Beneficiary centered care in services to persons with developmental disabilities.

This article provides an overview of the findings from the Evaluation of Medicaid's Community Supported Living Arrangements (CSLA) Program. Results suggest that CSLA provided a useful model of beneficiary centered care for persons with developmental disabilities. The implications of the findings of this evaluation for current management of Medicaid programs are discussed.     

Tourniquet inflation after intra-articular morphine and bupivacaine administration following knee arthroscopy

We performed a randomized doubled-blind study to evaluate whether there was a benefit in delay in tourniquet deflation with intra-articular administration of morphine and bupivacaine following operative arthroscopic surgery. In 34 patients the tourniquet was deflated immediately and in 38 patients the tourniquet remained inflated for 10 min following injection. The analgesic efficacy was assessed using pain scores and the amount of supplementary analgesia required. The results demonstrate no benefit in delay in tourniquet deflation.     

Explicit scoring criteria for the Rey-Osterrieth and Taylor complex figures

Explicit scoring criteria based on the Taylor-Osterrieth method were developed for the Rey-Osterrieth and Taylor Complex Figure Tests. Without such criteria, clinicians and researchers are left to develop their own idiographic scoring systems, leading to low interrater reliability, especially in the middle range of scores. Criteria were applied to the copy and 30-min recall protocols of 101 subjects infected with HIV. Results indicate that the criteria presented are reliable across a wide range of scores, making them useful for tracking subtle changes over time. Independent raters were within two points of each other on 90.1 % of the copy and 88.1% of recall scores, with a maximum disagreement of five points on two copy protocols. The Taylor figure was also found to be more easily remembered than the Rey-Osterrieth, calling into question their interchangeability. Explicit criteria are particularly useful in research settings. They ensure interrater reliability over time and across examiners in longitudinal studies, enhance the detection of subtle differences within the normal range, and allow comparison of results obtained by different investigators.     

Macrophage impairment underlies airway occlusion in primary respiratory syncytial virus bronchiolitis

Although respiratory syncytial virus (RSV) infection is the most important cause of bronchiolitis in infants, the pathogenesis of RSV disease is poorly described. We studied histopathologic changes in a panel of lung tissue specimens obtained from infants with fatal cases of primary RSV infection. In these tissues, airway occlusion with accumulations of infected, apoptotic cellular debris and serum protein was consistently observed. Similar observations were found after RSV infection in New Zealand black (NZB) mice, which have constitutive deficiencies in macrophage function, but not in BALB/c mice. A deficiency in the number of alveolar macrophages in NZB mice appears to be central to enhanced disease, because depletion of alveolar macrophages in BALB/c mice before RSV exposure resulted in airway occlusion. In mice with insufficient numbers of macrophages, RSV infection yielded an increased viral load and enhanced expression of type I interferon-associated genes at the height of disease. Together, our data suggest that innate, rather than adaptive, immune responses are critical determinants of the severity of RSV bronchiolitis.     

INHIBITION OF THE EFFECTS OF ANGIOTENSIN II ON ADRENAL STEROID PRODUCTION BY DIETARY SODIUM

The pressor octapeptide, angiotensin II, can stimulate the production of aldosterone by the adrenal cortex. The present results show that in the dog a high-sodium diet can eliminate the steroidogenic action of angiotensin II, which is thus dissociated from the pressor action which remains.Angiotensin II was infused intravenously for 48 hours into conscious, undisturbed hypophysectomized dogs that were receiving each day either 60 or 200 mEq of dietary sodium. Blood pressure and secretion of aldosterone, corticosterone, and cortisol were measured (1) throughout the infusion in some dogs, and (2) at the end of the infusion in all dogs. In those dogs receiving 60 mEq of sodium, angiotensin II elevated the blood pressure and produced sustained increases of secretion of aldosterone, corticosterone, and cortisol. In those dogs receiving 200 mEq of sodium, angiotensin II, while retaining its pressor activity, had no effect on the production of aldosterone, corticosterone, or cortisol after 24 hours. Thus, if angiotensin II can produce hypertension clinically, there need not be secondary aldosteronism as well.     

Sustained hemodynamic and antianginal effect of high dose oral isosorbide dinitrate.

Twenty-one patients with documented coronary atherosclerotic heart disease were studied to determine the effect of high dose oral isosorbide dinitrate (ISDN) on heart rate, blood pressure, and exercise time until angina pectoris. Patients were tested in two phases, initially with 0.4 mg of sublingual nitroglycerin and with sublingual placebo, and then with oral ISDN, mean dose 29 mg, and oral placebo. Both phases of the study were conducted in a randomized, double-blind, crossover manner. After ISDN was compared to oral placebo, heart rate increased at 30 to 300 min (P less than 0.01) (peak increase 18 beats/min at 60 min), and systolic blood pressure decreased from 45 to 300 min (P less than 0.005) (peak decrease 18 mm Hg at 60 min). Exercise time at 2 min after sublingual nitroglycerin increased 51% as compared to oral placebo, exercise time increased 54% at 1 hr (P less than 0.005), 37% at 3 hr (P less than 0.01), and 12% at 5 hr (NS). Twelve of 21 patients (57%) improved their exercise time until angina larger than or equal to 25% at 1 hr after oral ISDN. The exercise response to sublingual nitroglycerin was a good predictor of this response to oral ISDN.     

In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine

The reversible S-nitrosation and inhibition of mitochondrial complex I is a potential mechanism of cardioprotection, recruited by ischemic preconditioning (IPC), S-nitrosothiols, and nitrite. Previously, to exploit this mechanism, the mitochondrial S-nitrosating agent S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) was developed, and protected perfused hearts and isolated cardiomyocytes against ischemia–reperfusion (IR) injury. In the present study, the murine left anterior descending coronary artery (LAD) occlusion model of IR injury was employed, to determine the protective efficacy of SNO-MPG in vivo. Intraperitoneal administration of 1 mg/kg SNO-MPG, 30 min prior to occlusion, significantly reduced myocardial infarction and improved EKG parameters, following 30 min occlusion plus 2 or 24 h reperfusion. SNO-MPG protected to the same degree as IPC, and notably was also protective when administered at reperfusion. Cardioprotection was accompanied by increased mitochondrial protein S-nitrosothiol content, and inhibition of complex I, both of which were reversed after 2 h reperfusion. Finally, hearts from mice harboring a heterozygous mutation in the complex I NDUSF4 subunit were refractory to protection by either SNO-MPG or IPC, suggesting that a fully functional complex I, capable of reversible inhibition is critical for cardioprotection. Overall, these results are consistent with a role for mitochondrial S-nitrosation and complex I inhibition in the cardioprotective mechanism of IPC and SNO-MPG in vivo.     

Neuron number in the parahippocampal region is preserved in aged rats with spatial learning deficits

The entorhinal, perirhinal and parahippocampal cortices are anatomically positioned to mediate the bi-directional flow of information between the hippocampus and neocortex. Consistent with this organization, damage involving the parahippocampal region causes significant learning and memory impairment in young subjects. Although recent evidence indicates that neuron death in the hippocampus is not required to account for the effects of normal aging on learning and memory, other findings suggest that changes in parahippocampal interactions with the hippocampus may play a significant role. Prompted by this background, we tested the possibility that age-related deficits in hippocampal learning are coupled with neuron death in the parahippocampal region. The experiments took advantage of a well-characterized rat model of cognitive aging in combination with stereological methods for quantifying neuron number. The results demonstrate that total neuron number in the entorhinal, perirhinal and postrhinal cortices is largely preserved during normal aging. Furthermore, individual variability in hippocampal learning among the aged rats failed to correlate with neuron number in any region examined and there was no indication of selective or disproportionate loss among the aged animals with the most pronounced cognitive impairment. Taken together with earlier findings from the same study population, the results demonstrate that age-related cognitive decline can occur in the absence of significant neuron death in any major, cytoarchitectonically defined component of the hippocampal system. These findings provide an essential framework for identifying the basis of cognitive aging, suggesting that alterations in connectivity and other changes are more likely causative factors.