Tricyclic antidepressants. Prolonged plasma levels after overdose

Twenty-four patients hospitalized for overdose of a tricyclic antidepressant were monitored clinically, and serial plasma-drug measurements were taken for up to 144 hours. Six of 24 patients had maximum antidepressant plasma levels greater than or equal to 1,000 ng/ml, and their plasma levels at 96 hours ranged from 170 to 1,280 ng/ml. Patients ingesting substantial tricyclic overdoses may remain medically unstable for days. When high tricyclic levels persist, accurate psychiatric assessment is often impossible.     

Stimulation of RNA and protein synthesis in isolated chondrocytes by human serum

The stimulation of isolated chicken embryo chondrocytes was studied by measuring the incorporation of [3H]uridine and [3H]leucine into cold trichloroacetic acid precipitable material after exposure of the chondrocytes to serum. The doseresponse relationships for the incorporation of uridine and leucine were similar to that of thymidine previously demonstrated. Exposure of the cells to serum-containing buffer for 15 min sufficed both for the stimulation of incorporation into the cells and for the depletion of 28% of the stimulating activity from the medium. Stimulation persisted for at least 17 h after removal of the serum. Studies where actinomycin D was added to inhibit RNA synthesis suggested that prior RNA synthesis was required for most of the stimulation of protein synthesis by serum factors.     

Ionic requirements for the active ileal bile salt transport system

A new system of surface-induced profound hypothermia for infant cardiac operations has been developed in order to overcome problems inherent in the current techniques using crushed ice, water baths, and similar methods. The hypothermic chamber consists of two parts: a lower part, containing a refrigeration unit and a blower fan capable of lowering the air temperature in the chamber to -6 degrees C, and an upper part made of Plexiglas that has a completely detachable end to allow easy access to cannulas, the anesthesia hose, and the infant. A temperature panel recorder to monitor the infant's esophageal and rectal temperatures and the ambient chamber temperature is incorporated into the unit. Following evaluation in the animal laboratory, the hypothermic chamber has been successfully used in 10 infants without any complications attributable to the technique. This method provides a rapid and uniform drop of the body temperature and even skin cooling, eliminates the possibility of contact skin lesions, saves medical and paramedical personnel time in preparation of the infant and equipment, and allows observation of the child during the cooling phase. This hypothermic chamber has facilitated infant hypothermic operations.     

Recurrent hypernatremia; a proposed mechanism in a patient with absence of thirst and abnormal excretion of water

A 7-year-old girl twice developed severe hypernatremia (serum sodium values up to 194 mEq/l) without obvious cause. The ability of her kidneys to conserve water was normal, and increasing her plasma osmolality stimulated an appropriate ADH response. Unable to excrete a water load, her kidneys continued to conserve water even with a serum sodium concentration of 133 mEq/l. She was never thirsty and did not ingest sufficient fluid by choice. Although there was no demonstrable anatomic lesion, we postulate a localized defect of her thirst center. This may have modified release of ADH and resulted in an inability to dilute the urine by interrupting a pathway that could exist from the thirst center to the supraoptic nuclei. A therapeutic regimen based on these studies has prevented further hypernatremia.     

Rewarming from immersion hypothermia: a comparison of three techniques

Analysis of measurements from the tali of 21 individual fossil primates from Africa shows that the specimens fall into five clearly defined groups. Accordingly, these specimens have been included as groups along with extant species in a subsequent canonical analysis thus allowing the fossils to play their part in the determination of the canonical separations. The results of this procedure show that the five fossil groups lie in a part of the canonical space not occupied by any extant African primate. Their positions are between the envelope of Asiatic apes (Hylobates and Pongo) and the envelope of African forms near the edge which contains Pan and Papio. One fossil group is so similar to Hylobates that its talus may have functioned in locomotion in a parallel manner. Others lie near to Pongo in directions proceeding towards Pan and Papio and it is possible that this similarity may indicate remnants of morphological adaptation for climbing in these fossils. At the same time, however, individual specimens are closer to one or another of the extant groups and this considerable spread suggests that the locomotor adaptations as evidenced by talar morphology, of the primate fauna in Africa, may have been very different from those of the present day. This would not the inconsistent with the different habitats, floras and non-primate faunas that may have characterized the East African scene at these earlier times. Particular fossils from Olduvai and Kromdraai that are supposed to be australopithecine and therefore bipeds, are confirmed (Oxnard, '72; Lisowski et al., '74) as being totally different from man in their talar morphology and essentially rather similar to the majority of the other fossil tali examined.     

Pyogenic arthritis of the sacro-iliac joint. Long-term follow-up

Nine cases of sacro-iliac pyarthrosis are presented. The difficulty in localizing the infection is attributable mostly to failure to appreciate the posteriorly situated physical findings. This, and the difficulty with early roentgenographic demonstration of the lesion, may lead to unnecessary abdominal exploration (as in two of our patients) or to prolonged delay in diagnosis and hence spread of the infection. Awareness of the usual physical findings and prompt use of radioisotope scanning to localize the infection led to earlier diagnosis and avoidance of surgery in three patients seen recently. Antibiotic therapy, with or without surgery, led to cure in all patients, with minimum sequelae.     

Geotrichum septicemia

Although disseminated geotrichosis is an unusual disease (to our knowledge, only six cases have been reported), Geotrichum candidum is not a very virulent fungus. In our case, there was neutrophillic phagocytosis of the arthrosphores of G candidum, with rapid clearance of the fungus from the plasma of a chronically ill patient whose immune defenses were still intact.     

Conversion of proparathyroid hormone to parathyroid hormone: studies in vitro with trypsin

The conversion of proparathyroid hormone to parathyroid hormone (PTH) was studied in vitro employing pancreatic trypsin as a prototype converting enzyme. Digestion of intact radiolabeled bovine prohormone with trypsin (0.1%) (w/w) resulted in release of a peptide comigrating with intact hormone marker in systems resolving both on the basis of charge (urea polyacrylamide gels, pH 4.4) and size (sodium dodecyl sulfate-urea polyacrylamide gels, pH 7.2). Tryptic digestions of a synthetic analogue of bovine prohormone, ProPTH-(-6 + 34), consisting of the prohormone hexapeptide covalently bonded to the NIH2 terminus of the active fragment of the hormone, released in high yield the hexapeptide and the intact active hormone fragment before any other smaller fragments. Analyses of digestions were by: (i) thin-layer chromatography and amino acid analysis of digestion products; (ii) comparison of the biological activity of the prophormone substrate and the products of digestion; and (iii) peptide end-group analysis by the Edman method during progressive tryptic hydrolysis over 22 h. The latter experiments demonstrated cleavage of more than 75% of the hexapeptide-hormone peptide bond before cleavage of other trypsin-sensitive sites within the molecule. It is concluded that the specificity of cleavage at the hexapeptide-hormone bond in the process of intracellular hydrolysis of proparathyroid hormone resides primarily in the sequence and/or conformation of the precursor molecule; inasmuch as conversion of prohormone to hormone can be efficiently accomplished by pancreatic trypsin in vitro, there is, therefore, no need to postulate the existence of an intracellular converting enzyme within the parathyroid cell that possesses unique hydrolytic specificity.