Porosities in the outer table of the cranial vault (porotic hyperostosis) and orbital roof (cribra orbitalia) are among the most frequent pathological lesions seen in ancient human skeletal collections. Since the 1950s, chronic iron-deficiency anemia has been widely accepted as the probable cause of both conditions. Based on this proposed etiology, bioarchaeologists use the prevalence of these conditions to infer living conditions conducive to dietary iron deficiency, iron malabsorption, and iron loss from both diarrheal disease and intestinal parasites in earlier human populations. This iron-deficiency-anemia hypothesis is inconsistent with recent hematological research that shows iron deficiency per se cannot sustain the massive red blood cell production that causes the marrow expansion responsible for these lesions. Several lines of evidence suggest that the accelerated loss and compensatory over-production of red blood cells seen in hemolytic and megaloblastic anemias is the most likely proximate cause of porotic hyperostosis. Although cranial vault and orbital roof porosities are sometimes conflated under the term porotic hyperostosis, paleopathological and clinical evidence suggests they often have different etiologies. Reconsidering the etiology of these skeletal conditions has important implications for current interpretations of malnutrition and infectious disease in earlier human populations.

The causes of porotic hyperostosis and cribra orbitalia: a reappraisal of the iron-deficiency-anemia hypothesis.

A group of 19 healthy elderly subjects previously shown to differ in terms of their cortisol levels over a 4 year period were administered a neuropsychological test battery assessing memory, attention, and language. Correlational analyses performed on various corticosteroid measures showed that the slope of the change in cortisol levels over time predicted cognitive deficits in this elderly population. Aged subjects showing a significant increase in cortisol levels with years and with high current basal cortisol levels were impaired on tasks measuring explicit memory and selective attention when compared to aged subjects presenting either decreasing cortisol levels with years or increasing cortisol levels with moderate current basal cortisol levels. We further showed that subjects presenting a decrease in cortisol levels with years performed as well as young healthy subjects with regard to cognitive performance. Thus, impaired cognitive performance was associated with recent evidence of hypothalamic-pituitary-adrenal (HPA) dysregulation and elevated basal cortisol levels. These results are consistent with recent animal studies showing the existence of subpopulations of aged rats that differ in HPA activity and cognitive performance. Finally, the pattern of cognitive results related to the cortisol history of subjects is in agreement with a role played by the hippocampus in age-related HPA dysfunction and cognitive performance.

https://www.jneurosci.org/content/jneuro/14/5/2893.full.pdf

Basal cortisol levels and cognitive deficits in human aging

http://www.utdallas.edu/~tres/aging_seminar2011/Lupien.2005.pdf

Stress hormones and human memory function across the lifespan

Nucleation time: a key factor in the pathogenesis of cholesterol gallstone disease.

Although a large number of diseases, conditions, and syndromes associated with mental retardation have been described, it has been the discouraging experience of physicians dealing with retarded children that relatively few cases may be specifically classified or diagnosed despite intensive evaluations. Many of the children manifest facial peculiarities along with other physical findings and often resemble neither their parents nor their siblings. The clinician frequently has the feeling that the child should "fit into some syndrome"; however, each case usually presents an isolated and unique group of findings not resembling the picture seen in other retarded children who are evaluated. It was a rather unusual and exciting experience to find two unrelated children who seemed to resemble each other closely enough to make one wonder if they might not have the same "syndrome." After studying these two patients with their array of similar clinical findings, their reports and photographs were

Broad Thumbs and Toes and Facial Abnormalities: A Possible Mental Retardation Syndrome

ALBRIGHT and associates,1in 1942, described a group of patients with hypocalcemia, hyperphosphatemia, ectopic calcification and ossification, dyschondroplasia manifested by short metacarpal and metatarsal bones, and a characteristic short, round body and round face. Tetany, convulsive symptoms, lenticular opacities, and calcification of the basal ganglia were also present. Unlike persons with idiopathic hypoparathyroidism, these patients had normal parathyroid glands and there was little or no phosphate diuresis in response to the administration of parathyroid extract. Having named this syndrome pseudohypoparathyroidism, Albright and associates * postulated the presence of multiple, independent genetic defects to account for the stigmata noted and suggested that the hypocalcemia and hyperphosphatemia resulted from a failure of end-organ response to endogenous parathyroid hormone. Subsequently, there appeared case reports3of persons with some but not all of the stigmata described by Albright and associates. The term pseudopseudohypoparathyroidism has been applied to the condition in which hypocalcemia (and

The syndrome of pseudo-pseudohypoparathyroidism

A synthetic mixture of uroporphyrin isomers I, II, III and IV as free acids in the synthetic ratio of 1:1:4:2 was resolved by reverse-phase HPLC using a C0:PEL (ODS) 37-50 micron precolumn and a Micro Bondapak C18 analytical column eluted with acetonitrile (4%) in phosphate buffer (pH 6.95). Clinically important I and III isomers of uroporphyrin were readily resolved directly from acidified urine as porphyrin free acids.

Isomers of uroporphyrin free acids separated by HPLC

Growing role of early surgery in chronic pancreatitis: a practical clinical approach.

The proteins of human gallbladder bile with and without gallstones.

During the last decade the tremendous interest in the adrenocortical hormones has led to an appreciation of the central role of the liver in their metabolism. Early observations of corticoid metabolism in liver disease suggested that there was hyperactivity of the adrenal cortex. 1-5 This conclusion was based largely on measurements of the urine corticoids by techniques which did not detect the conjugated metabolites, the largest fraction of the adrenocortical endproducts. Studies utilizing more specific methods for the metabolites in plasma and urine have furnished data which are not in keeping with the earlier reports. 6-8 In man, the principal corticosteroids elaborated by the adrenal cortex are hydrocortisone (cortisol, 17-hydroxycorticosterone, pregn - 4 - ene -11β,17α,21 - triol - 3,20- dione, Compound F), corticosterone (pregn-4ene-11β,21-diol-3,20-dione, Compound B), and aldosterone (pregn-4-ene-11β,21-diol-3, 20-dione-18-al). The largest fraction is hydrocortisone (Fig. 1). The Porter-Silber reaction 9 measures the corticoids which react with phenylhydrazine because of their 17, 21-dihydroxy-20-ketone

Edwin Englert

Papers

The syndrome of pseudo-pseudohypoparathyroidism

Isomers of uroporphyrin free acids separated by HPLC

Growing role of early surgery in chronic pancreatitis: a practical clinical approach.

The proteins of human gallbladder bile with and without gallstones.

Corticosteroid Metabolism in Liver Disease