Hemodynamics and survival of patients with portopulmonary hypertension.

It is not known whether patients with pulmonary arterial hypertension associated with portal hypertension (portopulmonary hypertension (PPHTN) have different disease characteristics from those of patients with other forms of pulmonary arterial hypertension. We performed a retrospective cohort study of patients with PPHTN and patients with pulmonary arterial hypertension that was idiopathic, familial, or associated with anorexigen use (IPAH) to determine whether hemodynamics or survival were different between these groups. We included consecutive patients who underwent initial pulmonary artery catheterization and vasodilator testing at our center between January 1997 and May 2001 and who were followed until January 2004. Patients with PPHTN (N = 13) had a higher cardiac index and lower pulmonary vascular resistance than patients with IPAH (N = 33) (P < or = 0.001). Right atrial pressure and pulmonary artery pressure were similar between the groups. Patients with PPHTN had a higher risk of death in multivariate analysis (hazard ratio: [HR] = 2.8, 95% CI 1.04-7.4; P = 0.04). These findings were not affected by adjustment for differences in laboratory values, hemodynamics, or therapy. In conclusion, patients with PPHTN have a higher risk of death than that of patients with IPAH, despite having a higher cardiac index and lower pulmonary vascular resistance. Future studies of the specific mechanisms of and therapy for pulmonary arterial hypertension should focus on the distinctions between the different forms of this disease.     

Neural substrates of semantic memory.

Semantic memory is described as the storage of knowledge, concepts, and information that is common and relatively consistent across individuals (e.g., memory of what is a cup). These memories are stored in multiple sensorimotor modalities and cognitive systems throughout the brain (e.g., how a cup is held and manipulated, the texture of a cup's surface, its shape, its function, that is related to beverages such as coffee, and so on). Our ability to engage in purposeful interactions with our environment is dependent on the ability to understand the meaning and significance of the objects and actions around us that are stored in semantic memory. Theories of the neural basis of the semantic memory of objects have produced sophisticated models that have incorporated to varying degrees the results of cognitive and neural investigations. The models are grouped into those that are (1) cognitive models, where the neural data are used to reveal dissociations in semantic memory after a brain lesion occurs; (2) models that incorporate both cognitive and neuroanatomical information; and (3) models that use cognitive, neuroanatomic, and neurophysiological data. This review highlights the advances and issues that have emerged from these models and points to future directions that provide opportunities to extend these models. The models of object memory generally describe how category and/or feature representations encode for object memory, and the semantic operations engaged in object processing. The incorporation of data derived from multiple modalities of investigation can lead to detailed neural specifications of semantic memory organization. The addition of neurophysiological data can potentially provide further elaboration of models to include semantic neural mechanisms. Future directions should incorporate available and newly developed techniques to better inform the neural underpinning of semantic memory models.     

Pilot study to enhance HIV care using needle exchange-based health services for out-of-treatment injecting drug users

The introduction of highly active antiretroviral therapy (HAART) has resulted in marked reductions in mortality and acquired immunodeficiency syndrome (AIDS) incidence across all risk groups; however, the proportionate decrease among injecting drug users (IDUs) has been less impressive. Much of the disparity in benefit to IDUs has been a consequence of decreased access to and receipt of potent antiretroviral combinations. Strategies to increase access to and utilization of HAART have included entry into drug treatment and abstinence. Unfortunately, as few as 15%–20% of active drug users in the United States, and in many other countries, are in drug treatment at any one time. We report a pilot project among out-of-drug treatment IDUs infected with human immunodeficiency virus (HIV); HIV therapy was successfully provided to active heroin injectors using the Community Health Care Van (CHCV) at sites of needle exchange. Subjects were willing to initiate, but were not receiving, recommended HIV therapy and were not interested in formal drug treatment. Antiretroviral therapy regimens were selected and linked to heroin injection timing. Weekly visits were scheduled by CHCV staff to assess adverse side effects and encourage adherence. Of the 13 participants, the mean baseline HIV-1 RNA level and CD4 lymphocyte count were 162,369 (log 5.21) copies per milliliter and 265 cells per milliliter, respectively. By 6 months, the proportion whose HIV-1 RNA was below the limits of detection (<400 copies/mL) was 85% (N=11); 77% (N=10) had nondetectable levels by 9 months. By 12 months, 54% (N=7) had a persistently nondetectable viral load, and the net increase in CD4 lymphocyte count was 150 cells per milliliter. As an additional and unintended benefit of this pilot project, 9 (69%) subjects chose to enter drug treatment after achieving a nondetectable viral load. Entry into drug treatment was associated with durability of viral suppression. This small pilot study suggests that health services based on needle exchange may enhance access to HAART among out-of-treatment HIV-infected IDUs. In addition, it demonstrates that this population can benefit from this therapy with the support of a nontraditional, community-based health intervention.     

The effect of pre-vertebroplasty tumor ablation using laser-induced thermotherapy on biomechanical stability and cement fill in the metastatic spine

A biomechanical study comparing simulated lytic vertebral metastases treated with laser-induced thermotherapy (LITT) and vertebroplasty versus vertebroplasty alone. To investigate the effect of tumor ablation using LITT prior to vertebroplasty on biomechanical stability and cement fill patterns in a standardized model of spinal metastatic disease. Vertebroplasty in the metastatic spine is aimed at reducing pain, but is associated with risk of cement extravasation in up to 10%. Six pairs of fresh-frozen cadaveric thoracolumbar spinal motion segments were tested in axial compression intact, with simulated metastases and following percutaneous vertebroplasty with or without LITT. Canal narrowing under load, pattern of cement fill, load to failure, and LITT temperature and pressure generation were collected. In all LITT specimens, cement filled the defect without extravasation. The canal extravasation rate was 33% in specimens treated without LITT. LITT and vertebroplasty yielded a trend toward improved posterior wall stability (P = 0.095) as compared to vertebroplasty alone. Moderate rises in temperature and minimal pressure generation was seen during LITT. In this model, elimination of tumor by LITT, facilitates cement fill, enhances biomechanical stability and reduces the risk of cement extravasation.     

Expression of c-fos, fos B, and egr-1 in the medial preoptic area and bed nucleus of the stria terminalis during maternal behavior in rats

The spatial and temporal pattern of expression of the protein products of immediate early genes (IEGs) c-fos, fos B, and egr-1 were mapped in medial preoptic area (MPOA) and ventral bed nucleus of stria terminalis (VBST) during maternal behavior in rats. Immunocytochemical analysis indicated significant increases in the number of cells expressing c-Fos after 2 h of pup exposure, while Fos B levels showed a delayed response, reaching maximal levels after 6 h.     

Regulation of the acid-labile subunit of the insulin-like growth factor ternary complex in patients with insulin-dependent diabetes mellitus and severe burns

OBJECTIVE Little information is available regarding the regulation of serum acid-labile subunit (ALS) in human disease. We have studied alterations in serum ALS of the insulin-like growth factor (IGF) ternary complex in children with untreated insulin-dependent diabetes mellitus (IDDM) and subjects with severe burns before and after insulin therapy. In addition, we have investigated the effect of insulin plus GH on serum ALS in burn patients. DESIGN Serum samples were obtained from children with newly diagnosed and untreated IDDM before the initiation of insulin therapy and 1 month thereafter. Serum samples were also obtained from adult patients with severe burns who were on a continuous infusion of a carbohydrate-rich enteral diet via nasogastric and duodenal catheters under basal conditions, after a 1-week period of continuous insulin infusion, and after an additional week of insulin plus recombinant GH. PATIENTS Twenty children and adolescents with untreated IDDM, aged 1.2–16 years, and 6 young adult patients with severe burns aged 17–28 years were studied longitudinally. Control sera were obtained from age, sex and pubertal status matched subjects (for children with IDDM) and from fed healthy adults. MEASUREMENTS Serum insulin, GH, cortisol and IGF-I were measured by radioimmunoassay, and serum ALS levels were assessed by Western immunoblot before and after treatment periods. RESULTS Serum ALS levels were lower in untreated children with IDDM (69 ± 6% of control children). Insulin therapy significantly increased serum ALS (79 ± 5%, P<0.05) in these children. Patients with severe burns also had lower serum ALS levels (79 ± 10% of control adults). After one week of insulin therapy serum ALS levels increased to 90 ± 15% of control values (P<0.05). Addition of GH to insulin therapy for another week did not significantly further increase serum ALS levels (95 ± 27%). Serum IGF-I concentrations increased nearly 2.5-fold in diabetic subjects and fourfold in burn subjects at the end of the study periods. There were no proteolytic fragments of ALS in the sera studied. The deglycosylation pattern of ALS did not differ between diabetic and control sera. CONCLUSION Serum ALS levels were diminished in children with untreated IDDM and were partially restored after the initiation of insulin therapy. Serum ALS levels were also diminished in patients with severe burn injury and restored by insulin treatment. Addition of GH to insulin therapy did not significantly increase serum ALS levels over levels obtained during insulin therapy alone. These decreases in serum ALS were smaller than the decrease in serum IGF-I concentrations in both conditions, suggesting that IGF-I is the limiting factor for the ternary complex formation in the catabolic states. Insulin may regulate circulating ALS levels in catabolic states and helps to restore the IGF system.     

Advancing Nursing Practice with a Unit-based Clinical Expert

Objective: To explore patterns in the practice of nursing and patient outcomes.
Design: Qualitative field research.
Population, Sample, Setting: Populations were critical care nurses and critically ill adult patients in the 10-bed medical critical care unit of a 900-bed teaching hospital. A convenience-purposive sample of 27 nurses and 31 patients was studied in 1985.
Methods: Six months of participant observation, unstructured interviews, and the constant comparison method of grounded theory.
Findings: Markedly different patterns were found in expert and nonexpert practice. The substantive theory of conversion helped explain how the majority of nonexpert nurses advanced their practice. The metaphor of catalyzed conversion captures how a unit-based expert nurse serves as a catalyst to advance the practice of nonexperts. Presence, defined as the way of being within a given clinical context, differentiated nurses.
Conclusions: (a) Expert and nonexpert practices are substantively different, (b) Expert and nonexpert practice results in different patient outcomes, (c) Conversion helps explain changes in nonexpert practice.
Clinical Implications: A unit-based expert nurse can increase patient-focused care.     

The mechanism of yohimbine-induced renin release in the conscious rat

Summary These studies were designed to determine the role of the central nervous system, the sympathetic nervous system, the adrenal glands and the renal sympathetic nerves in yohimbine-induced renin release in conscious rats. Yohimbine (0.3–10 mg/kg, s.c.) caused time- and dose-related increases in plasma renin activity (PRA) and concentration (PRC) which were accompanied by time- and dose-related elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. Significant positive correlations were found between the increases in PRA and the increases in plasma NE and Epi concentrations caused by yohimbine, and propranolol (1.5 mg/kg, s.c.) blocked 90% of yohimbine (3 mg/kg, s.c.)-induced renin release. Over the entire spectrum of doses of yohimbine, the increases in PRA and plasma NE and Epi concentrations were positively correlated with the decreases in mean arterial pressure (MAP), but the -intercept was positive in every case and the 1 mg/ kg dose of yohimbine consistently increased PRA independent of any change in MAP. Complete renal denervation, as evidenced by a greater than 90% reduction in renal NE content, did not alter the increase in PRA caused by yohimbine (3 mg/kg, s.c.). An increase in circulating plasma catecholamine concentrations appeared to mediate yohimbine-induced renin release since propranolol prevented the rise in PRA caused by yohimbine in renal denervated rats. Prior adrenalectomy (Adx) also failed to prevent the rise in PRA produced by yohimbine (3 mg/kg, s.c.), but a combination of Adx and renal denervation caused a significant impairment of yohimbine-induced renin release. However, neither Adx alone nor the combination of Adx and renal denervation affected the increase in plasma NE concentration caused by yohimbine. Complete transection of the spinal cord at C₈ caused a drastic reduction in plasma catecholamine concentrations but did not change basal PRC. Yohimbine (3 mg/kg, s.c.) did not increase PRC or plasma catecholamine concentrations after spinal transection. Based on these results, we conclude that 1) the stimulation of renin release by yohimbine is a secondary neurohormonal consequence of the generalized increase in sympathetic activity caused by yohimbine, 2) the sympathoadrenal activation produced by yohimbine results from an action in the brain which is amplified by the simultaneous blockade of prejunctional ₂-adrenoceptors and 3) vasodepressor effects of the larger doses yohimbine cause a baroreflexly-mediated increase in sympathetic activity which interacts in a positive fashion with the central and peripheral sympathoexcitatory effects of yohimbine. Send offprint requests to T. K. Keeton