Case reports: hyperbaric oxygen therapy for the treatment of cerebral air embolism.

Cerebral air embolism is one of the most deleterious disorders that may affect divers, but it is also a possible complication of surgeries and medical procedures. We report our experience with iatrogenic cerebral air embolism and hyperbaric oxygen treatment.

Increase in thyroid follicular cell tumors in nelfinavir-treated rats observed in a 2-year carcinogenicity study is consistent with a rat-specific mechanism of thyroid neoplasia.

The carcinogenic potential of nelfinavir mesylate (nelfinavir) was evaluated in a 2-year oral (gavage) study on Sprague-Dawley rats at dose levels of 0 (control), 0 (vehicle control), 100, 300 and 1000 mg/kg per day. At the end of the treatment, increased incidences of thyroid follicular cell hyperplasia and neoplasms were observed at 300 (males) and 1000 mg/kg per day (both sexes). There were no other treatment-related effects and no tumors at other sites. Results from previous studies indicated a number of effects in the liver and thyroid, as well as metabolic profiles that suggested nelfinavir might cause thyroid hyperplasia/neoplasia secondary to hormone imbalance by altering thyroid hormone disposition. To investigate this hypothesis, the effects of nelfinavir on gene expression in rat hepatocytes and liver slices (in vitro), thyroxine plasma clearance, and thyroid gland function were evaluated. Compared to controls, gene expression analyses demonstrated an increased expression of glucuronyltransferase (UDPGT) and CYP450 3A1 in nelfinavir-treated rat hepatocytes and liver slices. In rats treated with nelfinavir (1000 mg/kg per day) for 4 weeks, liver weights and centrilobular hepatocellular hypertrophy were increased and minimal to mild diffuse thyroid follicular cell hypertrophy and follicular cell hyperplasia were evident in the thyroid gland. Thyroid-stimulating hormone (TSH) levels were significantly increased (three-fold), while tri-iodothyronine (T3)/tetra-iodothyronine (T4) and reverse T3(rT3) levels were unchanged, indicating that a compensated state to maintain homeostasis of T3/T4 had been achieved. Plasma 125I-thyroxine clearance was increased and the plasma thyroxine AUC0-48 was decreased (24%) compared to control. In conclusion, these data indicate that thyroid neoplasms observed in the nelfinavir-treated rats were secondary to thyroid hormone imbalance. Increased thyroxine clearance contributes to the effects of nelfinavir on thyroid gland function and is probably a result of UDPGT induction that leads to elevated TSH levels in the rat and eventual thyroid neoplasia. These results are consistent with a well-recognized rat-specific mechanism for thyroid neoplasms.

Assessment of the human risk associated with use of pork with possible presence of Salmonella typhimurium DT104 for dry-cured sausages.

We examined whether pork with suspected content of Salmonella Typhimurium DT104 (DT104) could be used for production of dry-cured sausages without jeopardizing consumer safety. The results of the risk assessment showed, that if Salmonella is present in raw pork, it is usually in low numbers. Additionally, during processing, an eventual presence of Salmonella will be reduced with at least two log units. The simulations showed that only 1-2 DT104 would be present in dry-cured sausages made by Danish pork, and this extremely seldom. Likewise, up to 4 DT104 would be present in dry-cured sausages made by foreign pork. It is not clear whether these low numbers of DT104 are capable of producing disease at all. However, if higher numbers are present, disease might occur. Therefore, we set up a monitoring and managing program, including a list with demands to processing in order to achieve minimum two-log reduction of any DT104 bacteria. The suggested scheme implies a far better and more systematic monitoring than the current system, ensuring the consumer a higher degree of food safety.

Keratinocyte differentiation marker suppression by arsenic: mediation by AP1 response elements and antagonism by tetradecanoylphorbol acetate.

Culture models of target cells are anticipated to help elucidate the mechanism by which inorganic arsenic acts as a carcinogen in humans. Present work characterizes the response of human keratinocytes, a target cell type, to arsenic suppression of their differentiation program. Four representative differentiation marker mRNAs (involucrin, keratinocyte transglutaminase, small proline-rich protein 1, and filaggrin) were suppressed by both arsenate and arsenite in normal, spontaneously immortalized (premalignant), and malignant keratinocytes with EC50 values in the low micromolar range. The suppression was almost completely reversed 9 days after removal of arsenate from the culture medium. In the case of the involucrin gene, suppression was mediated primarily by two functional AP1 response elements in the gene promoter. Both glucocorticoid and serum stimulation of differentiation occurred to a similar extent in the presence and absence of arsenic, indicating neither stimulation was a specific target of arsenic action and neither agent could overcome arsenic suppression. In contrast, 12-O-tetradecanoylphorbol-13-acetate prevented the suppression of keratinocyte transglutaminase, suggesting that arsenic acts upstream of protein kinase C.

Functional AP1 and CRE response elements in the human keratinocyte transglutaminase promoter mediating Whn suppression.

Expression of keratinocyte transglutaminase (TGM1) is critical for maturation of mammalian epidermis and occurs during squamous metaplasia. Examination of the TGM1 5'-flanking region in transient transfections of human epidermal cells revealed an AP1 site approximately 1.5kb upstream from the transcription start site and a CRE site approximately 0.5kb upstream that, combined, accounted for as much as 90% of the transcriptional activity. Upon incubation with nuclear extract, three electrophoretically separable protein complexes were formed by a CRE site oligonucleotide, one of which was competed by an AP1 response element. In super-shift analysis, c-Jun and JunD formed complexes with both the AP1 and CRE sequences. The AP1 and CRE sites were found to mediate the suppressive effects of the Whn transcription factor on the activity of the TGM1 promoter. Similarly, two previously described AP1 sites mediated Whn suppression of involucrin promoter activity.

Role of Sp1 response element in transcription of the human transglutaminase 1 gene.

This study addresses the contribution of an Sp1 response element in the proximal promoter of the transglutaminase 1 gene to transcription in normal epidermis and in a case of lamellar ichthyosis lacking transglutaminase 1 activity. The latter exhibited an Sp1 promoter mutation previously hypothesized to suppress transcription. In this study, several experiments indicated that the native Sp1 response element was functional, but it had only a small influence on transcription, and the previously observed mutation had no effect. These experiments involved mobility shift assays and transfections of promoter constructs in which the Sp1 site was mutated or lacking altogether. In addition the proximal 1.6 kb of the promoter from the affected individual was as active in transfections as the promoter from unaffected individuals. A search for sequence alterations in mRNA transcribed in keratinocytes from the patient revealed a novel single base mutation in codon 661 of the transglutaminase coding region predicted to result in premature termination of protein translation. The presence of this mutation in parental genomic DNA was confirmed by restriction digestion. Thus the lamellar ichthyosis phenotype in this case is likely attributable to a novel non-sense mutation in the coding region leading to reduced transglutaminase 1 mRNA levels rather than mutation of the Sp1 site.

Keratinocyte transglutaminase promoter analysis. Identification of a functional response element.

Keratinocyte transglutaminase catalyzes isopeptide bond formation to yield the highly insoluble cross-linked envelope during terminal differentiation of epidermal cells. Transcriptional response elements were identified in the 5'-flanking DNA of the gene for this enzyme by a combination of transient transfection and electrophoretic mobility shift analyses. Since human keratinocytes transcribed ineffectively transfected transglutaminase flanking DNA, a key feature of these experiments was the use of rat bladder epithelial cells as recipients. Serial deletion experiments identified by transient transfection an important response region containing three putative AP2-like response elements approximately 0.5 kilobases from the transcription initiation site. Oligonucleotides, each containing a single one of the elements, formed specific complexes with keratinocyte nuclear proteins. Two of the response elements were found to be functional by transfection in site-specific deletion experiments. Of these one formed specific DNA-protein complexes with nuclear proteins only from cells exhibiting keratinocyte differentiation. UV cross-linking experiments estimated the protein component of the complex to be approximately 85 kDa. This response element alone increased substantially the transcription of a minimal transglutaminase promoter in transient transfections. Further characterization of the putative transcription factor binding to this response element may provide insight into the regulation of keratinocyte transglutaminase.

[Treatment of carbon monoxide poisoning. Background and guidelines for oxygen therapy]. / Behandling af carbonmonoxydforgiftning. Baggrund og retningslinier for oxygenbehandling.

Treatment of carbon monoxide (CO) poisoning is still controversial. Standard treatment is pure oxygen either by means of a nasal catheter or oral-facial mask (normobaric oxygen treatment). Since 1960, hyperbaric oxygen (HBO) therapy has been applied in various centres, i.e. treatment in hyperbaric chambers with 100% O2 at 2-2.8 bars absolute pressure. Physically dissolved oxygen at this pressure is sufficient to maintain normal life functions at rest. HBO causes fast reoxygenation of tissues and accelerates the elimination of CO. In this paper, two cases treated with hyperbaric oxygen are reported. Aetiology, pathogenesis and possible sequelae of CO poisoning are reviewed. It is recommended, that all CO-victims, who have been or are unconscious at admission to the emergency ward, should be treated with HBO. In spite of there being comprehensive clinical literature concerning treatment of CO poisoning, there is still a great need for clinically controlled studies.

Motion sickness susceptibility in student navigators.

Identification of individuals highly susceptible to motion sickness could be of significant benefit in managing flying personnel in training. Several studies in the past four decades with this end have been primarily aimed at pilot trainees. The following study is a prospective evaluation of airsickness in Air Force navigation students. Motion Sickness Questionnaires and Minnesota Multiphasic Personality Inventories were given to the students at the beginning of navigator training. Airsickness was assessed by means of questionnaires and evaluation by a flight surgeon. Motion sickness among navigation trainees was found to be quite common. However, prediction of susceptible individuals by methods used was not reliable. Further investigation of airsickness susceptibility in navigation students by means of physiologic techniques is suggested.

A control, double-blind comparison of mepivacaine injection versus saline injection for myofascial pain.

In a double-blind study 28 patients with acute, localised muscle pain received four local injections of mepivacaine 0.5%, and 25 patients with the same type of pain received local injections of an equivalent volume of physiological saline. The group receiving saline tended to have more relief of pain, especially after the first injection. The results thus show that pain relief is not due merely to the local anaesthetic. The study therefore raises questions about the mechanism by which local injections into muscle relieves pain, since there is the possibility that a similar effect might also be achieved by merely inserting a needle into the trigger point. Physiological saline is considered to be a more appropriate fluid for injection therapy than local anaesthetics since it is less likely to produce side-effects.

Radioimmunoassay, enzyme immunoassay, spectrophotometry, and gas-liquid chromatography compared for determination of phenobarbital and diphenylhydantoin.

Sera from epileptic patients were assayed for phenobarbital and diphenylhydantoin by four different analytical procedures. Quantitative results obtained by radioimmunoassay (I) and enzyme immunoassay (II) were compared to each other and to the results obtained on aliquots of the same sample by gas-liquid chromatography (III) and ultraviolet spectrophotometry (IV). For phenobarbital the correlation coefficients were I vs. II, 0.909; I vs. III, 0.947; II vs. III, 0.917; I vs. IV, 0.950; II vs. IV, 0.953. For diphenylhydantoin the correlation coefficients were I vs. II, 0.953; I vs. III, 0.951; II vs. III, 0.957; I vs. IV, 0.862; II vs. IV, 0.898. The immunoassays can be substituted for liquid chromatography or ultraviolet spectrophotometry without changing the resulting clinical interpretations.