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Biomedical subjects

C Brandt

Publications and source records attributed to C Brandt.

At least 91 records · Page 5Linked to original sources
PubMed1985

Adaptation of hepatic ammonia metabolism after chronic valproate administration in epileptics treated with phenytoin.

The effects of phenytoin (PHT) on the modifications of ammonia (NH+4) metabolism caused by sodium valproate (VPA) are here studied in order to identify the drug combinations susceptible of evoking stuporous states in epileptics, a rare condition attributed to a hyperammonemic encephalopathy induced by VPA. During chronic treatment with PHT or VPA-PHT, the acute injection of VPA increases the kidney's output of NH+4. During chronic PHT treatments, the acute injection of VPA modifies the liver's NH+4 metabolism and the arterial hyperammonemia is high (mean = 90 mumol/l). During chronic VPA-PHT treatments, the acute injection of VPA does not affect the hepatic NH+4 metabolism, suggesting that adaptation occurs, and the arterial hyperammonemia is moderate (mean = 60 numol/l). Disturbances of the hepatic adaptive mechanisms may explain certain complications observed during multiple-drug regimens.

Adaptation, Physiological↗
PubMed1983

Sodium valproate associated with phenobarbital: effects on ammonia metabolism in humans.

Treatment with sodium valproate (VPA) in association with phenobarbital (PB) is accompanied by a greater systemic hyperammonemia than treatment by VPA alone. The anatomical origins of this difference were studied by injecting a dose of 1,500 mg VPA i.v. into six unmedicated patients and six epileptics chronically treated with PB and measuring the ammonium (NH4+) concentration difference between arterial blood and renal, hepatic, internal jugular, and femoral venous blood. In unmedicated patients, arterial [NH4+] rose moderately, secondary to an increased amount of NH4+ released into the general circulation by the kidney; the hepatic metabolism of NH4+ remained normal. In epileptics treated with PB, arterial [NH4+] rose massively, partly as a result of the increased NH4+ release by the kidney and partly because of disturbance of the hepatic metabolism of NH4+. These results provide a clearer understanding of the potentiation of the secondary effects of VPA by PB.

Adult↗
PubMed1983

Pulmonary response to repeated exposure to Micropolyspora faeni.

Most human exposure to agents that cause hypersensitivity pneumonitis (HP) result in transient episodes of HP that resolve quickly. We repeatedly injected Micropolyspora faeni, which is responsible for farmer's lung disease, into rabbits in an attempt to elucidate mechanisms for this phenomenom (i.e., resolution of abnormalities). The character and the extent of lung disease, the amount of anti-M. faeni serum antibody, and skin reactivity to M. faeni were evaluated after 3 sensitizing and 2, 4, or 8 challenge injections. We also determined the fate of 125I labeled M. faeni injected intratracheally into both normal and previously exposed rabbits. Increased numbers of lymphocytes, macrophages, and few polymorphonuclear leukocytes were present in interstitial and intraalveolar regions and bronchial walls. Interstitial fibrosis was not observed. The extent of cellular abnormalities was maximal after 2 challenges and regressed thereafter, despite continuing intratracheal injections. Serum anti-M. faeni antibody peaked after 4 intratracheal challenges. Anti-M. faeni antibody level at the time of death appeared to be proportional to the extent of inflammatory reaction within the lung. Previous exposure of rabbits to M. faeni was associated with more rapid appearance of 125I in blood in the first 2 h after intratracheal injection of 125I M. faeni. However, 24 h after injection, there was less 125I in the lungs and more in the urine of immunized rabbits than in normal rabbits. Repeated intratracheal injections of M. faeni into rabbits produces transient interstitial, intraalveolar, and peribronchial inflammatory infiltration that regresses without fibrosis despite continued antigenic challenge. Immunization appears to markedly decrease pulmonary exposure to antigen that results from an intratracheal injection of M. faeni.

Alveolitis, Extrinsic Allergic↗
PubMed1983

The renal origin of sodium valproate-induced hyperammonemia in fasting humans.

Acute administration of 1,500 mg of sodium valproate or chronic administration of 30 mg/kg/24 hours induced a more than twofold increase of renal ammoniagenesis in fasting subjects. Hyperammonemia was moderate, as normal hepatic ammonia detoxification persisted. Renal uptake of glutamine increased simultaneously.

Adult↗
PubMed1980

Heat shock induced alterations in polyadenylate metabolism in Drosophila melanogaster.

We have studied the effect of heat shock on poly(adenylic acid) [poly(A)] metabolism in Drosophila melanogaster cells by using hybridization of ribonucleic acid (RNA) samples to [3H]poly(uridylic acid). Shortly after heat shock begins, cytoplasmic poly(A) decays rapidly. Two components were detected. Component I constitutes 46% of the total cytoplasmic poly(A) and decays with a half-life of 10 min. Component II (54% of total) is more stable. A half-life was not estimated for component II because new synthesis was not blocked. Studies on the size of cytoplasmic poly(A) indicate component I is completely degraded while component II remains essentially unchanged. Nuclear poly(A) increases rapidly, peaking at 2 or 3 times the normal level after 90 min of heat shock. Studies on the size of nuclear poly(A) indicate the increase is not due to addition of poly(A) to existing poly(A) segments nor appreciably to newly synthesized RNA unless transit time is markedly increased. We conclude that nuclear poly(A) is added in large part to already existing nonadenylated primers. Studies with RNA and protein synthesis inhibitors show RNA and protein synthesis are not required for the changes in poly(A). As the temperature is raised above 34--35 degrees C, the effect on poly(A) metabolism becomes more severe. Changes in external pH, without increased temperature, also alter poly(A) levels. Poly(A) changes may therefore be a rapid response to a variety of physiological factors.

Animals↗
PubMed1977

Pharmacokinetics of cefazolin in patients with renal failure; special reference to hemodialysis.

The pharmacokinetic constants of cefazolin were determined comparatively in ten normal subjects, 12 patients with renal failure, and ten patients on repeated hemodialysis. Significant correlations could be established between the creatinine clearance values and the overall elimination rate constants (Ke), serum half-lives (T 1/2), plasmatic areas (Ftot), urinary recoveries (uo-6 hr), and renal clearances of the antibiotic (Cr). The pharmacokinetic changes produced by extrarenal removal were also studied. On the basis of the obtained results, a dosage schedule adjusted to renal status was proposed.

Cefazolin↗
PubMed1976

Adjustment of cephaloridine (Keflodin): dosage according to its pharmacokinetics.

The determination of the serum and urine concentrations of cephaloridine permitted calculation of the pharmacokinetic constants of this antibiotic: after administration of a 1-gram intravenous dose in five normal subjects; after administration of a 1-gram intramuscular dose in five normal subjects, five patients with renal impairment and five patients on maintenance hemodialysis. In normal subjects, serum half-life averaged 1.56 h (Ke=0.4445) after intravenous administration and 1.63 h (Ke=0.4254) after intramuscular administration of a 1-gram dose of the antibiotic. The urinary excretion of cephaloridine over the 6 h following its intramuscular administration in normal subjects amounted to 56.4% of the administered dose. The renal clearance of cephaloridine was 194 ml/min. A linear correlation (Ke=0.0670+0.0028 CrCl) was established between overall elimination rate-constant values and the creatinine clearances of the patients under investigation. These data were used to calculate the maintenance and loading doses and intervals adjusted to creatinine clearance values. Accurate dosage regimens adjusted to the renal status of each individual patient were derived from the calculated values.

Cephaloridine↗
PubMed1976

[Biliary elimination of metampicillin. Experimental and clinical study (author's transl)].

Under the conditions of the isolated rabbit liver perfusion, metampicillin was found to be excreted at a high rate in the biliary tract : bile contains 46,5% of the administered dose. Hepatic uptake of metampicillin seems to be early and marked. In man, the biliary elimination of this antibiotic varies according to the route of administration. Only moderate biliary levels of metampicillin were obtained after oral administration ; on the contrary, extremly high biliary concentrations were found when antibiotic was injected intravenously. When parenteraly administered, metampicillin appears to be a particularly suitable penicillin for the treatment of biliary tract infections.

Administration, Oral↗
PubMed1976

[Carcinoid of the small intestines with right cardiac involvement. Clinical, phonomechanographical hemodynamic and anatomical study].

The authors report a case of carcinoid of the small intestine with liver metastases in whom the entire right side of the heart was affected, with severe tricuspid incompetence and pulmonary stenosis. The extent of the fibrosis, which affected all three layers of the heart on the right side has lead the authors to reconsider the various factors which cause the heart failure in carcinoid syndrome. This must now be included in the wider category of APUD. The severity of the tricuspid lesions compared with the derangement of the valvular and subvalvular structures makes an argument in favour of surgical correction.

Carcinoid Tumor↗
PubMed1976

Cephacetrile--application of pharmacokinetic data to dosage determination.

This pharmacokinetic investigation was based on the determination of serum and urinary levles of cephacetrile in 50 subjects given single intramuscular or intravenous doses of 0.5 or 1 gm of the antibiotic; 30 normal subjects, 10 patients with renal insufficiency, and 10 patients with chronic nephritis undergoing maintenance haemodialysis were included in this study. In normal subjects, mean serum half-life was 1.09 hours (Ke = 0.6337) after intramuscular injection of 0.5 gm cephacetrile, 1.31 hours (Ke = 0.5276) after intramuscular injection of 1 gm, and 0.89 hours (Ke = 0.7806) after intravenous injection of 1 gm. Absorption half-life was 0.45 hours after intramuscular injection of 1 gm cephacetrile. The urinary elimination of cephacetrile over the first 6 hours after injection was on the average 72.7% of the administered dose. After intravenous injection of 1 gm of the antibiotic, the plasma clearance of cephacetrile was 407 ml/min., and its renal clearance 313 ml/min. A linear correlation was found between the values of overall elimination rate constant (Ke) and creatinine clearance in the subjects under investigation (Ke = 0.0080 + 0.0061 ClCr). The established pharmacokinetic characteristics were used to calculate the maintenance and loading doses as well as the intervals between injections adjusted to creatinine clearance. These data constitute true dosage schemes adapted to the particular case of each patient according to his kidney function.

Cephacetrile↗
PubMed1968

Conditional temperature-sensitive restriction of Pseudomonas bacteriophge CB3.

Restriction of Pseudomonas bacteriophage CB3 growth on some Pseudomonas aeruginosa hosts was studied. On restricting hosts, growth of this phage was severely inhibited below 32 C and hence was temperature-sensitive. Investigation of this phenomenon revealed that restricting hosts were not killed as a consequence of their infection under nonpermissive conditions. The ability of some hosts to restrict showed segregation in sexual crosses between restricting and nonrestricting hosts. However, the pattern of restriction among various hosts differed with the phage in question when other phages were compared with CB3. Temperature-shift experiments indicated that blockage of an early event in the phage lytic cycle occurred when restricting conditions were imposed on cells infected with CB3. This blockage could be eliminated by holding at permissive conditions until the cold-sensitive step was bypassed or by pulsing restricting cells for 5 min at 37 C.

Bacteriophages↗