John W. Vester

Evidence for a defect in tryptophan metabolism in chronic alcoholism.

IN addition to being a substrate for protein synthesis in the body, dietary tryptophan is metabolized to at least two physiologically important compounds, nicotinic acid and serotonin, via the intermediates outlined in Figure 1. The major urinary metabolites of these two compounds are respectively N-methylnicotinamide (and its 6-pyridone)1 and 5-hydroxyindoleacetic acid (5-HIAA).2 In this paper we wish to report a reduced rate of 5-HIAA excretion in the urine of patients with chronic alcoholism. Since the rate of N-methylnicotinamide formation from tryptophan was unchanged, the reduced 5-HIAA excretion may signify a defective conversion of tryptophan to serotonin in these addicts. Methods The .xa0.xa0.

Hepatic Glucokinase: A Direct Effect of Insulin

Particle-free extracts of the livers from rats on a normal diet were incubated with insulin for 4 minutes; during this time the glucokinase activity increased. This insulin effect is dependent upon the dose.

Hydrocortisone and/or Desiccated Thyroid in Physiologic Dosage XV. Thyroid Therapy, Serum CPK, and Other Indices in Muscular Dystrophy

Abstract The administration of desiccated thyroid in dosages increasing to 16 grains per day to 4 patients with muscular dystrophy reduced abnormally high levels of serum creatine phosphokinase (CPK) to normal. This therapy was also accompanied by a decrease in the urine creatine and creatinine. These dosages of desiccated thyroid appeared to be relatively innocuous, judging from clinical indices and laboratory observations during the 8 months of therapy. However, certain changes associated with spontaneous or induced excesses of thyroid hormones such as tachycardia and systolic hypertension were noted. In 2 of the patients an increase in hand strength may have occurred, judging from serial contractions of a rubber bulb attached to a recording ergometer. However, it is more likely that this represented increased aptitude in manipulating the bulb rather than increased strength. This conclusion is supported by the fact that muscle strength as reflected by a single contraction of an individual hand or as estimated by a physical therapist did not increase in any of the patients. The improvement in the performance on the recording ergometer occurred when the daily dosage of thyroid reached 5 or 7 to 13 grains. The subsequent loss of a part of this increment or even a deterioration of muscle strength may have resulted from thyrotoxic myopathy or progress of the disease as the daily intake of desiccated thyroid was raised to 16 grains.

Hydrocortisone and/or desiccated thyroid in physiologic dosage: XI. Effects of tryroid hormone excesses on lipids and other blood and serum solutes☆

Abstract The ingestion of a preparation of desiccated thyroid (Proloid) during a 12-week period in dosages increasing progressively at 2-week intervals from 3 to 25 grains per day was accompanied by a 20 to 30 per cent decrease in the serum total and the alpha and beta lipoprotein cholesterol. These decreases were first noted at the 10 grains per day level and, except for transient escape in the case of the beta lipoprotein cholesterol, persisted as the dosage was further increased. Cessation of the desiccated thyroid therapy was followed by rebound increases in these lipid fractions to values above the pretherapy levels. Alpha lipoprotein triglycerides decreased during thyroid therapy, while the total and beta lipoprotein triglycerides remained unchanged or increased sporadically. Serum levels of NEFA did not increase. Serum sodium definitely decreased during the ingestion of 20 or 25 grains of thyroid per day, reflecting perhaps a decrease in cellular osmolarity. Relative hyperkalemia appeared during the ingestion of desiccated thyroid in large amounts. Serum albumin decreased by about 0.5 Gm. per cent in the course of thyroid feeding; a concomitant rise in the globulin levels during the ingestion of 20 grains per day did not persist when the dosage was further increased. A transient rise was recorded in serum calcium, reminiscent of the hypercalcemia which may appear in spontaneous thyrotoxicosis; also, a nonsustained lowering of the serum inorganic phosphorus occurred at the 10 grain dosage level. Whole blood NPN and levels of uric acid and of creatinine in serum decreased during therapy with large dosages of desiccated thyroid per day; serum creatine increased. Levels of the fasting blood sugar and the serum carbon dioxide and chloride did not change during the ingestion of desiccated thyroid. Alkaline phosphatase and creatine phosphokinase activity decreased during thyroid feeding; the levels of acid phosphatase and of lactic and malic acid dehydrogenase were not altered.

Hypolipidemic effect of chlorophenoxyisobutyrate in adult-onset diabetes mellitus.

The administration of ethyl‐alpha (p‐chlorophenoxy) isobutyrate (CPIB, Atromid‐S) to 16 patients with adult‐onset diabetes mellitus was generally associated with decreases of 10 to 40 per cent or more in the serum total cholesterol and triglycerides, irrespective of normal or high pretherapy values. The alpha and beta lipoprotein cholesterol and triglycerides also decreased. Retinal exudates disappeared completely from one or both eyes in 2 out of the 3 patients with hard and soft exudates. Glucose tolerance generally did not change.

Laboratory indices in clofibrate therapy of juvenile‐onset diabetes

Clofibrate, 2 Gm. per day, was ingested for 12 to 15 months by 14 adult patients with diabetes of ;uvenile onset. Slight decreases in serum total cholesterol with occasional escape and in NEFA levels tcere recorded in most patients. The total triglycerides and the alpha and beta lipoprotein triglyceride and choleoterol did not change. The serum total proteins, albumin, and creatinine increased, serum globulins decreased, platelets rose, the bleedingtime was slightly prolonged, and the coagulation time shortened at the end of 12 to 15 months of observation, but these indices did not exceed the ranges of normal. Serum glutamic oxalacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) were higher at one month and then mturned to pretherapy values. Lactic acid dehydrogenase (LDH) and malic acid dehydrogenase (MDH) levels decreased gradually, while aldolase and cid phosphatase increased slightly. Serum alkaline phosphatase and creatinephosphokinase(CPK) were unaffected. Bromsulphalein (BSP) retention may have increased very slightly in 3 patients. Peak hyperglycemia following a glucose load was less. Serum protein‐bound iodine (PBl), renal indices, and urinary steroids, pressor materials, and gonadotropins did not change. Many of the above changes suggest slightly altered metabolic eqUilibria during drugtherapy but they may represent changes occurring independently of the drug therapy.

Insulin responses in myotonia dystrophica

Abstract The undue hyperinsulinemia which has been observed to follow glucose, tolbutamide, or glucagon administration to persons with myotonia dystrophica is a variable rather than a characteristic feature. In the series herein reported, most of the individuals responded to such stimuli with levels of serum immunoassayable insulin, growth hormone, inorganic phosphorus, and blood sugar indistinguishable from those recorded in our healthy control subjects.

Hydrocortisone and/or desiccated thyroid in physiologic dosage. XIX. Muscular dystrophy: creatine phosphokinase during thyroid and alpha-tocopheryl acetate therapy.

Abstract The administration of desiccated thyroid (up to 9 grains/day) and d-alpha-tocopheryl acetate (500 I.U.) for 7 months to 10 patients with muscular dystrophy was accompanied by a return of increased serum CPK levels toward or to normal. Muscle strength did not change during treatment. Therapy with thyroid and the tocopheryl acetate was associated with the expected increase in serum PBI, and T 3 binding to blood cells. The serum total and beta lipoprotein cholesterol and the serum total protein and albumin decreased. Serum inorganic phosphorus rose slightly. All the other blood, serum, and urine solutes measured did not change, including serum and urine creatine and creatinine, and the urinary steroids. The half-hour blood sugar level during an oral glucose tolerance test rose slightly during thyroid-tocopheryl acetate treatment, but the values reached were still within the normal range. Evidence of iron deficiency and slight reduction in erythrocyte survival was found in several subjects during treatment with thyroid and alphatocopheryl acetate, but pretherapy findings were unavailable.

Rod myopathy: Beta globulin peak and increased complement

Abstract A distinct beta globulin peak was consistently present on paper electropherograms of sera from three brothers with nemaline, i.e., rod myopathy. The C3 component complement was elevated in each of them; other constituents of the beta peak were not increased. Laboratory indices other than the serum creatinine levels, including serum cholesterol, triglycerides, PBI and insulin and growth hormone responses, blood cell karyotype, and plasma 11(OH)corticosteroids and urinary 17-ketosteroids, 11-desoxycortisol metabolites and Porter-Silber chromogens were unchanged. Serum creatinine was low.

Hypolipidemic and thyroid hormone effects of sodium dextrotriiodothyronine

Sodium dextrotriiodothyronine (Na‐DT3) at a dosage of 1 mg. per day for 24 weeks produced an approximately 75 mg. per cent decrease in serum total cholesterol in hyper‐and normolipidemic subjects. Na‐DT3 usually lowered the level of serum leva‐thyroxine (LT4) to the myxedema range, but the subjects remained euthyroid, suggesting that Na‐DT3 was exerting a thyroid hormone‐replacement effect. The failure to observe the changes to be expected in the in vitro levo‐triiodothyronine (LT3) uptake by blood cells when the serum protein‐bound iodine (PBI) had increased indicates that perhaps Na‐DT3 occupies binding sites other than those used by LT3 that Na‐DT3 is loosely bound to plasma proteins and is readily displaced by LT3, or both. An unexplained rise in urine total protein was observed during the first 6 weeks of Na‐DT3 therapy but not at 12 weeks. Serum total globulins were increased in the twenty‐fourth week. Minor changes within the normal range were recorded in plasma 11(OH)‐corticosteroids and in urine Porter‐Silber chromogens. All other indices remained within the pretherapy range.