Determination of Total Biotin by Liquid Chromatography Coupled with Immunoaffinity Column Cleanup Extraction: Multilaboratory Testing, Final Action 2016.02.

Single- and multilaboratory testing data have provided systematic scientific evidence that a simple, selective, accurate, and precise method can be used as a potential candidate reference method for dispute resolution in determining total biotin in all forms of infant, adult, and/or pediatric formula. Using LC coupled with immunoaffinity column cleanup extraction, the method fully meets the intended purpose and applicability statement in AOAC Standard Method Performance Requirement 2014.005. The method was applied to a cross-section of infant formula and adult nutritional matrixes, and acceptable precision and accuracy were established. The analytical platform is inexpensive, and the method can be used in almost any laboratory worldwide with basic facilities. The immunoaffinity column cleanup extraction is the key step to successful analysis.

EXEL-8232, a small-molecule JAK2 inhibitor, effectively treats thrombocytosis and extramedullary hematopoiesis in a murine model of myeloproliferative neoplasm induced by MPLW515L.

About 10% of patients with essential thrombocythemia (ET) or myelofibrosis (MF) that lack mutations in JAK2 harbor an activating mutation in the thrombopoietin receptor, MPLW515L. Distinct from the JAK2V617F retroviral transplant model, the MPLW515L model recapitulates many features of ET and MF, including severe fibrosis and thrombocytosis. We have tested EXEL-8232, an experimental potent JAK2 inhibitor, for efficacy in suppression of thrombocytosis in vivo and for its ability to attenuate MPLW515L myeloproliferative disease. EXEL-8232 was administered for 28 days q12 h by oral gavage at doses of 30 or 100 mg/kg, prospectively. Animals treated with EXEL-8232 at 100 mg/kg had normalized high platelet counts, eliminated extramedullary hematopoiesis in the spleen and eliminated bone marrow fibrosis, whereas the wild-type controls did not develop thrombocytopenia. Consistent with a clinical response in this model, we validated surrogate end points for response to treatment, including a reduction of endogenous colony growth and signaling inhibition in immature erythroid and myeloid primary cells both in vitro and upon treatment in vivo. We conclude that EXEL-8232 has efficacy in treatment of thrombocytosis in vivo in a murine model of ET and MF, and may be of therapeutic benefit for patients with MPL-mutant MPN.

Urgent coronary bypass surgery for failed percutaneous coronary intervention in the stent era: Is backup still necessary?

BACKGROUND: Current practice guidelines for performance of percutaneous coronary intervention (PCI) in the United States mandate availability of on-site surgical backup. With the decreasing frequency of urgent coronary bypass surgery (UCABG) with newer technologies, it is unclear whether such backup continues to be necessary. METHODS: A database of 5655 consecutive patients undergoing PCI at a single center between August 1, 1992, and December 31, 1997, was analyzed. Outcomes were determined as well as clinical, lesion, and procedural characteristics of patients during 4 time periods preceding and during use of coronary stenting. RESULTS: Frequency of UCABG for failed PCI decreased from 2.2% to 0.6% in the most recent time period (P <.01) with no change in incidence of in-hospital death or myocardial infarction. Incidence of stenting progressively increased to 72% in the latest period. Patients requiring UCABG had a higher prevalence of acute coronary syndromes (95%) and type B lesions (79%), but these characteristics were also common in patients who did not undergo UCABG. Although coronary stents were available during the last 3 periods studied, only 30% of UCABG patients had lesions or complications amenable to stenting, and stenting attempts in these patients were all unsuccessful. Despite stenting and use of perfusion balloons and intra-aortic balloon pumps, only 40% of patients having UCABG were stable and pain free on transfer to the operating room. CONCLUSIONS: Although use of UCABG for a failed PCI is currently very low, there are no satisfactory predictors, patients requiring UCABG are frequently clinically unstable, and availability of stenting does not reliably eliminate the need for UCABG or result in a decrease in mortality. This small group of patients continues to require readily available surgical standby.

Stenting for in-stent restenosis: A long-term clinical follow-up.

We studied the feasibility, safety, and short- and long-term outcomes of treating coronary in-stent restenosis with primary restenting. Thirty-one patients (32 lesions) were treated. Eleven patients had adjunctive rotational atherectomy. Clinical follow-up was obtained in all 31 patients at a mean of 9.1 +/- 5.5 months by direct phone contact with the patients, medical records, and subsequent hospitalization for recurrent symptoms and/or revascularization. There were no cardiac deaths or myocardial infarctions. In native vessels (26 patients), repeat target lesion revascularization was required in eight patients (31%); two other patients (7.7%) had angina and were treated medically. All vein graft lesions had recurrent restenosis. Significant predictors of recurrent clinical events were lesions in vein grafts, multivessel disease, and use of higher poststent deployment inflation pressures. Primary restenting for in-stent restenosis in native vessels is a safe approach with good short-term outcome. Recurrent restenosis remains a problem, as it does with other devices, particularly in vein graft lesions and in patients with multivessel disease. Restenting for in-stent restenosis should probably be used selectively. Cathet. Cardiovasc. Intervent. 48:143-148, 1999.

Frey syndrome: treatment with temporoparietal fascia flap interposition.

There is a 10% to 48% reported incidence of clinically significant gustatory sweating after parotid surgery or injury. Various medical and surgical treatments have been used in the attempt to treat this socially embarrassing condition. These treatments are not always effective and often have unwanted risks and adverse effects. They also do not address the post-parotidectomy defect. Prevention of Frey syndrome and correction of the postoperative contour deformity after parotidectomy have recently been achieved by interposition of temporoparietal fascia flap between the parotid gland and the cheek skin flap at the time of parotidectomy. This article presents the first report (to our knowledge) of an established case of Frey syndrome being treated with temporoparietal fascia flap interposition.

Detecting and differentiating white from red coronary thrombus by angiography in angina pectoris and in acute myocardial infarction.

To determine the ability to detect thrombus by angiography, angioscopy was performed before angiography in patients undergoing interventional procedures and the data collected in a blinded fashion. These data demonstrated that the sensitivity of angiography to detect white thrombus was 50% and the specificity was 95%, whereas the sensitivity and specificity to detect red thrombus was 100%, respectively; the positive and negative predictive value of detecting thrombus in general was 89% and 83%, respectively.

Angioscopy of culprit coronary lesions in unstable angina pectoris and correlation of clinical presentation with plaque morphology.

This study demonstrates that plaque disruption and thrombus are absent in a considerable number of patients with unstable angina and that culprit lesion morphologies as assessed by angioscopy may differ among the various clinical subsets of patients. Although plaque disruption and thrombus undoubtedly play an important role in the pathogenesis of unstable angina, alternative mechanisms may be responsible for ischemia in some patients.

Angioscopic assessment of coronary lesions underlying thrombus.

This study examines the characteristics of coronary lesions in which thrombus is found as assessed by angioscopy before percutaneous transluminal coronary angioplasty in patients with various coronary syndromes. Our findings demonstrate that the plaque underlying intracoronary thrombus is usually yellow and/or disrupted, and support in vitro observations that lipid-rich plaques are highly thrombogenic and that disruption of these plaques is associated with in situ thrombosis.

Significance of tumor thickness in soft palate carcinoma.

Tumor thickness is an important prognostic factor in tumors outside of the upper aerodigestive tract, such as cutaneous melanoma, colorectal carcinoma, and cervical carcinoma. Some studies have also suggested that tumor thickness may have similar prognostic value in the upper aerodigestive tract. This study examined the relationship between tumor thickness (measured with an ocular micrometer) and nodal disease and that between tumor thickness and survival in 44 patients with soft palate epidermoid carcinoma. There was a significant correlation between tumor thickness and nodal disease. None of the 24 lesions less than or equal to 2.86 mm had cervical adenopathy. All of the 15 lesions greater than or equal to 3.12 mm had palpable adenopathy. Tumor thickness correlated more directly with nodal disease than did T stage. Thicker lesions were associated with poorer survival. Tumor thickness is an important parameter in the head and neck and deserves further study.

Incidence and characteristics of preventable iatrogenic cardiac arrests.

We studied the contribution of iatrogenic illness to cardiac arrest among patients hospitalized in 1981 in a university teaching hospital. During this 1-year period, 28 (14%) of 203 arrests in which resuscitation was attempted followed an iatrogenic complication. Seventeen (61%) of the 28 patients died. The demographic characteristics of patients with iatrogenic arrest did not differ strikingly from those of other patients who arrested. However, patients with iatrogenic arrest were less likely to be in cardiogenic shock or to have suffered an acute myocardial infarction prior to arrest. They were more likely to survive to discharge from the hospital and to be taking digoxin or antiarrhythmic medication prior to arrest. Among the 28 cases of iatrogenic cardiac arrest, 18 (9% of all arrests) might have been prevented by stricter attention to the patient's history, findings on physical examination, and laboratory data. The most common causes of potentially preventable arrest were medication errors and toxic effects (44%) as well as suboptimal response by physicians to clinical signs and symptoms (28%), most frequently dyspnea and tachypnea. Rapid, appropriate response to abnormal drug levels, to electrocardiographic signs of adverse drug effects, and to signs and symptoms of congestive heart failure or toxic effects from digoxin might decrease the incidence of cardiac arrest among hospitalized patients.

Pulsed Doppler evaluation of atrial mechanical function after electrical cardioversion of atrial fibrillation.

Full recovery of atrial mechanical activity may not occur immediately after successful electrical cardioversion of atrial fibrillation to sinus rhythm. To examine the time course of recovery of left atrial mechanical function, serial two-dimensional, M-mode and transmitral pulsed Doppler echocardiographic studies were performed in 21 patients after elective direct current cardioversion of atrial fibrillation of 3 weeks' to 24 months' duration (mean 5 months). Over 3 months of follow-up, there were significant increases in both peak A wave velocity (p less than 0.005) and percent atrial contribution to total left ventricular filling (p less than 0.005). Compared with values in a normal control population, peak A wave velocity and percent atrial contribution to total left ventricular filling did not return to normal until 3 weeks after cardioversion in patients who remained in sinus rhythm. Left atrial dimension also decreased over the follow-up period (p less than 0.05) in patients with persistent sinus rhythm. These results may have important implications in guiding the appropriate duration of anticoagulant therapy after cardioversion, and in clinically assessing the hemodynamic benefit of restoring sinus rhythm in an individual patient.

Use of percutaneous transluminal coronary angioplasty and bypass surgery despite improved medical therapy for unstable angina pectoris.

To evaluate current strategies for the management of unstable angina, 104 consecutive patients admitted to the coronary care unit with unstable angina during a 6-month period were followed prospectively. Although 58 patients had symptomatic relief with the initiation of intensive medical therapy, 46 (44%) continued to have episodes of angina despite maximal tolerated triple-drug antianginal therapy as well as aspirin or heparin, or both. In-hospital mortality for the 104 patients was 4%. The incidence of myocardial infarction was 8%, and differed (p less than 0.01) for the medically responsive group (3%) vs the medically refractory group (13%). Based on clinical status and coronary anatomy, patients were referred for either bypass surgery (46%), coronary angioplasty (41%) or continued medical therapy (13%). Choice of therapy varied according to the extent of coronary disease, with coronary angioplasty attempted in 72% of patients with 1-vessel disease, 44% of patients with 2-vessel disease and 7% of patients with 3-vessel disease. Angioplasty was performed with an initial success rate of 88%, and compared favorably with bypass surgery in terms of in-hospital mortality (0 vs 11%), late mortality (2.8 vs 7.7%), freedom from angina (62 vs 69%) and subsequent employment (44 vs 27%) at 18 months follow-up. The favorable results of angioplasty in this prospective observational study suggest that additional randomized trials should be conducted in this important patient group.

Doppler echocardiography in cardiac tamponade: exaggerated respiratory variation in transvalvular blood flow velocity integrals.

Pulsed Doppler echocardiography has been used previously to demonstrate marked changes in transvalvular blood flow velocities during cardiac tamponade in laboratory animals and a small number of patients. To further assess the respiratory changes in transvalvular blood flow during tamponade, pulsed Doppler tracings of flow velocity profiles across all four cardiac valves were recorded during inspiration and expiration in 13 patients during cardiac tamponade, in 6 of the 13 patients after relief of tamponade by pericardiocentesis and in 8 normal control subjects. Flow velocity integrals were calculated for each valve during inspiration and expiration. In the setting of cardiac tamponade, inspiration caused an 85 +/- 46% increase in the flow velocity integral across the pulmonary valve, an 81 +/- 34% increase across the tricuspid valve, a 33 +/- 13% decrease across the aortic valve and a 35 +/- 8% decrease across the mitral valve. These phasic respiratory changes were markedly reduced after relief of tamponade (p less than 0.05 compared with tamponade) and were observed to only a minimal extent in the normal individuals (p less than 0.01 compared with tamponade). The exaggerated respiratory variations in transvalvular flow velocity integrals suggest that Doppler evaluation may be a valuable tool in the diagnosis of cardiac tamponade. Transmitral Doppler indexes of left ventricular filling during cardiac tamponade revealed that inspiration caused a shift to increased filling during late diastole, with a greater contribution of atrial systole to total left ventricular filling. These Doppler indexes did not vary significantly with respiration in the group studied after relief of tamponade or in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Partial dehiscence of a porcine prosthesis in association with aortic annular separation producing a false aneurysm of the ascending aorta.

A 44-year-old man developed intermittent left bundle branch block followed by complete heart block 18 months after aortic valve replacement, and aortic insufficiency and hemolytic anemia 5 years postoperatively. These abnormalities were associated with operative findings (7 years after aortic valve replacement) of total disruption of the aorta at the level of the aortic annulus. Echocardiographic findings of an enlarged and unusually shaped "aortic root" and angiographic findings of abnormally high origin of the coronary arteries relative to the valve ring, which should have suggested the diagnosis 2 years prior to successful surgical repair, are presented.