Effect of primary renal disease in patients with renovascular insufficiency

The effect of laboratory evidence of renal parenchymal abnormality on the results of renal revascularization in 83 patients with renovascular hypertension was determined. Primary renal disease (PRD) was defined as an abnormal urinalysis (proteinuria, hematuria, or casts) in the absence of urinary infection, or decreased renal function (elevated serum creatinine level greater than 1.5 mg/dl and/or decreased creatinine clearance). All patients were hypertensive on medical therapy preoperatively. Patients were defined as cured if postoperative diastolic blood pressure (BP) was less than 90 mm Hg on no medication and improved if BP less than 90 mm Hg on medication. Sixty-six patients (80%) were cured or improved following revascularization. Of 45 patients (63%) with evidence of PRD preoperatively, 28 (62%) were cured or improved compared with 33 patients without PRD, of whom all (100%) were cured or improved (p less than 0.001). Each of five patients with transplant renal artery stenosis had two operations; four were cured or improved. The serum creatinine level was elevated preoperatively in 37 cases. Eighteen of the 37 (49%) improved to within normal limits following operation. Fifteen patients had simultaneous bilateral renal artery revascularization, and 12 (80%) were cured or improved. Fourteen patients (17%) had concomitant vascular procedures: aortobifemoral bypass (seven), abdominal aneurysm resection (five), femoral endarterectomy (one), and aortoiliac bypass (one). Twelve of these 15 patients had PRD, and 8 of the 12 (67%) were cured or improved. Only one death occurred in the perioperative period. Thirty-eight patients (46%) had been treated for hypertension for more than 12 months before referral.(ABSTRACT TRUNCATED AT 250 WORDS)     

Large-vessel arterial occlusive disease in symptomatic upper extremity

Subclavian and axillary artery occlusive disease resulted in sufficient upper extremity symptoms to necessitate 30 vascular reconstructions in 28 patients over the past ten years. Female patients predominated, with a ratio of 2.5:1. The average age of the patients was 61 years. The incidence of diabetes mellitus was low (7%). Sixteen of 18 proximal subclavian lesions were on the left side, while more distal lesions were equally distributed on the left and right. Extrathoracic bypasses were used in all cases. Dacron grafts were used in 16 of 17 carotid-subclavian bypasses. Autogenous vein grafts were used in 11 of 13 bypasses to the axillary or brachial artery. Concomitant cervicodorsal sympathectomy was done in only four patients. The in-hospital graft patency rate was 93% and the long-term graft patency rate at one year and beyond was 88%.     

Selective changes in gene expression in cortical regions sensitive to amphetamine during the neurodegenerative process

Gene expression profiles in several brain regions of adult male rats were evaluated following a d-amphetamine (AMPH) exposure paradigm previously established to produce AMPH neurotoxicity. Escalating doses of AMPH (5-30 mg/kg) were given over the course of 16 h per day in an 18 degrees C environment for 2 days. This paradigm produces neurotoxicity but eliminates or minimizes the hyperthermia and seizure activity that might influence gene expression in a manner unrelated to the neurotoxic effects of AMPH. The expression of 1185 genes was monitored in the striatum, parietal cortex, piriform cortex and posteriolateral cortical amygdaloid nucleus (PLCo) using cDNA array technology, and potentially significant changes were verified by RT-PCR. Gene expression was determined at time points after AMPH when neurodegeneration was beginning to appear (16 h) or maximal (64 h). Expression was also determined 14 days after AMPH to find long-term changes in gene expression that might be biomarkers of a neurotoxic event. In the parietal cortex there was a two-fold increase in neuropeptide Y precursor protein mRNA whereas nerve growth factor-induced receptor protein I-A and I-B mRNA decreased 50% at 16 h after the end of AMPH exposure. Although these changes in expression were not observed in the PLCo, insulin-like growth factor binding protein 1 mRNA was increased two-fold in the PLCo at 16 and 64 h after AMPH. Changes in gene expression in the cortical regions were all between 1.2- and 1.5-fold 14 days after AMPH but some of these changes, such as annexin V increases, may be relevant to neurotoxicity. Gene expression was not affected by more than 1.5-fold at the time points in the striatum, although 65% dopamine depletions occurred, but the plasma membrane-associated dopamine transporter and dopamine D2 receptor were decreased about 40% in the substantia nigra at 64 h and 14 days post-AMPH. Thus, the 2-day AMPH treatment produced a few changes in gene expression in the two-fold range at time points 16 h or more after exposure but the majority of expression changes were less than 1.5-fold of control. Nonetheless, some of these lesser fold-changes appeared to be relevant to the neurotoxic process.     

Dysregulation of arousal and amygdala-prefrontal systems in paranoid schizophrenia

OBJECTIVE: The authors investigated impaired differentiation of limbic-prefrontal systems by autonomic arousal in schizophrenia. It was predicted that paranoid patients would be distinguished by a disjunction of hyperarousal but reduced amygdala and medial prefrontal activity relative to both healthy comparison subjects and patients with nonparanoid schizophrenia. METHOD: Pictures depicting facial expressions of fear were presented to 27 schizophrenia patients (13 paranoid, 14 nonparanoid) and 22 matched healthy comparison subjects in an implicit perception task to evoke limbic activity. Simultaneous functional magnetic resonance imaging and skin conductance arousal recordings were acquired during presentation of faces expressing fear or neutral emotion. Responses to fear stimuli were further examined by contrasting those that were associated with a skin conductance response ("with arousal") and those that were not ("without arousal"). RESULTS: In the comparison subjects, arousal dissociated amygdala/medial prefrontal ("visceral") networks and hippocampus/lateral prefrontal ("context") networks for fear perception. Excessive arousal responses were elicited in the schizophrenia subjects, but there was an associated reduction in amygdala/medial prefrontal activity. This disjunction was pronounced in paranoid patients relative to both healthy subjects and nonparanoid patients. Paranoid patients also showed a relatively greater prefrontal deficit for "without-arousal" responses. CONCLUSIONS: This is the first study to reveal a functional disconnection in autonomic and central systems for processing threat-related signals in patients with paranoid schizophrenia. Paranoid cognition may reflect an internally generated cycle of misattribution regarding incoming fear signals due to a breakdown in the regulation of these systems.     

Language-association cortex asymmetry in autism and specific language impairment

Language deficits are among the core impairments of autism. We previously reported asymmetry reversal of frontal language cortex in boys with autism. Specific language impairment (SLI) and autism share similar language deficits and may share genetic links. This study evaluated asymmetry of frontal language cortex in a new, independent sample of right-handed boys, including a new sample of boys with autism and a group of boys with SLI. The boys with autism were divided into those with language impairment (ALI) and those with normal language ability (ALN). Subjects (right-handed, aged 6.2-13.4 years) included 22 boys with autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal controls. MRI brain scans were segmented into grey and white matter; then the cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Group differences in volumetric asymmetry were predicted a priori in language-related regions in inferior lateral frontal (Broca's area) and posterior superior temporal cortex. Language impaired boys with autism and SLI both had significant reversal of asymmetry in frontal language-related cortex; larger on the right side in both groups of language impaired boys and larger on the left in both unimpaired language groups, strengthening a phenotypic link between ALI and SLI. Thus, we replicated the observation of reversed asymmetry in frontal language cortex reported previously in an independent autism sample, and observed similar reversal in boys with SLI, further strengthening a phenotypic link between SLI and a subgroup of autism. Linguistically unimpaired boys with autism had similar asymmetry compared with the control group, suggesting that Broca's area asymmetry reversal is related more to language impairment than specifically to autism diagnosis.     

A polymorphic variation in the interleukin 1A gene increases brain microglial cell activity in Alzheimer's disease

OBJECTIVE: To investigate the impact of possession of the -889 C/T polymorphism of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the interleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alzheimer's disease (AD), as demonstrated by the degree of microglial cell activity associated with each IL-1A and IL-1B genotype. METHOD: Microglial cell activity within the frontal cortex was determined in 68 patients with necropsy confirmed AD by image analysis as the percentage area of tissue occupied by ferritin immunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracted from frontal cortex or cerebellum. RESULTS: The microglial cell load was 31% greater in patients with IL-1A T allele, 62% greater with IL-1A TT genotype, but 108% greater with IL-1A TT genotype in combination with APOE epsilon4 allele. No effects on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone. CONCLUSIONS: Polymorphisms within IL-1A influence the degree of brain microglial cell activation, especially in bearers of APOE epsilon4 allele, reinforcing the importance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.     

A randomized controlled trial of integrated versus parallel housing services for homeless adults with severe mental illness

This study compared two contemporary approaches to linking housing and mental health services. In the integrated housing program, case management and housing services were provided by teams within a single agency and were closely coordinated. In the parallel housing condition, case management services were provided by mobile assertive community treatment teams and housing by routine community-based landlords. Adults with severe mental illness who were at high risk for homelessness (n = 121; 72.7% schizophrenia spectrum) were assigned randomly to integrated or parallel housing services and followed for 18 months. Integrated housing services led to more days of stable housing and greater life satisfaction than parallel housing services, especially for male participants. Integrated housing services were also associated with greater reductions in psychiatric symptoms. Closer integration between clinical and housing services, and greater use of supervised living settings, led to more time in stable housing for participants in the integrated housing services condition and was associated with greater gains in several outcome domains.