Significance of stem cell factor and soluble KIT in patients with systemic lupus erythematosus

Hyperketonemia has been identified as an important factor in diabetic pregnancy affecting growth and development of the offspring. In order to assess the immediate metabolic alterations in embryos caused by excess ketone bodies, we studied rat embryonic neural tissue exposed to a high concentration of beta-hydroxybutyrate in vitro. Beta-hydroxybutyrate inhibited oxygen uptake of the neural tissue of day 9 and day 10 embryos by 12.8% and 1 1.2%, but did not affect that of day 11 and day 12 tissue. In contrast, glucose utilization of the neural tissue of day 9 and day 10 embryos was not altered. However, a 30% decrease in glucose utilization was observed in the neural tissue of day 11 and day 12 embryos exposed to beta-hydroxybutyrate. Thus, beta-hydroxybutyrate induced different metabolic alterations in the embryonic neural tissue during early and late organogenesis, which suggests different modes of teratogenic action of ketone bodies in different parts of gestation.     

Lung inflammation in patients with systemic lupus erythematosus detected by quantitative 67Ga-citrate lung scanning

The severity of lung inflammation in 34 patients with systemic lupus erythematosus (SLE) was measured by quantitative 67Ga-citrate lung scanning. The severity of lung inflammation in SLE was represented by the 67Ga uptake index (GUI). Quantitative 67Ga lung scanning was also performed on 20 normal controls for comparison with the SLE patients. The patients were divided into two subgroups according to the following two criteria: (a) stable or flare stage according to clinical features; or (b) positive or negative results of chest X-ray. The GUI values of the subgroups were also compared. The results revealed a trend towards higher values of GUI in SLE patients than in the normal controls. The GUI values were also higher for SLE cases with a flare stage or a negative chest X-ray than in SLE cases with a stable stage or a positive chest X-ray. The statistical results reveal that the differences in the GUI values are not significant. However, we found that (1) positive chest X-ray findings may be a later manifestation of a lung inflammation and (2) the values of GUI parallel clinical features in SLE patients.     

Significance of intestinal inflammation in the pathogenesis of spondylarthropathies

The concept of spondylarthropathy (SpA) gathers together a group of chronic diseases with common clinical, biological, genetic and therapeutic characteristics. The concept forms a distinct entity, different from other rheumatic diseases. The target organs are not only the joint, but also the axial skeleton, the enthesis, the eye, the gut, the urogenital tract, the skin and sometimes the heart. The prevalence of this entity in the general population is estimated 1%, equal to the prevalence of rheumatoid arthritis. Genetical predisposition (HLA-B27) is one of the clues to the pathogenesis of the disease. Since reactive arthritis is induced by specific urogenital or enterogenic bacteria, and since the gut is implied in different forms of spondylarthropathies, especially in IBD, it was clear that the gut could play an important role by permitting exogenous factors to enter the body. This hypothesis was the rationale for investigating the gut in the spondylarthropathies by performing ileo-colonoscopies. In the first ileo-colonoscopic studies of SpA patients, histological signs of gut inflammation were found in a relatively great number of patients, mostly not presenting any clinical intestinal manifestations. These lesions were not seen in other inflammatory joint diseases. Further ileo-colonoscopic studies confirmed the strong relationship between gut and joint inflammation. In patients in whom a second ileo-colonoscopy was performed, remission of the joint inflammation was always connected with a disappearance of the gut inflammation, whereas persistence of locomotor inflammation was mostly associated to the persistence of gut inflammation. The hypothesis was proposed that some patients with a spondylarthropathy had a form of subclinical Crohn's disease in which the locomotor inflammation was the only clinical expression. This hypothesis was confirmed in prospective long-term studies in which the ileo-colonoscopied patients were reviewed 2 to 9 years later:about 6% of SpA patients not presenting any sign of Crohn's disease at first investigation but demonstrating gut inflammation on biopsy, developed full-blown Crohn's disease. By performing electronmicroscopy it was described that in patients with SpA the number of membranous (M) cells, which are scarce in normal ileum, is increased in number in inflamed mucosa. They showed a thin rim of cytoplasm covering groups of lymphocytes. In chronic inflammatory lesions necrotic M-cells, rupture of M-cells and lymphocytes entering the gut lumen was observed. The bursting of M-cells at the top of the lymphoid follicles leads to interruption of the gut epithelial lining and gives the luminal content access to the lymphoid tissue. This can be responsible for an exponential increase of local antigen stimulation. Accelerated luminal antigen presentation through a break in the epithelial layer, together with cytokines released from activated monocytes, might induce a second line of defense aiming at elimination of the massive antigen penetration into the mucosa. The postulated switch from secretory local immunity to a systemic type of local immune reaction could have different consequences:the local down-regulation of J chain in the IgA immunocytes could shift the production of polymeric IgA to monomers, jeopardizing secretory immunity; the disproportionate increase of IgG-producing cells could favor further inflammation and tissue damage through complement activation and arming of the killer cells, and cause autoimmune responses locally and in target organs at a distance (e.g. joint organs). The discovery of subclinical gut inflammation in the SpA had therapeutic consequences. Sulphasalazine (SASP) has been proven to be an active drug in the treatment of IBD. Since the gut could play a crucial role in SpA, it was logic to use this drug in the treatment of this disease. Multiple open and double-blind studies have proven the effectiveness of this drug in SpA.     

Local and systemic effects of macrophage cytokines in intestinal inflammation

The activation of macrophages and newly recruited monocytes appears to be common to both Crohn's disease and ulcerative colitis, despite different inductive stimuli. Similar activation occurs acutely during the course of invasive intestinal infections such as shigellosis, but is then usually downregulated. The macrophage cytokines tumor necrosis factor-alpha and interleukin-1 (IL-1) are centrally involved in the local inflammatory response, and blockade of either cytokine greatly attenuates the inflammatory lesion. Induction of focal vascular thrombosis and matrix degradation are thought to be an important component of this focal damage. Both cytokines and IL-6 are now recognized to contribute to the systemic effects of intestinal disease, including growth suppression, anorexia, and chronic anemia. Disturbance of sleep patterns, mood, and affect may also occur, and recent evidence points towards bidirectional interplay between macrophage cytokines and central nervous system function.     

Hypothermia in trauma patients

Accidental hypothermia (AH) can be defined as an unintentional decrease in core temperature below 35 degrees C during cold exposure by individuals without intrinsic thermoregulatory dysfunction. Pathophysiological changes can be attributed both to the severity of hypothermia and to co-morbid factors such as trauma, submersion, intoxication and underlying diseases. In trauma victims stratified according to the Injury Severity Score, the factor hypothermia is considered to be a poor prognostic sign for survival. In these patients rewarming therapy should be applied as soon as possible. In the Utrecht University Hospital, adult patients with AH are managed according to an algorithm based on their presenting hemodynamic conditions. Patients with perfusing cardiac rhythms and systolic pressures over 80 mmHg will receive continuous arteriovenous rewarming (CAVR). Arrested and hemodynamically instable patients are treated with cardiopulmonary bypass (CPB). In a 3-year period, 22 patients with AH were admitted to the emergency department. Fourteen patients had a trauma as the cause of hypothermia. Twenty patients were treated according to the algorithm (CAVR n = 18, CPB n = 2) and two patients were alternatively managed. Mortality in the CAVR group was 28% and total mortality reached 32%. Complications of CAVR are related to placement and removal of vascular catheters and may be severe in these patients with impaired coagulation. CAVR permits a good access to the (trauma-) patient and rewarming can be continued synchronously with diagnosis and treatment of various injuries.     

Early tracheostomy in trauma patients

The purpose of this study was to determine the current level of psychiatric training in internal medicine residencies, satisfaction with this training, and perceived need, if any, for more training. Surveys were mailed to all training directors of accredited primary care (N = 178) and categorical (N = 410) internal medicine residencies in the United States; 110 primary care (62%) and 238 categorical (58%) training directors returned the surveys. Seventy-five percent of categorical and 66% of primary care training directors thought their program should spend more time on psychiatric disorders. For all categories of psychiatric disorder, training intensity was greater and satisfaction with training higher in the primary care programs, but less than half of the directors were satisfied with their current level of training, e.g., 33% of categorical and 47% of primary care directors were satisfied with their residents training concerning depression. Training in somatoform disorders, psychotropic drugs, and office psychotherapy were most frequently identified as deficient. The most favored additions to the curriculum were psychiatric consultants in medical clinics and on medical wards. Although most outpatient care for psychiatric disorders is given by primary care physicians, internal medicine training directors perceive current levels of training in their residencies as inadequate. Innovative collaborations between medicine and psychiatry departments will be necessary if treatment of psychiatric disorders in primary care is to be improved.     

Sequential systemic platelet-activating factor and interleukin 8 primes neutrophils in patients with trauma at risk of multiple organ failure

Plasma from 33 patients at risk of multiple organ failure (MOF) after major trauma was tested for a priming effect on neutrophils, and for the presence of platelet-activating factor (PAF) activity and interleukin (IL) 8. Plasma sampled at 3, 6, 12 and 24 h after injury significantly primed normal neutrophils to release mean(s.e.m.) 1.26(0.19), 1.33(0.26), 1.04(0.14) and 0.86(0.13) nmol superoxide per min per 1.3 x 10(6) neutrophils respectively (P < 0.05). Priming at 3 h after injury was inhibited by mean(s.e.m.) 63.8(7.0) per cent by the PAF antagonist, WEB 2170 (P < 0.01). Mean(s.e.m.) plasma IL-8 was raised at 6 and 12 h after injury to 785(183) and 836(175) pg/ml (P < 0.01). At 12 h after injury the plasma IL-8 level correlated directly with the number of units of red blood cells transfused (r = 0.64, P < 0.01), and was significantly higher in the group of six patients who developed MOF (P < 0.05). These data suggest that after trauma the mediators PAF and IL-8 appear sequentially in the circulation, are potential mechanisms of circulating neutrophil priming, and that IL-8 may also be an early biochemical marker predicting the onset of MOF.     

The role of hypothermia in trauma patients

Socio-hygienic analysis of the mortality of disabled subjects is carried out on the basis of clinical and socio-statistical records with due consideration for the levels and structure of death causes, types and groups of disability, duration of stable disability, etc. Scientific approaches to analysis of mortality of disabled subjects as a medico-demographic problem have been outlined and basic information singled out to be used in development of special medicosocial programs.     

Causes of ear trauma in Kenyan patients

Ear trauma is one of the most important epidemiological factors in causation of deafness. The causation of otologic trauma in eighty three patients is analysed. The triad of pain, hearing loss and tinnitus comprised the most frequent presenting complaints. Physical assault was the most common causation in 49.4% of the cases, road traffic accidents in 19.3% and self-inflicted injury in 15.6%. Law enforcement agencies constituted the most prominent factor in assault cases. Iatrogenic trauma was confined to 13.3% who were all below ten years of age. Road traffic accidents and violence from law enforcers were significant contributors to severe otologic damage as defined by dead ears and cerebrospinal otorrhoea.     

Venous thromboembolism in multiple trauma patients

Thromboembolic complications are frequent in patients with multiple trauma. The efficacy of unfractionated heparin for venous thrombosis prophylaxis has not been established. Based on limited prospective data, low-molecular-weight heparin appears to be more effective than unfractionated heparin and at least as effective as compression devices for preventing thromboembolic complications in these patients. Vena cava filters should be considered in high-risk patients who cannot receive anticoagulant therapy, but long-term filter use without concomitant anticoagulant therapy is associated with a substantial risk of recurrent thromboembolism.     

Mortality in multiple trauma patients with fractures

A multicentered study was performed to determine the mortality rate of patients with multiple injuries with major pelvic and long bone fractures who have early total care of their injuries. A 2-year review of patients with ISSs > or = 18 with major fractures treated at the trauma centers in Buffalo, New York, Camden, New Jersey, Nashville, Tennessee, Baltimore, Maryland, Tampa, Florida, and Seattle, Washington was performed. This group of 676 patients was compared with a similar group of 906 patients from the American College of Surgeons' Multiple Trauma Outcome Study. Mortality was significantly reduced in the patients who had early total care of all their injuries including fracture stabilization for patients less than 50 years of age and those 50 years and older. In a subgroup of patients less than 50 years of age and an ISS of 18-34 and 35-45 there was a mortality reduction from 11.8% to 5.1% and from 25.8% to 11.5%, respectively, when the fractures were managed acutely. Similar reductions in mortality were found in the patients 50 years of age and older with early fracture stabilization with a reduction from 26.4% to 8% in patients with ISSs of 18-24 and a reduction from 42.3% to 18.4% in the patients with ISSs of 35-45. This study clearly shows the additional benefit of early fracture stabilization in reducing mortality rates in the patient with multiple injuries.     

Pancreatic trauma in patients with pancreatobiliary anomaly

One patient with a choledochal cyst and anomalous pancreaticobiliary junction had pancreatic transection causing bile peritonitis. Intraoperative cholangiopancreatography revealed this anomaly. In another patient with pancreas divisum, cannulation of the minor papilla (ERCP) demonstrated focal stenosis of the dorsal pancreatic duct, corresponding to the site of the minor laceration. The possibility of a coexisting pancreatobiliary anomaly should be considered in the diagnosis of pancreatic trauma, particularly in terms of the interpretation of pancreatograms.     

Sequelae of massive fluid resuscitation in trauma patients

Morphological and physiological characteristics of the two major motor axons supplying the commonly studied ventral longitudinal muscle fibers (6 and 7) of third-instar Drosophila melanogaster larvae were investigated. The innervating terminals of the two motor axons differ in the size of their synapse-bearing varicosities. The terminal with the larger varicosities also fluoresces more brightly when stained with the vital fluorescent dye 4-(4-diethylaminostyryl)-N-methylpyridinium iodide (4-Di-2-Asp) and occupies a larger total contact area on the muscle fiber. Through selective simultaneous recording of synaptic currents from identified boutons in living preparations during elicitation of synaptic potentials, it was shown that the axon with the smaller varicosities generates a large excitatory junction potential (EJP) in muscle 6 and that the axon with the larger varicosities generates a smaller EJP. Short-term facilitation is more pronounced for the smaller EJP. In preparations treated with 4-Di-2-Asp, the fluorescence of smaller varicosities increases with stimulation that elicits the large EJPs, indicating an activity-dependent entry of calcium that enhances mitochondrial fluorescence. The differences in morphology and physiology of the two axons are similar to, though less pronounced than, those observed in "phasic" and "tonic" motor axons of crustaceans.     

OR resuscitation for trauma patients

1. The results of multiple studies have shown evidence that immediate access to the operating room has significantly contributed to improved outcome in several categories of trauma patients. 2. "Walk through" table top exercises were held in the OR suite to identify problems. These mock resuscitations were particularly helpful in solving logistical and equipment problems. 3. Prehospital care providers were given classes regarding triage criteria and operating room logistics. 4. Continuing education for OR and trauma nurses included videotape review and critique of ORR, trauma-specific inservice programs presented by the trauma coordinators and physicians, and attendance at weekly videotape review and trauma conference presented by the Division of Trauma. Easy recognition of individual team members, an important issue, required the use of name badges.     

Effect of intra-articular versus systemic anti-inflammatory drugs in a rabbit model of temporomandibular joint inflammation

PURPOSE: In an attempt to better understand the time course of inflammatory mediator production or release in inflammatory joint disease, a rabbit model of acute temporomandibular joint (TMJ) inflammation was established. This model was used to evaluate the effects of specific anti-inflammatory agents administered either systemically (intraperitoneal, IP) or locally (intra-articular, IA) on the modulation of in vivo tissue levels of two prototypic inflammatory mediators, prostaglandin E2 (PGE2) and bradykinin (BK). MATERIALS AND METHODS: An experimental model of inflammation was created by administering carrageenan (carra) into one joint and an equivalent volume of saline (control) into the contralateral joint of 42 male New Zealand White rabbits. The development of hyperthermia was assessed by placement of a microthermister probe into the joint space. The inflammatory mediators, immunoreactive PGE2 (iPGE2) and BK (iBK), were recovered with microdialysis probes, and samples were assayed in conjunction with specific pharmacologic interventions. In the first part of the study, the time course for the release or production of iBK and iPGE2 was determined. In the second part, the effects of IP versus IA administration of dexamethasone and a nonsteroidal anti-inflammatory drug, ketorolac tromethamine, were compared. Dexamethasone and ketorolac were administered at 3 hours and 1 hour, respectively, before the peak release of the inflammatory mediators. RESULTS: The onset of IA hyperthermia, an index of inflammation, was evident by 90 minutes post-carra and reached a maximum of 1.2 degrees C above core temperature by 150 minutes post-carra. Intra-articular levels of iPGE2 and iBK peaked at 240 minutes (3.35+/-1.9 nmol/L) and 270 minutes (0.45+/-0.29 nmol/L), respectively, after the induction of inflammation in the superior joint space. iBK levels within the superior joint space were significantly decreased by dexamethasone and ketorolac. Ketorolac (50 microg) decreased iBK and iPGE2 levels when given IA or IP. With dexamethasone (3 mg), the levels of iBK were significantly reduced, and iPGE2 levels were not changed. CONCLUSIONS: This study shows that the rabbit model of TMJ inflammation, with concurrent collection of iBK and iPGE2 via microdialysis, is a reproducible and reliable method to investigate the time course of inflammatory mediator release and their modulation by either the local or systemic administration of anti-inflammatory medications.