Oral miltefosine treatment in children with mild to moderate Indian visceral leishmaniasis

BACKGROUND: Miltefosine is the first oral drug with demonstrable success in treating visceral leishmaniasis in adults. Because approximately one-half of the visceral leishmaniasis patients worldwide are children, we performed a Phase I/II dose ranging study in the pediatric population in India. METHODS: Thirty-nine (39) children (defined as < 12 years of age) with visceral leishmaniasis demonstrated by parasites in splenic aspirates, were treated with oral miltefosine daily for 28 days: 21 patients received 1.5 mg/kg/day (Group A); and 18 patients received 2.5 mg/kg/day (Group B). About one-half of these children had failed prior antileishmanial treatment. RESULTS: All patients were parasitologically negative and symptomatically improved by the end of therapy on Day 28 of therapy; the initial parasitologic cure rate was 100%. Two patients in each treatment group relapsed with fever, splenomegaly and parasite-positive splenic aspirates by the end of the 6-month follow-up. The per protocol final clinical cure rate was 19 of 21 = 90% in Group A and 15 of 17 = 88% in Group B. Miltefosine was well-tolerated. As per the adult experience, gastrointestinal adverse events were seen: 33 and 39% of children experienced vomiting and 5 and 17% experienced diarrhea in Groups A and B, respectively, but all episodes were mild to moderate in severity and commonly lasted <1 day without symptomatic treatment. CONCLUSION: Oral miltefosine was safe and approximately 90% effective in this initial clinical trial of childhood visceral leishmaniasis.     

Acute hepatitis A despite regular vaccination against hepatitis A and B

HISTORY AND CLINICAL FINDINGS: A 59-year-old woman, her 55-year-old husband, their daughter, son and the son's girlfriend were admitted with acute icterus 32-34 days after a dinner when they had eaten shellfish. The father had been immunised against hepatitis A and B with a combined vaccine (Twinrix(R)) and had completed the full vaccination schedule 47 days prior to this meal. His wife had been incompletely vaccinated with one injection 16 days prior and a second injection 13 days after the dinner. The other three participants of the dinner had not been immunised. The incubation time and clinical picture did not differ between the vaccinated and non-vaccinated patients. INVESTIGATIONS, TREATMENT AND COURSE: All 5 patients were anti-HAV IgM-positive, had high serum aminotransferases and serum bilirubin. All patients had an uneventful recovery. There was no difference in the clinical course between the vaccinated and non-vaccinated patients. CONCLUSION: Combined hepatitis A/B vaccination according to the recommended schedule does not guarantee protection in elderly persons. Before travelling in endemic areas, their antibody response after basic hepatitis A/B vaccination should be determined.     

Drug interaction of spirapril hydrochloride monohydrate and hydrochlorothiazide. A clinical study to compare the pharmacokinetics after administration of spirapril hydrochloride monohydrate tablets,hydrochlorothiazide tablets and fixed combination bi-layer tablets

The potential influence of concomitantly administered hydrochlorothiazide (CAS 58-93-5) on the pharmacokinetics of spirapril (CAS 94841-17-5)/spiraprilat (CAS 83602-05-5) and of concomitantly administered spirapril on the pharmacokinetics of hydrochlorothiazide was investigated in an open, randomised, 3-way crossover study in 12 healthy male subjects. The test drug was a newly developed bi-layer tablet containing a fixed combination of spirapril hydrochloride monohydrate and hydrochlorothiazide (Quadroplus). The reference formulations were tablets containing solely spirapril hydrochloride monohydrate (Quadropril) or hydrochlorothiazide (produced exclusively for study medication). For spirapril, spiraprilat and hydrochlorothiazide the 90% confidence intervals of the AUC(0-infinity) as a measure for the extent of absorption were entirely included within the equivalence range of 0.8 to 1.25 and the 90% confidence intervals of the Cmax as a measure for the rate of absorption were entirely included within the extended equivalence range of 0.7 to 1.43. Therefore, bioequivalence was concluded for the test and reference formulations. The results suggest that hydrochlorothiazide does not interact in the fixed combination with the pharmacokinetics of spirapril and vice versa.     

Cell detachment method using shock-wave-induced cavitation

The detachment of adherent HeLa cells from a substrate after the interaction with a shock wave is analyzed. Cavitation bubbles are formed in the trailing, negative pressure cycle following the shock front. We find that the regions of cell detachment are strongly correlated with spatial presence of cavitation bubbles. It is shown that the cavitation bubble collapse generates a transient high-speed flow along the substrate surface leading to rapid detachment of the cells. Flow trajectories are reconstructed from the video recordings using robust image-processing methods. From these trajectories, an estimate of the shear stress acting on the cells is obtained and the area of detachment is estimated with a kinetic model. Furthermore, it is suggested that the application of shock waves extends the known methods of cell detachment with the ability to control the process in space and time. (E-mail: c.d.ohl@tn.utwente.nl)     

Metabolic rate and O2 consumption in newborns during different states of vigilance.

In 135 asymptomatic newborn infants, 1--53 days of age, body weight 1,820--4,120 g, indirect calometry was performed. According to the state of wakefulness the infants showed during the testing procedure, they were divided into four groups of vigilance (V1--V4). Metabolic rate and oxygen consumption showed similar results between groups V1, V2 and V3 (deep sleep; REM sleep; wakefulness with no muscular activity). V4 infants (with muscular activity) had a higher metabolic rate and O2 consumption. Correlation between metabolic rate and body surface area is similar in V2 and V3 but shows a steeper slope in the V1 group. It is speculated that central regulatory mechanisms may account for this difference.     

Percutaneous drainage access: a simplified coaxial technique

We describe an access technique that we have used in 150 nephrostomy and biliary drainage procedures and for access to some abscesses and viscera. The system provides safe coaxial access with a 22-gauge removable hub needle, which then acts as a guide wire and is replaced by an 18-gauge cannula. A major advantage is that only one guide wire is used (0.038-inch) for the entire drainage procedure. No significant complications have occurred to date with this method.     

人工耳蜗术后早期电极阻抗变化规律的研究

目的探讨人工耳蜗植入术后电极阻抗值与电极位置的关系及电极阻抗的总体变化特点。方法对2018年9月至2019年9月在中国科学技术大学附属第一医院行人工耳蜗植入术的患者100例(100耳),于术中、术后3天、术后1月(开机时)及术后3月测试电极阻抗值,分析结果。结果①100例患者总体及不同分区电极阻抗均值术中时最低,开机时(术后1月)升至最高,开机后(术后3月)呈降低趋势,三个时间点均值比较,差异均有统计学意义(P<0.05);②在术中、术后1月与术后3月均为蜗顶区电极阻抗值最高,与蜗中区及蜗底区比较,差异均有统计学意义(P<0.05);③蜗顶区1号和2号电极的阻抗值在术后3天即已升高,与术中差异有统计学意义(P<0.05)。结论电极阻抗值总体变化趋势为术中最低,术后1月(开机时)升至最高,开机后下降。蜗顶区阻抗值术后3天即明显升高且始终较蜗中区和蜗底区高。     

Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC‐US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30–65 years with ASC‐US during 2005–2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV‐Proofer (n = 3,226) or for high‐risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n = 9,405) or Linear Array HPV‐Genotyping test (LA) (n = 1,533). Women with ≥1 subsequent examination in the register (n = 13,729) were followed for up to 9.5 years for high‐grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow‐up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8–89.6%] versus 59.3% [95% CI: 58.1–60.4%]) and higher positive predictive value (PPV) (38.2% [95% CI: 33.8%–43.1%] versus 19.5% [95% CI: 17.8–20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3–74.5%] versus 97.0% [95% CI: 95.5–98.4%]), and women testing mRNA negative had higher 3‐year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2–4.2%] versus 0.5% [95% CI: 0.3–0.7%]). Patterns were similar after 18 months and 5 years'; follow‐up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC‐US triage due to its low sensitivity and the substantial risk for precancer following a negative test.