Malaria Control and Elimination,Venezuela, 1800s–1970s

Venezuela had the highest number of human malaria cases in Latin American before 1936. During 1891–1920, malaria was endemic to >600,000 km² of this country; malaria death rates led to major population decreases during 1891–1920. No pathogen, including the influenza virus that caused the 1918 pandemic, caused more deaths than malaria during 1905–1945. Early reports of malaria eradication in Venezuela helped spark the world’s interest in global eradication. We describe early approaches to malaria epidemiology in Venezuela and how this country developed an efficient control program and an approach to eradication. Arnoldo Gabaldón was a key policy maker during this development process. He directed malaria control in Venezuela from the late 1930s to the end of the 1970s and contributed to malaria program planning of the World Health Organization. We discuss how his efforts helped reduce the incidence of malaria in Venezuela and how his approach diverged from World Health Organization guidelines.     

Primary empty sella syndrome, ACTH hypersecretion, and normal adrenocortical function. Report of two cases

Although the primary empty sella syndrome (PESS) is associated with normal endocrine function or subtle pituitary insufficiency, pituitary hormone hypersecretion associated with PESS has also been recognized. ACTH hypersecretion and primary empty sella syndrome have previously been reported in patients with either Cushing's disease or Addison's disease. This report describes two unique patients with ACTH hypersecretion, primary empty sella syndrome, and normal cortisol dynamics. The investigators speculate that this association may have resulted from infarction of hyperplastic adenohypophyseal corticotrophes due to production of an ACTH peptide with reduced biologic activity. These two cases emphasize that primary empty sella syndrome may be associated with ACTH hypersecretion and normal adrenocortical function.     

The regulation of urinary free 19-nor-deoxycorticosterone and its relation to systemic arterial blood pressure in normotensive and hypertensive subjects

19-Nor-deoxycorticosterone (19-nor-DOC) is a naturally occurring, potent mineralocorticoid present in hypertensive animal models as well as man. To investigate 19-nor-DOC's regulation and possible pathogenesis in hypertension, urinary free (UF) 19-nor-DOC was measured in 14 hypertensives, correlated with other corticosteroids and systemic arterial blood pressure (BP), and compared to basal and ACTH-stimulated values in 8 normotensive subjects. Seven of the 14 hypertensives had low-renin hypertension, 2 had primary aldosteronism, 1 had an adrenal carcinoma, and another had acromegaly. These studies determined that: 1) although the mean UF 19-nor-DOC was not increased in hypertensives (588 +/- 180 vs. 428 +/- 122 ng/day), 2 low-renin hypertensives had quite elevated levels (2186 and 2018); 2) the UF 19-nor-DOC in hypertensives was correlated with BP but not with PRA, aldosterone secretion, plasma potassium, basal plasma cortisol, or 17-hydroxycorticosteroids; 3) likewise, in normotensives, UF 19-nor-DOC did not correlate with basal plasma cortisol, cortisol secretion, or 17-hydroxycorticosteroids excretion but did correlate after ACTH stimulation. Therefore, although 19-nor-DOC is activated by ACTH administration, it is not correlated with basal parameters of cortisol production, suggesting that factors other than ACTH regulate basal 19-nor-DOC secretion. Furthermore 19-nor-DOC is elevated in some hypertensive patients, and it is directly related to the elevation of mean systemic BP. This suggests that, although 19-nor-DOC could contribute to hypertensive disease in some individuals, it does not appear to be due to excess ACTH.     

Biphasic 19-nor-deoxycorticosterone excretion after adrenal enucleation is associated with altered adrenal mitochondrial cytochrome P450 11 beta-, 18-, and 19-hydroxylase activities

After adrenal enucleation (AE) rats avidly retain sodium (early phase), but after 7-10 days they lose this sodium avidity (late phase). Although increased production of a mineralocorticoid, 19-nor-deoxycorticosterone (19-Nor-DOC), has been implicated, 19-Nor-DOC levels during the early and late phases of AE have not been systematically measured. Furthermore it is not known why 19-Nor-DOC production should increase during a time when production of 11 beta- and 18-hydroxylated corticosteroids are decreased in AE. The purpose of this study was to examine the 11 beta, 18-, and 19-hydroxylase pathways in the early and late phases of AE. The results demonstrate increased urinary 19-Nor-DOC and decreased 18-OH-DOC and corticosterone excretion in the early phase of AE at a time when adrenal mitochondrial 11 beta- and 18-hydroxylase activities were decreased but 19-hydroxylase activity was unchanged. During the late phase of AE, urinary 19-Nor-DOC had decreased and 18-OH-DOC and corticosterone had increased to levels indistinguishable from those in sham controls. This reduction in 19-Nor-DOC was associated with a decrease in 19-hydroxylase activity in AE. Since the 11 beta, 18-, and 19-hydroxylases have a common substrate (DOC), it is possible that differential flux of DOC through these pathways could account for the changes in steroid production in AE. These data suggest that the increased 19-Nor-DOC excretion in AE may be due to alterations in enzyme activity leading to a shunting of DOC into the 19-Nor-DOC pathway. In addition, the synchronicity of 19-Nor-DOC with sodium excretion suggests that it has an important role in the pathogenesis of the sodium retention in AE.     

Identifying inadequate response among patients with ankylosing spondylitis and psoriatic arthritis prescribed advanced therapy in a real-world,commercially insured adult population in the USA

Clinical Rheumatology - This study aimed to assess treatment patterns and frequency of inadequate response associated with advanced therapy initiation among patients with ankylosing spondylitis...     

Intranasal aerosolized insulin. Mixed-meal studies and long-term use in type I diabetes

We assessed the efficacy of intranasal aerosolized insulin containing laureth-9 as a surfactant in patients with Type I diabetes by fasting studies in 8 patients, mixed-meal studies in 15, and long-term home use in 8. The intranasal insulin (1 U per kilogram of body weight in 1 per cent laureth-9) was rapidly absorbed (in 15 minutes); it lowered the plasma glucose level by 50 per cent in 45 minutes in fasting normal controls and by 50 per cent in 120 minutes in fasting diabetics. The glucose-lowering potency depended on the insulin dose and surfactant concentration. Nasal irritation was proportional to surfactant concentration, with great variability among subjects. After intranasal insulin used before meals (1 U per kilogram in 1 per cent laureth-9), the two-hour postprandial glucose level increased above before-meal levels by 38 mg per deciliter, as compared with 191 mg per deciliter after intranasal placebo in patients with Type I diabetes (P less than 0.05). An outpatient feasibility study examining three months of use of intranasal aerosolized insulin before meals as a supplement to Ultralente insulin revealed that the aerosol was well tolerated, with glycemic control (as indicated by the percentage of glycohemoglobin, home glucose measurements, and hypoglycemic reactions) comparable to that during a subsequent three-month period of conventional subcutaneous insulin treatment. The results suggest that intranasal insulin has potential as an adjunct to subcutaneous insulin in the therapy of Type I diabetes.     

Metabolic clearance rates of androgens and oestrogens in ageing women

Using the constant infusion technique we have measured the metabolic clearance rates (MCR) for Δ⁴-androstenedione (A), testosterone (T), oestrone (E₁) and oestradiol (E₂) in a large group of postmenopausal women. Their mean ± SE age was 64.5 ± 1.6 yr, their ages ranged from 46–90 yr. When the MCRs for each steroid were related to age by linear regression analysis no significant correlation was found for any of the steroids. Similarly, when the women were grouped according to their age by decade, the mean MCR for each steroid showed no trend with increasing age.

There was no difference in the MCRs for A, T and E₁ of the post-menopausal women and a large group of pre-menopausal women. However, there was a significant decrease in the mean MCR for E₂ between the two groups which is probably related to the marked decrease in circulating E₂ in postmenopausal women. We conclude that for these steroids age, per se, does not appear to be a major determinant of the MCR.     

Isoelectric focusing of plant cell membranes

An isoelectric focusing method is described that discriminates plant cell organelle populations on the basis of surface charge. The isoelectric points (pI values) of the Golgi apparatus, the mitochondria, and putative plasma membrane from etiolated pea stem cells are reported. The pI of the pea Golgi apparatus is similar to that of the ³⁵SO₄-labeled membranes of developing Fucus embryos. The pI of Fucus³⁵SO₄-labeled membranes depends on whether the membranes are being polarly transported to the growing tip or randomly transported to the entire periphery of the zygote. Those subject to polar tip transport have a significantly greater negative surface charge than those being randomly transported. The implication of this result toward an understanding of the localization mechanism is discussed. The method is also capable of subfractionating glucan synthetase II-containing membranes (putative plasma membrane) from peas. The pI of putative plasma membrane from a pea stem homogenate is similar to the pI of the plasma membrane of whole protoplasts of Catharanthus leaf cells. Isoelectric focusing appears to be a useful technique to discriminate membranes and, hence, to provide new information and approaches to study cellular and developmental phenomena.