Generalised mitochondrial cytopathy is an absolute contraindication to orthotopic liver transplant in childhood

OBJECTIVE: To compare mask anesthesia induction and recovery characteristics between 2 inhalant anesthetic agents: isoflurane and sevoflurane. ANIMALS: 16 clinically normal, young adult Beagles. PROCEDURE: Using a cross-over design, dogs were randomly selected to receive sevoflurane or isoflurane via a face mask and a circle anesthetic system. Vaporizer setting concentrations were increased in stepwise, equal minimum alveolar concentrations (MAC) for each anesthetic until the vaporizer setting of 2.6% for isoflurane or 4.8% for sevoflurane (2 MAC) was reached. Concentration was kept constant until the dog had a negative tail clamp response and was intubated. End-tidal concentration was maintained at 1.8 to 2.0% or 3.3 to 3.8% for isoflurane or sevoflurane, respectively (1.4 to 1.6 MAC) for 30 minutes. Dogs were allowed to recover with only tail clamp stimulation until a positive response was obtained. Extubation was performed when a spontaneous swallow reflex was observed. Dogs were allowed to achieve sternal recumbency and stand unassisted without further stimulation. RESULTS: Sevoflurane induction resulted in shorter time to loss of palpebral reflex, negative tail clamp response, and time to tracheal intubation, and was of better quality than isoflurane induction. Both anesthetics were associated with rapid and smooth recovery. CONCLUSIONS: Sevoflurane mask induction is faster and of better quality, compared with isoflurane, in adult dogs. Recovery time and quality are comparable. CLINICAL RELEVANCE: On the basis of these results, sevoflurane is a suitable inhalant anesthetic for mask induction and recovery in adult dogs and appears to have some advantages over isoflurane, including faster and smoother mask induction.     

Surgery for lung cancer: age alone is not a contraindication

A retrospective analysis of the clinical features, operative procedures, postoperative complications and subsequent survival of 70 (50 male) elderly patients undergoing surgery for lung cancer compared with 74 (53 male) younger patients treated at the same hospital during the same period was performed, to determine if elderly people with lung cancer are less likely to benefit from and/or tolerate surgery. The elderly group had to wait longer for operation (p = 0.001) and were more likely to have pre-existing disease (p = 0.019). In contrast, they had fewer recognised postoperative complications (p = 0.032) and there was no difference between the two groups in perioperative mortality and subsequent survival. Surgical treatment of localised lung cancer represents the best chance for cure and this study suggests that age should not be a consideration in the decision to operate or not. The patient's general state of health should be assessed and management decisions based on individual status rather than on age.     

Fentanyl delivery from an electrotransport system: delivery is a function of total current, not duration of current

BACKGROUND: VS and V are common red cell antigens in persons of African origin. The molecular background of these Rh system antigens is poorly understood. STUDY DESIGN AND METHODS: Red cells from 100 black South Africans and 43 black persons from Amsterdam, the Netherlands, were typed serologically for various Rh system antigens. Allele-specific polymerase chain reaction and sequencing of polymerase chain reaction products were used to analyze C733G (Leu245Val) and G1006T (Gly336Cys) polymorphisms in exons 5 and 7 of RHCE and the presence of a D-CE hybrid exon 3. RESULTS: The respective frequencies of all VS+ and of VS+ V-(r's) phenotypes were 43 percent and 9 percent in the South Africans and 49 percent and 12 percent in the Dutch donors. All VS+ donors had G733 (Val245), but six with G733 were VS- (4 V+w, 2 V-). The four VS- V+w donors with G733 appeared to have a CE-D hybrid exon 5. T1006 (Cys336) was present in 12 percent and 16 percent of donors from the two populations. With only a few exceptions, T1006, a D-CE hybrid exon 3, and a C410T (Ala137Val) substitution were associated with a VS+ V-phenotype ((C)ces or r's haplotype). Two VS+ V-individuals, with the probable genotype, (C)ces/(C)ces), were homozygous for G733 and for T1006. CONCLUSIONS: It is likely that anti-VS and anti-V recognize the conformational changes created by Val245, but that anti-V is sensitive to additional conformational changes created by Cys336.     

The Salmonella typhimurium AhpC polypeptide is not essential for virulence in BALB/c mice but is recognized as an antigen during infection

The OxyR regulon is known to mediate protection against oxidizing agents in Salmonella typhimurium. We reported previously that ahp, one of the OxyR-regulated loci, is induced during macrophage interaction (K. P. Francis, P. D. Taylor, C. J. Inchley, and M. P. Gallagher, J. Bacteriol. 179:4046-4048, 1997). We now report on the effects of disrupting ahp or oxyR on virulence in a BALB/c mouse model. Surprisingly, insertion of a Mudlux derivative within ahpC was found to result in attenuation, while irreversible inactivation of the locus through insertion of a cml cassette did not. An SL1344 derivative carrying an oxyR::kan disruption was also found to be as virulent as the parental strain. Moreover, both cell-mediated and humoral responses to AhpC were found to develop during the course of infection, probably through T-helper-cell (type I) activation. These results indicate that, although not essential for virulence, AhpC is expressed by S. typhimurium during infection of BALB/c mice and constitutes a target for the immune system.     

Failure of hippocampectomy to facilitate classical conditioning at an optimal interstimulus interval is not due to a "ceiling effect."

Examined the effects of amphetamine injection (2 mg/kg), hippocampal lesions, and cortical lesions in 30 naive New Zealand albino rabbits during classical conditioning of the rabbit nictitating membrane response. An optimal interstimulus interval (ISI) was employed. Whereas neocortical and hippocampal damage had no significant effect on the rate of acquisition, amphetamine treatment produced a marked facilitation. A control group of amphetamine-treated Ss receiving explicitly unpaired presentations of the conditioned stimulus/stimuli (CS) and unconditioned stimulus/stimuli (UCS) failed to exceed spontaneous response rates throughout training. The failure of hippocampectomy to accelerate conditioning under an optimal ISI does not appear to be due to a ceiling effect. Rather, it is suggested that the response system is predisposed to conditioned responses of a given latency. Optimal ISIs may fall within this range. Thus, in short or long intervals, temporal aspects of the motor response must be adjusted to conform to the stimulus configuration. It appears that the hippocampus is a likely source of response modulation. Thus, loss of hippocampal input accelerates conditioning under nonoptimal intervals at the expense of proper timing. Conditioning under an optimal interval would occur at normal rates because no modulation is required. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sucrose: is it not only sweet, but also an analgesic?

Case reports about vasopressin-induced cutaneous necrosis are not frequent. Here we report a further case, of which skin manifestations included not only mottling, cyanosis, ecchymosis, bullae and gangrene, but also amber-like change in focal areas. Besides, intermittent paling of the skin with or without deep pain sensation of the limbs over non-injection sites was observed that might be a warning sign of impending skin necrosis. Based on the literature about vasopressin-induced skin necrosis we discuss the possible role of coagulation enhancement of this molecule.     

Delayed deliveries in multiple pregnancies: is this reasonable?

A gene polymorphism of the angiotensin II (AII) type 1 receptor has been described previously (A to C transversion at position 1166). Besides the epidemiological studies needed to determine a possible relationship between the polymorphism and some cardiovascular diseases, no study has been conducted to determine the impact of the polymorphism on vascular functions. At subthreshold concentrations, within the physiological range, AII potentiates alpha-adrenergic-dependent vascular tone. We investigated phenylephrine-induced tone and its amplification by AII (10 pmol/l) in human internal mammary artery rings mounted in organ baths. We performed concentration-response curves to phenylephrine (0.1-100 micromol/l) before and after pretreatment with AII (10 pmol/l). Patients had the genotype AA (n = 20) or the A to C transversion (AC/CC, n = 30). Contractions to phenylephrine (0.1-100 micromol/l) were significantly higher in rings from AC/CC than from AA patients (maximum response: 1.47+/-0.07 vs. 1.22+/-0.06 mN/mg, p < 0.001). AII (10 pmol/l) induced a significant potentiation of phenylephrine-induced contraction (e.g. 58.9% increase in tone with 1 micromol/l phenylephrine, p < 0.001) which was significantly lower in the AC/CC than in the AA group (46+/-9 vs. 66+/-7% with 1 micromol/l phenylephrine, p < 0.01). Contractions to AII (1 or 100 nmol/l) were not significantly affected by the genotype. Although the study was performed in arteries from patients with a coronary artery disease, these changes in vascular reactivity might be of interest in the understanding of the relationship between a possible higher probability of cardiovascular disorder and the genetic polymorphism of the AII type 1 receptor.     

Menopause: when hormone replacement therapy is not an option. Part I

Although the perimenopausal period is often experienced as a positive life transition, it is frequently accompanied by a variety of distressing physical and emotional sequelae. Hormone replacement therapy (HRT) has been hailed as the first-line treatment for many of these symptoms. A significant number of women, however, are unable to take exogenous hormones because of absolute or relative contraindications to therapy. Other women are unwilling to use this treatment for a variety of reasons, including reluctance to use unnatural exogenous hormones and fear of unknown risks of HRT. This two-part review discusses the physiology of menopause and its related symptoms, as well as the risks and benefits of both oral and non-oral routes of hormone administration. Self-help measures and alternative therapeutic options are recommended for the treatment of menopausal symptoms, which include vasomotor instability, urogenital atrophy, psychologic disturbances, and risk of osteoporosis and cardiovascular disease.     

Telomerase is not an epidermal stem cell marker and is downregulated by calcium

An understanding of the basic mechanisms responsible for the pathogenesis of liver neoplasms is needed in order to develop better therapeutic strategies. The present study utilized a pharmacogenetic mouse model to assess the role of cytochrome P4501A1 (Cyp1a1) in modulating genetic damage to oncogenic and tumor suppressor loci following in utero exposure to the polycyclic aromatic hydrocarbon, 3-methylcholanthrene (MC). Analysis of the Ha-ras, Ki-ras, INK4a and p53 genes was carried out with lysates from paraffin-embedded liver tissue from transplacentally-treated mice. The lysates were subjected to DNA amplification by the PCR technique followed by allele-specific oligonucleotide hybridization screening and SSCP analysis. All of the 26 neoplasms screened (23 hepatocellular carcinomas, two hepatocellular adenomas and one sarcoma) exhibited a GGC-->CGC (GLY13-->ARG13) transversion at the Ki-ras gene locus. None of the tumors had Ki-ras mutations at codon 12 of exon 1. Approximately 12% (3/26) of the liver tumors exhibited point mutations in exon 1 of the INK4a gene, with each of the three tumors exhibiting two point mutations. Analysis of exon 2 of the INK4a gene showed the presence of a CCG-->CTG (PRO73-->LEU73) transition in two of the 26 neoplasms. No mutations were found in exons 1 or 2 of the Ha-ras gene, or in exons 5-8 of the p53 gene. Analysis of tumor RNAs showed overexpression of Ha-ras, cip1 and c-jun in approximately 38% of the liver tumor samples. The results of this study suggest that mutagenic damage to oncogenes and tumor suppressor genes may be critical factors in mediating transplacentally-induced liver tumorigenesis. The fact that Ki-ras mutations were found in all of the tumors suggests that mutation at this gene locus may be an early event in liver tumor pathogenesis, while mutation in tumor suppressor genes may occur later during tumor progression. These combined results are consistent with the pathogenesis of cancer in humans.     

Filmed versus live delivery of full-spectrum home training for primary enuresis: Presenting the information is not enough.

To extend availability of a behavioral treatment package for enuresis, two outcome studies compared the effectiveness of live versus videotape delivery. In Study 1, 40 primary enuretics were randomly assigned to live or film delivery. Outcome was superior for the live delivery. Overall, pretreatment measures of family and child psychosocial adjustment failed to predict treatment response. The results were replicated with 18 children, and an impact assessment suggested that film delivery resulted in higher confidence of children in their parents but lower confidence of parents in their children. Delivery of treatments by videotape may provide a way to identify nonspecific factors in psychological interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed endolymphatic hydrops: an analysis of 12 cases

Delayed Endolymphatic Hydrops (DEH) is a clinical entity which is characterized by an early phase with a profound sensorineural hearing loss in one ear. After a prolonged period of time (from 1 to 68 years) a late phase of the disease appears with different otologic symptoms. The ipsilateral type of endolymphatic hydrops appears in the deaf ear with consequent episodic vertigo. The contralateral type develops symptoms of endolymphatic hydrop in the previously normal ear, with the onset of fluctuating hearing loss and/or episodic vertigo. This paper is a review of 12 cases of DEH (7 ipsilateral and 5 contralateral, age ranging from 19 to 79 years). Diagnosis was established on the basis of clinical history and the results of audio-vestibular investigations, specifically designed to detect signs of endolymphatic hydrops (including the glycerol-test and neuroradiological imaging of the cerebello-pontine angle). In 8 patients the levels and frequency of anti-collagen I-II-IV-V, anti-laminin autoantibodies, complement, Ig and immuno-complexes were measured. Viral infections (measles, mumps, influenza) were thought to have caused the early phase in 6 cases. In the entire group of 12 patients the delay between the onset of the ear loss and vertigo averaged 12 years. In the group of the ipsilateral DEH, caloric tests showed in 5 cases a reduced or absent response of the deaf ear. About contralateral DEH, caloric tests showed bilateral reduced response in 2 cases, and, in 3 cases, a decreased response only in the previously normal ear. Regarding immunological study, an abnormal level of Ig and Complement was detected in 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

A novel wound dressing with an antibiotic delivery system stimulated by microbial infection

The aim of this study was to develop a new wound dressing with controlled release of antibiotics only in the presence of infection. In the first experiment using an infected dorsal pouch of rats, exudate containing proteinases from pouches contaminated with Staphylococcus aureus or Pseudomonas aeruginosa showed significantly higher hydrolytic activity toward Boc-Val-Pro-Arg-MCA than that from noninfected wounds. The authors then developed a new type of wound dressing (AGX), a drug delivery system in which gentamicin is bound to polyvinylalcohol hydrogel through an enzymatically degradable peptide linker containing a -(D)-Phe-Pro-Arg-sequence. To investigate in vitro effectiveness, AGX was incubated with exudate from S. aureus infected or P. aeruginosa infected wounds. Gentamicin was selectively released from AGX in the presence of the exudate from S. aureus infected or P. aeruginosa infected wounds, but was not released in the presence of exudate from noninfected wounds. Next, AGX or the polyvinylalcohol hydrogel that served as control was incubated with S. aureus in the presence of human plasma. After 24 hours, S. aureus concentration was markedly lower in the case with AGX than in that with polyvinylalcohol hydrogel. These results indicate that proteinases from wounds infected with S. aureus or P. aeruginosa cleaved the linker and gentamicin was released.     

Nucleus accumbens dopamine modulates response rate but not response timing in an interval timing task.

While previous work has demonstrated that systemic dopamine manipulations can modulate temporal perception by altering the speed of internal clock processes, the neural site of this modulation remains unclear. Based on recent research suggesting that changes in incentive salience can alter the perception of time, as well as work showing that nucleus accumbens (NAc) shell dopamine (DA) levels modulate the incentive salience of discriminative stimuli that predict instrumental outcomes, we assessed whether microinjections of DA agents into the NAc shell would impact temporal perception. Rats were trained on either a 10-s or 30-s temporal production procedure and received intra-NAc shell microinfusions of sulpiride, amphetamine, and saline. Results showed that NAc DA modulations had no effect on response timing, but intra-NAc shell sulpiride microinfusions significantly decreased response rates relative to saline and amphetamine. Our findings therefore suggest that neither NAc shell DA levels, nor the resultant changes in incentive salience signaled by this structure, impact temporal control. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Evidence that phentolamine is not an inhibitor of extraneuronal uptake

1. Tracheal segments from guinea-pigs pretreated with 6-hydroxydopamine were incubated in isoprenaline at 37 degrees C for 5 min in the absence or presence of phentolamine. Catechol-O-methyl transferase was inhibited by 100 mumol l-1 U-0521. Tissues were prepared for fluorescence histochemistry and accumulated isoprenaline in trachealis smooth muscle cells (fluorescence) was measured by microphotometry. 2. Phentolamine, in concentrations up to 100 mumol l-1, had no effect on isoprenaline fluorescence. 3. It is concluded that phentolamine does not inhibit extraneuronal uptake in concentrations used to block alpha-adrenoceptors in isolated tissue experiments. Thus, is can be present in experiments designed to examine the effects of extraneuronal uptake inhibitor drugs on beta-adrenoceptor-mediated responses.     

Recovery from habituation in Caenorhabditis elegans is dependent on interstimulus interval and not habituation kinetics.

The habituation of the tap withdrawal reflex of Caenorhabditis elegans was assessed to determine whether the kinetics of recovery from habituation were dependent on the interstimulus interval (ISI) uscd during habituation training or alternately, on the rate and asymptotic level of habituation produced at a given ISI. Two groups of intact animals were trained at either a 10-s (CON10) or a 60-s (CON60) ISI Laser ablation was used to alter the habituation kinetics in one further group of animals (PLM10) independent of ISI. Although the PLM10 animals trained at a 10-s ISI habituated like CON60 worms the recovery from habituation of the PLM10 animals very closely resembled the recovery of the CON10 worms. Thus recovery kinetics are dictated by consequences of a given ISI which do not impact upon habituation rate and asymptote. This suggests the recruitment of multiple ISI-dependent processes during habituation in C. elegans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)