Superiority of proximal embolization of the gastroduodenal artery with the Amplatzer vascular plug 4 before yttrium-90 radioembolization: a retrospective comparison with coils in 134 patients.

PURPOSE: To evaluate the effectiveness of proximal embolization of the gastroduodenal artery (GDA) using the Amplatzer Vascular Plug 4 (AVP 4) compared with pushable coils to avoid hepaticoenteric collaterals of the GDA stump, which may serve as pathways for nontarget embolization. MATERIALS AND METHODS: One hundred thirty-four patients scheduled for 90-yttrium radioembolization (Y-90 RE) using either plugs (n = 67) or standard coils (n = 67) for GDA occlusion were retrospectively analyzed. Parameters recorded were length of the perfused GDA stump, distance device to the GDA origin, perfused proximal side branches after embolization, and durability of vessel occlusion at Y-90 RE. RESULTS: Length of the residually perfused GDA stump was 3.89 ± 2.86 mm for the AVP 4, which was significantly shorter compared with 5.78 ± 3.85 mm for coils (p = 0.005). Distance of the plug to the GDA origin was 1.41 ± 2.60 mm, which was also significantly shorter than 4.73 ± 3.44 mm for coils (p < 0.001). This resulted in significantly fewer patients with residually perfused side branches in the AVP 4 group (n = 2; 3.0%) compared with the coil group (n = 18; 26.9%; p < 0.001). At Y-90 RE, no GDA reperfusion was found after plug embolization compared with 2 cases after coil embolization (3.0%; p = 0.156). Only one patient had a radiation-induced duodenal ulcer after coil embolization, whereas no Y-90-related toxicity was identified after plug embolization. CONCLUSION: Use of the AVP 4 for embolization of the GDA allowed an optimal proximal and more effective target vessel occlusion compared with coil embolization, which can avoid complications caused by extrahepatic gastrointestinal deposition of Y-90 microspheres by way of residually perfused proximal side branches.

Past suicide attempts in depressed inpatients: clinical versus research assessment.

The objective of this study was to compare structured clinical assessment versus research measurement of suicidal risk among inpatients with major depression. Fifty depressed inpatients underwent a structured clinical and an independent research assessment of suicidal risk. Agreement between both assessments and its impact upon time to first readmission was tested. A false negative rate of 25% in the clinical screening of past suicide attempts was associated with older age, concealment, and reported lower frequency of suicidal thoughts. Mean times to first readmission (2.5 years follow-up) were 74 weeks (discordant responders) and 118 weeks (concordant responders). A failure to detect 25% of patients with past suicide attempt history in the clinical assessment was associated with older age and concealment of suicidal thoughts.

Novel therapies in asthma: leukotriene antagonists, biologic agents, and beyond.

Asthma is one of the most common conditions seen in clinical practice and carries both a significant disease burden in terms of patient morbidity and a high economic burden in both direct and indirect costs. Despite this, it remains a comparatively poorly understood disease, with only modest advances in treatment over the past decade. Corticosteroids remain the cornerstone of therapy. Both patient compliance with medications and physician adherence to evidence-based guidelines are often poor, and a high percentage of patients continue to have inadequately controlled disease even with optimal therapy. Following a contextual overview of the current treatment guidelines, this review focuses on novel asthma therapies, beginning with the introduction of the leukotriene receptor antagonist zafirlukast in the 1990s, continuing through advanced endoscopic therapy and into cytokine-directed biologic agents currently in development. Along with clinically relevant biochemistry and pharmacology, the evidence supporting the place of these therapies in current guidelines will be highlighted along with data comparing these agents with more conventional treatment. A brief discussion of other drugs, such as those developed for unrelated conditions and subsequently examined as potential asthma therapies, is included.

Application of botulinum toxin to clinical therapy: advances and cautions.

The therapeutic use of botulinum toxin Type A has followed a novel and unanticipated pathway of applications, from its initial application by Scott to paralyze the extraocular muscles of the eyes to correct strabismus. In the late 1970s, Scott formed a company, called Oculinum Inc, to make botulinum toxin Type A available for this ophthalmic application. From this modest and limited beginning, it has found use for treatment of a plethora of cosmetic, neuromuscular, and skeletal disabilities, including cervical dystonia, blepharospasm, and temporary improvement in the appearance of moderate to severe glabellar lines. Botulinum toxin Type A is now being used as therapy in voiding disorders, migraine and tension-type headache, writer's cramp, and laryngeal muscle hyperactivity syndromes. It has reduced the spasm and pain associated with perianal fissures. It has found application in the reduction of glandular function in severe primary axillary hyperhidrosis and sialorrhea. Additional applications are being studied in the area of pain management based on its apparent ability to inhibit neuropeptide release from nociceptors.

Effectiveness of repeat angiographic assessment in patients designated for radioembolization using yttrium-90 microspheres with initial extrahepatic accumulation of technitium-99m macroaggregated albumin: a single center's experience.

PURPOSE: To evaluate the efficacy of a workflow consisting of repeat assessment in patients planned for yttrium-90 ((90)Y) radioembolization in case of nontarget visceral technetium-99m ((99m)Tc)-macroaggregated albumin (MAA) accumulation despite initial prophylactic coil embolization of nonhepatic arteries. MATERIALS AND METHODS: In 341 patients with primary and secondary liver cancer, pretreatment hepatic angiograms, as well as single-photon emission computed tomography coregistered with magnetic resonance imaging scans, were obtained. Extrahepatic tracer deposition was identified in 33 patients (9.7%) necessitating repeat assessment. Images were reviewed to correlate the site of MAA accumulation with causative gastrointestinal vessels, and repeat angiograms served as reference standard. RESULTS: At repeat angiography, the source of extrahepatic flow was identified and eliminated in 31 of 33 patients (93.9%). In 20 patients (60.6%), successful embolization of nontarget vessels was achieved, in 13 patients (39.4%), MAA was administered more distally. Afterward, extrahepatic MAA deposition was eliminated in 30 patients (90.9%). CONCLUSION: The algorithm of repeat assessment in case of extrahepatic MAA accumulation has proven highly effective to eliminate extrahepatic shunting, thus decreasing the risk of postradioembolization complications due to inadvertent visceral microsphere deposition.

Pulmonary arterial hypertension: classification and therapy with a focus on prostaglandin analogs.

Pulmonary arterial hypertension, part of the larger spectrum of disorders causing pulmonary hypertension, is a complex and progressive disease of multiple etiologies that ultimately leads to vascular remodeling, right-sided heart failure, and death. Advances in treatment over the past 15 to 20 years have dramatically reduced the morbidity and mortality of the disease, but often have significant drawbacks. Of the more recently approved therapies, the prostaglandin analogs have been shown to have the greatest therapeutic benefit but are also the most difficult to administer, many being given as continuous intravenous infusions in the ambulatory setting. After a case presentation highlighting some of the challenges that accompany treatment with these agents, this article reviews the diagnosis and classification of pulmonary hypertension and pulmonary arterial hypertension and gives a brief overview of the various other pharmacologic agents used in its treatment. A more comprehensive review of the biochemistry of prostaglandins and the pharmacology and clinical use of this class of drugs follows. Recommended treatment guidelines are also discussed.

Value of diffusion weighted MR imaging as an early surrogate parameter for evaluation of tumor response to high-dose-rate brachytherapy of colorectal liver metastases.

BACKGROUND: To assess the value of diffusion weighted imaging (DWI) as an early surrogate parameter for treatment response of colorectal liver metastases to image-guided single-fraction ¹9²Ir-high-dose-rate brachytherapy (HDR-BT). METHODS: Thirty patients with a total of 43 metastases underwent CT- or MRI-guided HDR-BT. In 13 of these patients a total of 15 additional lesions were identified, which were not treated at the initial session and served for comparison. Magnetic resonance imaging (MRI) including breathhold echoplanar DWI sequences was performed prior to therapy (baseline MRI), 2 days after HDR-BT (early MRI) as well as after 3 months (follow-up MRI). Tumor volume (TV) and intratumoral apparent diffusion coefficient (ADC) were measured independently by two radiologists. Statistical analysis was performed using univariate comparison, ANOVA and paired t test as well as Pearson's correlation. RESULTS: At early MRI no changes of TV and ADC were found for non-treated colorectal liver metastases. In contrast, mean TV of liver lesions treated with HDR-BT increased by 8.8% (p = 0.054) while mean tumor ADC decreased significantly by 11.4% (p < 0.001). At follow-up MRI mean TV of non-treated metastases increased by 50.8% (p = 0.027) without significant change of mean ADC values. In contrast, mean TV of treated lesions decreased by 47.0% (p = 0.026) while the mean ADC increased inversely by 28.6% compared to baseline values (p < 0.001; Pearson's correlation coefficient of r = -0.257; p < 0.001). CONCLUSIONS: DWI is a promising imaging biomarker for early prediction of tumor response in patients with colorectal liver metastases treated with HDR-BT, yet the optimal interval between therapy and early follow-up needs to be elucidated.

Novel oral anticoagulants in development: Dabigatran, Rivaroxaban, and Apixaban.

Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists, such as warfarin. Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. A variety of novel anticoagulants with improved pharmacologic and clinical profiles are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of small molecule factor Xa inhibitors and thrombin inhibitors. With their potentially consistent and predictable clinical profile, oral formulation, and decreased need for coagulation monitoring, these new agents will likely increase the use and duration of anticoagulation treatment in thromboembolic disorders and reduce the burden associated with long-term management.

Hypertension and cognitive function in the elderly.

Alzheimer's disease is the most prevalent and common form of cognitive impairment, ie, dementia, in the elderly followed in second place by vascular dementia due to the microangiopathy associated with poorly-controlled hypertension. Besides blood pressure elevation, advancing age is the strongest risk factor for dementia. Deterioration of intellectual function and cognitive skills that leads to the elderly patient becoming more and more dependent in his, her, activities of daily living, ie, bathing, dressing, feeding self, locomotion, and personal hygiene. It has been known and demonstrated for many years that lowering of blood pressure from a previous hypertensive point can result in stroke prevention yet lowering of blood pressure does not prevent the microangiopathy that leads to white matter demyelinization which when combined with the clinical cognitive deterioration is compatible with a diagnosis of vascular dementia. It is known from many large studies, ie, SHEP, SCOPE, and HOPE, that lowering of blood pressure gradually will not and should not worsen the cognitive impairment. However, if the pressure is uncontrolled a stroke which might consequently occur would further worsen their cognitive derangement. So an attempt at slow reduction of blood pressure since cerebral autoregulation is slower as age increases is in the patient's best interest. It is also important to stress that control of blood glucose can also be seen as an attempt to prevent vascular dementia from uncontrolled hyperglycemia. Vascular dementia is not considered one of the reversible causes of dementia. Reversible causes of cognitive impairment are over medication with centrally acting drugs such as sedatives, hypnotics, antidepressants, and antipsychotics, electrolyte imbalance such as hyponatremia, azotemia, chronic liver disease, and poor controlled chronic congestive heart failure. Criteria for the clinical diagnosis of vascular dementia include cognitive decline in regards to preceding functionally higher level characterized by alterations in memory and in two or more superior cortical functions that include orientation, attention, verbal linguistic capacities, visual spacial skills, calculation, executive functioning, motor control, abstraction and judgment. Patients with disturbances of consciousness, delirium (acute confusional states), psychosis, serious aphasia, or sensory-motor alterations that preclude proper execution of neuro-psychological testing are also considered to have probably vascular dementia. Furthermore, these are ten of the other essential cerebral or systematic pathologies present that would be able to produce a dementia syndrome.

Cognitive function and antihypertensive treatment in the elderly: a 6-year follow-up study.

Both antihypertensive treatment and statins were proved to reduce mortality and morbidity from cardiovascular disease in the elderly. Yet their effect on cognitive functions of the elderly is unclear. In this study, 518 elderly were interviewed at their home six years ago. BP was measured and antihypertensive drug treatment and cognitive functions were evaluated. 318 of the original sample were re-examined (81% of the survivors). We evaluated the selective survival in relation to changes in BP, the specific drug usage and cognitive functioning. Beta blocker treatment increased the odds of survival but also the odds of decline in MMSE and memory scores. ACE-I treatment was also associated with decline in memory. Subjects treated with CCB had improved MMSE scores, memory, and performed better on tasks requiring concentration. Statins treatment in this study did not show any affect on cognitive functions. Although most subjects were treated by more than one antihypertensive drug, less than half were normalized at baseline and only one quarter at follow-up. Despite the low normalization rate, antihypertensive treatment regimen had been hardly changed during the six years follow-up. The use of statins, however, increased dramatically: from 6% at baseline to almost half at follow-up. According to our findings CCB emerges as the best option for reducing BP in elderly patients. It appeared to improve cognitive functions without hampering survival.

Hypertension and cognitive function in the elderly.

Alzheimer's disease is the most prevalent and common form of cognitive impairment, ie, dementia, in the elderly followed in second place by vascular dementia due to the microangiopathy associated with poorly-controlled hypertension. Besides blood pressure elevation, advancing age is the strongest risk factor for dementia. Deterioration of intellectual function and cognitive skills that leads to the elderly patient becoming more and more dependent in his, her, activities of daily living, ie, bathing, dressing, feeding self, locomotion, and personal hygiene. It has been known and demonstrated for many years that lowering of blood pressure from a previous hypertensive point can result in stroke prevention yet lowering of blood pressure does not prevent the microangiopathy that leads to white matter demyelinization which when combined with the clinical cognitive deterioration is compatible with a diagnosis of vascular dementia. It is known from many large studies, ie, SHEP, SCOPE, and HOPE, that lowering of blood pressure gradually will not and should not worsen the cognitive impairment. However, if the pressure is uncontrolled a stroke which might consequently occur would further worsen their cognitive derangement. So an attempt at slow reduction of blood pressure since cerebral autoregulation is slower as age increases is in the patient's best interest. It is also important to stress that control of blood glucose can also be seen as an attempt to prevent vascular dementia from uncontrolled hyperglycemia. Vascular dementia is not considered one of the reversible causes of dementia. Reversible causes of cognitive impairment are over medication with centrally acting drugs such as sedatives, hypnotics, antidepressants, and antipsychotics, electrolyte imbalance such as hyponatremia, azotemia, chronic liver disease, and poor controlled chronic congestive heart failure. Criteria for the clinical diagnosis of vascular dementia include cognitive decline in regards to preceding functionally higher level characterized by alterations in memory and in two or more superior cortical functions that include orientation, attention, verbal linguistic capacities, visual spacial skills, calculation, executive functioning, motor control, abstraction and judgment. Patients with disturbances of consciousness, delirium (acute confusional states), psychosis, serious aphasia, or sensory-motor alterations that preclude proper execution of neuro-psychological testing are also considered to have probably vascular dementia. Furthermore, these are ten of the other essential cerebral or systematic pathologies present that would be able to produce a dementia syndrome.

General characteristics of treatable, reversible, and untreatable dementias.

The modification of cognitive function with age has been the focus of numerous studies. Most of the research has suggested that these changes, at least in the majority of individuals, occur only at a very advanced stage; however, those conditions that are treatable and potentially reversible are acute in onset and often associated with acute confusional states. Therefore, physicians should be aware of the possibility of reversible causes of cognitive change in their elderly patients, including certain medications responsible for memory loss and other organ system diseases. In addition, the authors stress that not all memory loss in geriatric patients is due to Alzheimer's disease and that when history and physical examination provide evidence of hypertension and magnetic resonance imaging provides evidence of leukoaraiosis, a diagnosis of vascular dementia should be considered.

Effects of caloric restriction and exercise training on skeletal muscle histochemistry in aging Fischer 344 rats.

The purpose of this study was to determine the effects of calorie restriction and exercise on hindlimb histochemistry and fiber type in Fischer 344 rats as they advanced from adulthood through senescence. At 10 months of age, animals were divided into sedentary fed ad libitum, exercise (18 m/min, 8% grade, 20 min/day, 5 days/week) fed ad libitum, and calorie restricted by alternate days of feeding. Succinic dehydrogenase, myosin adenosine triphosphatase (mATPase at pH 9.4), nicotine adenonine dinucleotide reductase, and Periodic Acid Shiff histochemical stains were performed on plantaris and soleus muscles. The results indicated that aging resulted in a progressive decline in plantaris Type I muscle fiber in sedentary animals, while exercise resulted in maintenance of these fibers. The percent of plantaris Type II fibers increased between 10 and 24 months of age. Exercise also resulted in a small, but significant, increase in the percentage of plantaris Type IIa fibers at 24 months of age. The soleus fiber distribution for Type I fibers was unaffected by increasing age in all groups of animals. The implications of these results suggest the implementation of exercise as a lifestyle modification as early as possible.

A clinical, physiology and pharmacology evaluation of orthostatic hypotension in the elderly.

Orthostatic hypotension is very common in the elderly. It increases morbidity and is an independant predictor of all cause mortality. It is defined as a fall in systolic blood pressure greater than 20 mm Hg or a fall in diastolic blood pressure greater than 10 mm Hg within 3 minutes of standing. Symptoms include light headedness, weakness, blurred vision, fatigue and lethargy and falls. Most patients have orthostatic hypotension due to non neurogenic causes. Drugs like antihypertensives and tricyclic antidepressants are very common causes of orthostatic hypotension. Diagnosis is based on the history and a thorough clinical examination. Based on the history and physical examination, further testing of the heart, kidneys and autonomic nervous system may be required in selected patients. Non pharmacological methods like slow position change, increased fluid and sodium intake, compression stockings and elevation of head of the bed are the key to management of orthostatic hypotension. After these methods, pharmacological treatment with fludrocortisone and midodrine should be tried. Other drugs like desmopresin acetate, xamoterol, erythropoetin and ocreotide can be used as second line agents in selected patients.

Effects of exercise on emerging and traditional cardiovascular risk factors.

BACKGROUND: Common cardiovascular disease risk factors (e.g., insulin and aerobic fitness) are improved with exercise; however, few studies have addressed the potential for training to modify emerging cardiovascular disease risk factors such as homocysteine and high-sensitivity C-reactive protein. METHODS: Sedentary adults (n = 324, 48.9 +/- 8.4 years) were randomized to four groups differing in training intensity (moderate = 45-55% or high = 65-75% of heart rate reserve) and frequency (low = 3-4, 30-min sessions/week or high = 5-7, 30 min-sessions/week). RESULTS: Within-group changes in homocysteine, insulin, and aerobic fitness were significant (all P < 0.0125). Furthermore, homocysteine increased in the high-intensity-low-frequency (0.98 +/- 2.32 micromol/L) and high-intensity-high-frequency (0.93 +/- 2.56 micromol/L) groups, while aerobic fitness increased in the moderate-intensity-high-frequency (0.99 +/- 2.01 mL min(-1) kg(-1)) and high-intensity-high-frequency (1.77 +/- 2.97 mL min(-1) kg(-1)) groups (all P < 0.003). The change in aerobic fitness was greater in the high-intensity-high-frequency compared to the moderate-intensity-low-frequency group (1.77 +/- 2.97 vs. 0.36 +/- 2.10 mL min(-1) kg(-1), P = 0.0014) (effect size estimate = 0.60 mL min(-1) kg(-1)). The main effects for intensity, with respect to the change in insulin (effect size estimate = 0.46 microU/mL), and frequency, with respect to the change in aerobic fitness (effect size estimate = 0.38 mL min(-1) kg(-1)), were significant (P < 0.0125). CONCLUSION: Although frequent bouts of higher intensity exercise were particularly effective in reducing fasting insulin and improving fitness, they resulted in slightly increased homocysteine levels.

Treatment of sexual disinhibition in dementia: case reports and review of the literature.

Behavioral problems are common in dementia patients. They are complex in nature and are often the presenting symptoms of dementia. Its management poses continuous challenge. Gabapentin is an antiepileptic agent that has a role in the management of behavioral problems in demented patients such as agitation and aggression. Its role in treating sexual disinhibition has never been addressed. We describe 3 nursing home residents in 2 dementia units whose sexual disinhibition was effectively treated with gabapentin.