Visceral afferent pathways to the thalamus and olfactory tubercle: behavioral implications

The goal of this study was to support the hypothesis that visceral signals may integrate and influence behavior by way of direct pathways from the nucleus tractus solitarii (NTS) to the olfactory tubercle and the midline/intralaminar thalamus. An anterograde tracer, biotinylated dextran amine (BDA) was iontophoresed bilaterally into the caudal NTS to optimize terminal labeling. NTS-cortical projections traversed both limbs of the diagonal bands providing heavy innervation, and terminated lightly within layer 3 of the olfactory tubercle. NTS-thalamic projections terminated within anterior and, as previously shown, posterior divisions of nucleus paraventricularis thalami and avoided the adjoining mediodorsal thalamic nucleus. Heretofore unrecognized projections were traced to the parafascicular and reuniens thalamic nuclei, and the peripeduncular nucleus. Control experiments identified the nucleus gracilis as the principal source of ascending projections to ventroposterior lateral, posterior and intralaminar thalamic nuclei. Our data corroborate the supposition that olfactory signals may integrate with visceral stimuli in the striatal compartment of olfactory tubercle. NTS projections encompass thalamic nuclei that project topographically to the prefrontal cortex, hippocampus and ventral (limbic) striatum, regions activated by visceral stimulation. Structural data support the idea that compartments of the non-discriminative thalamus may contribute to perception and behavioral responses to visceral stimulation.     

Psychophysiology of pain: diagnostic and therapeutic implications

Pain problems occupy muct of the time and therapeutic efforts of physicians. Nonmedical practitioners and cultists have likewise attracted many people seeking pain relief. In many cases the cultists seem to do as well as the ethical practitioner. A realistic view of pain takes into account the significance of the pain to the individual, the degree of anxiety and/or depression that contributes to the aggravation and prepetuation of the pain, and finally the manipulative and defensive value that the pain may have to the individual. A purely mechanistic approach which would attempt to distinguish "real pain", ie, pain associated with a demonstrable lesion, and "imagined pain" will prove counterproductive. Likewise accusations of consciously pretended pain or malingering tend to be nontherapeutic. A sound therapeutic approach is to regard all pain as real, realizing that the pain of depression may be the most unendurable type of pain. Major psychotropic drugs for relief of anxiety and for treatment of depression have appplication in the management of selected pain problems.     

Choroidal hemangioma: MR findings and differentiation from uveal melanoma

Transgenic mice (T26) bearing the envelope, regulatory, and accessory genes of HIV- I develop renal disease resembling human HIV-associated nephropathy (HIVAN). Effects of vehicle (VEH) and the angiotensin-converting enzyme inhibitor captopril (CAP) were examined in wild-type (WT) or T26 mice treated from 7 to 100 d of age. Mortality was lower in CAP T26 mice (30 mg/kg: 8%; 100 mg/kg: 12%) than VEH T26 mice (52%). The urinary protein/creatinine ratio was increased in VEH T26 mice (19.5+/-7.60) versus WT mice (6.1+/-0.83), but not in low-dose (7.3+/-0.94) or high-dose (8.2+/-1.02) CAP T26 mice. Blood urea nitrogen was higher in VEH T26 mice (52+/-16.2 mg/dl) than VEH WT mice (24+/-0.8). Blood urea nitrogen was also elevated in CAP WT (high dose: 43+/-2.1 mg/dl) and T26 mice (high dose: 42+/-2.4 mg/dl). Glomerular injury was higher in VEH T26 mice (6.8+/-0.58) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 1.1+/-0.17; high dose: 0.7+/-0.13). Tubulointerstitial injury was also greater in VEH T26 mice (1.1+/-0.10) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 0.4+/-0.10; high dose: 0.3+/-0.10). These data validate recent nonrandomized studies of captopril in HIV-infected patients, and suggest that an angiotensin-converting enzyme substrate is an important mediator in HIVAN. A randomized placebo-controlled trial of captopril in HIVAN may be warranted.     

Pneumococcal infections: penicillin resistance and therapeutic implications]

OBJECTIVE: We studied the prevalence of viral hepatitis B, C and D markers in chronic hepatopathies from Cluj. MATERIAL AND METHODS: Sera of 297 patients with chronic hepatopathies (236 adults and 61 children) have been tested for viral hepatitis markers: HBsAg, anti-HBc, anti-HBs, HBeAg, anti-HBe, anti-HDV, anti-HCV, by automated ELISA. RESULTS: HBV infection markers in 32% (adults) and 4.9% (children), and HDV infection markers in 11.8% (adults) and 26.3% (children). Double (HBV and HCV) and triple infection (HBV, HDV and HCV) were observed in 28.4% (adults), 4.9% (children), and 3.4% (adults), 0% (children), respectively. CONCLUSIONS: Hepatitis virus infection markers, especially HBV and HCV play an important role in the determinism of chronic hepatopathies from Cluj area, both in children and adults.     

Breast cancer metastasis-associated genes: prognostic significance and therapeutic implications

The metastatic spread of breast cancer accounts for most of its morbidity and mortality; therefore, identifying the genes and gene products involved in breast cancer metastasis formation should be useful for better diagnosis, prognosis, treatment, and follow-up of patients with metastatic breast cancer. Unfortunately, little is known about these genes or the functions of their encoded products. Abnormalities in at least three broad gene categories (oncogenes, regulatory genes or effector genes, and tumor-suppressor genes) have been shown to contribute to the origin and/or progression of breast neoplasias. Such abnormalities are mainly manifested by quantitative changes in gene expression, resulting in loss of normal cellular regulation and enhanced cellular diversification. In addition, qualitative genetic alterations, such as gene amplifications and mutations, may also be involved in breast cancer progression. The role(s) of different breast cancer metastasis-associated genes, if known, in the complex multistep process of invasion and metastasis is discussed along with studies that have identified new molecular probe(s) that may be useful in predicting metastasis formation and outcome in breast cancer and for selecting candidates for adjuvant therapy. Understanding the genetic and thus molecular basis of metastasis formation should also provide important insights on the development of new therapeutic approaches for treatment of metastatic breast cancers based on gene targeting and repair of genetic defects that control metastatic properties.     

Tyrosine kinase: implications in tumor pathology and therapeutic perspectives

PURPOSE: Both generalist and pulmonologist physicians care for patients with severe chronic obstructive pulmonary disease (COPD). We studied patients hospitalized with severe COPD to explore whether supervision of care by pulmonologists is associated with greater costs or better survival. SUBJECTS AND METHODS: We studied 866 adults with severe COPD enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), a prospective study at five academic medical centers. Patients were admitted to the hospital or transferred to an intensive care setting for treatment of severe COPD, defined by hypoxia (PaO2 <60 mm Hg) and hypercapnia (PaCO2 >50 mm Hg) or hypercapnia alone if on supplemental oxygen. Resource intensity was measured using a modified version of the Therapeutic Intervention Scoring System and estimated hospital costs. To account for differences in the patient case mix, propensity scores were developed to represent each patient's probability of having a pulmonologist as attending physician and each patient's probability of being in an intensive care unit (ICU) at study admission. RESULTS: Of the 866 patients studied, 512 had generalists and 354 pulmonologists as their attending physicians. The median patient age was 70 years; 52% were male; 14% died within 30 days. After adjusting for baseline differences in patient characteristics, there were no differences in resource intensity and hospital costs in those treated by pulmonologists or generalists. Adjusted average resource intensity scores for the entire hospitalization were 16.5 for pulmonologists and 17.0 for generalists (P = 0.34). Estimated hospital costs were the same ($6,400) for patients treated by pulmonologists and generalists (P = 0.99). Patients with pulmonologists as attending physicians did not experience better survival. Comparing patients of pulmonologists to patients of generalists, the adjusted hazard ratio for 30-day mortality was 1.6 (95% confidence interval: 0.98, 2.5); the hazard ratio for 180-day mortality was 1.2 (0.9, 1.7). CONCLUSIONS: Our findings suggest that for patients hospitalized with exacerbation of severe COPD, those with pulmonologist attending physicians do not have higher hospital resource use or better survival than those with generalist attending physicians.     

Helicobacter pylori and gastric acid: biological and therapeutic implications

Helicobacter pylori is highly adapted to its unusual ecological niche in the human stomach. Urease activity permits H. pylori survival at a pH of <4 in vitro and is required for the organism to colonize in animal models. However, urease does not play an important role in the survival of the organism in a pH range between 4 and 7. Other mechanisms of pH homeostasis remain poorly understood, but preliminary studies indicate that novel proteins are produced when H.pylori cells are shifted from pH 7 to 3, and the gene encoding a P-type adenosine triphosphatase that may catalyze NH4+/H+ exchange across the cytoplasmic membrane has been cloned. Mechanisms of pH homeostasis in other enteric bacteria are reviewed and provide insight into additional pathways that may be used by H. pylori. An important adaptation of H. pylori to the gastric environment may be its ability to alter gastric acid secretion. Acute infection is associated with transient hypochlorhydria, whereas chronic infection is associated with hypergastrinemia and decreased somatostatin levels. Thus, the survival of H. pylori in the gastric environment may be attributed to both the development of specialized intrinsic defenses and the organism's ability to induce physiological alterations in the host environment.     

Gene therapeutic strategies for neuroprotection: implications for Parkinson''s disease

The model used for calculating perfusion by MRI techniques that use endogenous water as a tracer assumes that arterial water is a freely diffusible tracer. Evidence shows that this assumption is not valid in the brain at high blood flow rates, at which movement of water into and out of the microvasculature becomes limited by diffusion across the blood-brain barrier. In this work, the arterial spin-labeling technique is used to show that fraction of arterial water that is dependent on blood flow rate remains in the vasculature and does not exchange with brain tissue water. By using perfusion measurements without and with magnetization transfer (MT) effects, one can distinguish arterial label that exchanges into tissue because blood has much smaller MT than brain tissue. Using this technique, the extraction fraction for water is measured in the rat brain at various cerebral blood flow rates. At high flow rates (approximately 5 ml/g/min), the extraction fraction for water is found to be about 45% in rat brain. Disruption of the blood-brain barrier with D-mannitol caused an increase in the extraction fraction for water. It was possible to form an image related to the extraction fraction for water. The ability to estimate the amount of vascular water exchanging with tissue water by MRI may represent a noninvasive approach to detect the integrity of the blood-brain barrier.     

Developmental pathways leading to externalizing behaviors in 5 year olds born before 29 weeks of gestation

Recent studies have improved our understanding of the cytogenesis, biology, and therapy of chronic lymphocytic leukemia (CLL). This review highlights this recent progress reported over the past year. We have improved our understanding of the cytogenetic abnormalities in CLL and soon may see identification of new tumor suppressor genes that may be deleted in the leukemia cells of a large number of patients with this disease. We have achieved a better understanding of the surface antigens that help govern the pattern of tissue-infiltration of leukemia cells in vivo. Studies on the immune pathophysiology of CLL are providing clues to potential mechanisms leading to the immunodeficiency associated with this disease. Combination chemotherapy with purine analogues is showing promise for improved efficacy in CLL. Finally, new therapies incorporating bone marrow transplantation, and possibly gene therapy, increasingly are being considered for the therapy of patients with this disease.     

Narrow complex tachycardia with VA block: diagnostic and therapeutic implications

To review our experience with cases of narrow complex tachycardia with VA block, highlighting the difficulties in the differential diagnosis, and the therapeutic implications. Prior reports of patients with narrow complex tachycardia with VA block consist of isolated case reports. The differential diagnosis of this disorder includes: automatic junctional tachycardia, AV nodal reentry with final upper common pathway block, concealed nodofascicular (ventricular) pathway, and intra-Hissian reentry. Between June 1994 and January 1996, six patients with narrow complex tachycardia with episodes of ventriculoatrial block were referred for evaluation. All six patients underwent attempted radiofrequency ablation of the putative arrhythmic site. Three of six patients had evidence suggestive of a nodofascicular tract. Intermittent antegrade conduction over a left-sided nodofascicular tract was present in two patients and the diagnosis of a concealed nodofascicular was made in the third patient after ruling out other tachycardia mechanisms. Two patients had automatic junctional tachycardia, and one patient had atrioventricular nodal reentry with proximal common pathway block. Attempted ablation in the posterior and mid-septum was unsuccessful in patients with nodofascicular tachycardia. In contrast, those with atrioventricular nodal reentry and automatic junctional tachycardia readily responded to ablation. The presence of a nodofascicular tachycardia should be suspected if: (1) intermittent antegrade preexcitation is recorded, (2) the tachycardia can be initiated with a single atrial premature producing two ventricular complexes, and (3) a single ventricular extrastimulus initiates SVT without a retrograde His deflection. The presence of a nodofascicular pathway is common in patients with narrow complex tachycardia and VA block. Unlike AV nodal reentry and automatic junctional tachycardia, the response to ablation is poor.     

Microalbuminuria: prognostic and therapeutic implications in diabetic and hypertensive pregnancy

Microalbuminuria is defined as urinary excretion of albumin that is persistently above normal, although below the sensitivity of conventional semiquantative test strips. Several studies have reported that Type 1 diabetic patients with microalbuminuria are apparently more likely to develop diabetic nephropathy eventually progressing to renal failure. Microalbuminuria is also a strong predictor of mortality in Type 2 diabetes, and is correlated with increased blood pressure in patients with benign essential hypertension. Radioimmunoassay revealed a significantly higher urinary albumin excretion rate in normal pregnant women in the third trimester of pregnancy, compared to the second and first, and compared to non-pregnant women. Microalbuminuria was found in 30% of women who had a record of gestational diabetes mellitus. Published results are controversial regarding the assumption that microalbuminuria is an early predictor of pregnancy-induced hypertensive complications.     

Type II diabetic nephropathy: its clinical course and therapeutic implications

Type II diabetes is responsible for more end-stage renal disease in the United States than any other single condition. Until recently, the majority of research in diabetic nephropathy has focused on patients with type I diabetes despite the fact that type II nephropathy is a more prevalent condition. The notion that there are major differences between the nephropathy of these two types of diabetes is not supported by recent literature. The biggest difference appears to be related to ethnic risk. Histopathologic differences are now being described as well. Clinical interventional trials are few compared to type I diabetes; however, it seems that maneuvers that improve renal prognosis in patients with type I diabetes (blood pressure control, blood glucose control, and the use of angiotensin-converting enzyme inhibitors) apply to the type II population as well. Some of the calcium channel blockers lower proteinuria to a degree that suggests renoprotection and may further improve outcome.     

The MacArthur Treatment Competence Study: Legal and therapeutic implications.

This article assesses the legal and public policy implications of the MacArthur Treatment Competence Study (e.g., P. S. Appelbaum and T. Grisso, Grisso et al, and Grisso and Appelbaum; see records 82:39258, 82:35494, and 82:37814, respectively). The study's finding that treatment incapacity cannot be equated with mental illness or any particular diagnostic category creates the need for individualized determinations of incompetence. The incidence of involuntary hospitalization and treatment that are based on assertions of the state's parens patriae power will be reduced, thereby increasing voluntary hospitalization and treatment of those with mental illness. The study suggests ways of improving the disclosure of treatment information in the informed consent process and provides support for the movement toward a presumption of competence. It is suggested that the legal changes that will be fueled by the study (increasing the efficacy of hospitalization and treatment, strengthening the therapist–patient relationship, and destigmatizing mental illness) have therapeutic advantages. (PsycINFO Database Record (c) 2010 APA, all rights reserved)