Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors.

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, His6-(ZHER2:4)2 (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of 99mTc might improve the availability of the labeled conjugate, and Tc(I)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare 99mTc-labeled His6-(ZHER2:4)2 and to evaluate its targeting properties compared with the targeting properties of 125I-4-iodobenzoate-His6-(ZHER2:4)2 [125I-His6-(ZHER2:4)2]. METHODS: The labeling of His6-(ZHER2:4)2 with 99mTc was performed with an IsoLink kit. The specificity of 99mTc-His6-(ZHER2:4)2 binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of 99mTc-His6-(ZHER2:4)2 and 125I-His6-(ZHER2:4)2 in tumor-bearing BALB/c nu/nu mice were determined. RESULTS: The labeling yield for 99mTc-His6-(ZHER2:4)2 was approximately 60% (50 degrees C), and the radiochemical purity was greater than 97%. The conjugate was stable during storage and under histidine and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%IA/g]) of 2.6 %IA/g for 99mTc-His6-(ZHER2:4)2 and 2.3 %IA/g for 125I-His6-(ZHER2:4)2 at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. CONCLUSION: The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.     

Economic Evaluation of Nebivolol in the Treatment of Hypertension

OBJECTIVE: To examine the economic consequences of effective antihypertensive treatment using the novel vasodilating beta1-adrenoceptor antagonist nebivolol (Nebilet) from the perspective of the healthcare provider. METHODS: The evaluation was based on a postmarketing surveillance study in Germany involving 8682 moderately hypertensive patients. Using the Framingham Risk Model, the antihypertensive effectiveness of nebivolol after 6 weeks of treatment was extrapolated to estimate the reductions in 10-year risks of cardiovascular events. Data sources included direct costs for medical and invasive cardiovascular interventions in Germany, costs of therapy in the US and the UK, and estimates on the prevalence of cardiovascular events issued by the American Heart Association. RESULTS: Six-week antihypertensive treatment resulted in a DBP reduction of 13.7 mm Hg. The rate of responders, defined as those patients achieving DBP <90 mm Hg, was 70%. SBP was reduced by 26.1 mm Hg. According to the Framingham Risk Model, 313 deaths would be avoided. Coronary heart disease (CHD) could be reduced by 94 cases (from 1339 to 1245 events) and 150 strokes would be avoided (from 518 to 368 events) in a 10-year period. This reduction of 244 cardiovascular events among the 8682 patients investigated corresponded to cost savings of between Euro 250,000 and Euro 2.5 million, depending on the healthcare environment and the intervention applied. CONCLUSION: Treatment of moderately hypertensive patients with nebivolol can be considered cost effective. Nebivolol has the potential to decrease the overall long-term costs of medical care for patients with hypertension.     

Grafts of porcine intestinal submucosa for repair of cervical and abdominal esophageal defects in the rat.

Porcine small intestinal submucosa (SIS) is a cell-free collagen matrix that has demonstrated its ability as scaffold material for constructive remodeling of damaged or missing tissue. The purpose of this study was to evaluate the morphology and function of esophagoplasty in rat using a porcine SIS scaffold for the repair of a semi-circumferential defect in the cervical or in the abdominal esophagus. Sixty-seven rats underwent surgical excision of the anterior wall either of the cervical or of the abdominal esophagus and subsequent repair of the defect with an SIS patch graft. Outcomes of weight gain, signs of dysphagia, hematological and serum chemistry parameters, and barium swallow studies were used to assess the progress of healing and function over a 150-day time period. The grafts were studied for gross changes and histology at predetermined time points. Ninety-four percent of the SIS-treated rats survived, showing no significant differences in survival rate between groups. The grafted animals did well, without signs of dysphagia, and gaining weight. Barium swallow studies showed no evidence of fistula, significant stenosis, or diverticula. No hematological or serum biochemistry abnormalities were found. By 150 days, the SIS graft was replaced with esophageal-derived tissues. Specimens were completely lined by keratinized stratified squamous epithelium and showed complete regeneration of muscle fibers and scarce immunoreactivity for nerve. In the rat model, a patch graft technique using porcine SIS appears to induce esophageal regrowth either in cervical and abdominal esophagus. The repair mechanism occurred through a regenerative healing process.     

Multidimensional approach to the differences between muscular and articular temporomandibular patients: coping, distress, and pain characteristics.

OBJECTIVE: This study analyzes the differences in psychological variables and symptomatology between temporomandibular disorder diagnosis subgroups. STUDY DESIGN: The sample included 114 temporomandibular disorder patients that were evaluated in coping, distress, and temporomandibular characteristics. Diagnostic muscular (n = 58) and articular (n = 56) subgroups were compared in these variables through a MANCOVA. RESULTS: Muscular patients show a higher level of general distress, specifically in the anxiety and somatization subscales and a more active coping style, with a tendency of a minor use of humor and a higher number of parafunctional habits, specifically, biting nails, hangnails, and lips. CONCLUSION: We discuss the differences found in order to design the targets of the psychological intervention of temporomandibular patients.     

The clinical phenotypes of juvenile bipolar disorder: toward a validation of the episodic-chronic-distinction.

BACKGROUND: Recent research has addressed the issue of subtyping juvenile bipolar disorder (JBD). Accordingly, we set out to find out, in a naturalistic sample of bipolar children and adolescents with mania and mixed mania, whether the most useful subtyping should be based on clinical features (elated vs. irritable) or course (episodic vs. chronic). METHODS: We studied 136 patients, 81 male patients (59.6%) and 55 female patients (40.4%), mean age 13.5 +/- 2.9 years, meeting the DSM-IV diagnosis of bipolar disorder, assessed by a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version [K-SADS-PL]). RESULTS: Regarding course, 77 patients (56.6%) had an episodic course and 59 patients (43.4%) had a chronic course. Patients with chronic course were significantly younger, had an earlier onset of JBD, and presented a more frequent comorbidity with disruptive behavior disorders. According to the prevalent mood disturbance, 75 patients (55.1%) showed an elated and 61 patients (44.9%) showed an irritable mood. Elated mood was more frequent in patients with episodic course, whereas irritable mood was more frequent in the patients with chronic course. CONCLUSIONS: These findings suggest that chronic versus episodic course may be a putative differential feature. Further validation of such a distinction would require prospective studies, temperament evaluation, gender and neurobiologic approaches, and differential psychopharmacologic assignment and response.     

Characteristics of Acute Asthma Patients Attended Frequently Compared with Those Attended Only Occasionally in an Emergency Department

Asthma patients that depend on emergency department (ED) services are generally considered to have extremely poor disease control and prognosis. It is important to identify characteristics related to poor disease control and frequent visits to the ED to apply appropriate clinical management. This study comprised a cross-sectional survey of consecutive patients with asthma exacerbation (age ≥12 years) presenting at the adult ED of a large, tertiary care, university-affiliated hospital over a 2-month period. The frequent visitors (FV) were defined by ≥3 visits to the ED in the preceding year, and the occasional visitors (OV) by ≤2 visits. Eighty-six patients (61 females and 25 males) were included in the study (mean age 38 ± 18 years). Of these patients, 51.2% were FV and 48.8% were OV. Sixty-nine percent had annual income lower than A$3000 and 66.3% had ≤8 years of the formal education. Only 18.6% had used inhaled corticosteroids, 79.1% identified the asthma attack severity, 70.9% increased or initiated inhaled β-agonist, 20.9% increased or initiated steroid therapy, and 55.8% had an asthma action plan for attack. The number of hospital admissions in past year (OR 4.3, P = .02), use of home nebulizer (OR 3.6, P = .05) and the lack of a written asthma action plan (OR 3.3, P = .03) were independently associated with frequent visits to the ED. We conclude that a substantial proportion of the patients that visit the ED are FV. These patients are more likely to have hospital admission in the past year, to use a home nebulizer, and to lack a written asthma action plan. They should be considered the most important target for asthma education.     

Bradycardia related to hypoglycaemia.

Alterations in blood glucose levels are known to be involved in electrocardiogram changes. Various types of arrhythmias have been reported. We present here the case of an 81-year-old woman presenting with transient atrial fibrillation while being treated for hypoglycaemia with dextrose infusion, and finally developing a sinus rhythm. The presence of alterations in glucose blood levels should always be considered as a potential cause of transient atrial fibrillation.