AT base pairs are the main target for mutations at the hprt locus of rat skin fibroblasts exposed in vitro to the monofunctional alkylating agent N-ethyl-N-nitrosourea

Spectra of N-ethyl-N-nitrosourea (ENU)-induced mutations differwidely among various in vitro and in vivo mutational systems.To investigate possible reasons for these differences, a mutationalsystem is needed in which the same target gene is used for comparisonin the same type of cells in vitro and in vivo. In the presentstudy, this was achieved by analysing at the molecular level35 hprt mutant rat fibroblast clones obtained from cell populationsexposed in vitro to ENU and comparing the mutational spectrumwith the previously determined spectrum of ENU-induced hprtmutants in the same target cells exposed in vivo. Twenty-eightmutants contained a single base pair alteration in the hprtcoding sequence. Most of these changes were found at AT basepairs (19/28), the AT to TA transversion being the most frequentkind of mutation (12/19), which is probably caused by O²-ethylthymine.Transversions at AT base pairs showed all mutated T's to belocated in the nontranscribed strand of the hprt gene, suggestinga strand specific fixation of mutations induced by O²-ethylthymine,which appears to be a general feature of ENU- and ENNG-inducedhprt mutations in mammalian cells. GC to AT transitions, probablycaused by O⁶-ethylguanine, were detected at a lower frequency(7/28). This in vitro mutational spectrum was very similar tothat of the same target cells exposed in vivo to ENU. A comparisonof the mutational spectra in AGT-proficient and AGT-deficientrodent cells exposed to ethylating agents showed that in contrastto the situation in AGT-proficient rat fibroblasts, GC to ATbase pair changes (and not AT to TA) are the predominant mutationsin AGT-deficient hamster cells. ⁴To whom correspondence should be addressed     

Administration of Half-Dose Theophylline Together with Ketotifen to Asthmatic Children—A Double-Blind, Placebo-Controlled Study

Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 μg/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T + K-Placebo (T group); T + K (T + K group); half-dose T + K (T/ 2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T + P, T + K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects.     

Anxiety and hippocampus volume in the rat.

In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.     

Multicolored Asian lady beetle hypersensitivity: a case series and allergist survey.

BACKGROUND: Multicolored Asian lady beetles (Harmonia axyridis) have been used as a biological control agent against crop-destroying aphids in the United States. Outside their natural habitat, H. axyridis seeks refuge in homes during fall and winter, leading to patient complaints and symptoms of rhinitis, wheezing, and urticaria on exposure to the beetles. OBJECTIVE: To gain a better understanding of the character and spectrum of allergic disease provoked by exposure to home-infesting lady beetles. METHODS: Eight patients with allergic symptoms suspected of being caused by H. axyridis and consistent with an IgE-mediated process were identified and interviewed. A whole-body extract from H. axyridis was prepared. Western blots using the patients' serum identified specific IgE antibodies in the extract. Through a novel technique, immunohistochemical analysis using beetle sections overlayed with patient serum was performed. A random survey of allergists from across the United States was also performed to evaluate experience with cases of lady beetle allergy. RESULTS: Western blots revealed IgE binding to 5 proteins with molecular weights of approximately 8.6, 21, 28, 31, and 75 kDa. Specific IgE bound to proteins localized in the beetle's mouth and leg areas. The allergist survey revealed positive responses in North Central, Mid-Atlantic and New England states. CONCLUSION: In 8 patients with allergic symptoms on exposure to high levels of lady beetles, specific IgE bound to proteins from H. axyridis. There was also an increased frequency of suspected cases of lady beetle allergy in endemic areas.     

Proximal nerve conduction studies in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of proximal upper limb motor nerve conduction study abnormalities in chronic inflammatory demyelinating polyneuropathy (CIDP), using standard percutaneous stimulations up to Erb's point. METHODS: Electrophysiologic data relating to proximal conductions of median and ulnar nerves of 22 patients with CIDP were retrospectively analyzed and compared to those of 22 controls with sensory neuropathy. Distal conduction results were also reviewed. RESULTS: The findings demonstrate independent high sensitivity of abnormal upper limb proximal nerve conduction studies in CIDP. Demonstration of conduction block of >20% and temporal dispersion of >15% had low specificity. However, conduction block was highly specific with cut-off values of >30% at axilla and >50% at Erb's point. Specificity was considerably improved using a cut-off value of >30% at proximal levels for temporal dispersion. Diagnostic sensitivity improved significantly with proximal studies with the criteria used in this population. No adverse effects had occurred as result of proximal stimulations. CONCLUSIONS: Proximal studies are safe, sensitive and reliable procedures in cases of suspected CIDP. Their use appears justified although adequate cut-off values are desirable to optimize their specificity. SIGNIFICANCE: This study indicates that proximal upper limb nerve conductions are appropriate in investigating suspected CIDP, as detailed in recently established electrophysiologic criteria. However, specificity is largely dependent on cut-off values for conduction block and temporal dispersion.     

Totally extra-peritoneal repair of inguinal hernia by a glove-balloon: technical innovation.

Totally extra-peritoneal (TEP) laparoscopic repair of an inguinalhernia involves the creation of an extra-peritoneal space by blunt dissection or the use of commercial balloons. This new technique demonstrates the use of a device to create this extra-peritoneal space, without the need for any commercial balloons. The extra-peritoneal space was created using a glove-balloon. A total of 107 consecutive TEP repairs were carried out using the glove-balloon technique, these included ten bilateral and 17 recurrent inguinal hernias. This method is simple, cost-effective and easy to teach.     

Postoperative Cognitive Dysfunction in Patients with Preoperative Cognitive Impairment: Which Domains Are Most Vulnerable?

Background: The authors explored the database of the first International Study of Postoperative Cognitive Dysfunction study to specify the domains of cognitive function that were most vulnerable and to determine the pattern of deterioration in patients with preoperative cognitive impairment.

Methods: One thousand two hundred eighteen patients were included in the first International Study of Postoperative Cognitive Dysfunction, where neuropsychological testing was performed at entry to the study, at 1 week, and at 3 months after surgery. The authors' analyses determined the extent to which seven neuropsychological measures changed after surgery with focus on the relation with preoperative cognitive impairment, defined as a preoperative score 1.5 SD below healthy controls in the memory test.

Results: Preoperative cognitive impairment was found in 74 patients at baseline. At 1 week, cognitive deterioration was seen in all tests, but in particular in the Letter Digit Coding and the time of the Stroop interference test, with 14% and 16% of the total sample (n = 1,016) exceeding 2 SD, respectively. At 3 months, deterioration was more uniform. Significantly fewer in the preoperative cognitive impairment group had deterioration in the memory test, both at 1 week and at 3 months, with no patient displaying a deterioration exceeding 2 SD.