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Biomedical subjects

M L Thomas

Publications and source records attributed to M L Thomas.

At least 217 records · Page 12Linked to original sources

Regulation of calcium homeostasis in the fetal and neonatal rat.

Circulating levels of calcium (Ca) and immunoreactive parathyroid hormone (IPTH), and the renal cyclic AMP responses to PTH, calcitonin (CT), and vasopressin (VP) were measured in fetal and neonatal rats. Serum Ca increased from a mean value of 9.1 mg/dl on the 19th day of gestation to 10.9 on day 20. Circulating IPTH decreased from 875 pg/ml to 213. Serum Ca declined rapidly after birth to a nadir of 7.6 by 3 h and IPTH increased to 2,006 pg/ml, indicating that fetal and newborn parathyroids are capable of responding appropriately to changes in circulating Ca. Renal responsiveness to hormones was assessed in vitro in the presence of methylisobutylxanthine, a phosphodiesterase inhibitor. The tissue cyclic AMP response to PTH and CT (15- to 18-fold over basal) was greatest at gestational days 18 and 19, progressively declined throughout the remainder of gestation, and remained low during the first 24 h after birth (6- to 7-fold). Renal cyclic AMP response to VP remained consistently low throughout this period. The depressed renal cyclic AMP response to PTH at the time of birth may contribute to the hypocalcemia found in newborn rats.

Adenylyl Cyclases↗

Sex differences during the development of vitamin D deficiency in the rat: serum parathyroid hormone, calcitonin, calcium, and phosphorus.

Male and female Holtzman rats were raised from weaning on a vitamin D-deficient diet (-D). Control (+D) animals were raised on the same diet and orally given 70 IU vitamin D3 twice each week. Serum Ca levels fell at the same rate in -D males and females. In contrast, serum parathyroid hormone increased more rapidly in males than females, but reached the same maximal level in both sexes. There were no sex differences in serum Ca or parathyroid hormone in the +D group. Serum calcitonin increased with age in all groups. This increase began at an earlier age in females than in males in both +D and -D animals. In both sexes, the increase occurred several weeks earlier in +D than in -D animals, and within each of these groups, males had higher phosphate levels than females. Female rats exhibited greater longevity on the -D diet than their male counterparts. Results of this study document prominent sex differences in the endocrine regulation of Ca homeostasis that were revealed during the development of vitamin D deficiency in the rat.

Aging↗

Is the postphlebitic leg always postphlebitic? Relation between phlebographic appearances of deep-vein thrombosis and late sequelae.

One hundred and thirty legs of 67 patients were examined 5-10 years after the patient had suffered a phlebographically proved deep-vein thrombosis. Forty-seven of the limbs were normal at the time of the phlebogram, 83 contained thrombus. There was little correlation between the phlebographic severity of the thrombus and the late symptoms and signs: 32% of the legs with no thrombosis had symptoms, while 33% of the legs which had suffered severe thrombosis had no symptoms. Postphlebitic symptoms were more common in legs with aging thrombus at the time of phlebography, but upper limit of the thrombus, the age of the patient, and preexisting symptoms did not affect the incidence of late sequelae. The development of a "postphlebitic leg" does not depend solely on the extent of the initial thrombosis and can apparently develop in the absence of thrombosis.

Female↗

Evidence for presence of an internal thiolester bond in third component of human complement.

Treatment of the third component of human complement (C3) with methylamine results in a loss of hemolytic function and the appearance of a thiol group. Studies with [14C]methylamine have indicatd a stoichiometric and covalent reaction with the native protein. Hydrazine-inactivated C3 and C3b prepared with bovine trypsin were unreactive with [14C]-methylamine. Alkylation experiments with [1-14C]iodoacetamide have further established a 1:1 correspondence between methylamine incorporation and expression of the reactive thiol. Autoradiographic analyses of [14C]methylamine-treated C3 and methylamine-inactivated [1-14C]carboxyamidomethylated C3 after NaDodSO4/polyacrylamide gel electrophoresis have shown a specific incorporation of each radiolabel into the alpha polypeptide chain. [14C]Methylamine-treated C3 was immobilized on Sepharose 4B by reaction of the protein thiol with a mixed disulfide. Digestion with bovine trypsin in 4 M urea released 96% of the bound absorbance (at 280 nm) units; the radiolabel remained associated with the Sepharose beads. Peptide material labeled with 14C was eluted with dithiothreitol, carboxymethylated with [3H]iodoacetic acid, and chromatographed on Sephadex G-75. On Edman degradation S-[3H]carboxymethylcysteine was released at step 9 and gamma-glutamyl[14C]-methylamide was released at step 12. We interpret these data to indicate the presence of an internal thiolester bond in native C3. In addition, evidence is presented for an identical reactive site in alpha 2-macroglobulin.

Amino Acids↗

Pharmacokinetics and bacteriological efficacy of moxalactam (LY127935), netilmicin, and ampicillin in experimental gram-negative enteric bacillary meningitis.

Moxalactam (LY127935) is a 1-oxa-beta-lactam which was active in vitro against the majority of 128 strains of gram-negative enteric bacilli isolated from meningitis in neonates. Pharmacokinetics and bacteriological efficacy of LY127935 were studied in a lapin meningitis model. The average penetration of this investigational oxa-cephalosporin into cerebrospinal fluid of infected rabbits was 23% compared with 25% for netilmicin and 11% for ampicillin. The cerebrospinal fluid concentrations of LY127935 produced median bactericidal titers of 1:64 to 1:128 against five coliform organisms (two Escherichia coli K1 strains, Klebsiella pneumoniae, Salmonella saint-paul, and Citrobacter diversus) used in these experiments compared with median titers of 1:2 to 1:8 for netilmicin and 1:2 to 1:4 for ampicillin. LY127935 was statistically significantly more effective than netilmicin or ampicillin in reducing cerebrospinal fluid bacterial colony counts and in sterilizing cerebrospinal fluid of experimentally infected rabbits. These results suggest that LY127935 has theoretical advantages over netilmicin and ampicillin for therapy of gram-negative bacillary meningitis.

Ampicillin↗

125I-fibrinogen uptake following phlebography of the leg. Comparison of ionic and nonionic contrast media.

The incidence of venous thrombosis diagnosed with the 125I-fibrinogen uptake test was investigated in a prospective, randomized, double-blind study with the patient serving as his own control, using an ionic contrast medium (methylglucamine iothalamate 280) in one leg and a nonionic medium (metrizamide) in the other. The incidence of thrombosis was significantly lower with metrizamide (7%) than with methylglucamine iothalamate (28.6%). The authors conclude that metrizamide is the contrast medium of choice for phlebography.

Adult↗

The value of large volume selective arteriophlebography of the renal veins in the pre-operative assessment of renal carcinoma.

The accuracy of large volume selective arteriophlebography in demonstrating the main renal veins in 28 patients with renal carcinoma is presented. The diagnosis was shown to be correct at operation in 96% of examinations. It is suggested that the technique is valuable and safe and should form part of the routine pre-operative assessment of patients with renal carcinoma.

Adult↗

Pharmacokinetic properties of netilmicin in newborn infants.

Netilmicin and gentamicin susceptibilities of 258 gram-negative organisms and 25 strains of Staphylococcus aureus were nearly identical. The pharmacokinetic properties of netilmicin were evaluated in 101 newborn infants and related to birth weight, gestational age, chronological age, and route of administration. Mean peak serum concentrations of 5.6 to 6.9 and 7.8 to 8.4 mug/ml were observed 30 min after 3- and 4-mg/kg doses, respectively, were given intramuscularly. The peak concentrations were directly related to gestational age. The average serum half-life values varied from 3.4 to 4.7 h and in general were inversely related to birth weight, gestational age, and postnatal age. The pharmacokinetics of netilmicin in 10 infants were similar after intramuscular and intravenous administration. A comparative study of netilmicin and gentamicin in seven neonates revealed greater variability in serum concentrations of gentamicin and a shorter half-life for netilmicin. There was evidence of accumulation of netilmicin in 12 low-birth weight, premature infants who received 4-mg/kg doses for an average of 6.4 days. Serum and urine levels of netilmicin were measured up to 11 days after discontinuation of the drug. These data are well characterized by a two-compartment model. Additional studies of efficacy and long-term toxicity of netilmicin in neonates are necessary.

Bacteria↗

Comparative pharmacokinetics of amoxicillin and ampicillin in infants and children.

The pharmacokinetics of amoxicillin and ampicillin were studied in 24 infants and children. Mean peak serum concentrations of 5.4 micrograms/ml in fasting and 3.2 micrograms/ml in nonfasting patients were observed after 15 mg/kg amoxicillin doses. Area under the curve values and serum half-life values were similar in fasting and nonfasting patients. The pharmacokinetics of amoxicillin (15 mg/kg) were compared to those of ampicillin (25 mg/kg). Peak serum concentrations, area under the curve values and half-life times were comparable for the two drugs. Amoxicillin (25 mg/kg) and ampicillin (25 mg/kg) were compared in cross-over fashion in 11 children. Serum concentrations of amoxicillin were consistently larger than those of ampicillin; the differences were of borderline significance at one and two hours and statistically significant at four and six hours after the dosage. The bioavailability of amoxicillin was twice that of ampicillin. Amoxicillin was detected in approximately half of the saliva samples studied. Although the salivary concentrations in many children exceeded the inhibitory level for most pneumococci and group A streptococci and for many non-beta lactamase-producing Haemophilus influenzae type b strains, the clinical relevance of these observations is unknown.

Amoxicillin↗

Complications of ascending phlebography of the leg.

Forty patients were studied prospectively for complications of ascending phlebography. The commonest immediate complication was pain at the site of injection and the commonest delayed complication pain in the foot or calf. Out of 30 patients with pain in the foot and calf, 15 had venous thrombosis. Review of 200 case notes disclosed only one recorded complication--namely, necrosis of the dorsal skin of the foot. Complications of the procedure reported by referring clinicians over 10 years comprised four cases of necrosis of the dorsum of the foot and two of gangrene of the foot, in one of which the gangrene spread to the leg. Major complications of ascending phlebography are rare, though when they occur may cause serious morbidity. If a scrupulous technique is used contrast phlebography remains the most accurate method of diagnosing venous disease of the leg.

Foot Dermatoses↗