Growth of textured thin Au coatings on iron oxide nanoparticles with near infrared absorbance.

A homologous series of Au coated iron oxide nanoparticles with hydrodynamic diameters smaller than 60 nm was synthesized with very low Au-to-iron mass ratios, as low as 0.15. The hydrodynamic diameter was determined by dynamic light scattering and the composition by atomic absorption spectroscopy and energy dispersive x-ray spectroscopy. Unusually low Au precursor supersaturation levels were utilized to nucleate and grow Au coatings on iron oxide relative to the formation of pure Au nanoparticles. This approach produced unusually thin coatings by lowering autocatalytic growth of Au on Au, as shown by transmission electron microscopy. Nearly all of the nanoparticles were attracted by a magnet, indicating a minimal number of pure Au particles. The coatings were sufficiently thin to shift the surface plasmon resonance to the near infrared with large extinction coefficients, despite the small particle hydrodynamic diameters observed from dynamic light scattering to be less than 60 nm.

Serial factitious disorder and Munchausen by proxy in pregnancy.

Factitious disorder, including Munchausen syndrome, is seldom documented among pregnant patients but can have powerful consequences. We report on a 44-year-old woman who, over a period of two decades, self-induced labour and delivery in five consecutive pregnancies. She precipitated labour by rupturing her own amniotic sac with a fingernail or cervical manipulation, or misappropriating and self-administering prostaglandin suppositories from the hospital unit on which she worked as a nurse. Preterm deliveries resulted in fetal demise in one case and in neonatal intensive care treatment for two of the offspring. One of the surviving children has cerebral palsy attributable to the mother's factitious illness behaviour, which raises the spectre of Munchausen by proxy maltreatment. The patient sought attention and care through the ruses, which have never been uncovered by her obstetric and gynaecologic caregivers. Indeed, she underwent an unnecessary hysterectomy because of the illusion of heavy menstrual bleeding. Most recently, the patient has been engaging in surreptitious autophlebotomy to force blood transfusions.

Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure?

BACKGROUND: The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established. METHODS AND RESULTS: We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was >16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 24+/-8 mm Hg). The time constant of LV relaxation (average, 51+/-15 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 349+/-140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient. CONCLUSIONS: Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function.

Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations.

Noninvasive monitoring of antiangiogenic therapy was performed by serial power Doppler ultrasound imaging of murine tumors treated with recombinant interleukin 12, the results of which were correlated with assessments of tumor vascularity by microscopy. Growth of established K1735 tumors, but not of IFN-gamma-unresponsive K1735.N23 variants, was suppressed by treatment. Serial Doppler imaging of K1735 tumor vascularity during treatment revealed a progressive change from a diffuse perfusion pattern to a more punctate distribution. Quantitative analysis of the images revealed that color-weighted fractional average, representing overall tumor perfusion, consistently decreased in these tumors, primarily because of a decrease in fractional tumor cross-sectional area carrying blood flow. In contrast, these parameters increased in nonresponsive tumors during treatment. Confocal microscopy of thick tumor sections revealed a reduction in the density and arborization of vessels labeled in vivo by fluorochrome-conjugated lectin with effective treatment. Immunohistological examination of thin tumor sections confirmed the preferential loss of small vessels with successful therapy. Similar changes in tumor vascular anatomy and perfusion were also observed during recombinant interleukin 12 treatment of two other responsive murine tumor types. These results indicate that power Doppler ultrasound is a sensitive, noninvasive method for reporting functional consequences of therapy-induced vascular anatomical changes that can be used to serially monitor tumor perfusion and efficacy of antivascular therapy in clinical trials.

A comparison of monopolar electrosurgery to a new multipolar electrosurgical system in a rat model.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to compare collateral tissue damage and wound healing in incisions created by electro-dissociation and conventional electrosurgery. Conventional electrosurgery has been used as an alternative to the scalpel to improve hemostasis. However, the heat generated by this instrument can cause tissue damage surrounding the incision, limiting its use around nerves and large blood vessels. A new technology, Coblation (Arthrocare Corp., Sunnyvale, CA), uses "electro-dissociation" to achieve similar results by creating charged particles from a conductive medium to make an incision while simultaneously achieving hemostasis. This new approach to electrosurgery may reduce soft tissue damage. METHODS: Two prospective, matched design experiments were performed. In experiment I, both devices were set at the same electrical power in watts and then used to create an incision on the tongue of rats. In experiment II, the electrical power settings of both devices were adjusted until they created incisions of the same size. Epithelial destruction and collateral tissue damage were measured in histologically prepared tissue in both experiments, and the wound healing process was observed in experiment II at 0, 3, 7, and 14 days after surgery. RESULTS: The results showed that the electro-dissociation method created significantly less epithelial destruction and collateral tissue damage in both experiments. Granulation tissue formation was also significantly less extensive in the electrodissociation-induced incision after 7 and 14 days of recovery. CONCLUSIONS: Wound healing may be faster than with conventional electrosurgery if the Coblation device is used.

An explanatory model for Munchausen by proxy abuse.

OBJECTIVE: In Munchausen by proxy (MBP) abuse, a caretaker fabricates or induces illness in another person to obtain emotional gratification. In representative cases, a mother is the perpetrator and her child is the victim. In view of the limits of current explanatory models, we use personal accounts of MBP perpetrators, physicians, and family members as a window into understanding this counterintuitive behavior. METHOD: As subspecialty clinicians and consultants, we supplemented our extensive direct experience with MBP with a review of published reports of MBP located via MEDLINE and PsycINFO (1980 onward). We also examined the books devoted to the subject and incorporated personal accounts of MBP perpetrators and of family members and professionals involved with them. RESULTS: Factors contributing to the onset and continuation of MBP are the perpetrator's experiencing a particular drive (e.g., intense anger or frustration); lacking or overcoming internal inhibitions against abusive actions; and overcoming external inhibitions, such as the potential intercession of a spouse or pediatrician. As a result, the MBP parent experiences release from unpleasant emotions and a sense of renewed control. MBP behavior gains "habit strength" each time it occurs. CONCLUSIONS: Psychodynamic explanations of MBP, while favored by some authors, are inherently speculative and tend to be low in predictive value. We suggest broadening these traditional explanations by emphasizing observable behaviors and verifiable background factors. The behavioral perspective we outline helps explain how MBP behavior is learned, why it is more prevalent among mothers, and why it is so difficult for perpetrators to stop.

Development of a multifrequency conductance catheter-based system to determine LV function in mice.

Transgenic mice offer a valuable way to relate gene products to phenotype, but the ability to assess the cardiovascular phenotype with pressure-volume analysis has lagged. Conductance measurement offers a method to generate an instantaneous left ventricular (LV) volume signal in the mouse but has been limited by the volume signal being a combination of blood and LV muscle. We hypothesized that by developing a mouse conductance system that operates at several simultaneous frequencies, we could identify and correct for the myocardial contribution to the instantaneous volume signal. This hypothesis is based on the assumption that mouse myocardial conductivity will vary with frequency, whereas mouse blood conductivity will not. Consistent with this hypothesis, we demonstrated that at higher excitation frequency, greater end-diastolic and end-systolic conductance are detected, as well as a smaller difference between the two. We then empirically solved for LV blood volume using two frequencies. We combined measured resistivity of mouse myocardium with an analytic approach and extracted an estimate of LV blood volume from the raw conductance signal. Development of a multifrequency catheter-based system to determine LV function could be a tool to assess cardiovascular phenotype in transgenic mice.

Arthroscopic excision of a ganglion cyst from the elbow.

Ganglia are benign lesions that are uncommonly seen about the elbow. When conservative treatment fails, surgical excision is recommended, usually through an open approach. The author presents the first report of a case of arthroscopic excision of a large anterior elbow cyst. The success of the excision, documented by magnetic resonance imaging at 18 months postoperatively, shows that the arthroscopic approach is a safe and viable alternative to open excision of ganglion cysts of the elbow.

Validation of a mouse conductance system to determine LV volume: comparison to echocardiography and crystals.

The application of left ventricular pressure-volume analysis to transgenic mice to characterize the cardiac phenotype has been problematic due to the small size of the mouse heart and the rapid heartbeat. Conductance technology has been miniaturized for the mouse and can solve this problem. However, there has been no validation of this technique. Accordingly, we performed echocardiography followed by simultaneous ultrasonic crystals, flow probe, and conductance studies in 18 CD-1 mice. Raw conductance volumes were corrected for an inhomogenous electrical field (alpha) and parallel conductance (G(pi)) yielding a stroke volume of 14.1 +/- 3.7 microliter/beat, end-diastolic volume of 20.8 +/- 6.5 microliter, and end-systolic volume of 9.0 +/- 5.8 microliter. The mean conductance volumes were no different from those derived by flow probe and echocardiography but did differ from ultrasonic crystals. G(pi) was determined to be 14.9 +/- 8.7 microliter. However, hypertonic saline altered dimension and pressure in the mouse left ventricle. Although G(pi) can be determined by the hypertonic saline method, saline altered hemodynamics, questioning its validity in the mouse. Although mean measures of absolute volume may be similar among different techniques, individual values did not correlate.

Managing psychiatric disorders in primary care: 2. Anxiety.

Most anxious patients are first seen and treated by primary care physicians. Treatment is generally long-term, and often the results are not what either patient or physician would regard as optimal. Nevertheless, timely and appropriate intervention can markedly improve function--it may make the difference between a generally satisfying life and one lived in fear and isolation.

Munchausen by Internet: detecting factitious illness and crisis on the Internet.

Within the past few years, the Internet has exploded into a medium of choice for those interested in health and medicine. Along with the promise of immediate access to authoritative resources via websites, the Internet offers "virtual support groups" through formats such as chat rooms and newsgroups. These person-to-person exchanges, typically focusing on a specific topic, can be invaluable sources of information and compassion for patients and their families. However, individuals may misuse these Internet groups at times, offering false stories of personal illness or crisis for reasons such as garnering attention, mobilizing sympathy, acting out anger, or controlling others. I present four such cases and, based on experience with these and other cases of "virtual" factitious disorder and Munchausen by proxy, summarize indicators of factitious Internet claims and the reactions that participants usually experience once the ruse is recognized.

Stent-based gene therapy.

Delivery of gene therapy to inhibit intimal hyperplasia has been proposed to prevent postangioplasty restenosis. We sought to apply gene therapy by using a stent-based technique. There are several hurdles that must be overcome before gene-stent therapy can be applied successfully in clinical trials. These include increasing the efficiency of gene delivery through atherosclerotic plaque; increasing intramural retention times; preventing the inflammatory reaction that stents coated with biodegradable polymers can elicit; overcoming the risk of systemic gene delivery; and accessing the adventitia via percutaneous approach. We evaluated a gene-stent delivery mechanism based on microporous metal microneedles developed with nanotechnology in an attempt to overcome some of these problems. A novel approach to the transfection of genes by microfabricated technology was evaluated in smooth muscle cells in culture. We demonstrated that microneedles can deliver gene therapy to smooth muscle cells in culture and can produce controlled penetration of the IEL and intima. We conclude that taller microneedles need to be developed to reach the media in diseased human arteries and that this technology has the potential to be incorporated in a stent to deliver gene therapy in atherosclerotic plaque.

Managing psychiatric disorders in primary care: 1. Depression.

Because of their established rapport with patients, primary care physicians are in an excellent position to intervene in mild-to-moderate depression and refer patients with more severe symptoms for psychiatric evaluation. The key is to build a solid therapeutic partnership--by communicating interest, respect, support, and empathy for the patient's emotional situation--before turning to the prescription pad.

Potential interaction between ritonavir and carbamazepine.

Ritonavir (RTV), a protease inhibitor, and carbamazepine (CBZ), an anticonvulsant, were administered concurrently to a patient who had human immunodeficiency virus infection and epilepsy. The combination resulted in elevated serum concentrations of CBZ, with accompanying vomiting, vertigo, and transient liver dysfunction. After discontinuing RTV and reducing the dosage of CBZ, the serum concentration of CBZ returned to the optimal range, symptoms subsided, and liver function returned to baseline. Carbamazepine is metabolized in the liver to a large extent by the cytochrome P450 (CYP) system, especially CYP3A4, 2C8, and 1A2, whereas RTV is metabolized primarily by CYP3A and is a potent inhibitor of this enzyme. Careful clinical monitoring may help prevent adverse drug interactions when these drugs are administered concurrently.

Thrombotic thrombocytopenic purpura associated with clopidogrel.

BACKGROUND: The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel. METHODS: The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2). RESULTS: Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis. CONCLUSIONS: Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.