Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due to Bordetella pertussis in a Murine Model

The prevalence of asthma and allergic disease has increased in many countries, and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether acellular pertussis vaccine (Pa) enhanced or prevented B. pertussis-induced exacerbation of allergic asthma. Groups of mice were immunized with Pa, infected with B. pertussis, and/or sensitized to ovalbumin. Immunological, pathological, and physiological changes were measured to assess the impact of immunization on immune deviation and airway function. We demonstrate that immunization did not enhance ovalbumin-specific serum immunoglobulin E production. Histopathological examination revealed that immunization reduced the severity of airway pathology associated with sensitization in the context of infection and decreased bronchial hyperreactivity upon methacholine exposure of infected and sensitized mice. These data demonstrate unequivocally the benefit of Pa immunization to health and justify selection of Pa in mass vaccination protocols. In the absence of infection, the Pa used in this study enhanced the interleukin-10 (IL-10) and IL-13 responses and influenced airway hyperresponsiveness to sensitizing antigen; however, these data do not suggest that Pa contributes to childhood asthma overall. On the contrary, wild-type virulent B. pertussis is still circulating in most countries, and our data suggest that the major influence of Pa is to protect against the powerful exacerbation of asthma-like pathology induced by B. pertussis.     

Impact of automatic orders to discontinue vancomycin therapy on vancomycin use in an antimicrobial stewardship program.

We examined the possible unintended consequences of a 72-hour automatic order to discontinue vancomycin therapy in an antimicrobial stewardship program (ASP). Of 120 patients, 11 had vancomycin therapy discontinued at 72 hours without a call to the ASP, and 7 experienced a treatment interruption of 6-36 hours. All discontinuation of therapy was considered appropriate, and the 7 treatment interruptions did not have clear clinical consequences. Only one-third of patients had ASP stickers that warned of impending discontinuation of vancomycin therapy placed appropriately in the medical record.     

Lipoprotein (a) levels in those with high molecular weight apo (a) isoforms may remain low in a significant proportion of patients with end-stage renal disease.

BACKGROUND: Studies have reported an increase in median Lipoprotein (Lp) (a) in patients with high molecular weight (HMW) apolipoprotein (apo) (a) isoforms and renal impairment. Some studies identify Lp (a) levels as a risk factor for vascular disease in renal failure whilst others have demonstrated an association with apo (a) isoform type and vascular disease. METHODS: A total of 239 patients at end-stage renal failure (ESRF) were studied prior to the initiation of dialysis. Blood was taken for Lp (a) levels and apo (a) isoforms. Clinical vascular disease (CVD) was assessed on the basis of clinical history and Rose questionnaire. The control group for Lp (a) levels consisted of 228 healthy volunteers. RESULTS: Despite a higher median Lp (a) level in those with HMW isoforms, 30% of patients had Lp (a) levels <10 mg/dl. Overall, 49% patients were identified as having CVD. Diabetes, smoking history and Lp (a) levels were significantly associated with CVD in logistic regression analysis, although when patients with low molecular weight (LMW) and HMW isoforms were analysed separately, Lp (a) levels were not significantly associated with CVD in those with LMW isoforms. The rates of CVD in those with HMW isoform and low Lp (a) levels were significantly lower than those with HMW isoforms and elevated Lp (a) levels, 34 vs 57% (P < 0.01). CONCLUSIONS: Although median Lp (a) levels in those patients at ESRF with HMW isoforms are higher than controls, in a third of such patients Lp (a) levels remain relatively low. These patients have lower rates of CVD than those with high levels of Lp (a).     

Hybrid Anterior Cruciate Ligament Reconstruction: Introduction of a New Technique for Anatomic Anterior Cruciate Ligament Reconstruction

Recently, anatomic or double-bundle reconstruction of the anterior cruciate ligament (ACL) has been presented in an effort to more accurately restore the native anatomy. These techniques create 2 tunnels in both the femur and tibia to reproduce the bundles of the ACL. However, the increased number of tunnels, particularly on the femoral side, has raised some concerns among authors and surgeons. We describe a technique to reconstruct the 2 distinct bundles of the ACL by using a single femoral tunnel and 2 tibial tunnels, the “hybrid” ACL reconstruction. The femoral tunnel is drilled through an anteromedial arthroscopy portal, which allows placement in a more anatomic position. Fixation in the femur is achieved with a novel device that separates a soft-tissue graft into 2 independently functioning bundles. Once fixed in the femur, the anteromedial and posterolateral bundles of the graft are passed through respective tunnels at the anatomic footprint on the tibia. These bundles are independently tensioned, which creates a reconconstruction that is similar to the native ACL. The technique presented provides surgeons with an alternative to other double-bundle techniques involving 4 tunnels.     

Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.     

Effect of a blood transfusion protocol and low dose steroid regime on renal transplant survival

The effects of introduction of a low steroid regime and pre-transplant blood transfusion were evaluated. The kidney and patient survival rates for the period before such a policy was adopted were compared with the period after this policy. There has been a highly significant rise in patient survival rates to the present level of 95 per cent at three years. There was a similar rise in three year graft survival rates from less than 40 per cent to 66 per cent.     

Cerebral-blood-flow-velocity measurements in neonates: Technique and interobserver reliability

The interobserver reliability for absolute cerebral-blood-flow-velocity measurements by colour and duplex Doppler sonography was tested in 32 neonates with a mean birth weight of 1489 (SD 644) g, and a gestational age of 29.9 (SD 3.5) weeks. Using standardized technique, two observers recorded on videotape, the Doppler spectrum of the anterior cerebral artery, the intracranial internal carotid artery and the middle cerebral artery. Peak systolic flow, end diastolic flow, mean flow velocity, resistive index and pulsatility index were computed from 3 consecutive waveforms by each observer. The estimates of interobserver reliability using the intraclass correlation coefficient of the examiners varied from 0.95 to 1.00. Therefore, cerebral blood flow velocity can be reliably measured in premature infants.