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Biomedical subjects

C M Berlin

Publications and source records attributed to C M Berlin.

At least 37 records · Page 2Linked to original sources

Caffeine pharmacokinetics in preterm infants older than 2 weeks.

We studied 17 preterm infants receiving caffeine, and measured their plasma levels of caffeine and the theophylline metabolite by high-pressure liquid chromatography. The half-life was calculated by computer analysis using the least-square method. The mean gestational age of our patients was 29.7 +/- 1.9 weeks (mean +/- SD) and they were studied at 20.7 +/- 6.6 days (mean +/- SD) postnatal age. The caffeine half-life was 52.03 +/- 23.87 h (means +/- SD) and the theophylline half-life was 77.04 +/- 65.01 h (mean +/- SD).

Caffeine↗

Autoantibodies against RNA polymerase I in scleroderma and Sjögren's syndrome sera.

Anti-RNA polymerase I antibodies were detected by radioimmunoassay in the sera of 8 out of 9 Sjögren's syndrome patients, 11 out of 19 individuals with scleroderma, and 19 out of 19 systemic lupus erythematosus patients. The results of the radioimmunoassay were confirmed by demonstrating the ability of the patients' IgG to inhibit RNA polymerase I activity in vitro. Sera from four patients in each category were also tested for reaction with individual subunits of RNA polymerase I. All 4 SLE sera, 3 out of 4 scleroderma sera and 1 out of 4 Sjögren's syndrome sera contained antibodies against the 65 kDa (S3) subunit of RNA polymerase I in addition to antibodies against one other subunit. Sera from the remaining scleroderma and Sjögren's syndrome patients tested in this assay contained only anti-S3 antibodies. These results demonstrate that anti-RNA polymerase I antibodies are characteristic of a variety of rheumatic autoimmune sera.

Autoantibodies↗

Antibodies against nuclear poly(A) polymerases in rheumatic autoimmune diseases.

Sera from 53 patients, 26 with systemic lupus erythematosus (SLE), 8 with rheumatoid arthritis (RA), 9 with Sjogren's syndrome (SS), and 10 with scleroderma (Scl), were screened for the presence of antibodies against liver-type poly(A) polymerase and tumor-type poly(A) polymerase. Sixty percent of the patients with the above four autoimmune diseases have antibodies directed against liver poly(A) polymerase, whereas sera from 74% of the patients contained anti-hepatoma poly(A) polymerase antibodies. About 25% of the patients produced antibodies exclusively against the tumor poly(A) polymerase. IgG containing anti-liver or anti-tumor poly(A) polymerase antibodies inhibited the activity of the respective enzyme. IgG containing antibodies against liver and tumor enzymes inhibited the activity of both enzymes, whereas IgG from sera that did not react with poly(A) polymerase had no effect on either enzyme. These data demonstrated the specificity of these autoantibodies and confirmed the results of the radioimmunoassay.

Antibody Specificity↗

Systemic deficiency of the first component of the pyruvate dehydrogenase complex.

An infant with lactic acidosis and developmental delay had neuropathological changes consistent with Leigh's necrotizing encephalomyelopathy. Total pyruvate dehydrogenase complex (PDC) activity was low relative to controls in lymphocytes (0.2 versus 1.9 +/- 0.6 SD nmol/min/mg protein) and cultured skin fibroblasts (0.9 versus 2.7 +/- 1.0). Liver, muscle, heart, and kidney mitochondria oxidized several substrates normally, but did not oxidize pyruvate. PDC activity was absent in these mitochondria (0.1 versus 9.8 +/- 4.2 in liver and 0.7 versus 75 +/- 26 in muscle) and was very low in all tissue homogenates. Activity of the first component was low in liver mitochondria, whereas activities of the second and third components were normal. Western blot analysis of tissue proteins showed normal amounts of second and third component of PDC but undetectable to trace amounts of both alpha and beta subunits of the first component of PDC in liver, brain, kidney, heart, and skin fibroblasts. Thus, profound systemic deficiency of PDC was due to lack of both subunit proteins of the first component of PDC.

Fibroblasts↗

Tourette's syndrome.

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Attention Deficit Disorder with Hyperactivity↗

Neuropathology of oral-facial-digital syndromes.

A 3-month-old female infant with oral-facial-digital syndrome (OFD-I) was found to have extensive malformations of the brain and spinal cord. Our review of other case reports indicated that the most common central nervous system malformations found in OFD-I include cerebral epithelial (ependymal) cysts, agenesis of the corpus callosum, cerebral micropolygyria, and hypoplasia or dysplasia of the cerebellum, pons, and medulla. It is suggested that the individuals with OFD-I syndrome should be carefully studied clinically and pathologically for complex nervous system anomalies.

Abnormalities, Multiple↗

Anti-protein kinase NII antibodies in rheumatic autoimmune diseases.

Antibodies against nuclear protein kinase NII were detected by radioimmunoassay in the sera of patients with systemic lupus erythematosus and mixed connective tissue disease but not in sera from normal individuals or from patients with rheumatoid arthritis. Immunoglobulins derived from sera containing the anti-kinase antibodies inhibited the activity of protein kinase NII in vitro but had no effect on the activity of cytoplasmic cyclic AMP-dependent protein kinase.

Animals↗

Disposition of dietary caffeine in milk, saliva, and plasma of lactating women.

Caffeine is present in many dietary substances; its appearance from these sources in human milk has not previously been studied in detail. Fifteen lactating women ingested a known amount of a caffeinated beverage (36 to 335 mg). Simultaneous milk and saliva samples were collected at intervals for the subsequent 12 hours and assayed for caffeine content. Eleven of 15 mothers excreted measurable caffeine in milk. Caffeine was detected by 15 minutes in saliva and milk; peak levels in milk (2.09 to 7.17 micrograms/mL) and saliva (1.24 to 9.22 micrograms/mL) were achieved within 1 hour. Elimination half-lives were 1.3 to 13.5 hours (mean 4.0 +/- 3.7 [SD] hours) for saliva and 1.5 to 14.5 hours (mean 6.1 +/- 4.4 [SD] hours) for milk. Assuming each infant would ingest 90 mL of milk every three hours for 24 hours after maternal ingestion of caffeine, it is possible to estimate potential exposure of the nursing infant to caffeine. The amount of caffeine available for infant absorption ranged from 0.01 to 1.64 mg or 0.06% to 1.5% of the maternal dose. Caffeine was not present in the infants' urine collected for five hours after the first nursing period. The maternal ingestion of a single cup of caffeinated beverage does not appear to present significant doses of caffeine to the nursing infant.

Adult↗

Kwashiorker in a child in central Pennsylvania. A seven-year follow-up.

Follow-up of a child who had severe protein malnutrition from the ages of 3 to 6 1/2 months demonstrated intellectual and social functioning within the normal range seven years after diagnosis and treatment. Treatment consisted of peripheral alimentation, followed by an elemental infant formula (lactose free), with nutritional education of the family.

Child Development↗

Antipyrine disposition in milk and saliva of lactating women.

Widely used to study hepatic drug metabolism, antipyrine rapidly distributes in total body water. Antipyrine distribution was studied in seven lactating women. Duration of lactation ranged from 2 to 19 mo. In all subjects the drug was rapidly absorbed; in five women peak concentrations were attained in milk and saliva by 1 hr and in the other two women by 3 hr (first point at which collections were made). In two women in whom antipyrine was measured at 10-min intervals during the first hour, peak concentrations in both milk and saliva were attained by 10 min after antipyrine. The time course for antipyrine disappearance from milk paralleled that from saliva for each subject. Antipyrine half-life (t1/2) varied from 5.6 to 20.3 hr for saliva (mean +/- SD = 11.5 +/- 4.8) and from 5.7 to 21.7 hr for milk (mean +/- SD = 11.6 +/- 5.4). In the two women with the shortest salivary antipyrine t1/2 (5.6 and 7.5 hr), antipyrine was readministered many months later, after they had stopped lactating. The salivary antipyrine t1/2 rose from 5.6 to 13.3 hr in one subject and from 7.5 to 14.6 hr in the other. The corresponding decrease in antipyrine clearance was 0.93 to 0.55 and 1.41 to 0.60 ml/min/kg. This observation suggests that in some subjects lactation may influence drug metabolism. The amount of antipyrine available to each nursing infant was estimated by assuming the the infant nursed 3 ounces every 4 hr for 24 hr after maternal antipyrine administration. The amount of antipyrine available to the nursing infant was calculated to range from 3.0 to 11.1 mg (mean +/- SD = 6.4 +/- 2.9 mg) or from 0.25% to 1.07% (mean +/- SD = 0.59 +/- 0.29%) of the maternal dose.

Adult↗

Antibodies to distinct polypeptides of RNA polymerase I in sera from patients with rheumatic autoimmune disease.

Sera from patients with rheumatic autoimmune diseases were screened for antibodies directed against RNA polymerase I by using a solid-phase radioimmunoassay. Significant levels of the antibodies were detected in the sera of all patients with either systemic lupus erythematosus or mixed connective tissue disease and in 78% of the individuals with rheumatoid arthritis. No detectable anti-RNA polymerase I antibodies were found in the sera from healthy subjects. Individuals taking hydralazine, three of whom exhibited symptoms of drug-induced lupus, had barely detectable levels of the antibodies. Immunoglobulins obtained from sera containing anti-RNA polymerase I antibodies, as determined by the radioimmunoassay, could inhibit RNA polymerase I activity in vitro. Sera from patients with systemic lupus erythematosus contained immunoglobulins directed against the polymerase I-associated polypeptide of Mr 65,000 as well as against the polypeptides of Mr 120,000 or Mr 25,000, or both. Sera from individuals with rheumatoid arthritis reacted with the polypeptide of Mr 65,000 only. The antibodies in the sera of patients with mixed connective tissue disease were directed against the Mr 42,000 polypeptide or a combination of the Mr 65,000, 42,000, and 25,000 polypeptides. These data suggest that the production of anti-RNA polymerase I antibodies may be a unique characteristic of individuals with rheumatic autoimmune diseases and that the production of antibodies against specific polypeptides of RNA polymerase I may be indicative of the particular class of disease.

Antibody Specificity↗

Pharmacologic considerations of drug use in the lactating mother.

The recent increase in the incidence of breast-feeding has given impetus to the study of the excretion of drugs and chemicals into human milk. It appears that the major route of drug appearance in milk is via diffusion from the maternal circulation. In general, maternal plasma levels of a drug dictate milk levels. Un-ionized drugs with high lipid solubility and minimal binding to maternal plasma protein diffuse best. The amount of a drug excreted in milk is usually not more than 1 to 2% of the maternal dose. Most studies have been done with single-dose or short-term drug administration. Very few data are available for the mother who receives continuous drug therapy. Environmental chemicals such as insecticides are also a cause for special concern. They are highly lipid soluble and may remain in body fat for very long periods. Indeed, lactation may be the only route of elimination. The effect of even small amounts of these agents on the growing infant is unknown. Further studies are needed to determine the amount of these agents secreted and the possible risk to the nursing infant.

Animals↗