Cardiovascular effects produced by R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin in the preoptic area of conscious rats

The effect of ancrod-induced defibrinogenation on thrombosis and bleeding time was determined in anesthetized rats. Functional plasma fibrinogen levels were reduced 42, 71, 94 and 93% by ancrod doses of 5, 10, 20 and 30 U/kg, respectively, while a 2.5 U/kg dose was without significant effect. Ancrod inhibited vena cava thrombosis induced by partial stasis of blood flow combined with mild vascular injury. Thrombus weight was decreased 85 and 93% by the 10 and 20 U/kg doses, but was unaffected at lower doses. In contrast, ancrod doses of up to 30 U/kg did not significantly decrease carotid artery thrombi formed in response to oxidative transmural vessel injury. Ancrod caused a dose-dependent increase in bleeding time measured by puncturing small mesenteric arteries with a hypodermic needle. The bleeding time increase was approximately 38% in response to the 2.5 and 5 U/kg doses, and 182% in response to the 10 U/kg dose. These studies demonstrate that ancrod-induced reductions in plasma fibrinogen more effectively inhibit venous compared to arterial thrombosis, although these activities require doses that also increase bleeding time in small arteries.     

The Second Canadian Gastroesophageal Reflux Disease Consensus: moving forward to new concepts

Gastroesophageal reflux disease (GERD) is a disease with serious consequences that may result in significant impairment in quality of life and disease morbidity. Across all grades of severity of symptoms and severity of underlying esophageal disease, proton pump inhibitors (PPIs) provide therapeutic gains over prokinetics (PKs) or H2 receptor antagonists (H2RAs). The potential cost effectiveness of using medications with higher acquisition costs that may lower health care costs overall is often disregarded when conducting cost comparisons with medications having lower 'up-front' costs. Limiting therapy to less effective agents condemns many patients to protracted suffering, repeated physician visits and needless reinvestigation of symptoms that could have been resolved by appropriate initial therapy. Based on current data, use of any classification of symptom severity as a basis for selecting one class of therapeutic agents over another for first line therapy (i.e. PKs, H2RAs for 'mild' GERD, versus a PPI for 'severe' disease) is unwarranted.     

DNA recognition by the EcoK methyltransferase. The influence of DNA methylation and the cofactor S-adenosyl-L-methionine

The methyltransferase of the EcoK type I restriction/modification system is trimeric, M2S1, where the S subunit determines the sequence specificity of the enzyme. The methyltransferase has a strong preference for hemimethylated substrate DNA and, therefore, we have investigated the effect of the methylation state of DNA on binding by the enzyme, together with the effects on binding of the cofactor S-adenosyl-L-methionine. Our results indicate that the methyltransferase has two non-interacting S-adenosyl-L-methionine binding sites, each with a dissociation constant of 3.60 (+/- 0.42) microM determined by equilibrium dialysis, or 2.21 (+/- 0.29) microM determined by the displacement of a fluorescent probe. Ultraviolet light-induced crosslinking showed that S-adenosyl-L-methionine binds strongly only to the modification (M) subunits. Changes in the sedimentation velocity of the methyltransferase imply a protein conformational change due to S-adenosyl-L-methionine binding. Gel retardation results show that the binding of S-adenosyl-L-methionine to the methyltransferase enhances binding to both specific and non-specific DNAs, but the enhancement is greater for the specific DNA. Differences in binding affinities contribute to the recognition of the specific nucleotide sequence AAC(N)6GTGC by the methyltransferase in preference to a non-specific sequence. In contrast, although the complexes of unmodified and hemimethylated DNAs with the methyltransferase have different mobilities in non-denaturing gels, there appears to be no contribution of binding affinity to the distinction between these two substrates. Therefore, the preference for a hemimethylated substrate must be due to a difference in catalysis.     

Electrical pacing of the paralyzed human larynx

This study represents the first attempt to electrically pace the paralyzed human larynx. The goal was to determine if electrical stimulation of the posterior cricoarytenoid muscle could produce functional abduction of the vocal fold in pace with inspiration. An external apparatus was used to sense inspiration and reanimate the unilaterally paralyzed larynx of a thyroplasty patient. Stimuli were delivered through a needle electrode to locate and pace the abductor muscle. The magnitude of electrically induced abduction was comparable to spontaneous movement on the normal side. The abduction was appropriately timed with inspiration: this finding demonstrated that this simple pacing system could effectively modulate stimulation with patient respiration.     

Outcome of patients with haemorrhagic shock: an indicator of performance in a trauma centre

The survival rate of patients admitted to the Royal Prince Alfred Hospital (RPAH) from the central Sydney area with a major injury has improved since regionalization of trauma services in early 1992. This improvement has been attributed to education, better hospital care and changing trauma epidemiology. This study was conducted to assess whether the outcome of patients admitted with haemorrhagic shock had improved. This is proposed as a more subtle indicator of hospital performance than overall survival rates. A prospective before and after study was carried out comparing outcome in the 18 months preceding 1 January 1992 with that in the subsequent 18 months. Entry criteria to the study included all primary retrievals from the central Sydney area to RPAH with injury severity scores (ISS) > 15. Outcomes were compared generally and in those who were in a state of haemorrhagic shock (systolic blood pressure < or = 90 mmHg) on arrival at the emergency department. Three hundred and eight patients were entered into the study. Stratification showed similar numbers, demographic features and mechanisms of injury in the two groups. Forty patients were in a state of haemorrhagic shock on admission. The overall mortality was reduced from 31% to 11% (P < 0.001) over the two phases of the study. The mortality from blood loss in the 40 shocked patients fell from 10/25 in the first period to 2/15 (P = 0.07) in the latter. These improved survival rates were felt to reflect the value of the educational and organizational initiatives introduced following designation of the hospital as a trauma centre.     

Effects of sex and MK-801 on auditory-processing deficits associated with developmental microgyric lesions in rats

Neonatally induced microgyric lesions produce defects in rapid auditory processing in adult male rats. Given that females across species are less susceptible to the deleterious effects of neural injury and that treatment with neuroprotective agents at the time of injury can reduce neural damage, the authors tested the effects of sex and neuroprotectant exposure on the behavioral consequences of microgyric lesions in rats. Results showed that sham but not microgyric males were able to perform the task at the fastest rate of stimulus presentation. Microgyric females, in contrast, discriminated at all stimulus conditions and did not differ from female shams. Microgyric males treated with MK-801 had reduced cortical damage and performed the discrimination at the fastest condition. Results suggest that females are less susceptible to the behavioral effects of neocortical microgyria and that MK-801 may ameliorate the behavioral consequences of these lesions in male rats.