Transvenous biventricular pacing in a child after congenital heart surgery as an alternative therapy for congestive heart failure

Transvenous Biventricular Pacing in Children. Cardiac resynchronization therapy improves short-term and long-term hemodynamics in adult patients with congestive heart failure and left bundle branch block. We describe the feasibility of transvenous biventricular pacemaker implantation in a 6-year-old child with heart failure and wide QRS complex after congenital heart surgery. Myocardial tissue Doppler imaging was used to demonstrate intraventricular dyssynchrony and resynchronization after cardiac resynchronization therapy. During 1-year follow-up, symptomatology and hemodynamic parameters improved.     

A new sign of inappropriate lower back pain

The treatment of lower back pain constitutes a major problem for orthopaedic surgeons. Identifying the patients who have a non-organic component to their lower back pain is often difficult. Waddell et al. (Waddell G, McCulloch HA, Kummel E, Venner RM. Non-organic physical signs in low-back pain. Spine 1980; 5: 117-25) devised a set of five physical signs to assist in determining this. These signs are time consuming and can be difficult to interpret. We have developed a sign that is simple, quick and easy to perform. In a set of 94 patients, we have compared our sign with Waddell's signs. Our sign has a highly significant correlation with Waddell's signs (chi2 = 55.093, P < 0.001), and thus we would suggest it as an accurate alternative to Waddell's signs.     

CTGF expression in mesangial cells: involvement of SMADs,MAP kinase,and PKC

BACKGROUND: The induction of excess matrix in renal fibrosis seems to be mediated, at least in part, by the transforming growth factor-beta (TGF-beta)-mediated induction of connective tissue growth factor (CTGF) in mesangial cells. METHODS: By examining CTGF protein and mRNA expression and promoter activity in the presence or absence of TGF-beta or inhibitors, the signaling pathways controlling basal and TGF-beta-induced CTGF expression in mesangial cells were investigated. RESULTS: TGF-beta enhances CTGF mRNA and protein expression in mesangial cells. Mutation of a consensus SMAD binding element in the CTGF promoter completely abolished TGF-beta-induced CTGF expression and reduced basal CTGF expression. The previously identified basal control element-1 (BCE-1) site, but not Sp1 contributes to basal CTGF promoter activity. Ras/MEK/ERK, protein kinase C (PKC) and tyrosine kinase activity also contribute to basal and TGF-beta-induced CTGF promoter activity in cultured mesangial cells. CONCLUSIONS: The TGF-beta-induction of CTGF in mesangial cells requires SMADs and PKC/ras/MEK/ERK pathways. SMADs are involved in basal CTGF expression, which presumably reflects the fact that mesangial cells express TGF-beta endogenously. TGF-beta also induces CTGF through ras/MEK/ERK. Inhibiting ras/MEK/ERK seems not to reduce phosphorylation (that is, activation) of SMADs, suggesting that SMADs, although necessary, are insufficient for the TGF-beta-stimulation of the CTGF promoter through ras/MEK/ERK. Thus, maximal TGF-beta induction of CTGF requires synergy between SMAD and ras/MEK/ERK signaling.     

Medicare spending for injured elders: are there opportunities for savings?

Claims for injury care provided to aged fee-for-service (FFS) beneficiaries cost Medicare more than $8 billion in 1999, almost 6 percent of Medicare claims spending for elders. More than one-fifth of aged FFS beneficiaries had an injury that resulted in a claim. Fractures, which were experienced by one in seventeen aged beneficiaries, were responsible far 67 percent of total injury claims expenses. Medicare could realize substantial savings if these injuries could be prevented; the program should consider underwriting effective prevention activities.     

Validation of FLEXICULT SSI-Urinary Kit for use in the primary health care setting

The efficacy of the FLEXICULT SSI-Urinary Kit for point-of-care diagnosis and susceptibility testing of urinary tract pathogens was evaluated. The kit, which was exclusively developed for urine culture in the primary health care setting, is designed as an ordinary Petri dish divided into 6 compartments: I large one for quantitative analysis and 5 smaller ones for susceptibility testing. The agar in each small compartment contains 1 of 5 antimicrobials (trimethoprim, sulfamethoxazole, ampicillin, nitrofurantoin and mecillinam) at a concentration adjusted to the breakpoint, and growth in these compartments indicates resistance. The kit was tested in-house with 116 urinary tract pathogens and by 19 general practitioners in a field trial with 121 diagnostic urine specimens. The kit was flooded with the urine specimens for a couple of seconds, incubated overnight and read the following day. Quantitative readings were evaluated by comparing with standardized inoculi and the susceptibility tests were compared with the MIC value of the strain for each of the 5 antimicrobials. In the field trial, the quantitation had an overall error rate of 4% and correctly determined susceptibility in 93% of the tested bacteria. Although identification of the isolates is not a feature of this kit, it is suitable for point-of-care diagnosis and for susceptibility testing of uncomplicated urinary tract infections in the primary health care setting.     

MTHFR 677C-->T polymorphism and risk of coronary heart disease: a meta-analysis

Context  In observational studies, individuals with elevated levels of plasma homocysteine tend to have moderately increased risk of coronary heart disease (CHD). The MTHFR 677CT polymorphism is a genetic alteration in an enzyme involved in folate metabolism that causes elevated homocysteine concentrations, but its relevance to risk of CHD is uncertain. Objective  To assess the relation of MTHFR 677CT polymorphism and risk of CHD by conducting a meta-analysis of individual participant data from all case-control observational studies with data on this polymorphism and risk of CHD. Data Sources  Studies were identified by searches of the electronic literature (MEDLINE and Current Contents) for relevant reports published before June 2001 (using the search terms MTHFR and coronary heart disease), hand searches of reference lists of original studies and review articles (including meta-analyses) on this topic, and contact with investigators in the field. Study Selection  Studies were included if they had data on the MTHFR 677CT genotype and a case-control design (retrospective or nested case-control) and involved CHD as an end point. Data were obtained from 40 (34 published and 6 unpublished) observational studies involving a total of 11 162 cases and 12 758 controls. Data Extraction  Data were collected on MTHFR 677CT genotype, case-control status, and plasma levels of homocysteine, folate, and other cardiovascular risk factors. Data were checked for consistency with the published article or with information provided by the investigators and converted into a standard format for incorporation into a central database. Combined odds ratios (ORs) for the association between the MTHFR 677CT polymorphism and CHD were assessed by logistic regression. Data Synthesis  Individuals with the MTHFR 677 TT genotype had a 16% (OR, 1.16; 95% confidence interval [CI], 1.05-1.28) higher odds of CHD compared with individuals with the CC genotype. There was significant heterogeneity between the results obtained in European populations (OR, 1.14; 95% CI, 1.01-1.28) compared with North American populations (OR, 0.87; 95% CI, 0.73-1.05), which might largely be explained by interaction between the MTHFR 677CT polymorphism and folate status. Conclusions  Individuals with the MTHFR 677 TT genotype had a significantly higher risk of CHD, particularly in the setting of low folate status. These results support the hypothesis that impaired folate metabolism, resulting in high homocysteine levels, is causally related to increased risk of CHD.      

One-year audit of admissions to the Intensive Care Unit of the Queen Elizabeth Central Hospital,Blantyre

The intensive care unit at Queen Elizabeth Central Hospital (QECH) has 4 beds and offers level 2 care. A retrospective audit of all admissions to the unit during 2002 was carried out. There were a total of 339 admissions giving a bed occupancy rate of 82 %. Surgical patients made up 81 % of admissions. 45% of all admissions were ventilated. Overall mortality was 38%. Ventilated patients had a mortality of 71% compared with 10% for non-ventilated. Data are also presented for mortality within the surgical and paediatric surgical admissions.     

Computer control versus manual control of systemic hypertension during cardiac surgery

BACKGROUND: We recently demonstrated the feasibility of computer controlled infusion of vasoactive drugs for the control of systemic hypertension during cardiac surgery. The objective of the current study was to investigate the effects of computer controlled blood pressures on hemodynamic stability when compared to conventional manual control. METHOD: Systemic artery blood pressures were managed either by computer (80 patients) or by a well-trained anesthesiologist (80 patients). The vasodilator drugs sodium nitroprusside and nitroglycerin were used. Hemodynamic stability was determined from the standard deviation of the mean arterial pressure samples and from the percentages of time that arterial pressure was hypertensive or hypotensive. RESULTS: The average standard deviation of the mean arterial pressure samples was smaller for the computer controlled than for the manually controlled group: 7.5+/-2.2 (mean+/-SD) versus 8.9+/-2.3 mmHg (P<0.0001). The systemic artery pressure was less hypertensive and less hypotensive in the computer controlled than in the manually controlled group: 9.4+/-5.7 versus 13.1+/-6.0% (P<0.0001) and 8.0+/-5.9 versus 11.8+/-7.4% (P<0.0001), respectively. CONCLUSION: We conclude that, compared with manual control, computer control of systemic hypertension significantly improved hemodynamic stability during cardiac surgery.     

Use of E mu-PIM-1 transgenic mice short-term in vivo carcinogenicity testing: lymphoma induction by benzo[a]pyrene, but not by TPA

E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to their low spontaneous tumour incidence and their increased sensitivity towards the lymphomagen ethylnitrosourea these mice may present an interesting model for short-term carcinogenicity testing. Here, we report on the further exploration of this transgenic mouse model with two additional carcinogens known to have, among others, the lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and 12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week (by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1 mice during the observation period of 40 weeks. B[a]P also induced tumours of the forestomach within this observation period, though at a lower incidence and apparently equally effective in wildtype and transgenic mice. TPA, on the other hand, was unable to induce lymphomas (or tumours in any other organ) in either transgenic or wildtype animals within the observation period of 44 weeks, when applied dermally at the maximum tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular analysis showed that B[a]P-induced lymphomas in transgenic mice were of T-cell origin, 80% of which had elevated levels of c-myc expression. None of the lymphomas had increased N-myc expression and mutation analysis of the ras-gene family revealed a K-ras mutation in only one out of eight tumours investigated. Also, none of the lymphomas showed aberrant expression of p53 as determined by immunohistochemistry. It is concluded that the E mu-pim-1 mouse model will not be very suitable for short-term carcinogenicity testing in general: only genotoxic chemicals that have the lymphohaematopoietic system as target for carcinogenesis in wild- type mice, appear to be efficiently identified.