The art of observation: William Osler and the method of Zadig.
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Clinical Competence↗
Biomedical subjects
F A Neelon
Publications and source records attributed to F A Neelon.
A woman with too much facial hair. Evaluating the possibility of attenuated 21-hydroxylase deficiency in hirsutism.
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Adrenal Hyperplasia, Congenital↗
The assessment of pituitary function.
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Adolescent↗
Acetaminophen and liver disease.
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Acetaminophen↗
Hypothalamic insufficiency: the cause of hypopituitarism in sarcoidosis.
Ten patients with generalized sarcoidosis and hypopituitarism were studied. Six of these 10 patients presented with sarcoid involvement of the optic nerves resulting in asymmetric visual field defects. All patients had deficiencies of two or more anterior pituitary hormones and seven had abnormalities of water metabolism. Despite hypopituitarism, nine patients had a pituitary responsive to the synthetic hypothalamic releasing factors, thyrotropin releasing hormone and gonadotropin releasing hormone, and the tenth patient had a partially responsive pituitary. The demonstration of pituitary responsiveness allows us to infer hypothalamic insufficiency as the major cause for hypopituitarism in these patients. The combination of visual field defects and hypopituitarism in sarcoidosis is a medically treatable condition that simulates the clinical presentation of a pituitary tumor.
Adolescent↗
Acetaminophen and hepatic dysfunction in infectious mononucleosis.
Two family members developed severe hepatitic dysfunction in association with infectious mononucleosis and acetaminophen administration. Since severe hepatitis is an extremely rare complication of infectious mononucleosis, we postulate that the hepatic dysfunction was induced by acetaminophen.
Acetaminophen↗
Relationship between phosphaluria and acute hypercapnia in the rat.
Standard clearance studies were performed in mechanically ventilated intact and acutely thyroparathyroidectomized (TPTX) rats to document and characterize the effect of hypercapnia (HC) on urinary phosphorus excretion (U(P)V). HC as compared to normocapnia (NC) was associated with an increase in U(P)V in intact (62.5 vs. 7.93 mug/min) and TPTX (30.5 vs. 0.59 mug/min) rats, an increase in filtered load of phosphorus in intact (218 vs. 191 mug/min) and TPTX (243 vs. 146 mug/min) rats, an increase in blood bicarbonate concentration in intact (27.8 vs. 26.0 meq/liter) and TPTX (24.5 vs. 22.3 meq/liter) animals, and a decrease in blood pH in intact (7.15 vs. 7.42) and TPTX (7.07 vs. 7.39) rats. Additional TPTX rats with NC and HC were studied during phosphorus infusion at a comparable filtered load of phosphorus (NC = 307 mug/min and HC = 328 mug/min). U(P)V was 18.5 mug/min in NC and 85.2 mug/min in HC animals. Intact NC animals infused with NaHCO(3) achieved a blood bicarbonate of 45.9 meq/liter compared to 26.0 meq/liter in intact NC NaCl-infused rats. U(P)V was 10.0 mug/min in the NaHCO(3) and 7.93 mug/min in NaCl-infused animals. In intact HC animals infused with NaHCO(3), blood pH was 7.36 compared to 7.42 in NC intact NaCl-infused animals. U(P)V was 83.2 mug/min in the HC bicarbonate-infused and 7.93 mug/min in the NC NaCl-infused rats. These experiments demonstrate that elevated blood carbon dioxide tension per se increases U(P)V. Increases in filtered load of phosphorus and blood bicarbonate which are associated with HC contribute to the phosphaturia as does parathyroid hormone. The phosphaturia is not dependent upon reduction of extracellular pH.
Acidosis↗
Hypoparathyroidism: a possible cause of osteomalacia .
A 17 year old man with longstanding hypocalcemia and hyperphosphatemia presented with incapacitating bone pain and progressive weakness nad bowing of the legs. The serum abnormalities were due to idiopathic hypoparathyroidism as evidenced by a decreased serum concentration of parathyroid hormone and an appropriate rise in urinary cyclic AMP and phosphate excretion, and serum calcium concentration, in response to exogenously administered parathyroid extract. The serum concentration of 1,25-dihydroxycholecalciferol was appropriately decreased. The bone findings were due to osteomalacia as documented by physical findings, bone roentgenograms, and bone biopsy. Normal renal tubular function, blood pH, and serum concentration of 25-hydroxycholecalciferol and elevated serum alkaline phosphatase excluded the common causes of osteomalacia. The data are consistent with the hypothsis that lack of parathyroid hormone causes both hypocalcemia and a decreased serum concentration of 1,25-dihydroxycholecalciferol which, in turn, limit the availability of calcium and cause defective synthesis of bone matrix resulting in abnormal mineralization.
Adolescent↗
Adrenal physiology and pharmacology.
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Adrenal Cortex↗
Stimulation of cartilage macromolecule synthesis by adenosine 3',5'-monophosphate.
The role of cyclic AMP in the regulation of cartilage macromolecule synthesis in vitro was studied in pelvic cartilage from 10-12 day chick embryos. Incubation of cartilages in medium containing 0.5 mM cyclic AMP resulted in a 30% inhibition of 35SO4-2, [3H]leucine and [3H]uridine incorporation into proteoglycan, total protein and RNA, respectively. Higher concentrations of cyclic AMP had no greater effects. In contrast, butyrylated cyclic AMP derivatives (0.5-5.0 mM) added to the incubation medium stimulated (50-100%) the incorporation of these radiolabeled precursors into cartilage macromolecules. Theophylline, in concentrations (0.1-0.5 mM) which raise intracellular cyclic AMP, also increases the incorporation of radiolabeled precursors into macromolecules. The data indicate that exogenous cyclic AMP and butyrylated cyclic AMP derivatives have paradoxical effects on cartilage macromolecule synthesis. Butyrylated cyclic AMP derivatives, not exogenous cyclic AMP, mimic the effects of intracellular cyclic AMP. Incubation of embryonic chicken cartilage with exogenous cyclic AMP results in the extracellular degradation of the cyclic AMP to adenosine. Adenosine (0.125 mM) inhibits precursor incorporation into cartilage macromolecules. The metabolism of exogenous cyclic AMP generates sufficient adenosine to account for the observed inhibitory effects of exogenous cyclic AMP on cartilage macromolecule synthesis. Butyrylated cyclic AMP derivatives are not degraded during incubation with cartilage. The data indicate that cartilage is a tissue in which the effect of cyclic AMP is to stimulate anabolic processes.
Animals↗
Renal cyclic adenosine monophosphate: an accurate index of parathyroid function.
Measurement of total urine cyclic 3':5'-adenosine monophosphate (cyclic AMP) only incompletely discriminates between normal, hyperparathyroid, and nonparathyroid hypercalcemic patients. Only a fraction of total urine cyclic AMP is contributed by parathyroid hormone (PTH) action on the proximal nephron (renal cyclic AMP); the remainder is derived from plasma by glomerular filtration. We dtermined total urine and plasma cyclic AMP and PTH (by carboxy-terminal specific radioimmunoassay) in control, hyperparathyroid, nonparathyroid hypercalcemic, and surgically hypoparathyroid patients. Renal cyclic AMP was calculated as total urine cyclic AMP minus the filtered component. Of these determinations, only renal cyclic AMP segregated normal from hyperparathyroid, and hyperparathyroid from nonparathyroid hypercalcemic patients with complete accuracy. These data suggest that measurement of renal cyclic AMP provides an accurate index of parathyroid activity and allows clinical discrimination and appropriate treatment of the sub-groups of patients with malignancy and nonparathyroid hypercalcemia from those with hyperparathyroidism.
Adult↗
1,25-Dihydroxycholecalciferol deficiency: the probable cause of hypocalcemia and metabolic bone disease in pseudohypoparathyroidism.
Pseudohypoparathyroidism (PsH) is a genetic disease characterized by hypocalcemia, hyperphosphatemia, and metabolic unresponsiveness to parathyroid hormone (PTH). The administration of PTH elicits neither a significant rise in serum calcium (calcemic response) nor a decrease in the renal tubule reabsorption of phosphorus (phosphaturic response). The diminished phosphaturic response is due to an inability of PTH to generate cyclic AMP in renal tubule cells. We investigated the question of whether hypocalcemia and deficient calcemic response to PTH are due to a similar cyclic AMP defect in bone or to an acquired vitamin D deficiency. Four patients were studied. The active form of vitamin D (1,25-dihydroxycholecalciferol) was measured in 3 and was low. Treatment with vitamin D2 restored the serum calcium and the calcemic response to PTH to normal without changing the impaired renal response. Bone biopsy was performed in 2 patients and showed morphologic evidence of increased osteoclastic activity and osteomalacia. The data indicate that the hypocalcemia and bone disease in PsH are due to active vitamin D deficiency, possibly resulting from the genetic renal lesion.
Adult↗
Chiasmal syndrome due to intrasellar abscess.
A 43-year-old woman had diabetes insipidus and amenorrhea. There was panhypopituitarism on endocrine testing and visual field examination showed inexorably progressive loss to bitemporal hemianopsia. All radiographic findings were normal, but craniotomy disclosed the cause of this chiasmal syndrome to be an intrasellar abscess which, on culture, grew a Gram-positive anaerobe, Peptococcus. Intrasellar or pituitary abscess is rare, but it must always be considered in the differential diagnosis of the chiasmal syndrome, since loss of pituitary and visual function may occur much more rapidly than with the tumors most often responsible for this syndrome and since surgical cure is possible.
Adult↗
A comparison of the structure of hamster pancreatic insulin and insulin extracted from a transplantable hamster islet-cell carcinoma.
Insulin has been isolated from pancreases of the Syrian hamster and from a transplantable islet-cell tumor of the hamster. Acid/ethanol extraction, ether precipitation, ion exchange and gel filtration chromatography gave preparations of suitable purity for structural studies. Using trypsin cleavage, automatic Edman degradation and manual Edman degradation, a complete sequence of the pancreatic insulin B chain was determined. By automatic Edman degradation, the amino-terminal 10 residues of the pancreatic A chain were assigned and the sequence of carboxy-terminal eleven residues could be deduced by homology to other mammalian and avian insulins. The sequence assigned to hamster insulin A chain is identical to that of the rat, mouse and spiny mouse. The sequence of hamster insulin B chain is identical to rabbit and spiny mouse B chain. In terms of protein evolution, hamster insulin thus appears to occupy an intermediate position between rabbit and rat insulins. Amino acid composition, tryptic peptide composition and partial sequence analysis of the hamster tumor insulin showed no differences from hamster pancreatic insulin.
Adenoma, Islet Cell↗
Stimulation of cartilage amino acid uptake by growth hormone-dependent factors in serum. Mediation by adenosine 3':5'-monophosphate.
The effects of growth hormone-dependent serum factors on amino acid transport and on cartilage cyclic AMP levels in embryonic chicken cartilage were studied in vitro. Cartilages incubated in medium containing rat serum showed a significantly greater uptake of alpha-amino [1-14C] isobutyrate or [1-14C] cycloleucine than control cartilages incubated in medium alone. Normal rat serum (5%) added to the incubation medium also caused an increase in cartilage cyclic AMP content (from as little as 23% to as much as 109%). The factors in serum which increase cartilage cyclic AMP and amino acid uptake are growth hormone dependent, since neither growth hormone itself nor serum from hypophysectomized rats restores these serum factors. Studies comparing the ability of sera with varying amounts of growth hormone-dependent factors to stimulate amino-aminoisobutyrate transport and to increase cartilage cyclic AMP show a striking linear correlation between the two effects (r=0.977). Theophylline and prostaglandin E1, WHICH RAISE CARTILAGE CYCLIC AMP also increase amino-aminoisobutyrate transport. Exogenous cyclic AMP, N6-monobutyryl cyclic AMP and n6, 02'-dibutyryl cyclic AMP increase cartilage amino-aminoisobutyrate transport. The data are compatible with the thesis that growth hormone-dependent serum factors increase cartilage amino acid transport by elevating cartilage cyclic AMP.
Amino Acids↗