痛

黑暗!黑暗!!黑暗!!!这样的世界看不到半点光明。孤独的舞者终究还是孤独地倒下,然后又孤独地消失。黑暗呀,为什么老是缠绕着我?一声“妈妈”划破了天际,却也突不出黑暗的包围。谁来应我一声呀,妈妈,你在哪里呀?我的心在不停地挣扎,告诉自己:“不怕,不怕。”可这是在黑暗里呀,周     

Experimental model of atrophic rhinitis in gnotobiotic pigs.

To study the pathogenesis of atrophic rhinitis, gnotobiotic pigs (n = 6) were inoculated intranasally with a sterile sonicate of a toxigenic strain of Bordetella bronchiseptica (0.16 mg of protein per ml) at 5 days of age, and they were then inoculated intranasally with 1 ml (5,250 CFU/ml) of a live, toxigenic strain of Pasteurella multocida at 7 days of age. Pigs were necropsied at 2, 5, 9, 14, 21, and 28 days postinoculation; those pigs necropsied after 5 days had developed turbinate atrophy. Other gnotobiotic pigs received the following inoculation protocols: (i) a sterile sonicate of a nontoxigenic strain of B. bronchiseptica (0.2 mg of protein per ml), followed by toxigenic P. multocida (n = 4); (ii) toxigenic P. multocida alone (n = 7); (iii) diluent (sterile tryptose broth) (n = 2); (iv) the sterile sonicate of toxigenic B. bronchiseptica alone (n = 2); or (v) the sterile sonicate of a nontoxigenic strain of B. bronchiseptica alone (n = 2). Turbinate atrophy did not occur in the latter groups except for one pig inoculated with only toxigenic P. multocida. These studies show that turbinate atrophy occurs in pigs given the toxigenic B. bronchiseptica sonicate and then given live, toxigenic P. multocida. This experimental regimen is a useful model for (i) studying the pathogenesis of atrophic rhinitis and (ii) testing vaccine strategies.     

How nonclinical are community samples?

Mental health services are underutilized in our society by both adults and children. This finding presents a potential problem for researchers conducting community‐based research. Previous studies have demonstrated that community‐based researchers frequently do not screen participants for the presence of psychopathology nor do they ascertain whether therapeutic services are currently utilized. The present study explored the prevalence of psychopathology and treatment involvement in a sample of families recruited from the community. Results indicated that a fifth of the participants in this community‐based sample met diagnostic criteria for a psychiatric disorder or were in treatment for psychological difficulties at the time of recruitment for this study. Furthermore, mothers, fathers, and adolescents who met the criteria according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV; American Psychiatric Association, 1994 ) for a psychological disorder had higher symptomatology than those who did not meet criteria. Methodological suggestions are provided. © 2008 Wiley Periodicals, Inc.     

Ketamine protects hippocampal neurons from anoxia in vitro

Ketamine, a dissociative, general anesthetic, blocks the excitation produced by activating one class of excitatory amino acid receptors, the N-methyl-D-aspartate receptor in the rat. We have found that ketamine can protect hippocampal neurons in culture and slice from anoxia. When added to cultures immediately prior to anoxic exposure, ketamine prevented the neuronal destruction seen after a day of anoxia. Neurons appeared undamaged and had normal resting and action potentials. Adenosine triphosphate levels in ketamine-protected anoxic cultures were approximately two-thirds of normal controls. Ketamine also prevented the irreversible loss of the population spike seen in hippocampal slices after prolonged perfusion with anoxic buffer. These results suggest that ketamine may have therapeutic potential in preventing anoxic damage from stroke in man.     

A less costly regimen of alglucerase to treat Gaucher's disease.

BACKGROUND. Alglucerase (Ceredase) provides effective enzyme-replacement treatment for patients with Gaucher's disease, but at the usually recommended dose of 60 U per kilogram of body weight every two weeks (130 U per kilogram per month), it costs $382,200 per year for a 70-kg patient. Theoretical considerations suggest that more frequent administration would be more efficient. METHODS. Fourteen patients with type 1 Gaucher's disease that was moderately severe to severe were given 30 U of alglucerase per kilogram per month, in divided doses given either daily or three times weekly, or 120 U given three times weekly. The effect of the treatment on the size of the liver and spleen and on blood counts was compared with published data on patients who received a total dose four to five times as large as the lower dose we used and who received treatment every two weeks. RESULTS. The response to 30 U of alglucerase per kilogram per month, fractionated into three or seven doses weekly, was approximately the same as that reported after the administration every two weeks of a dose four or five times as large, given in the large infusions usually recommended. A fourfold increase in the dose given three times weekly, from 2.3 to 9.2 U per kilogram, did not substantially increase the rate of improvement. CONCLUSIONS. The treatment of Gaucher's disease with smaller total doses of alglucerase given more frequently yields satisfactory results. A dose of 2.3 U per kilogram three times weekly yields major financial benefits with no sacrifice of therapeutic effect. Even taking into account the increased ancillary costs of more frequent administration, this method of administering alglucerase reduces the annual cost of the drug for a 70-kg patient to about $100,000.     

Hyperactive vestibulo-ocular reflex in cerebellar degeneration: pathogenesis and treatment

We studied a patient with a cerebellar degeneration and hyperactive vestibulo-ocular reflex (VOR). He complained of oscillopsia and blurred vision with head movement. A twofold increase in VOR gain (peak eye velocity/peak head velocity) at high frequencies was associated with a VOR time constant of 6 seconds (low normal). Visual cancellation ("suppression") of the VOR and smooth pursuit were also abnormal. We hypothesized that his high VOR gain was due to dysfunction of olivocerebellar projections. Physostigmine reduced his VOR gain, consistent with the hypothesis that these projections are cholinergic.     

Optimizing the fellowship interview process: Perspectives from applicants and program directors of the comprehensive endocrine surgery fellowship program

BackgroundApproximately 80% of general surgery residents undertake some form of fellowship training. Our objective was to characterize goals and burdens of the interview process among applicants to Comprehensive Endocrine Surgery Fellowship programs.MethodsParticipants included trainees from 2013 to 2019. Results for ranking questions are presented as a mean rank reported out of the total number of selections.ResultsResponse rate was 54% (n = 75). The most important goal for interviews was meeting the faculty (mean rank 2.4/9), followed by “behind the scenes information” and “make a good impression” (mean rank 3.6 and 3.7, respectively). The most substantial burden for the applicant was expense (mean rank 2.1/7), followed by time away from residency (mean rank 3.1/7). The economic burden of 51% of the applicants was $2,500 to $7,500. Geographic location and expense were the top 2 reasons applicants declined offers of interviews. Despite the process, 76% of respondents indicated that no improvements to the interview process are necessary. Alternative strategies such as videoconferencing or centralized interviews received little support (<10%).ConclusionDespite identifying several burdens, survey respondents believed that in-person interviews are an integral component of the fellowship application process. Indeed, 70% of applicants do not have a first-choice program before interviews, and meeting the faculty is ranked as the greatest priority goal. Our data illustrate the importance of individual specialties evaluating and optimizing their own processes for fellowship interviews.     

Thiopentone inhibits beta-adrenergic responses in myocardial tissue

The purpose of this study was to determine the importance of inhibition of beta-adrenergic function in thiopentone-induced myocardial depression. Using an isolated, electrically stimulated rat left atria model, contractile dose-response curves to thiopentone (200 μM, 400 μM, 600 μM, 800 μM) were shifted to the right in preparations treated with 10^{− 3} M dibutyryl cyclic adenosine monophosphate (cAMP) compared with atria stimulated with 10^{− 6} M isoprenaline, demonstrating that inhibition of beta-adrenergic mechanisms by thiopentone is physiologically important. Depression by thiopentone was similar in atria treated with 10^{− 5} M forskolin compared with preparations stimulated with 10^{− 6} M isoprenaline, indicating that thiopentone does not block beta-adrenergic receptors. It is concluded that thiopentone depresses myocardial function by several mechanisms, one of which involves inhibition of the adenyl cyclase cascade. The adenyl cyclase enzyme is a likely site where thiopentone inhibits the system; however, other components of the cascade may also be involved. L’objectif de cette étude consiste à déterminer l’influence de l’inhibition de l’activité β-adrenergique sur la dépression myocardique induite par le thiopentone. A l’aide d’un modèle constitué d’une oreillette gauche de rat stimulée électriquement, la relation dose-effet du thiopentone sur la contractilité (200 μM, 400 μM, 600 μM, 800 μM) se déplace vers la droite dans des préparations traitées avec de l’adénosine monophosphorique cyclique (cAMP) 10^{− 3} M comparativement à des oreillettes stimulées avec de l’isoprénaline 10^{− 6} M, ce qui démontre que l’inhibition β-adrénergique provoquée par le thiopentone est physiologiquement importante. La dépression de l’oreillette provoquée par le thiopentone est identique à celle que produit la forskoline 10^{− 5} M comparativement à celle de l’isoprénaline 10^{− 6} M, ce qui indique que le thiopentone n’inhibe pas les récepteurs β-adrénergiques. Les auteurs concluent que le thiopentone déprime la fonction myocardique par plusieurs mécanismes qui impliquent l’inhibition de la cascade de l’adényl cyclase. L’inhibition du système se produit vraisemblablement au niveau de l’enzyme adényl cyclase; cependant, il est possible que d’autres éléments de la cascade de l’adényl cyclase soient impliqués.