Acute cholecystitis complicating mumps.
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Acalculous Cholecystitis↗
Biomedical subjects
B Atkins
Publications and source records attributed to B Atkins.
Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the Cytokine Working Group.
PURPOSE: To evaluate the antitumor effects and toxicities of whole brain irradiation (WBI) with temozolomide (TMZ) administered by prolonged oral dosing in patients with melanoma metastatic to the brain. BACKGROUND: Patients with melanoma metastatic to the central nervous system (CNS) have an extremely poor prognosis and appear to benefit little from WBI. TMZ is an alkylating agent chemically similar to dacarbazine (DTIC) with good oral bioavailability and CNS penetration. TMZ has broad preclinical antitumor activity which in melanoma is comparable to that of DTIC. The combination of TMZ and WBI may provide enhanced antitumor activity against CNS metastasis from melanoma. PATIENTS AND METHODS: Patients with measurable CNS metastases with or without systemic disease were treated with WBI, 30 Gray over ten fractions (days 1-5 and 8-12). TMZ, 75 mg small middle dotm(2 small middle dot)day, was started on day 1, continued daily for 6 weeks and repeated every 10 weeks. RESULTS: Thirty-one patients were treated. There was one CNS complete response of 4.5 months and two CNS partial responses of 2 months and 7 months duration; the latter patient also had a 4-month complete remission of systemic metastases. Toxicities were limited to a single episode of grade 3 transaminase elevation and two episodes of grade 3 neutropenia, one complicated by fatal sepsis. The median progression-free interval for both CNS and extracranial sites was 2 months (range 1 week-11 months), and median survival 6 months (range 2-12 months). CONCLUSIONS: WBI has lower than expected activity in CNS metastasis of malignant melanoma. Although TMZ can be safely administered with WBI, the combination has limited anti-tumor activity.
Administration, Oral↗
Disseminated mucormycosis due to Saksenaea vasiformis in an immunocompetent adult.
A case of disseminated infection due to Saksenaea vasiformis in a previously well adult male is presented. The clinical presentation was that of septic shock with a distinctive rash. At postmortem, endocarditis and widespread dissemination were evident.
Fatal Outcome↗
Infectious diseases in rugby players: incidence, treatment and prevention.
Participation in rugby football can expose individuals to a variety of infectious diseases both on and off the field of play. The close physical contact and trauma inherent in playing rugby facilitates the transmission of viral, bacterial and fungal pathogens between players and may also lead to the acquisition of potentially lethal infections from the environment, such as tetanus. In the past few years there have been a number of reported outbreaks of infection amongst rugby players in the medical literature. The appearance of HIV infection has focused attention on the potential for transmission of this and other blood-borne viruses such as hepatitis B and C viruses from bleeding wounds sustained on the rugby field. As a result, various expert bodies have produced guidelines on the management of players with bleeding wounds. Opportunities are now available to rugby players to play outside their own countries, including the third world. This can bring them into contact with a wide range of travel-associated infections, some of which may be life threatening. In view of the above it is clear that rugby players and those who coach and manage rugby teams require information and education on the subject of infection and its prevention, as well as access to appropriate medical care and expertise. Many of the infections seen in rugby players are preventable, e.g. by promoting hygienic facilities and conduct in changing rooms and on the field of play, by exclusion of infected players from contact with others and, in some cases, by immunisation or chemoprophylaxis. Players who present with infections should be assessed, correctly diagnosed (using laboratory investigations where appropriate) and treated, and measures should be taken to prevent spread to team-mates and other contacts while respecting the confidentiality of the individual. Any outbreaks of infection should be reported to the appropriate authorities. There is evidence to suggest that strenuous physical exercise such as playing rugby can make individuals susceptible to certain types of infection and prolong time to recovery. More information is required on the true frequency and effects of infection in rugby players.
Anti-Infective Agents↗
Fusidic acid in bone and joint infections.
The prominence of staphylococci as the causative agent in bone and joint infections suggests that fusidic acid (FA) has a potentially important role in their treatment. FA has been studied in a broad range of orthopaedic infections, mostly in combination with other antimicrobials. For susceptible organisms, particularly Staphylococcus aureus, it has demonstrable efficacy in acute osteomyelitis, chronic osteomyelitis, specialised forms of osteomyelitis such as calcaneal and vertebral infection, septic arthritis, prosthetic and other device-related infections. A small number of studies have also examined the use of FA alone for the treatment of bone infections, with evidence of good efficacy, as well as the local application of FA in plaster-of-Paris (POP) beads, or incorporated into bone cement, again with promising results. Further studies are required to confirm the efficacy of FA in the treatment of orthopaedic infections caused by methicillin-resistant strains of S. aureus.
Animals↗
Chronic hypoxemia causes extracellular glutamate concentration to increase in the cerebral cortex of the near-term fetal sheep.
Fetal hypoxia is an important cause of neurologic morbidity and mortality. Hypoxia-induced increase in extracellular glutamate concentration can lead to excitotoxic neuronal death in adults. The objective of this study was to test whether chronic fetal hypoxemia increases extracellular glutamate concentration in the unanesthetized intact cerebral cortex of the near-term fetal sheep. Microdialysis probes were implanted into the parasagittal parietal cortex and periventricular white matter of near-term fetal sheep. At 124 +/- 1 days of gestation, extracellular glutamate concentration was determined before and during 24 h of fetal hypoxemia. Chronic hypoxemia was produced by tightening a vascular occluder placed around the maternal common iliac artery. Larger decreases in fetal arterial oxygen content were associated with larger increases in extracellular glutamate concentration in the parietal cortex (Kendall's tau = 0.81, N = 7, p = 0.005). No such relationship was detected in the periventricular white matter. Chronic hypoxemia increases extracellular glutamate concentration in the intact cerebral cortex of the unanesthetized near-term fetal sheep.
Animals↗
Nitrate and nitrite anion concentration in the intact cerebral cortex of preterm and nearterm fetal sheep: indirect index of in vivo nitric oxide formation.
Pregnant sheep with a microdialysis probe implanted in the fetal cerebral cortex were used to determine if nitrate and nitrite anions (nitrate/nitrite) could be quantitated in the microdialysate as an indirect index of in vivo nitric oxide formation. Pregnant ewes (term, about 147 days) were surgically instrumented at gestational day (GD) 90 (n = 3; preterm) and GD 121 (n = 3; nearterm). Three days later, following an overnight probe equilibration period, five dialysate samples were collected continuously on ice at 1-h intervals (infusion rate of 1 (microl/min). The nitrate/nitrite concentration was determined by reducing a 10-microl aliquot of each dialysate fraction with hot acidic vanadium followed by chemiluminescence quantitation of the nitric oxide product. The lower limit of quantitative sensitivity of the method is 25 picomoles. Nitrate/nitrite concentration was 16.6+/-7.3 microM for the preterm fetus and 19.7+/-1.9 microM for the nearterm fetus. The data demonstrate that nitrate/nitrite, as an index of in vivo nitric oxide formation, can be quantitated in microdialysate samples collected from the intact fetal sheep cerebral cortex.
Animals↗
Adrenarche results from development of a 3beta-hydroxysteroid dehydrogenase-deficient adrenal reticularis.
Adrenarche is the increased adrenal production of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) that occurs during the prepubertal period. To date, the exact mechanism initiating adrenarche is unknown, although many factors have been postulated. In the present study, we examined the hypothesis that alterations in intra-adrenal expression of 3beta-hydroxysteroid dehydrogenase (3betaHSD) or 21-hydroxylase (CYP21) within the inner reticularis zone leads to the increased production of 19-carbon (C19) steroids. After conversion of cholesterol to pregnenolone, 17alpha-hydroxylase/17,20-lyase (CYP17) can metabolize pregnenolone through to DHEA. The enzyme 3betaHSD competes for substrate with CYP17 and effectively removes steroid precursor from the pathway leading to DHEA. On the other hand, deficiency in CYP21 expression is known to cause excessive production of adrenal C19 steroids, suggesting that CYP21 could play a role in adrenarche. Thus, a decrease in 3betaHSD or CYP21 expression would allow substrate to flow toward the synthesis of DHEA. To determine whether adrenarche results from a decreased expression of 3betaHSD or CYP21 in the reticularis, immunohistochemical localization of 3betaHSD and CYP21 was performed, and staining intensities compared using adrenal glands from children ages 4 months to 4 yr (n = 12), ages 5-7 yr (n = 9), ages 8-13 yr (n = 9), and adults ages 25-56 yr (n = 8). There were no differences in the zonal expression of CYP21. No difference in 3betaHSD staining was observed between the glomerulosa and fasciculata from any age group. However, children age 8 yr and older show a significant decrease in 3betaHSD expression in reticularis as compared with the fasciculata. No significant difference was noted for 3betaHSD levels between the fasciculata and reticularis for children age 7 yr or younger. The level of 3betaHSD expression in the reticularis continued to decrease in the adult adrenals examined. These findings suggest that as children mature there is a decreased level of 3betaHSD in the adrenal reticularis that may contribute to the increased production of DHEA and DHEAS seen during adrenarche.
17-Hydroxysteroid Dehydrogenases↗
Ethanol-induced changes in prostaglandin E concentration in the intact cerebral cortex of preterm and near-term fetal sheep.
Ethanol-induced changes in fetal prostaglandin E (PGE) concentration may play a role in the toxic effects of prenatal ethanol exposure. Using the novel technique of in utero microdialysis, the present study tested the hypothesis that acute ethanol exposure changes PGE concentration in the intact cerebral cortex of preterm (93 +/- 1 days of gestation) and near-term (124 +/- 1 days of gestation; term, approximately 147 days) fetal sheep. Fetal sheep were surgically instrumented with a microdialysis probe placed in the parasagittal parietal cortex. Three days later, the effects of maternal infusion of 1 g of ethanol/kg maternal body weight on preterm (n = 6) and near-term (n = 7) fetal cerebral cortical and plasma PGE concentrations were determined. In the preterm fetal cerebral cortex, PGE concentration was increased after ethanol infusion in all six animals studied. The median peak increase was 160% with a 95% confidence interval of 115 to 784%. There was considerable variation in the time of occurrence, magnitude, and duration of this increase. In the near-term fetal cerebral cortex, an increase in PGE concentration was observed after ethanol infusion in 5 of the 7 animals studied, whereas a decrease in PGE concentration was observed in the other two animals. Overall, ethanol did not increase significantly near-term fetal cerebral cortical PGE concentration. For both age groups, ethanol infusion had no effect on fetal plasma PGE concentration. These data indicate that ethanol can affect PGE production in the fetal cerebral cortex and that this effect seems to be gestational-age-dependent.
Animals↗
Adrenarche is associated with decreased 3 beta-hydroxysteroid dehydrogenase expression in the adrenal reticularis.
The increased production of adrenal dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) which occurs during the prepubertal period is known as adrenarche. One hypothesis for adrenarche is that alterations in intra-adrenal expression of steroidogenic enzymes within the inner reticularis zone leads to the increased production of 19-carbon steroids. We tested the hypothesis that at the time of adrenarche there is decreased expression of 3 beta HSD in the reticularis. Immunohistochemical localization of 3 beta HSD was performed and staining intensities compared between adrenal glands from children ages 4 months to 7 years (N = 11) and ages 8 to 11 years (N = 6). No difference was observed between the levels of staining in the glomerulosa and fasciculata from either age group. However, the reticularis from the older children exhibited diminished 3 beta HSD immunoreactivity. These findings suggest that as children mature there is a decreased level of 3 beta HSD in the adrenal reticularis which may contribute to the increased production of DHEA and DHEAS seen during adrenarche.
3-Hydroxysteroid Dehydrogenases↗
Inhibition of glycoprotein processing by L-fructose and L-xylulose.
A number of unusual and rare carbohydrates were tested as potential inhibitors of various glycosidases, as well as inhibitors of N-linked oligosaccharide processing. The best inhibitors of several arylglycosidases and of glucosidase I were L-xylulose and L-fructose. Both of these sugars showed some inhibitory activity towards yeast alpha-glucosidase but were inactive against beta-glucosidase and other arylglycosidases. The inhibition of yeast alpha-glucosidase by L-xylulose was of a competitive nature and required a concentration of 1 x 10(-5) M for 50% inhibition. Both L-xylulose and L-fructose also inhibited the purified soybean glucosidase I, with 50% inhibition occurring at about 1 x 10(-4) M, but showed no inhibitory activity against soybean glucosidase II. When influenza virus-infected MDCK cells were raised in the presence of L-xylulose, there was a dose-dependent inhibition in the formation of complex types of oligosaccharides on the viral glycoproteins consistent with the inhibition of the processing glucosidase I. This inhibition resulted in the occurrence of oligosaccharides on the viral glycoproteins that were characterized as Glc3Man9(GlcNAc)2 structures. L-Fructose also inhibited glycoprotein processing in cell culture, and the inhibition resulted in the formation of similar oligosaccharides to those seen with L-xylulose. However, L-fructose was a poorer inhibitor than L-xylulose and required much higher concentrations for the same degree of inhibition. Neither of these compounds inhibited protein synthesis or the formation of lipid-linked saccharides in culture MDCK cells, even when tested at concentrations of 5 mg/ml (about 30 mM) of culture media.
Animals↗
Glutamate release from the ovine fetal brain during maternal hemorrhage. A study using chronic in utero cerebral microdialysis.
BACKGROUND: Glutamate has been implicated in the pathophysiology of neuronal injury associated with cerebral hypoxia-ischemia. A model using chronic in utero microdialysis was developed to sample the extracellular space of the fetal brain. Using this model, we tested the hypothesis that glutamate efflux from the parasagittal parietal cortex of near-term fetuses would increase during maternal hemorrhage. METHODS: Twelve near-term fetal sheep were instrumented with vascular catheters, and a microdialysis probe(s) was implanted into the parasagittal parietal cortex. After a 3-day recovery period, the animals were subjected to maternal hemorrhage until either the fetal pH was < 7.00 or the fetus died. The extracellular glutamate concentration in the collected dialysate was determined by high pressure liquid chromatography (HPLC). RESULTS: Maternal hemorrhage resulted in an 80-90% decrease in uterine blood flow, a decrease fetal po2, and a mixed metabolic and respiratory fetal acidosis. There were two groups of fetuses, survivors (n = 5) and nonsurvivors (n = 7). The nonsurvivor group showed a large increase (10-30-fold) in peak glutamate release (P = 0.0015). Survivors demonstrated a small (threefold) increase that was not statistically significant (P = 0.065), unless one animal with very low probe recovery was excluded (P = 0.0048). CONCLUSIONS: Extracellular glutamate release from the fetal brain can occur during maternal hemorrhage with fetal acidemia. The pathophysiologic role (if any) of glutamate release in the survivors remains to be elucidated. Our results are consistent with the hypothesis that in utero release of glutamate occurs during periods of fetal asphyxia. This experimental preparation of chronic fetal brain microdialysis can be used to monitor the brain extracellular concentration of any dialyzable substance in response to stress, including maternal hemorrhage.
Animals↗
Dose-dependent effects of acute in vivo ethanol exposure on extracellular glutamate concentration in the cerebral cortex of the near-term fetal sheep.
The cerebral cortex is a target site of ethanol teratogenesis. L-Glutamate is a major excitatory neurotransmitter that plays an important neurotrophic role in brain development. It has been proposed that optimal function of the glutamate neuronal system is required for normal brain development; overactivation could lead to excitotoxic-induced neuronal injury, whereas underactivation could delay/restrict brain development. The objective of this study was to test the hypothesis that acute in vivo ethanol exposure alters basal glutamate release in the fetal cerebral cortex. The experimental approach involved measuring fetal cortical extracellular glutamate concentration using the technique of in vivo microdialysis. Near-term fetal sheep were chronically instrumented with a microdialysis probe placed in the parasagittal cortex. At 124 +/- 3 days of gestation, the effects of maternal intravenous infusion of 2 g or 4 g ethanol/kg maternal body weight or an equivalent volume of saline, given as four equally divided doses over 5 hr, on fetal cerebral cortical extracellular glutamate concentration were determined. None of the three treatment regimens produced fetal or maternal demise during the time course of the study. There was an ethanol dose-dependent increase, p = 0.005, in extracellular glutamate concentration in the fetal cerebral cortex. This increase was paroxysmal in nature and was not directly related to the fetal blood ethanol concentration. In view of the proposed role for glutamate in neuronal development, this apparent ethanol-induced increase in glutamate release may be important in the pathogenesis of ethanol teratogenesis involving the cerebral cortex.
Alcohol Drinking↗
Antibodies to native DNA in discoid lupus erythematosus.
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Adult↗
Proceedings: Anti-DNA antibodies in discoid lupus erythematosus.
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Antibodies↗
Criteria for classification of S.L.E.
Of 38 patients with systemic lupus erythematosus (S.L.E.) followed in this clinic during the past two years raised levels of anti-DNA antibodies were found in 36. The recently proposed criteria for the classification of S.L.E. were met in 33 of these 36 patients. Three patients with raised DNA antibody titres and some of the features of S.L.E. did not meet the criteria for a classification of S.L.E.
Adolescent↗
Quantitative estimation of protein by electroimmunodiffusion on Cellogel acetate membranes.
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Acetates↗
Ethanol increases uterine blood flow and fetal arterial blood oxygen tension in the near-term pregnant ewe.
Fetal hypoxia is a hypothesized mechanism of ethanol teratogenesis. The objective of this study was to test this hypothesis by determining the effects of maternal ethanol infusion on uterine blood flow (UBF) and fetal oxygen status. UBF was measured with an electromagnetic flow probe placed around the left maternal uterine artery of the surgically recovered instrumented near-term pregnant sheep at 124 +/- 3 days of gestation (term = 147 days). Experimental treatment involved maternal infusion of 2 g (n = 3) or 4 g (n = 5) ethanol/kg maternal body weight, or 0.9% saline (n = 4) over a 5-h period. Arterial blood samples were collected at regular intervals to monitor maternal ethanol concentration and fetal PO2. Maternal ethanol infusion produced a dose-dependent increase (p = 0.0009) in UBF. Ethanol infusion also increased (p = 0.03) fetal arterial PO2. Overall, these findings indicate that fetal hypoxia is not a mechanism of ethanol teratogenesis.
Abnormalities, Drug-Induced↗