost 75% of the staff sample (n=102) reported high or very high stress due to business travel. Self reported spouse stress was associated with six out of eight travel factors. Female spouses, those with children, and younger spouses reported greater stress. Self reported staff stress was significantly associated with four out of nine travel factors. Further insight into how business travel affects families and staff (including children's behavioural changes) and how families cope was gained through responses to written questions. CONCLUSIONS: The findings support the notion that lengthy and frequent travel and frequent changes in travel dates which affect family plans, all characteristic of WBG missions, negatively affects many spouses and children (particularly young children) and that the strain on families contributes significantly to the stress staff feel about their travel. Policies or management practices that take into consideration family activities and give staff greater leeway in controlling and refusing travel may help relieve stress.

Adaptation, Psychological↗
PubMed2001

Hypercoagulable states in renal transplant candidates: impact of anticoagulation upon incidence of renal allograft thrombosis.

INTRODUCTION: Although multiple studies of demographic variables have been associated with allograft thrombosis, these results are not routinely reproducible. Are ESRD patients with hypercoagulable states (HCS) (antithrombin III deficiency, protein S or C deficiency, activated protein C resistance, and anticardiolipin antibodies) at predictably greater risk for allograft thrombosis? METHODS: Between 1996 and 1999, all renal transplant candidates were screened for hypercoagulability risk factors [HRF] (multiple arteriovenous access thromboses, prior deep vein thrombosis, prior allograft thrombosis, collagen vascular disease, multiple miscarriages, diabetes, autoimmune disease, and Fabry's disease). HRF(+) candidates were then tested for HCS status. We administered preemptive posttransplant i.v. Heparin in HCS(+) patients and observed the impact of this intervention upon the incidence of allograft thrombosis. We compared demographic data and incidence of allograft thrombosis in an historic control (346 patients transplanted between June 31, 1992, and March 5, 1996) not tested for HCS and a study cohort (502 patients transplanted between March 6, 1996, and June 31, 1999) prospectively screened for HRF. HRF(+) patients who were HCS(+) in the study cohort received i.v. heparin immediately after transplant and p.o. warfarin as outpatients. RESULTS: Demographic characteristics previously implicated in allograft thrombosis were equivalently distributed in both cohorts with the exceptions that more living-donor transplants (33.1% vs. 15.3%) were performed in study cohort, CIT>24 hr occurred in more control patients (37.3% vs. 22.1%) and more study patients (16.7% vs. 0%) received tacrolimus. Hypercoagulable states were found upon reevaluating five of seven controls (71.4%), who lost prior allografts to thrombosis. Hypercoagulable states were prospectively detected in 10 study patients with hypercoagulability risk factors. Most (9 of 10) study patients receiving anticoagulation have achieved long-term allograft function. Study group allograft thrombosis incidence was reduced (1.59% vs. 4.05%). Hypercoagulable states were demonstrated in most episodes of allograft thrombosis. Control patients who lost prior allografts to thrombosis were anticoagulated after retransplantation and 100% achieved long-term allograft function. CONCLUSIONS: Long-term allograft function has been achieved in 90% of study patients when prophylactically anticoagulating study patients with hypercoagulable states. A 2.6-fold reduction in the expected incidence of allograft thrombosis was observed in anticoagulated patients with hypercoagulable states.

Adult↗
PubMed2001

The omega-loop region of the human prothrombin gamma-carboxyglutamic acid domain penetrates anionic phospholipid membranes.

The hydrophobic omega-loop within the prothrombin gamma-carboxyglutamic acid-rich (Gla) domain is important in membrane binding. The role of this region in membrane binding was investigated using a synthetic peptide, PT-(1-46)F4W, which includes the N-terminal 46 residues of human prothrombin with Phe-4 replaced by Trp providing a fluorescent probe. PT-(1-46)F4W and PT-(1-46) bind calcium ions and phospholipid membranes, and inhibit the prothrombinase complex. PT-(1-46)F4W, but not PT-(1-46), exhibits a blue shift (5 nm) and red-edge excitation shift (28 nm) in the presence of phosphatidylserine (PS)-containing vesicles, suggesting Trp-4 is located within the motionally restricted membrane interfacial region. PS-containing vesicles protect PT-(1-46)F4W, but not PT-(1-46), fluorescence from potassium iodide-induced quenching. Stern-Volmer analysis of the quenching of PT-(1-46)F4W in the presence and absence of 80% phosphatidylcholine/20% PS vesicles suggested that Trp-4 is positioned within the membrane and protected from aqueous quenching agents whereas Trp-41 remains solvent-accessible in the presence of PS-containing vesicles. Fluorescence quenching of membrane-bound PT-(1-46)F4W is optimal with 7- and 10-doxyl-labeled lipids, indicating that Trp-4 is inserted 5 to 7 A into the bilayer. This report demonstrates that the omega-loop region of prothrombin specifically interacts with PS-containing membranes within the interfacial membrane region.

1-Carboxyglutamic Acid↗
PubMed2001

Angiotensin II type 1 receptor regulation and differential trophic effects on rat cardiac myofibroblasts after acute myocardial infarction.

Fibroblast growth in the scar and surviving tissue is a key element of the remodeling post myocardial infarction. The regulation of fibroblast growth after acute myocardial infarction remains to be determined. Recently, Angiotensin II has been demonstrated to be a mitogen for neonatal cardiac fibroblasts. In this study adult rat cardiac fibroblasts were isolated from different regions of the infarcted rat heart and Angiotensin II effects examined. Adult Wistar-rats were sham operated or left coronary artery ligated. After 4 days, hearts were removed and fibroblasts from sham operated, infarct- and non-infarct regions of the left ventricle isolated. Radioligand binding studies were performed and cell number, cell area, total protein, and AT(1) receptor mRNA after stimulation determined. Radioligand binding studies demonstrated that myofibroblasts expressed a single class of high affinity Angiotensin II AT(1) receptors. Myofibroblasts from the infarct area revealed a lower maximal binding capacity, compared to sham operated myocardium. Conversely, myofibroblasts from the non-infarct area had a higher expression of Angiotensin II AT(1) receptor mRNA compared to sham operated myofibroblasts. Angiotensin II (1 microM, 48 h) increased cell-number in sham operated and non-infarct, but not in infarct myofibroblasts. Angiotensin II elevated total protein in sham operated, non-infarct, and infarct myofibroblasts. In addition, Angiotensin II increased cell area in sham operated and infarct myofibroblasts. These data demonstrate that Angiotensin II acted as a mitogen in sham operated and non-infarct myofibroblasts and stimulated hypertrophy in infarct myofibroblasts. These regional different effects of Angiotensin II might participate in the remodeling post myocardial infarction.

Angiotensin II↗
PubMed2001

Nosocomial bloodstream infections in patients with implantable left ventricular assist devices.

BACKGROUND: Implantable left ventricular assist devices (LVAD) are used as a bridge to transplantation but are associated with a high risk of infection including nosocomial bloodstream infections (BSI). METHODS: We retrospectively reviewed the medical records of all patients with implantable LVAD at the Cleveland Clinic with 72 hours or longer of LVAD support from January 1992 through June 2000, to determine the attack rate, incidence, and impact of nosocomial BSI in patients with LVAD. A nosocomial BSI was defined using Centers for Disease Control and Prevention definition. An LVAD-related BSI was defined as one where the same pathogen is cultured from the device and the blood with no other obvious source. Two hundred fourteen patients were included in the study (17,831 LVAD-days). RESULTS: One hundred forty BSI were identified in 104 patients for an attack rate of 49% and incidence of 7.9 BSI per 1000 LVAD-days. Thirty-eight percent of the BSI were LVAD associated. The most common pathogens causing BSI were coagulase-negative staphylococci (n = 33), Staphylococcus aureus, and Candida spp. (19 each), and Pseudomonas aeruginosa (16 each). A Cox proportional hazard model found BSI in patients with LVAD to be significantly associated with death (hazard ratio = 4.02, p < 0.001). Fungemia had the highest hazard ratio (10.9), followed by gram-negative bacteremia (5.1), and gram-positive bacteremia (2.2). CONCLUSIONS: Patients with implantable LVAD have a high incidence of BSI, which are associated with a significantly increased mortality. Strategies for prevention of infection in LVAD recipients should focus on the drive line exit site until technical advances can achieve a totally implantable device.

Bacteremia↗
PubMed2001

Molecular characterization and expression study of a histidine auxotrophic mutant (his1-) of Nicotiana plumbaginifolia.

The histidine auxotroph mutant his 1(-) isolated from Nicotiana plumbaginifolia haploid protoplasts was first characterized to be deficient for the enzyme histidinol phosphate aminotransferase that is responsible for one of the last steps of histidine biosynthesis. Expression of the mutated gene at the RNA level was assessed by northern analysis of various tissues. Transcriptional activity was unimpaired by the mutation and, in contrast, a higher level of expression was obtained when compared to the wild-type. The cDNA sequence encoding the mutated gene was isolated by RT-PCR and compared to the wild-type gene. A single point mutation corresponding to the substitution of a G nucleotide by A was identified at position 1212 starting from the translation site. The alignment of the deduced amino acid sequences from the mutated and wild-type gene showed that this mutation resulted in the substitution of an Arg by a His residue at position 381. This Arg residue is a conserved amino acid for histidinol phosphate aminotransferase of many species. These results indicate that the identified mutation results in an altered histidinol phosphate aminotransferase enzyme that is unable to convert the substrate imidazole acetol phosphate to histidinol phosphate and thereby leads to the blockage of histidine biosynthesis. Possible consequences of this blockage on the expression of other amino acid biosynthesis genes were evaluated by analysing the expression of the dhdps gene encoding dihydrodipicolinate synthase, the first key enzyme of the lysine pathway.

Amino Acid Sequence↗
PubMed2001

11C-methionine PET imaging of leptomeningeal metastases from primary breast cancer--a case report.

Leptomeningeal metastases (LM) is often an elusive disease frequently diagnosed at an advanced clinical stage. Early diagnosis may allow for prompt initiation of treatment with minimal tumor burden and maximal chance of survival, especially in solid tumors such as breast cancer. Although the method of choice for imaging LM currently is by gadolinium enhanced magnetic resonance imaging (MRI), the technique has a high sensitivity but low specificity. We report the first case of Carbon 11-labelled methionine (Cmet) positron emission tomography (PET) imaging of leptomeningeal metastases in a patient with primary breast cancer. This patient presented with clinical features suggestive of LM, but had inconclusive cerebrospinal fluid (CSF) findings. Although, the contrast enhanced MRI revealed calvarial and meningeal lesions, it is known that meningeal enhancement on MRI does not always indicate metastases. In this clinical dilemma the strong methionine uptake on PET helped steer the diagnosis in favor of cancerous infiltration even before the CSF cytology became positive for malignancy.

Breast Neoplasms↗