Hydrolytic and depolymerising enzyme activity of Prevotella intermedia and Prevotella nigrescens

OBJECTIVE: Prevotella intermedia has been reported to be associated with periodontal disease whilst P. nigrescens has predominantly been isolated from more specific conditions and healthy sites. The aim of the present study was to compare the enzyme activity of these species.
MATERIALS AND METHODS Nine strains of P. intermedio and 12 strains of P. nigrescens were studied. Lipolytic. saccharolytic, nucleolytic and proteolytic activity was determined by traditional microbiological and chromo-genic substrate methods.
RESULTS: All strains hydrolysed gelatine, casein. DNA and RNA. Lipase activity was produced by all strains except P. nigrescens ATCC 33563^T. Lipolytic activity of P. nigrescens strains decreased as the environmental glucose concentration was increased. Only two strains, both P. intermedia , hydrolysed benzyl-arg-p-nitroanilide. All strains hydrolysed alkaline pnitrophenolphosphate (except P. intermedia DAL 100). produced glycylprolyl dipeptidase activity and demonstrated elastase-like activity. All but three strains (2 P. intermedia and I P. nigrescens) hydrolysed suc-ala-ala-pro-phe-p-nitroanilide. Overall, no qualitatively analysed enzyme activity was exclusive to all strains of either species. Quantitatively analysed activity exhibited a high degree of variability both within and between species.
CONCLUSIONS: P. intermedia and P. nigrescens degrade natural and synthetic substrates, but intra- and interspec-ies activity is variable.     

美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.      

美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

Growth hormone therapy for protein catabolism

GH and IGF-I have shown remarkable consistency of effect in a wide range of catabolic conditions. Doses of around 10 IU/m2/day of GH and 80 micrograms/kg/day of IGF-I over short periods of time can improve net protein synthesis and preserve lean body mass. Most studies have reported metabolic endpoints, but favorable clinical effects have included decreased hospital stay and mortality in burns, improved respiratory muscle function in COAD, preserved grip strength post- operatively, and improvements in cardiac and bowel failure. Adverse effects of GH treatment are uncommon and usually related to glycaemic control. GH and IGF-I have differential effects on insulin concentrations--increasing or decreasing concentrations, respectively. The hypoglycaemic effects of IGF-I are dependent on route of administration and are avoided by subcutaneous delivery. Occasional patients have needed to discontinue GH treatment due to hyperglycaemia, although the anabolic action of GH may be partially mediated by increased insulin levels. The co-administration of GH and IGF-I has theoretical advantages by both increasing IGF binding-protein concentrations and balancing glycaemic control. An initial study with combination therapy in calorically-restricted volunteers has shown anabolic effects greater than with either agent alone. This approach requires further study in catabolic patients. There is a need for large, well-designed trials with clinical rather than purely metabolic end-points, and some of these are already underway. Should these studies confirm the early findings, financial considerations will become paramount, although it remains possible that treatment may be self-financing if lengths of hospital admissions are shortened.      

The efficacy of subcutaneous recombinant human erythropoietin in the correction of phlebotomy-induced anemia in autologous blood donors

The efficacy of subcutaneous recombinant human erythropoietin (rhEPO) (500 U/kg; administered twice a week during the 3 weeks before surgery) in the recovery of preoperative hemoglobin concentrations within a 3- week period was studied in 40 patients, each of whom donated 2 units (900 mL) of blood for their own use before total hip replacement surgery. Twenty autologous blood donors received rhEPO (EPO group) and 20 were not treated (control group). The initial hemoglobin concentration (14.0 +/− 1.0 g/dL [140 +/− 10 g/L]) was completely recovered before surgery (14.0 +/− 1.6 g/dL [140 +/− 16 g/L]) in the EPO group, while a decrease from 13.8 +/− 1.1 to 12.2 +/− 1.3 g per dL (138 +/− 11 to 122 +/− 13 g/L) was observed in the control group. The preoperative reticulocyte count showed more than sixfold increase in the EPO group, whereas a twofold to threefold increase was found in the control group. Serum ferritin concentration fell to 42 +/− 29 micrograms per L in the EPO group and to 54 +/− 35 micrograms per L in the control group. The postoperative serum erythropoietin concentration in the EPO group was significantly lower than that in the control group, but it did not differ from the pretreatment value and was attended by a higher hemoglobin concentration after surgery. Only transient flu-like symptoms were mentioned by patients who were treated with rhEPO. Changes in blood pressure or platelet count or other adverse events were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral sumatriptan in the acute treatment of migraine and migraine recurrence in general practice

We investigated the efficacy, safety and tolerability compared with placebo of a second dose of oral sumatriptan 100 mg in 1349 general practice patients who had already treated a moderate or severe migraine headache with 100 mg sumatriptan 4 h earlier. Headache was relieved by the first sumatriptan dose in about 70% of patients, but the second dose did not produce significantly more relief than placebo, either in nonresponders or in the group as a whole, nor did it reduce other symptoms (photophobia, nausea, vomiting, etc,) at 8 h, or influence the incidence of headache recurrence. The drug was well-tolerated, and a further single dose was effective in treating recurrence after initial relief. A single 100 mg dose of sumatriptan is an effective acute treatment for migraine. A second dose should be reserved for treating headache recurrence.      

Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies?

This article reviews the pathophysiology and pharmacology of emesis in relation to migraine pathogenesis. Also, the place of antiemetic and gastrointestinal prokinetic agents in current and future acute migraine treatment strategies is reviewed. The mechanisms of action of current and novel acute migraine therapies are considered with respect to the neurogenic and vascular hypotheses. Control of migraine-associated nausea and vomiting is often achieved with the benzamide dopamine D₂ receptor antagonist metoclopramide. This drug also has 5HT₃ receptor antagonist activity and reproducibly stimulates gastric motility to increase the availability of orally administered drugs. Other antiemetic and gastroprokinetic agents with potential value for the treatment of migraine-associated nausea and vomiting could speed absorption of oral antimigraine therapies without central nervous system side effects. Domperidone, a dopamine D₂ receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide. Cisapride, a benzamide 5HT₄ receptor agonist gastrointestinal prokinetic drug, lacks dopamine antagonist activity. A controlled comparison of these agents as migraine co-therapies could provide information on the importance of peripheral and central mechanisms in migraine-associated nausea and vomiting and improve antimigraine treatment options.     

Detection of antibodies to Trypanosoma cruzi among blood donors in the southwestern and western United States. II. Evaluation of a supplemental enzyme immunoassay and radioimmunoprecipitation assay for confirmation of seroreactivity

BACKGROUND: Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic to Latin America and may be transmitted in the United States via blood donated by infected immigrants. Blood- borne pathogens such as T. cruzi require supplemental testing for confirmation of seroreactivity. STUDY DESIGN AND METHODS: A study was undertaken to determine an optimal scheme for confirmation of seroreactivity in repeatedly reactive samples identified by the Chagas antibody enzyme immunoassay (EIA). The procedure for initial confirmation involves three purified antigens coated onto three separate polystyrene beads and uses an EIA format. If the sample is reactive with two of three or three of three antigens, it is confirmed as seroreactive. If none or one of three beads is reactive, the sample is indeterminate and subjected to a radioimmunoprecipitation assay (RIPA). The RIPA must demonstrate characteristic bands at 32, 34, and 90 kDa. RESULTS: When tested with sera from persons with potentially cross-reactive diseases (n = 39) or against a presumed negative population from southeast Wisconsin (n = 289), the confirmatory EIA had a specificity of 100 percent. Sensitivity was 100 percent (28/28) with xenodiagnosis-positive sera and 97.6 percent (80/82) with chagasic sera from Latin America. The RIPA showed a specificity of 100 percent in EIA- nonreactive samples (n = 100) and a sensitivity of 100 percent with both xenodiagnosis-positive (28/28) and chagasic (82/82) sera. CONCLUSION: The confirmatory EIA and the RIPA together provide a highly specific and sensitive means of confirming seroreactivity for antibodies to T. cruzi.