How will area regeneration impact on health? Learning from the GoWell study.

OBJECTIVES: To establish the theoretical and perceived links between area regeneration and health in a Scottish context in order to inform a comprehensive evaluation of regeneration activity. The evaluation will include health outcomes. STUDY DESIGN: Mixed method combining and comparing key informant interviews with policy analysis. METHODS: Analysis of identified links between elements of regeneration activity and health was undertaken of published policies and strategies which described regeneration for Scotland and the city of Glasgow. Interviews with key informants explored their understanding of the inputs to regeneration, and the pathways between regeneration and better health outcomes. RESULTS: The policy analysis and interviews revealed a holistic approach to a complex problem. Both identified a need for action to improve housing, neighbourhoods and services, education, employment, community participation and social issues. Improved health was identified as an emergent property. Interviewees identified a need to augment the established structural components with a more person-centred approach, fostering confidence and higher aspirations, but were uncertain how to achieve this. The interviews revealed a lack of confidence that current practice would deliver all the components of the holistic model. CONCLUSIONS: A holistic model of regeneration appears to inform policy, but is proving difficult to deliver. Improved health and reduced health inequalities were not primary objectives but emergent properties. In light of this, the ability of regeneration to actively maximize positive health impacts, particularly if this requires focused planning or opportunity costs to other activities, is questioned.

Calcium antagonists in heart transplant recipients: effects on cardiac and renal function and cyclosporine pharmacokinetics.

OBJECTIVE: Cyclosporine increases transmembrane calcium flux in mesangial and vascular smooth muscle cells, which may explain cyclosporine-induced decreases in renal bloodflow and glomerular filtration rate. Calcium antagonists, thus, may play a role in the prevention/reversal of cyclosporine nephrotoxicity. DESIGN: In a single-blind, randomized, cross-over study the authors evaluated the effects of a one-week treatment with nifedipine 20 mg bid, diltiazem 120 mg bid or placebo on cardiac and renal functions of six stable heart transplant recipients treated chronically with cyclosporine. RESULTS: Both calcium antagonists lowered blood pressure compared with placebo, but only nifedipine increased cardiac output and, therefore, decreased total peripheral resistance significantly more than diltiazem. Nifedipine induced a significant increase in effective renal plasma flow and an insignificant increase in glomerular filtration rate, whereas diltiazem caused a reduction in these parameters. Cyclosporine pharmacokinetics were not affected by either calcium antagonist to a clinically significant extent. CONCLUSIONS: Nifedipine and diltiazem exert distinctly different cardiac and renal hemodynamic effects in cardiac transplants, which may have clinical consequences.

Behavioral versus EEG-based monitoring of all-night sleep/wake patterns.

Faint tones were presented at intervals (average 16 s) throughout a night's sleep; whenever they heard them, subjects pressed a palm-mounted button to switch them off. At the same time, electroencephalogram (EEG) was recorded. Button-press responses occurred in all EEG stages of sleep except Stage 4, although there was only one behavioral response (BR) in Stage 3 and one in REM. The mean probability of response (PR)/Stage was Stage 1 = 0.235, Stage 2 = 0.016, Stage 3 = 0.001, Stage 4 = 0.000, Stage REM = 0.0004. Also, responses sometimes failed to occur in EEG Stage wake (PR = 0.94), particularly near sleep onset. If the criterion for wakefulness is cognitive response to external stimulation, only in EEG Stages 3, 4, and REM can accurate distinctions between sleep and wakefulness be made. If EEG is the criterion, then the data suggest that cognitive response is possible during Stages 1 and 2 "sleep." The concept of a sleep onset period (SOP), characterized by lengthening response times and intermittent response failure (thereby reflecting neither true sleep or wakefulness), may provide a useful resolution of this definitional dilemma.

Effect of nifedipine and propranolol on blood flow, venous compliance and blood pressure in essential hypertension.

To determine the efficacy of nifedipine combined with propranolol in the treatment of hypertension, 23 patients with essential hypertension uncontrolled while they were receiving propranolol, 120 mg/d, entered a dose response trial of four 8-week periods while continuing propranolol therapy. Therapy during the four periods consisted respectively of a placebo, 30 mg/d of nifedipine, 30 or 60 mg/d of nifedipine, and 30 or 60 mg/d of nifedipine along with only 60 mg/d of propranolol. Studies of forearm blood flow and venous compliance were carried out in nine of the patients. Ten patients dropped out after the first period. The mean blood pressures while the patients were recumbent after the first, second and third periods were 163 +/- 17/100 +/- 6, 147 +/- 13/89 +/- 10 and 141 +/- 19/84 +/- 10 mm Hg respectively. There was no evidence of tolerance in the four patients who received 30 mg/d of nifedipine during the third period. There was a significant dose-diastolic pressure response (p less than 0.0006) without a change in heart rate in the eight who received 60 mg/d of nifedipine during this period. After 16 weeks of therapy with nifedipine 11 patients had a diastolic pressure less than 90 mm Hg while recumbent. While mean blood pressure and heart rate for the group were not significantly increased at the end of the fourth period, in three of the patients the diastolic pressure while recumbent increased to over 90 mm Hg. This suggests that 120 mg/d of propranolol is the minimum dose required for concomitant therapy. Adverse symptoms were mild and transient. Forearm plethysmography showed that nifedipine induced arteriolar but not venous dilation and that propranolol attenuated the vasodilator effect of nifedipine. The author concludes that nifedipine was safe and effective in combination with propranolol in this group of patients with essential hypertension.

The evolution of renal osteodystrophy in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

Since the introduction of continuous ambulatory peritoneal dialysis by Popovich et al [1] and the subsequent modification of the technique by Oreopoulos et al [2], an increasing number of patients with end-stage renal disease are maintained on this new treatment modality. To date, there has not been any report of the effect of CAPD on the evolution of renal osteodystrophy which is one of the major complications of chronic renal failure. In this report we will present the results of our radiological and biochemical studies of renal osteodystrophy in 28 patients who have been on CAPD from 6 to 23 months.

Calcium metabolism in adult outpatients with epilepsy receiving long-term anticonvulsant therapy.

Long-term anticonvulsant drug therapy may lead to abnormalities of calcium metabolism resulting in osteomalacia. The prevalence and severity of altered calcium metabolism was studied in an adult outpatient population of persons with epilepsy receiving anticonvulsant therapy for a minimum of 2 years. Assessment of calcium metabolism was based on serum concentrations of calcium, phosphorus, alkaline phosphatase and 25-hydroxycholecalciferol and of plasma parathyroid hormone, intestinal absorption of isotopic calcium and skeletal bone mineral mass as determined by in vivo neutron activation or x-ray photodensitometry.Thirty-nine patients who had been receiving anticonvulsant therapy for an average of 20 years were studied; none had clinical evidence of metabolic bone disease. Decreased serum calcium concentration was noted in 10%, decreased serum phosphorus concentration in 10% and elevated serum alkaline phosphatase concentration in 44%. The mean serum 25-hydroxycholecalciferol concentration was significantly lower (P < 0.001) than in a control group (11.6 v. 19.6 mg/mL). None of 18 patients studied had an increased plasma concentration of parathyroid hormone, and only 1 of 17 patients had decreased intestinal absorption of isotopic calcium. Bone mineral mass was decreased in 44% of 32 patients studied.It was concluded that long-term treatment with anticonvulsant drugs leads to mild abnormalities of calcium metabolism and decreased bone mineral mass in a substantial percentage of adult outpatients with epilepsy. These abnormalities probably predispose the patients to the development of clinically significant metabolic bone disease.

Detection and pathogenesis of visceral calcification in dialysis patients and patients with malignant disease.

Scintiscanning to detect the uptake of bone-seeking radioactive isotopes by soft tissue is a promising technique for the in vivo study of visceral calcification. Visceral uptake of such radioisotopes was studied in 40 patients: 22 undergoing long-term dialysis, 9 with malignant disease and hypercalcemia and 9 with primary hyperparathyroidism and hypercalcemia.Fifteen patients, 11 undergoing dialysis and 4 with malignant disease, had radioisotope uptake in the lungs, and 5, 3 undergoing dialysis and 2 with malignant disease, had uptake in the stomach. None of the patients with primary hyperparathyroidism had visceral uptake, nor did the patients with uptake have radiologic evidence of pulmonary or gastric calcification. The dialysis patients with visceral uptake had a mean calcium x phosphate product of 84.3 +/- 23.7 (standard deviation), which was significantly greater (P < 0.001) than that of patients without such uptake (59.2 +/- 14.0). Similarly, in patients with malignant disease and visceral uptake the Ca x P product was 72.2 +/- 6.4 - significantly greater (P < 0.005) than that of patients without such uptake (49.3 +/- 6.7).These findings indicate that scintiscanning for the visceral uptake of a bone-seeking radioisotope is a simple and effective technique for the in vivo study of visceral calcification. An elevation in the Ca x P product seems to be the single most important factor in the production of visceral calcification.

Metabolic balance studies in patients with Paget's disease receiving salmon calcitonin over long periods.

Metabolic balance and calcium kinetic studies were performed in four patients with Paget's disease before treatment with salmon calcitonin and during the early and late stages of the treatment, which lasted 9 to 19 months, A significant decrease in bone turnover and 24-hour urine hydroxyproline and serum alkaline phosphatase values was observed in all patients. In contrast, the calcium, phosphorus and magnesium balances did not change significantly. In agreement with this, the partial body calcium, measured by in vivo neutron activation analysis, did not change. Intestinal calcium absorption increased initially, but returned to baseline levels 9 to 19 months after the study began. During the initial period there was a small, significant, but transient decrease in tubular reabsorption of phosphorus; this was accompanied by a significant decrease in serum phosphorus values--probably a direct effect of calcitonin rather than evidence of secondary hyperparathyroidism. Administration of salmon calcitonin to patients with Paget's disease decreases bone turnover without affecting calcium and phosphorus balances.

Oxygen tension in spinal cord gray matter during exposure to hyperbaric oxygen.

Adult female rats were exposed to 60 psig of 100% oxygen for 60 minutes. Oxygen tensions in the gray matter of the lumbosacral enlargement of the spinal cord, electroenecephalograms, electrocardiograms, and respirations were monitored before, during, and after the compression periods. Oxygen tensions were found to rise sharply to as high as 1050 mm Hg during compression and remained at significantly high levels throughout the entire hour of exposure. These data support the hypothesis that spinal cord lesions induced by exposure to hyperbaric oxygen are the result of excessive tissue oxygenation.

Microanalysis of individual mitochondrial granules with diameters less than 1000 angstroms.

A scanning electron microscope was converted to an electron microprobe with high spatial resolution by the addition of a transmitted electron detector and a solid-state x-ray detector. Spectra obtained from mitochondrial granules of chondrocytes in situ confirm the suspected presence of calcium and phosphorus. Contamination during analysis can lead to false indications of silicon in living tissue.