不同HIV蛋白酶抑制剂对鼠胰岛素瘤细胞功能的影响

目的：探讨不同HIV蛋白酶抑制剂对胰岛beta-细胞功能的影响。方珐：体外观察不同浓度ritonavir或amprenavir干预48h对鼠胰岛素瘤INS-1细胞葡萄糖刺激的胰岛素释放速率的影响，胰岛素测定采用ELISA法，并用细胞内DNA含量标准化。用苔盘蓝染色细胞计数、MTT试验评估ritonavir或amprenavir对INS-1细胞活力的影响。结果：Ritonavir治疗可以显著降低基础胰岛素分泌速率及葡萄糖刺激的胰岛素释放速率，并呈剂量依赖关系（r分别为-0．861，-0．839，均P〈0．01）。10μmol／L ritonavir分别降低基础胰岛素分泌和葡萄糖刺激的胰岛素释放达46％和47％。Amprenavir对胰岛素释放功能没有影响。结论：不同HIV蛋白酶抑制剂对胰岛beta-细胞功能的影响不同。     

Disturbance caused by varying propagation delay in non-occluding hearing aid fittings

The disturbance caused by various short propagation delays to the perception of external sounds and own voice for a non-occluding hearing aid was investigated. Ten normal-hearing and 10 mildly hearing-impaired individuals listened to external sounds and their own voice while wearing non-occluding devices providing 10dB of linear gain. Participants rated the disturbance caused by delays of 2, 4 and 10ms to music, running speech, and their own voices. The results indicated greater disturbance for the longest delay for both subject groups when judging own voice, with the ratings of the hearing-impaired participants being lowest. Normal-hearing participants also judged the 10-ms delay as more disturbing for the external sounds. Owing to the listening conditions with constant gain from 800Hz and above, the results apply directly only to this experiment. Disturbance ratings for all delays were low, which suggests that any of those tested would be acceptable for this application.     

A non‐fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient

Post‐transplant infections in allogeneic haematopoietic cell transplant (allo‐HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non‐fatal case of Lichtheimia corymbifera infection in an allo‐HCT recipient.     

Individualized 6‐mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia: A NOPHO randomized controlled trial

Objectives

This randomized controlled trial tested the hypothesis that children with non‐high‐risk acute lymphoblastic leukemia could benefit from individualized 6‐mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation minimal residual disease (MRD) positivity and event‐free survival.

Methods

392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6‐mercaptopurine (25 mg/m²/day) from days 30 to 85, while the experimental arm received stepwise increments of additional 25 mg/m²/day beginning on days 50 and/or 71 unless dose‐limiting myelosuppression had occurred.

Results

In the experimental arm, 166 patients (42%) received one dose increment, and 62 (16%) received two. Fifty‐seven of 387 (15%) patients in the experimental arm were MRD positive at end of consolidation vs 77 of 389 (20%) in the control arm (P = .08). Five‐year probability of event‐free survival was 0.89 (95% CI: 0.85‐0.93) in the experimental arm vs 0.93 (0.90‐0.96) in the control arm (P = .13). The median accumulated length of 6‐mercaptopurine treatment interruptions was 7 (IQR 2‐12) in the experimental arm vs 4 (IQR 0‐10) in the control arm (P = .002).

Conclusion

This study found no benefit from individualized 6‐mercaptopurine increments compared to standard therapy.     

Left Ventricular Morphology of the Giraffe Heart Examined by Stereological Methods

The giraffe heart has a relative mass similar to other mammals, but generates twice the blood pressure to overcome the gravitational challenge of perfusing the cerebral circulation. To provide insight as to how the giraffe left ventricle (LV) is structurally adapted to tackle such a high afterload, we performed a quantitative structural study of the LV myocardium in young and adult giraffe hearts. Tissue samples were collected from young and adult giraffe LV. Design‐based stereology was used to obtain unbiased estimates of numbers and sizes of cardiomyocytes, nuclei and capillaries. The numerical density of myocyte nuclei was 120 × 10³ mm^?3 in the adult and 504 × 10³ mm^?3 in the young LV. The total number (N) of myocyte nuclei was 1.3 × 10¹¹ in the adult LV and 4.9 × 10¹⁰ in the young LV. In the adult LV the volume per myocyte was 39.5 × 10³ µm³ and the number of nuclei per myocyte was 4.2. The numerical density of myocytes was 24.1 × 10⁶ cm^?3 and the capillary volume fraction of the adult giraffe ventricle was 0.054. The significantly higher total number of myocyte nuclei in the adult LV, the high density of myocyte nuclei in the LV, and the number of nuclei per myocyte (which was unusually high compared to other mammalian, including human data), all suggest the presence of myocyte proliferation during growth of the animal to increase wall thickness and normalize LV wall tension as the neck lengthens and the need for higher blood pressure ensues. Anat Rec, 296:611–621, 2013. © 2013 Wiley Periodicals, Inc.     

Plasma N-terminal Pro-atrial Natriuretic Peptide Predicts Death after Premature Myocardial Infarction,but not as well as Radionuclide Ejection Fraction. A Ten-year Follow-up Study

Objective –To assess N-terminal pro-atrial peptide (N-ANP) as a predictor of total and cardiac death in patients with previous premature myocardial infarction (MI). Design –In this prospective cohort study, we measured plasma N-ANP by ELIZA assays and ejection fraction (EF) by radionuclide ventriculography in a cohort of 247 patients (193 men and 54 women) who had had MI at a relatively young age (males: first MI at age &#104 55; females &#104 60). Results –After 10 years 44 patients had died, 36 from cardiac causes. After using a stepwise procedure to adjust for other prognostic factors (i.e. plasma total homocysteine (tHcy), C-reactive protein and age), the relative risk (RR) was 2.00 (95% confidence interval (CI) 1.05-3.80) ( p = 0.03) for death of all causes and 2.32 (95% CI 1.19-4.55) ( p = 0.01) for cardiac death when the top quartile was compared to the three lower quartiles of N-ANP. When radionuclide EF entered the Cox model, N-ANP became insignificant as a predictor of mortality. Conclusion –N-ANP was a significant predictor of total death and cardiac death in young survivors of MI, but radionuclide EF was a more independent prognostic variable.     

Ready for action: a role for the human midbrain in responding to infant vocalizations

Infant vocalizations are among the most biologically salient sounds in the environment and can draw the listener to the infant rapidly in both times of distress and joy. A region of the midbrain, the periaqueductal gray (PAG), has long been implicated in the control of urgent, survival-related behaviours. To test for PAG involvement in the processing of infant vocalizations, we recorded local field potentials from macroelectrodes implanted in this region in four adults who had undergone deep brain stimulation. We found a significant difference occurring as early as 49 ms after hearing a sound in activity recorded from the PAG in response to infant vocalizations compared with constructed control sounds and adult and animal affective vocalizations. This difference was not present in recordings from thalamic electrodes implanted in three of the patients. Time frequency analyses revealed distinct patterns of activity in the PAG for infant vocalisations, constructed control sounds and adult and animal vocalisations. These results suggest that human infant vocalizations can be discriminated from other emotional or acoustically similar sounds early in the auditory pathway. We propose that this specific, rapid activity in response to infant vocalizations may reflect the initiation of a state of heightened alertness necessary to instigate protective caregiving.