Chronic Q fever endocarditis.

Eight patients with chronic Q fever endocarditis were treated with tetracycline for up to 40 months. In addition, five of these patients received co-trimoxazole. Six patients had prosthetic valves. Two patients who had Q fever endocarditis on their native valves required valve replacement because of haemodynamic difficulties: in only one did the Q fever endocarditis contribute to the haemodynamic difficulty. One patient died. It is suggested that medical treatment is continued until clinically and haematologically there is no evidence of endocarditis and the Q fever phase 1 antibody titre is less than 200. No recurrence of Q fever endocarditis has been detected in three of our patients who have now stopped treatment.     

Noninvasive detection of multivessel disease after myocardial infarction by exercise radionuclide ventriculography

The ability of exercise radionuclide ventriculography to detect multivessel coronary artery disease in patients who survived a single myocardial infarction was assessed. Seventy-four patients who had had myocardial infarction at least 8 weeks earlier underwent cardiac catheterization and exercise radionuclide ventriculography. Thirty-eight patients had had an inferior infarction: 25 with multivessel disease and 13 with single vessel disease of the right coronary artery. Thirty-six patients had had an anterior infarction: 26 with multivessel disease and 10 with single vessel disease of the left anterior descending coronary artery.

Among patients with anterior infarction there was no significant difference between patients with single vessel disease and patients with multivessel disease with regard to resting ejection fraction, exercise ejection fraction, and the mean change from rest to exercise. Patients with single vessel disease had a decrease in ejection fraction from rest to exercise of 2.2 ± 2.7% units (mean) ± standard error [SE]), compared with a decrease of 5.4 ±1.3% units in those with multivessel disease (p = not significant [NS]). Seventeen of 26 (65%) patients with multivessel disease and 6 of 10 (60%) with single vessel disease had a decrease in ejection fraction of at least 5 percentage units (p = NS).

In patients with inferior infarction there was no difference in the mean resting ejection fraction in those with single vessel disease (53 ± 2%) compared with those with multivessel disease (50 ±2%); however, the mean exercise ejection fraction in patients with single vessel disease (57 ± 3%) was significantly higher (p < 0.005) than that in patients with multivessel disease (45 ± 2%). Sixteen of the 25 patients with multivessel disease (64%) but only 1 patient with single vessel disease (7.7%) had a decrease in ejection fraction of at least 5 percentage units (p < 0.001).

A new wall motion abnormality developed in 8 patients with anterior infarction and 11 with inferior infarction with multivessel disease and none with single vessel disease. The sensitivity and specificity in predicting multivessel disease using the criteria of the development of a new wall motion abnormality or a decrease in ejection fraction with exercise of at least 5 percentage units were 80 and 92% for the patients with inferior infarction, but only 69 and 40% for the patients with anterior infarction.

These results suggest that exercise radionuclide angiography can be used to discriminate between single and multivessel disease after inferior myocardial infarction. For patients with anterior infarction, only a new abnormality in wall motion accurately predicts multivessel disease, but this occurred in only one third of such patients.     

Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses.

BACKGROUND: Cardiac resynchronization therapy (CRT) for congestive heart failure patients with delayed left ventricular (LV) conduction is clinically beneficial in approximately 70% of patients. Unresolved issues include patient selection, lead placement, and efficacy of LV pacing alone. Being an electrical approach, detailed electrical information during CRT is critical to resolving these issues. However, electrical data from patients have been limited because of the requirement for invasive mapping. OBJECTIVES: The purpose of this study was to provide observations and insights on the variable electrophysiologic responses of the heart to CRT using electrocardiographic imaging (ECGI). METHODS: ECGI is a novel modality for noninvasive epicardial mapping. ECGI was conducted in eight patients undergoing CRT during native rhythm and various pacing modes. RESULTS: In native rhythm (six patients), ventricular activation was heterogeneous, with latest activation in the lateral LV base in three patients and in the anterolateral, midlateral, or inferior LV in the remainder of patients. Anterior LV was susceptible to block and slow conduction. Right ventricular pacing improved electrical synchrony in two of six patients. LV pacing in three of four patients involved fusion with intrinsic excitation resulting in electrical resynchronization similar to biventricular pacing. Although generally electrical synchrony improved significantly with biventricular pacing, it was not always accompanied by clinical benefit. CONCLUSION: Results suggest that (1) when accompanied by fusion, LV pacing alone can be as effective as biventricular pacing for electrical resynchronization; (2) right ventricular pacing is not effective for resynchronization; and (3) efficacy of CRT depends strongly on the patient-specific electrophysiologic substrate.     

Obstetric anal sphincter injury: prospective evaluation of incidence

PURPOSE: An obstetrically damaged anal sphincter is the principal cause of the development of fecal incontinence in otherwise healthy females. Reports suggest that such damage complicates as many as 35 percent of primiparous vaginal deliveries, with 13 percent of first-time mothers becoming symptomatic. In maternity units delivering 3,000 patients annually, it would follow that 390 symptomatic patients would develop new symptoms each year. This incidence of dysfunction does not reflect current clinical practice. We have investigated this discrepancy to establish the actual incidence of anal sphincter trauma associated with childbirth. METHODS: During a six-week period, 159 females (105 primiparous and 54 para-I) were prospectively assessed postnatally using a standardized symptom questionnaire, endoanal ultrasound, and anal manometry. This group constituted 84 percent of all eligible deliveries occurring in the unit during the study period. RESULTS: One patient developed fecal urgency after this delivery; there were no reports of fecal incontinence. Anal sphincter injuries were identified ultrasonically in 6.8 percent of primiparous patients, 12.2 percent of para-I patients having vaginal deliveries, and 83 percent of patients having forceps deliveries overall. Manometric data provided confirmatory evidence, with significantly reduced maximum squeeze pressures in patients with a disrupted anal sphincter (P<0.0005). CONCLUSIONS: A symptom questionnaire is inadequate to identify anal sphincter injuries. The incidence of sphincter injury in relation to vaginal delivery has been overestimated in previous published work. This study demonstrates that the true incidence is 8.7 percent overall and that symptoms of sphincter dysfunction are uncommon this is in keeping with current clinical practice.     

Bioactive nano‐fibrous scaffold for vascularized craniofacial bone regeneration

There has been a growing demand for bone grafts for correction of bone defects in complicated fractures or tumours in the craniofacial region. Soft flexible membrane like material that could be inserted into defect by less invasive approaches; promote osteoconductivity and act as a barrier to soft tissue in growth while promoting bone formation is an attractive option for this region. Electrospinning has recently emerged as one of the most promising techniques for fabrication of extracellular matrix such as nano‐fibrous scaffolds that can serve as a template for bone formation. To overcome the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA)‐poly (ε) caprolactone (PCL)‐Hydroxyapatite based bioceramic (HAB), namely, PVA‐PCL‐HAB. The scaffold prepared by dual electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic PCL by combination with a hydrophilic PVA and the HAB can contribute to enhance osteoconductivity. We characterized the physicochemical and biocompatibility properties of the new scaffold material. Our results indicate PVA‐PCL‐HAB scaffolds support attachment and growth of stromal stem cells; [human bone marrow skeletal (mesenchymal) stem cells and dental pulp stem cells]. In addition, the scaffold supported in vitro osteogenic differentiation and in vivo vascularized bone formation. Thus, PVA‐PCL‐HAB scaffold is a suitable potential material for therapeutic bone regeneration in dentistry and orthopaedics.     

Dealing with the complex drug–drug interactions: Towards mechanistic models

Unmanageable severe adverse events caused by drug‐drug interactions (DDIs), leading to market withdrawals or restrictions in the clinical usage, are increasingly avoided with the improvement in our ability to predict such DDIs quantitatively early in drug development. However, significant challenges arise in the evaluation and/or prediction of complex DDIs caused by inhibitor drugs and/or metabolites that affect not one but multiple pathways of drug clearance. This review summarizes the discussion topics at the 2013 AAPS symposium on “Dealing with the complex drug‐drug interactions: towards mechanistic models”. Physiologically based pharmacokinetic (PBPK) models, in combination with the established in vitro‐to‐in vivo extrapolations of intestinal and hepatic disposition, have been successfully applied to predict clinical pharmacokinetics and DDIs, especially for drugs with CYP‐mediated metabolism, and to explain transporter‐mediated and complex DDIs. Although continuous developments are being made towards improved mechanistic prediction of the transporter‐enzyme interplay in the hepatic and intestinal disposition and characterizing the metabolites contribution to DDIs, the prediction of DDIs involving them remains difficult. Regulatory guidelines also recommended use of PBPK modeling for the quantitative prediction and evaluation of DDIs involving multiple perpetrators and metabolites. Such mechanistic modeling approaches culminate to the consensus that modeling is helpful in predicting DDIs or quantitatively rationalizing the clinical findings in complex situations. Furthermore, they provide basis for the prediction and/or understanding the pharmacokinetics in populations like patients with renal impairment, pediatrics, or various ethnic groups where the conduct of clinical studies might not be feasible in early drug development stages and yet some guidance on management of dosage is necessary. Copyright © 2014 John Wiley & Sons, Ltd.     

Common variable immunodeficiency in an adult

Primary immunodeficiency syndromes are rarely diagnosed among adults. In this report, we describe a young male who had common variable immunodeficiency. He was treated with intravenous immunoglobulin and, on follow up, has been free of opportunistic infections.