Late mortality after head injury.

OBJECTIVES: To investigate mortality trends in a cohort of people admitted to a regional head injury unit with all severities of injury in the calendar year 1981. METHODS: A computerised database with details of 1919 admissions was compared with deaths registered by the NHS Central Register, Scotland for the years 1981 to mid-2002. Death certificate information for matches was analysed. RESULTS: The 1919 admissions referred to 1871 individuals, comprising 93 severe, 205 moderate, and 1573 minor injuries according to Glasgow coma scale criteria. There were 57 deaths (42 severe head injuries, eight moderate, seven minor) during the initial admission, and 340 (six severe, 33 moderate, 301 minor) in the subsequent years. Substance abuse, principally alcohol, was a factor in 37 deaths, suicide accounted for 20, and accidents for 25. The great majority of these latter deaths were in people under the age of 70 years. CONCLUSION: Premature deaths after predominantly minor head injury are commonly alcohol related or the result of suicide or accidents.

Beta (CC)-chemokines as modulators of sleep: implications for HIV-induced alterations in arousal state.

Sleep is altered early in the course of HIV infection, before the onset of AIDS, indicating effects of the virus on neural processes. Previous observations suggest HIV envelope glycoproteins are possible mediators of these responses. Because some beta (CC)-chemokine receptors serve as co-receptors for HIV and bind HIV envelope glycoproteins, we determined in this study whether selected CC chemokine ligands alter sleep and whether their mRNAs are detectable in brain regions important for sleep. CCL4/MIP-1beta, but not CCL5/RANTES, injected centrally into rats prior to dark onset increased non-rapid eye movements sleep, fragmented sleep, and induced fever. mRNA for the chemokine receptor CCR3 was detectable under basal conditions in multiple brain regions. These data suggest some CC chemokines may also be involved in processes by which HIV alters sleep.

Development of a sexually dimorphic projection from the bed nuclei of the stria terminalis to the anteroventral periventricular nucleus in the rat.

The principal nucleus of the bed nuclei of the stria terminalis (BSTp) is larger in male rats and conveys olfactory information relevant for reproduction to the hypothalamus. In males, the BSTp provides a massive projection to the anteroventral periventricular nucleus of the preoptic region (AVPV), which in contrast to most sexually dimorphic nuclei contains more neurons in female rats. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the BSTp of adult female rats failed to demonstrate the strong projection to the AVPV observed previously in males. The ontogeny of this robust sex difference was examined by using the axonal marker DiI. The projection from the BSTp to the AVPV is established between postnatal day 9 (P9) and P10 in male rats and seems to be maintained during the juvenile period. Although labeled fibers extended from the BSTp toward the preoptic region in both male and female neonates, a similar connection with the AVPV was not apparent in female rats at any of the ages studied, and the density of labeled axons in the AVPV of P10 males was 20-fold greater than that of P10 females. A projection from the BSTp to the medial preoptic nucleus was also weaker in females but was much more substantial than that to the AVPV. These findings suggest that a sex- and region-specific activity influences the development of the projection from the BSTp to the AVPV, producing a sexually dimorphic architecture in pathways that convey olfactory information to the hypothalamus.

Similarity in gallstone formation from 900 kcal/day diets containing 16 g vs 30 g of daily fat: evidence that fat restriction is not the main culprit of cholelithiasis during rapid weight reduction.

Diets containing essentially no fat, 1-2 g fat per day, have resulted in cholesterol gallstones. Greater fat may result in less gallbladder stasis. Do gallstones form with greater fat content? We studied 272 moderately obese subjects who had normal gallbladder ultrasonograms. The 900 kcal/day liquid diets contained either 16 g fat (N = 94) or 30 g fat (N = 178) each day for 13 weeks. A second gallbladder ultrasound was performed. Sixteen of 94 (17.0%) of the 16-g fat group developed stones with a weight loss of 18 (+/- 7) kg and a body mass index (BMI) decrease of 6 (+/- 2) kg/m2. Twenty of 178 (11.2%) of the 30-g fat group developed stones (P = 0.18, no difference in stone formation) with similar weight loss of 20 (+/- 7) kg (P = 0.08) and BMI decrease of 7 (+/- 2) kg/m2 (P = 0.04). Substantial fat for rapid weight-reducing diets resulted in gallstone formation. Since experiments have shown that our higher fat diet, containing 10 g fat per meal, results in maximal gallbladder emptying, cholelithiasis from rapid weight loss may not be solely attributable to gallbladder stasis.

Suppression of p140trkA does not abolish nerve growth factor-mediated rescue of serum-free PC12 cells.

Programmed cell death, the intrinsic form of apoptosis, plays an integral role in those neurodegenerative events associated with age-related neuropathology. Neurotrophins (NTs), such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3, are required for survival of certain neurons, and thus their clinical use to counteract age- and pathology-associated neurodegeneration has been suggested, although mechanistic descriptions for NT cell rescue from apoptosis are not definitive. Here we attempted to isolate the individual actions of high-affinity tyrosine kinase (Trk) receptors and p75NGFR, the common low-affinity NT receptor, in NT rescue of apoptotic PC12 cells. Our results showed that whereas inhibiting Trk receptor phosphorylation abolishes NGF rescue of serum-deprived PC12 cells from apoptosis, TrkA suppression with antisense oligonucleotides did not. Also, although BDNF did not rescue naive serumless PC12 cells, which lack the BDNF-specific TrkB receptor, it significantly increased survival of TrkA-suppressed serum-starved PC12 cells. These data confirm the hypothesis that binding of any NT to Trk-free p75NGFR-bearing cells blocks apoptosis but also suggest that if Trk receptors are expressed, prohibiting Trk phosphorylation also blocks NT-mediated rescue from apoptosis.

Role of the cholinergic system in the regulation of neurotrophin synthesis.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are members of the family of neurotrophins that are highly expressed in the adult hippocampus, and to a lesser extent, in the cerebral cortex and olfactory bulb. Since neuronal expression of neutrophins is controlled by some neurotransmitters and there is a topographical correlation between neurotrophin expression and cholinergic terminal distribution from the cholinergic basal forebrain (CBF) neurons in these areas, the question arises as to whether the cholinergic system can also regulate neurotrophin gene expression in the CNS. When CBF neurons were selectively and completely destroyed by intraventricular injection of 192 IgG-saporin, resulting in a cholinergic deafferentation of the hippocampus, cortex, and olfactory bulb, there were no significant changes in NGF, BDNF and/or NT-3 mRNA levels in these areas from 1 week to 5 months after the lesion. These results suggest that afferents from CBF neurons may not play a significant role in maintaining basal levels of neurotrophin gene expression in the adult rat brain under physiological conditions. However, potential cholinergic regulation of brain neurontrophin expression may occur under other circumstances.

Novel low-dosage hormonal replacement therapy complements dietary treatment of moderately hypercholesterolemic postmenopausal women.

It is not known whether female hormonal replacement therapy (HRT) influences fasting plasma lipoprotein lipids in diet-treated hypercholesterolemic subjects. Thirteen moderately hypercholesterolemic postmenopausal women were studied during dietary treatment alone with a low fat, low cholesterol diet for the 3 months and during the subsequent 2 y of HRT with dl-norgestrel (0.075 mg daily) and estradiol-17 beta (1 mg, 25 of 28 days) with maintenance of the same diet. Hormonal replacement therapy decreased plasma total cholesterol by 11 +/- 3% (5.7 vs. 6.4 mmol/L, p < 0.005), due to a 17 +/- 3% mean reduction (p < 0.001) in the concentration of plasma low density lipoprotein cholesterol (3.9 vs. 4.7 mmol/L, p < 0.001). The ratio of plasma total cholesterol to high density lipoprotein cholesterol fell significantly by 17 +/- 4% (4.1 vs. 4.9, p < 0.005). Mean fasting plasma concentrations of total triglycerides (1.1 vs. 1.6 mmol/L, p < 0.005) fell by 31 +/- 6%, and very low density lipoprotein triglycerides (0.56 vs. 0.83 mmol/L, p < 0.02) by 33 +/- 9%. Hormonal replacement therapy was well-tolerated, improved mood levels, and increased the mineral content of the vertebral spine significantly, while effectively relieving vasomotor flushing. Hormonal replacement therapy complements the dietary treatment of hypercholesterolemia.

In vitro glial responses to nerve growth factor.

Nerve growth factor (NGF) stimulates expression of the low affinity neurotrophin receptor p75NGFR mRNA in primary cultures of neonatal rat cortical type I astrocytes. Nerve growth factor treatment altered glial morphology in glial fibrillary acidic protein positive (GFAP+) cell cultures derived from newborn (P0) and 3-day-old (P3) rat pups. When P0- or P3-derived primary glial cultures were serum-deprived, in the presence of 200 pM NGF for 5 days, the flat polygonal glia present in culture assumed a fibrous morphology, an effect not seen in the untreated serum-deprived controls. The NGF effect on astrocytic morphology was blocked by continuous serum treatment. Nerve growth factor did not stimulate astrocytic proliferation under these culture conditions, as assayed by cell cycle analysis using 3H thymidine autoradiography. P0-derived primary glial cultures expressed the signal transducing neurotrophin receptors p145trkB and p140trkA as determined by reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR products were identified by sequencing or restriction enzyme analysis. Astrocytes internalized 125I-NGF at 37 degrees C but not at 4 degrees C, consistent with energy requirements for internalization. Also, internalization of 125I-NGF was abolished by the addition of a 300-1,000-fold excess of unlabeled NGF. Thus, astroglial cells in culture internalize NGF through a specific receptor-mediated process, express trkA and full-length trkB mRNAs at low levels, and respond to exogenous NGF by expressing a fibrous morphology under serum-free culture conditions.

Thoracic manifestations of ovarian hyperstimulation syndrome.

OBJECTIVE: To determine the thoracic manifestations of severe ovarian hyperstimulation syndrome, the major serious complication of induction of superovulation with exogenous gonadotropins. PATIENTS AND METHOD: The authors reviewed the medical records and available images for 771 patients who had received gonadotropins to induce superovulation for in-vitro fertilization and embryo transfer or intrauterine insemination of concentrated sperm. The patients, ranging in age from 28 to 43 years, had been treated between October 1990 and July 1992. RESULTS: In 22 patients (3%) severe hyperstimulation syndrome was diagnosed clinically and confirmed with ultrasonography. Pleural effusion occurred in five of these (23%), one of whom required thoracentesis. Atelectasis, associated with adult respiratory distress syndrome (ARDS) and internal jugular vein thrombosis, developed in one patient, and ventilation-perfusion mismatch of uncertain cause occurred in another. CONCLUSIONS: Respiratory distress in patients with ovarian hyperstimulation syndrome is most likely due to lung restriction caused by ascites, the large cystic ovaries, or pleural or pericardial effusion. Pulmonary embolism and ARDS may rarely occur. Pulmonary manifestations, not previously well recognized, form an important part of this syndrome, and radiologic input with regard to assessment, monitoring and management are needed.

Symptomatic pulmonary complications from liquid acrylate embolization of brain arteriovenous malformations.

PURPOSE: To describe symptomatic pulmonary emboli from brain arteriovenous malformation embolization with liquid acrylates and to analyze the reasons for these complications and describe preventive techniques. METHODS: The clinical records of 182 patients embolized with acrylate glue since 1978 for treatment of brain AVMs were searched for evidence of symptomatic pulmonary complications. Originally iso-butyl-2-cyanoacrylate and more recently n-butyl-2-cyanoacrylate were used in all patients. Arteriovenous malformation morphology, amounts and techniques of glue injection, and clinical and radiologic investigations in the symptomatic patients were recorded. RESULTS: Three patients had pulmonary symptoms within 48 hours of glue injection. One patient with a left frontal arteriovenous malformation had embolization with an isobutyl-2-cyanoacrylate/pantopaque/acetic acid mixture; severe pleuritic chest pain developed 2 days later. One patient with a left temporal and one with a left cerebellar arteriovenous malformation had embolization with n-butyl-2-cyanoacrylate/lipiodol mixtures; a cough, pleuritic chest pain, and bloody sputum developed in both within 24 hours. Two patients experienced a significant drop in PO2. No flow-arrest techniques were used for any of the injections in these three patients. All patients demonstrated significant changes on chest x-ray and CT chest examinations. All were treated conservatively and recovered spontaneously. CONCLUSIONS: Symptomatic pulmonary complications can occur after acrylate glue injection, particularly when delivery systems without flow arrest are used in high-flow vascular brain lesions. Techniques using acetic acid to delay polymerization time and "sandwich" techniques in which glue is pushed with dextrose are also more susceptible to this complication.

Normal fasting volume and postprandial emptying of the denervated donor gallbladder in liver transplant recipients.

BACKGROUND/AIMS: Truncal vagotomy causes gallbladder dilatation and possibly cholelithiasis. During liver transplantation, when the gallbladder is transplanted with the donor liver, the gallbladder and liver are extrinsically denervated. The aim of this study was to determine whether extrinsic denervation affects gallbladder volume and postprandial emptying. METHODS: To evaluate fasting gallbladder volume, 26 transplant recipients underwent ultrasonography. Twenty-eight normal volunteers were controls. To evaluate postprandial contractility, seven transplant recipients underwent radionuclide gallbladder-emptying studies. Gastric emptying and cholecystokinin release were simultaneously determined after a fatty meal to exclude a difference in gallbladder stimulus. Sixteen normal volunteers were controls. RESULTS: There were no differences in fasting gallbladder volume or postprandial contractility, gastric emptying, and cholecystokinin release between transplant patients and controls. Median fasting and postprandial gallbladder volumes for the transplant recipients (95% confidence) were 16 mL (12-34 mL) and 3 mL (0-8 mL), respectively, and for controls were 18 mL (13-21 mL; P = 0.73) and 3 mL (1-6 mL; P = 0.97), respectively. CONCLUSIONS: These data do not show gallbladder dilatation or impaired postprandial gallbladder contraction in the extrinsically denervated gallbladder. This finding suggests that gallbladder dilatation may be caused by the unopposed activity of the sympathetic system after truncal vagotomy.

Right phrenic nerve injury in orthotopic liver transplantation.

Right hemidiaphragm paralysis has been previously documented in patients after orthotopic liver transplantation (OLT) and it may contribute to the development of postoperative pulmonary problems. It has been postulated that a crush injury to the right phrenic nerve during OLT is the cause of dysfunction of the right hemidiaphragm. To assess the incidence and effect of right phrenic nerve injury after OLT, we prospectively studied 48 adult liver recipients. Twelve patients who underwent liver resection (LR), in whom the suprahepatic vena cava was not clamped, were used as a comparison group. Diaphragm excursion by ultrasound and pulmonary function were performed preoperatively and postoperatively; transcutaneous phrenic nerve conduction studies were performed postoperatively. Right phrenic nerve injury and hemidiaphragm paralysis occurred in 79% and 38% of the liver recipients but not after LR. Conduction along the right phrenic nerve was absent in 53% and reduced in another 26%. Left phrenic nerve conduction and left hemidiaphragm excursion were normal in both liver recipients and the patients who had LR. Liver recipients with no conduction in the right phrenic nerve had a significantly greater decrease in vital capacity in the supine position (29 +/- 9.8%) compared with those with some conduction (14 +/- 6.9%, P < 0.001). However, neither the time on the ventilator nor the hospital stay was significantly different in the latter two groups. Complete recovery of phrenic nerve conduction and diaphragm function took until nine months in some patients. Right phrenic nerve injury is common after OLT and it is the cause of right hemidiaphragm dysfunction.

[Right diaphragmatic paralysis after liver transplantation]. / Paralysie diaphragmatique droite après transplantation hépatique.

Right hemidiaphragm paralysis has been previously documented in patients after orthotopic liver transplantation (OLT) and it may contribute to the development of postoperative pulmonary problems. It has been postulated that a crush injury to the right phrenic nerve during OLT is the cause of dysfunction of the right hemidiaphragm. To assess the incidence and effect of right phrenic nerve injury after OLT, we prospectively studied 51 adult liver recipients that we compared with twelve patients who underwent liver resection (LR) without suprahepatic vena cava clamping. We studied the diaphragm excursion by ultrasound, the pulmonary function tests and the transcutaneous phrenic nerve conduction. Righ phrenic nerve injury and hemidiaphragm paralysis occurred respectively in 79% and 38% of the liver recipients but not after LR. Conduction along the right phrenic nerve was absent in 53% of the patients and reduced in another 26%. Left phrenic nerve conduction and left hemidiaphragm excursion were normal in both groups. Liver recipients with no conduction in the right phrenic nerve had a significantly greater decrease in vital capacity in the supine position compared to those with some conduction (29% vs 14%; P < 0.001). However, neither the time on the ventilator or the hospital stay were significantly different between the two groups. Complete recovery of phrenic nerve conduction and diaphragm function may take up to nine months. Right phrenic nerve injury is common after OLT and causes right hemidiaphragm dysfunction.

Expression of p75NGFR TrkA, and TrkB mRNA in rat C6 glioma and type I astrocyte cultures.

Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) we have investigated the expression of the neurotrophin receptors p75NGFR, trkA, and trkB mRNAs in cultures of rat pup type I astrocytes and in the C6 rat glioma cell line. All three neurotrophin receptor mRNAs are expressed in both C6 cells and in type I astrocytic cultures. p75NGFR mRNA levels are increased by either cycloheximide or nerve growth factor (NGF) treatment of C6 cells as measured using RT-PCR. Type I astrocyte cultures also expressed p75NGFR mRNA and NGF treatment increased p75NGFR mRNA levels in these cultures. TrkB mRNA levels were increased by cycloheximide treatment of type I astrocyte cultures but not by NGF treatment. Using RT-PCR, trkA mRNA was detected in astrocytic cultures as well as in the rat C6 and PC-12 cell lines. We conclude that cultures of type I astrocytes express active NGF receptors and that glia can elicit a response to NGF as seen by an increase in p75NGFR mRNA levels following exposure to NGF.