Head trauma was induced in rats by a weight-drop device, falling over the exposed skull over the left hemisphere. The neurological state of the rats was evaluated by a neurological severity score at 1 h and 18 h post head trauma. At 18 h post head trauma, rats were decapitated and tissue from the vicinity of the injury and from a corresponding area in the contralateral hemisphere was taken for specific gravity (SG) determination using linear gradient columns. Slices were taken from the same sites for incubation in Krebs-Ringer solution, and the concentrations of prostaglandin (PG)E2, 6-keto-PGF1 alpha, and thromboxane B2 accumulated in the medium during 1 h were measured by radioimmunoassay. In one experimental group, rats were pretreated with intraperitoneal dexamethasone sodium phosphate (4 mg/kg) 18 and 2 h before head trauma, and a third dose was given 8 h post head trauma. Another group was treated with intraperitoneal indomethacin (10 mg/kg) 1 h before and 7 h after head trauma. Other groups were treated immediately and 8 h after head trauma with 4, 8, 15, or 30 mg/kg of dexamethasone sodium phosphate. Another group of rats was treated with free dexamethasone (10 mg/kg) right after head trauma and 8 h later. Head trauma induced edema, as expressed by decreased SG, in the left hemisphere of all traumatized rats. Neither treatment protocol affected the neurological severity score of the injured rats or the SG of the contused hemisphere. PG synthesis, on the other hand, was significantly reduced following indomethacin or free dexamethasone, both in sham and traumatized rats, but not in dexamethasone sodium phosphate-treated rats. We conclude that pretreatment with indomethacin, dexamethasone sodium phosphate, or dexamethasone, used in the present protocols, does not affect posttraumatic cerebral edema. Thus, the role of PGs as mediators of edema formation remains unclear.

Animals↗

PubMed1988

Experimental closed head injury in rats: mechanical, pathophysiologic, and neurologic properties.

A model of closed head injury in rats was developed using a calibrated weight-drop device. The development of edema was studied in various brain regions (cerebral hemispheres, brain stem, cerebellum) using a linear specific gravity gradient column. Regional brain tissue density was measured within 1 min, at 15 and 60 min, 18 h, 4 and 10 days after injury to the left cerebral hemisphere, and was compared with values in sham-operated and control rats. Significant edema (i.e., reduced specific gravity) occurred only in the traumatized hemisphere and was maximal at 18 h. A neurologic severity score (NSS) was developed to evaluate the status of the rat after injury. Specific gravity was significantly correlated with NSS at 18 h after injury. The affected hemisphere displayed hemorrhagic lesions as early as one hour post head trauma (HT), which evolved into hemorrhagic necrosis at 18 h. A pathologic score, evaluated 18 h post HT based on size and severity of the lesion, was correlated with the NSS and evaluated for each rat at one hour and 18 h postimpact. This correlation was found to be highly significant. This model of brain injury may be useful in future studies on the effects of therapeutic agents.

Animals↗

PubMed1988

Comparison of soluble dexamethasone sodium phosphate with free dexamethasone and indomethacin in treatment of experimental neoplastic spinal cord compression.

In an experimental rat model of neoplastic spinal cord compression, the in vivo effect of steroidal and nonsteroidal anti-inflammatory agents on the water content, prostaglandin E2 (PGE2) production, and specific gravity of the compressed cord segments were assessed, as well as the effect on the course of the disease. Paraplegic animals presented a consistent increase in the water content, PGE2 synthesis, and specific gravity in the compressed cord segments. The effect of treatment given on onset of paraplegia with either dexamethasone sodium phosphate (Dex-p; 10 mg/kg twice daily), or free dexamethasone (F-dex; 8.25 mg/kg twice daily) or indomethacin (10 mg/kg twice daily), was evaluated after 30 hours of therapy. Both F-dex and indomethacin eliminated spinal cord edema but varied in the rate of inhibitory effect on PGE2 production (dexamethasone less than indomethacin). Dexamethasone sodium phosphate failed to reduce spinal cord edema and PGE2 synthesis, but specific gravity changes were corrected by each of the administered agents. Evaluation of the effect of treatment on the course of the disease required dose reduction by 50% for Dex-p and F-dex, and to 25% for indomethacin, to avoid lethal toxicity. Treatment was started on appearance of the first sign of neurologic dysfunction (Grade 1) and continued to paraplegia (Grade 5). In the saline-treated rats, the mean time interval between Grades 1 and 5 was 2.7 +/- 0.3 days. Free dexamethasone, Dex-p, and indomethacin significantly prolonged this interval by 57%, 54%, and 48% respectively (P less than 0.005). The three agents differed in their ability to control the increases in water content and in PGE2 production, but proved almost equally effective in the prompt control of the specific gravity changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Familial carnitine deficiency: further evidence for autosomal recessive transmission with variable expression.

Carnitine deficiency occurring in families has been rarely reported and the genetic transmission has not yet been clearly elucidated. Five members of one family showing marked heterogeneity of carnitine deficiency states are presented. In three patients, there was no correlation between measurable carnitine levels in serum and muscle and the clinical findings. The parents, who are remote relatives from an isolated village in Kurdistan (Iraq), had low muscle carnitine levels; however, they were asymptomatic. One son, with systemic carnitine deficiency causing muscle weakness and recurrent episodes of severe hepatic encephalopathy, died at 3 years of age. His brother had mild proximal muscle weakness associated with low muscle carnitine levels. He was successfully treated with L-carnitine and prednisone. A daughter is asymptomatic, but with low serum and muscle levels of carnitine. The marked heterogeneity of carnitine deficiency states within one family, where both parents had low muscle carnitine levels, suggests an autosomal recessive inheritance with variable expression.

Carnitine↗

PubMed1988

Anaesthetic considerations in facial reconstruction for Down's syndrome.

Sixty-three patients with Down's syndrome underwent facial reconstructive surgery under general anaesthesia in order to improve their acceptability and potential for functioning effectively in society. Preoperatively, one-third of the patients had respiratory illnesses, 11 (17.5%) had cardiac anomalies, and 5 (7.9%) had endocrinological abnormalities. Anaesthesia was based on spontaneous ventilation of halothane and N2O in oxygen via an endotracheal tube with appropriate monitoring. Only one patient had an intraoperative complication, an episode of ventricular dysrhythmia, but postoperatively 9 patients required nasopharyngeal airways or endotracheal intubation in order to maintain a patent upper airway. The anaesthetic considerations for facial reconstructive surgery in Down's syndrome are discussed.

Adolescent↗

PubMed1988

Indomethacin and dexamethasone treatment in experimental neoplastic spinal cord compression: Part 1. Effect on water content and specific gravity.

Water content and specific gravity were measured in the cervical, high thoracic, thoracic, and lumbar segments in an experimental model of neoplastic epidural spinal cord compression in rats harboring a thoracolumbar tumor. Increased content of water was observed only in the compressed lumbar cord segments of paralyzed rats (P less than 0.04). A progressive increase in specific gravity values of the compressed segments accompanied the increasing severity of neurological dysfunction (P less than 0.003 in paraplegic rats). Electron microscopy of the compressed cord revealed enlarged interstitial spaces, myelin breakdown, and extravasated blood cellular elements. Treatment with dexamethasone (10 mg/kg q 12 hr x 3) failed to reduce the increased content of water, but corrected specific gravity changes. Treatment with indomethacin (10 mg/kg q 12 hr x 3) reduced both elevated water content and specific gravity values back to normal levels. In untreated animals, the interval between the first neurological sign (limp tail) and paraplegia was 2.8 +/- 0.34 days (mean +/- SE). Treatment with dexamethasone lengthened this period by 28.6% (P less than 0.05); treatment with indomethacin lengthened it by 66.4% (P less than 0.005). We conclude that, because the specific gravity measurements in this model reflect complex pathophysiological processes, their translation into water content values is not advisable. Pharmacological intervention with indomethacin compares favorably with dexamethasone in reduction of spinal cord edema and in delaying the onset of paraplegia.

Animals↗

PubMed1988

Indomethacin and dexamethasone treatment in experimental neoplastic spinal cord compression: Part 2. Effect on edema and prostaglandin synthesis.

Edema formation and prostanoid production (prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in a model of neoplastic epidural cord compression (NSCC) in rats harboring a thoracolumbar tumor. Tumor-free and tumor-bearing animals were randomized for three treatments at 12-hour intervals with saline, dexamethasone (10 mg/kg i.p.), or indomethacin (10 mg/kg i.p.). Increase in water content was observed only in the compressed lumbar cord segments of paralyzed rats; the cervical and thoracic segments did not differ from controls. The rate of release of prostaglandins was evenly distributed along the spinal segments in tumor-free rats. In tumor-bearing rats, a consistent significant increase in PGE2 production was found in the compressed lumbar segment in the presence of neurological dysfunction: early (limp tail), P less than 0.05; paraplegia, P less than 0.001. A significantly elevated PGE2 synthesis preceded the increase in water content by 2 to 3 days. A 2-fold increase in TXB2 was detected in only one of three experiments, and synthesis of 6-keto-PGF1 alpha was elevated to 4 times the normal value (P less than 0.005) in two of three experiments. Dexamethasone failed to inhibit prostaglandin synthesis in the spinal cord of normal controls or paralyzed rats, whereas in nonneural tissues (liver, uterus) it reduced synthesis of the three metabolites by at least 50%, thus demonstrating a differential effect on central nervous system (CNS) vs. non-CNS tissues. Dexamethasone also failed to reduce the increased water content of the compressed segments.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Cerebrohepatorenal syndrome of Zellweger: a peroxisomal deficiency disorder. Case report and review.

The cerebrohepatorenal syndrome of Zellweger (CHRS) is a rare, fatal disorder in newborn infants. Recent research points to a primary absence of tissue peroxisomes, with resulting biochemical defects, as the basic pathology of the condition. We report on an infant with classic neurological and dysmorphic features of CHRS. Increased serum levels of pipecolic acid, bile acid precursors and very-long-chain fatty acids (VLCFA) together with total histological absence of liver peroxisomes confirmed the diagnosis. To our knowledge, this is the first case in Israel to be fully documented by biochemical and ultrastructural techniques. A high index of suspicion is essential among clinicians if further cases are not to be overlooked.

Facial Bones↗

PubMed1988

Experimental closed head injury in rats: prostaglandin production in a noninjured zone.

In a model of closed head injury in rats, a calibrated weight drop device was allowed to fall onto the skull's convexity over the left hemisphere 1 to 2 mm lateral from the midline. Prostaglandin (PG) levels were determined in the frontal cortex region remote from the site of injury where no macroscopic damage could be seen. Differential patterns of temporal changes were evident for PGE2, PGD2, thromboxane (TX) B2, and 6-keto-PGF1 alpha in the contused hemisphere, but no changes were found in the contralateral hemisphere. The major changes in PG levels were increased levels of PGD2 and 6-keto-PGF1 alpha that persisted from 18 hours until 10 days after injury. The ratio between TXB2 and 6-keto-PGF1 alpha, which reflects the vascular tone, increased during the early postinjury period (15 minutes and 1 hour) and decreased later, up to 10 days. Thus, a sustained imbalance in favor of the vasodilator is apparent; this may suggest an improved blood supply to the region. Both PGD2 and PGI2 have protective effects in the brain. We suggest that their endogenous increase may be part of a repair mechanism at the periphery of the injured zone.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

Au/InSb(110) interface profiles from synchrotron-radiation and polar-angle-dependent x-ray photoemission.

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Journal Article↗