Thiamphenicol during the first trimester of human pregnancy: Placental transfer in vivo,placental uptake in vitro,and inhibition of mitochondrial function

Thiamphenicol (TAP) was administered as a single oral dose of 500 mg (8–9 mg/kg) to pregnant women about to undergo therapeutic abortions. The length of gestations varied from 7 to 12 weeks. The concentrations of TAP were determined by electron capture gas chromatography in maternal serum, placenta, amniotic fluid, and various embryonal/fetal tissues when abortion occurred 1.5 to 20 hr after drug administration. TAP was rapidly transferred across the placental membranes and was fairly evenly distributed in the tissues of the embryonal/fetal compartment. The placental concentrations of TAP were usually higher than the corresponding maternal serum levels (1.1 to 7-fold), suggesting some active role of the placenta in TAP uptake. This was confirmed by in vitro studies with immature and term placenta tissue. From a bathing medium containing 10 μg/ml (comparable to therapeutic blood levels) TAP was accumulated in the intracellular compartment to concentrations about 2.6 times those in the medium. This process was time and temperature dependent. Inspite of the low content of mitochondrial particles in human fetal liver the relatively few mitochondria present exhibited high protein synthesis in vitro which decreased with increasing gestational age. Mitochondrial protein synthesis was inhibited by TAP, and a 50% reduction of amino acid incorporation was observed at 10–15 μg TAP/ml. Such levels of the drug are required for successful chemotherapy. To ascertain such therapeutic drug levels, TAP is usually given at 3 g daily (divided, e.g., into three doses 1 g each). The data obtained for a single application of 0.5 g TAP suggest inhibition of mitochondrial protein synthesis during therapy. While the pharmacokinetic characteristics of TAP suggested that this compound might be well suited to treat intrauterine bacterial infections sensitive to TAP, the drug concentrations reached in human embryonal tissues in vivo are known to produce embryolethality in pregnant rats at comparable developmental stages. The findings reported here raise serious concerns about the suitability of TAP for repeated administration to pregnant women during the first trimester of gestation.     

Early albumin infusion to infants at risk for respiratory distress

In a randomized prospective study, 100 high-risk infants (selected on the basis of a cord serum protein level of 4·6 g/100 ml or less, gestational age under 37 weeks, birthweight 2500 g or less, and/or arterial pH below 7·25) received 8 ml/kg of either 25% salt-poor albumin or 5% dextrose in water before the age of 2 hours. All infants were then managed supportively with warmth, appropriate oxygen supplementation, isotonic fluid infusion, and close monitoring, without further administration of colloid or hypertonic alkali solutions over the first 4 hours of life.     

A rat model of chronic respiratory infection with Pseudomonas aeruginosa.

Chronic, nonlethal, pulmonary infection of rats by Pseudomonas aeruginosa can be initiated by intratracheal inoculation of 10(4) bacteria enmeshed in agar beads. The number of bacteria recoverable from the lung increased to approximately 10(6) within 3 days and remained at that number during 35 days of observation. Histologic examination of the infected lungs revealed lesions resembling those seen in lung tissue of humans with acute or chronic nonbacteremic, Pseudomonas aeruginosa pneumonia, including the presence of goblet-cell hyperplasia, focal areas of necrosis, and acute and chronic inflammatory infiltrate. This model should be useful for investigating the interactions between microbial virulence factors and host defense mechanisms.     

Response of physicians to medical complaints in men and women.

Workups by physicians in response to five common complaints in a sample of 104 men and women--52 married couples--were evaluated by chart audit. For the total group of complaints, back pain, headache, dizziness, chest pain, and fatigue, the physicians' workups were significantly more extensive for men than they were for women. These data tend to support the argument that male physicians take medical illness more seriously in men than in women.     

Endoscopic argon-ion laser phototherapy of bleeding gastric lesions.

An argon-ion laser, coupled to a flexible fiberoptic endoscope, was used to photocoagulate experimentally produced bleeding gastric ulcers in dogs. Argon-ion laser phototherapy rapidly and effectively achieved hemostasis in all bleeding ulcers. Bleeding arteries up to 2 mm in diameter were photocoagulated. Intact normal gastric mucosa was exposed to laser energy for varying periods of time to determine if transmural photothermal injury occurred. Exposure for greater than 15 seconds at 1.0 w of throughput power caused microscopical evidence of transmural injury. Healed, laser-treated ulcers could not be differentiated from nontreated control ulcers or normal stomach one month after injury. The Beer law and the heattransfer factors relating to soft tissues are discussed. The coupled argon-ion laser-endoscope may be a safe tool to treat self-limited superficial bleeding gastric lesions.     

Dialysance and clearance measurements during clinical dialysis-a plea for standardization.

Mass transfer and dialysance measurements were determined using (1) whole blood solute concentrations with blood flow rates, (2) plasma solute concentrations with plasma flow rates, and (3) plasma solute concentrations with whole blood flow rates by standard formulas during 30 clinical hemodialyses. Resulting values by these three methods were compared for potassium, urea, and creatinine. The three techniques yield significantly different values and, accordingly, the type of measurement must be specified before such clinical measurements of solute transport are interpretable. Multiple mechanisms to account for the differences are suggested and include minimal or no immediate effect of a single coil blood transit on intracellular solute concentrations for all solutes studied.