The intravascular contribution to fmri signal change: monte carlo modeling and diffusion-weighted studies in vivo

Understanding the relationship between fMRI signal changes and activated cortex is paramount to successful mapping of neuronal activity. To this end, the relative extravascular and intravascular contribution to fMRI signal change from capillaries (localized), venules (less localized) and macrovessels (remote, draining veins) must be determined. In this work, the authors assessed both the extravascular and intravascular contribution to blood oxygenation level-dependent gradient echo signal change at 1.5 T by using a Monte Carlo model for susceptibility-based contrast in conjunction with a physiological model for neuronal activation-induced changes in oxygenation and vascular volume fraction. The authors compared our Model results with experimental fMRI signal changes with and without velocity sensitization via bipolar gradients to null the intravascular signal. The model and experimental results are in agreement and suggest that the intravascular spins account for the majority of fMRI signal change on T₂^*-weighted images at 1.5 T.     

Myocardial perfusion and function in dogs with moderate coronary stenosis

MRI studies of first-pass contrast enhancement with polylysine-Gd-DTPA and myocardial tagging using spatial modulation of magnetization (SPAMM) were performed to assess the feasibility of a combined regional myocardial blood flow and 2D deformation exam. Instrumented closed-chest dogs were imaged at a baseline control state (Cntl) followed by two interventions: moderate coronary stenosis (St) achieved by partial occlusion of the left anterior descending (LAD) and moderate coronary stenosis with dobutamine loading (StD). Hypoperfusion of the anterior region (ANT) of the myocardium (LAD distribution) relative to the posterior wall (POS) based on the upslope of the signal intensity time curve from the contrast-enhanced MR images was demonstrated only with dobutamine loading (ANT:POS Cntl=1.077 ± 0.15 versus ANT:POS StD=0.477 ± 0.11, P<0.03) and was confirmed with radio-labeled microspheres measurements (ANT:POS Cntl=1.18 ± 0.2 ml/min/g versus ANT:POS StD=0.44 ± 0.1 ml/min/g; P<0.002). Significant changes in regional myocardial shortening were only seen in the StD state (P<0.02); the anterior region showed impaired myocardial shortening with dobutamine loading (P=NS), whereas the nonaffected POS region showed a marked increase in shortening when compared with Cntl (Cntl=0.964 ± 0.02 versus StD=0.884 ± 0.03; P<0.001). These results demonstrate that an integrated quantitative assessment of regional myocardial function and semiquantitative assessment of myocardial blood flow can be performed noninvasively with ultrafast MRI.     

Triazolam-induced changes in alcoholic thought processes

 This study was designed to examine and contrast cognitive effects (explicit memory and access to semantic knowledge) of the benzodiazepine Halcion (triazolam) in ten normal volunteers and ten cognitively unimpaired detoxified alcoholics. The two groups were indistinguishable from one another under placebo conditions on all measures of cognitive functioning. Under Halcion test conditions (0.375 mg PO), both groups were about equally impaired in their recall of to-be-remembered information. However, alcoholics, were more likely to recall information that they were not asked to remember (intrusion errors) on all measures of explicit remembering. Alcoholics also generated relatively uncommon (low frequency) responses from semantic memory, rather than common, categorically related associations in response to stimuli such as types of vegetables, flowers, and fruit following the administration of Halcion, but were not different from normal volunteers in the types of responses generated under placebo conditions. These findings suggest that a drug challenge that simulates many of the effects of acute alcohol administration induces alcoholics to think and remember differently (qualitatively) from normal volunteers. Received: 7 July 1997 / Final version: 22 September 1997     

Cost-effectiveness analysis: What is it and how it influence neurology

Cost-effectiveness analysis (CEX) refers to a set of research methods that consider the resources consumed by a medical technology in decisions about how best to use the technology. This analytic method is an evolving, controversial, and often misunderstood field in health services research. The basic set of principles underlying CEA is deceptively simple, but sufficient methodological challenges and controversies exist that have, thus far, limited its use in the development of health policy and in bedside decision making. Nonetheless, neurologists like other specialty groups may feel concerned that the results from such analyses may prove unfavorable to their specialty and the patients they serve. This article reviews the fundamental notions surrounding CEA, provides examples from the literature with particular relevance to the neurological community, and highlights critical issues for neurologists regarding the future of CEA.     

Positive and negative symptoms covary during clozapine treatment in schizophrenia

Although negative symptoms were traditionally considered to be unresponsive to neuroleptic medication, recent studies have demonstrated that negative symptoms do improve during neuroleptic treatment and that such improvement tends to occur concurrently with improvement in positive symptoms. Clozapine is an atypical neuroleptic that is effective in a significant proportion of otherwise neuroleptic-nonresponsive schizophrenic patients; in contrast to conventional neuroleptics, clozapine is also purported to possess unique efficacy in the amelioration of negative symptoms. How clozapine-associated reduction in negative symptoms relates to change in positive symptoms is not clear. To study the relationship between change in positive and negative symptoms during clozapine treatment, we monitored symptomatology in 40 DSM-III-R schizophrenic patients before and about 8 weeks after a trial of clozapine. Both positive and negative symptoms improved significantly. There was a significant correlation (r = .63,p <.01) between change in positive symptoms and change in negative symptoms; as with conventional neuroleptics, negative symptoms improved concomitantly with positive symptoms during clozapine treatment. Clozapine's apparent greater efficacy on negative symptoms may be related to its greater efficacy on positive symptoms in otherwise neuroleptic-refractory patients and its lesser propensity to cause extrapyramidal side-effects.     

Radical radiotherapy for T4 carcinoma of the skin of the head and neck: A multivariate analysis

Sixty-seven patients with 68 stage T4 carcinomas of the skin of the head and neck were treated with radical radiotherapy at the University of Florida between October 1964 and November 1989. Thirty-three lesions were previously untreated and 35 were recurrent. Twenty-nine lesions were squamous cell carcinomas, 37 were basal cell carcinomas, and 2 were basosquamous carcinomas. Minimum follow-up was 2 years. The 5-year local control, local control including surgical salvage, and cause-specific survival probabilities were 53%, 74%, and 75%, respectively. Local control rates with radiotherapy alone were poorer in patients with recurrent lesions (41% vs. 67%, p = .07) or bone involvement (40% vs. 62%, p = .08). Results were analyzed by multivariate methods using local control, local control with surgical salvage, and cause-specific survival as endpoints. The parameters analyzed were histology; size of primary lesion; previous treatment (previously untreated vs. recurrent); involvement of bone, nerve, or cartilage; and skeletal muscle invasion. Three important prognostic factors were identified, each predictive of poorer ultimate local control and cause-specific survival rates: (a) bone involvement (p < .01); (b) recurrent lesions (p < .01); and (c) nerve involvement (p < .02). Radiotherapy alone can control advanced carcinomas of the skin of the head and neck, although lesions that have recurred after prior treatment and those with involvement of bone or nerve are associated with a lower likelihood of cure.     

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.