Cortisol daily rhythm in saliva of healthy school children

Aim : To investigate the daily rhythm of cortisol levels in saliva of school children. Subjects and methods : Probands (10–14 years, both genders) were recruited via personal contact and school visits. Exclusion criteria included hormonal and dental treatments during the trial, pharmaceuticals containing cortisol, or poor oral hygiene. Each volunteer collected 20 saliva samples during one day at defined times starting immediately after waking up and ending at night. Additionally, they completed a sampling diary. Saliva samples were analysed in duplicate using a commercial cortisol luminescence kit. Results : Cortisol concentration in saliva followed a daily rhythm. Within 20 minutes after waking up cortisol reached the highest level of 9.69 (±3.89) nmol/L. After 90 minutes cortisol concentration decreased linearly by 50% and stagnated at 4.14 (±1.93) nmol/L for 3 to 8 hours. Thereafter, levels decreased gradually reaching almost zero after 14 hours. Overall, no gender‐specific differences in saliva cortisol levels were observed except for 3 time points: 3, 10 and 11 hours after waking. Conclusion : This study establishes guidelines for a normal secretion pattern, plus explores pain level measurements and their correlation to saliva cortisol levels in this age group.     

The wisdom behind third molar extractions

The literature pertaining to the extraction of third molars is extensive. There is a large individual variation and a multitude of practitioners’ beliefs and biases relating to the extraction of especially asymptomatic and pathology free third molars. With the current emphasis in dentistry being placed on clinicians to make evidence‐based decisions, the routine removal of third molars has been re‐assessed and questioned. The purpose of this paper was to evaluate past and present knowledge of third molar extractions and relate it to logical considerations relevant to science and the evidence‐based decision‐making process. This paper endeavours to encourage and stimulate clinicians to re‐evaluate their views on third molar extractions based on suggested guidelines and current evidence.     

Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis

AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.     

致中国西宁市医师

2009年6月,美国哈佛大学医学院神经内科Caplan教授参加了在北京召开的天坛国际脑血管病会议。会后Caplan教授应邀前往青海省西宁市,参观了青海省人民医院。访问结束后,Caplan教授为我们留下了几段话,耐人寻味,本期一并刊出,以飨读者。     

The mani left ti without a trace: A case study of aphasic processing of empty categories

We present the case of an aphasic patient who shows a selective impairment in interpreting syntactic structures on a test of sentence comprehension involving object manipulation. KG makes errors in assigning the antecedents of phonologically empty NPs called traces (Chomsky, 1982 a,b) in sentences like John seems to Bill to be shaving. He is significantly better at choosing the correct antecedent of another type of empty NP, namely subject- and object- controlled PRO (John persuaded Bill to shave, John promised Bill to shave). He has no trouble choosing the correct antecedents of overt pronouns and reflexives and shows no difficulty with syntactic structures that do not contain an empty category. His difficulty with trace is apparent in sentences which have a certain degree of complexity. He also misassigns the antecedent of subject-controlled PRO under one condition: when an overt reflexive or pronoun has PRO as its antecedent (John promised Bill to shave himself). The pattern of impairment suggests that KG cannot utilise one part of a parser/interpreter specifically devoted to the identification and co-indexation of empty categories when other processing demands are high, due to a specific impairment to this component, a capacity limitation, or both. The data support a theory of syntactic structure and parsing which incorporates different types of empty categories.     

Volatile nitrosamines and tobacco-specific nitrosamines in the smoke of Thai cigarettes: a risk factor for lung cancer and a suspected risk factor for liver cancer in Thailand

In Thailand, smoking of commercial cigarettes and of handmadecigarettes has drastically increased in recent decades. Cancerof the lung and of the upper aerodigestive tract have also increasedin Thailand as they have in many other countries. It is ourworking hypothesis that the increase of primary cancer of theliver, especially of cholangiocarcinoma in the north-easternprovinces of Thailand is associated with the use of tobaccoin men infested with the liver fluke Opisthorchis viverrini(OV). Bioassays have shown that volatile nitrosamines and tobacco-specificnitrosamines induce cholangiocarcinoma in laboratory animalsand that the hepatocarcinogenic action of nitrosodimethylaminein hamsters is significantly increased by infestation with theliver fluke OV. The endogenous formation of nitrosamines issignificantly increased by OV infestation. This report presentsanalytical data on the concentration of volatile nitrosaminesand tobacco-specific nitrosamines in mainstream smoke of nineleading brands of commercially produced Thai cigarettes whichrepresent ~85% of the market share in Thailand. Observed ranges(ng/cigarette) were 8.5–31.9 for nitrosodimethylamine,8.8–49.6 for nitrosopyrrolidine and 4.2–18.9 fornitrosodi-n-butylamine. These values are exceptionally highcompared with the smoke of light and blended cigarettes fromNorth America and Western Europe. Among the tobacco-specificnitrosamines, the range was 28–730 for nitrosonornicotineand 16–370 for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.There was a correla-tion between volatile and tobacco-specificnitrosamines, and tar and nicotine deliveries in the mainstreamsmoke. The analytical data are in line with the rate for lungcancer and support our working hypothesis that nitrosamines,and especially the tobacco-specific nitrosamines, are associatedwith the increased risk for primary liver cancer among thoseThai people who smoke cigarettes and also carry OV infestation.     

The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit

Thrombopoietin (c-Mpl ligand) has recently been purified and is considered to be the humoral regulator of platelet production. To see whether this molecule possessed the physiologic characteristics necessary to mediate the feed-back loop between blood platelets and the bone marrow megakaryocytes, we determined the relationship between blood levels of thrombopoietin and changes in the circulating platelet mass. We developed a model of nonimmune thrombocytopenia in rabbits by the subcutaneous administration of busulfan. Compared with pretreatment plasma, plasma taken from all thrombocytopenic rabbits at their platelet nadir contained increased amounts of thrombopoietin. All of this activity was neutralized by soluble c-Mpl receptor. We subsequently measured the level of thrombopoietin in the circulation over the entire time course after the administration of busulfan. As the platelet mass declined, levels of thrombopoietin increased inversely and proportionally and peaked during the platelet nadir. With return of the platelet mass toward normal, thrombopoietin levels decreased accordingly. When platelets were transfused into thrombocytopenic rabbits near the time of their platelet count nadir, the elevated levels of thrombopoietin decreased. In addition, platelets were observed to remove thrombopoietin from thrombocytopenic plasma in vitro. These results confirm that thrombopoietin is the humoral mediator of megakaryocytopoiesis and suggest that the platelet mass may directly play a role in regulating the circulating levels of this factor.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

The value of flow cytometric analysis of platelet glycoprotein expression of CD34+ cells measured under conditions that prevent P- selectin-mediated binding of platelets

In the present study, we show by adhesion assays and ultrastructural studies that platelets can bind to CD34+ cells from human blood and bone marrow and that this interaction interferes with the accurate detection of endogenously expressed platelet glycoproteins (GPs). The interaction between these cells was found to be reversible, dependent on divalent cations, and mediated by P-selectin. Enzymatic characterization showed the involvement of sialic acid residues, protein(s). The demonstration of mRNA for the P-selectin glycoprotein ligand 1 (PSGL-1) in the CD34+ cells by polymerase chain reaction (PCR) analysis suggests that this molecule is present in these cells. Under conditions that prevent platelet adhesion, a small but distinct subpopulation of CD34+ cells diffusely expressed the platelet GPIIb/IIIa complex. These cells were visualized by immunochemical studies. Furthermore, synthesis of mRNA for GPIIb and GPIIIa by CD34+ cells was shown using PCR analysis. The semiquantitative PCR results show relatively higher amounts of GPIIb mRNA than of PF4 mRNA in CD34+CD41+ cells in comparison with this ratio in platelets. This finding is a strong indication that the PCR results are not caused by contaminating adhering platelets. MoAbs against GPIa GPIb alpha, GPV, P- selectin, and the alpha-chain of the vitronectin receptor did not react with CD34+ cells. The number of CD34+ cells expressing GPIIb/IIIa present in peripheral blood stem cell (PBSC) transplants was determined and was correlated with platelet recovery after intensive chemotherapy in 27 patients. The number of CD34+CD41+ cells correlated significantly better with the time of platelet recovery after PBSC transplantation (r = .83, P = .04) than did the total number of CD34+ cells (r = .55). Statistical analysis produced a threshold value for rapid platelet recovery of 0.34 x 10(6) CD34+CD41+ cells/kg. This study suggests that if performed in the presence of EDTA the flow cytometric measurement of GPIIb/IIIa on CD34+ cells provides the most accurate indication of the platelet reconstitutive capacity of the PBSC transplant.