Atheroablation with the Kensey catheter: a pathologic study

The mode of action of the Kensey catheter, a new atheroablation device, was investigated. Fresh above-the-knee amputated legs were used for recanalization of the superficial femoral artery. The variables used were identical to those of clinical trials, including a rotational speed of 50,000 rpm and an injection rate of 40 mL/min. The debris produced by the catheter was studied cytologically, and the arterial segments were examined histologically. The particle size in the debris ranged from 1 to 2,000 microns. The softer plaques produced a fine fibrin dust background with long strips of intima ranging from 10 to 2,000 microns. Complicated calcified plaques produced larger background material (10-120 microns) but smaller strips of intima (50-800 microns). Dissections and perforations occurred. Some of the debris produced by the atheroablation process was used to embolize a canine heart and kidney. Small focal infarctions were found in the heart, and large and multiple infarcts were seen in the kidney. In clinical studies the debris appears to be tolerated in the lower extremities. Its safety in the kidney and heart are questioned.     

Acute injury of the ligaments of the knee: magnetic resonance evaluation

Eleven acutely injured knees and 13 normal knees were examined by magnetic resonance imaging (MRI) to assess the value of this modality in detecting acute ligamentous injury of the knee. The presence of torn ligaments in the injured knees was determined by arthroscopy and/or arthrotomy in ten cases and clinical follow-up in one case. The anterior and posterior cruciate ligaments (ACL and PCL) were demonstrated by sagittal spin echo (SE) images through the intercondylar notch (TE = 30 ms; TR = 2,000 ms). The tibial and fibular collateral ligaments (TCL and FCL) were evaluated on coronal SE images (TE = 30 ms, TR = 200 or 530 ms; TE = 120 ms, TR = 2,000 or 2,120 ms). The ACL and PCL were considered torn on MR if they appeared disrupted or were not seen in their normal anatomical positions. The collateral ligaments were considered torn if abnormal high-intensity signal was noted in adjacent soft tissues on TE = 120 ms images or if disruption of a ligament was apparent. Eleven of 15 torn ligaments and 80 of 81 normal ligaments were correctly identified by these criteria. It is concluded that MR imaging may be useful in detecting acute injury of ligaments of the knee.     

CD47 agonist peptide PKHB1 induces immunogenic cell death in T‐cell acute lymphoblastic leukemia cells

T‐cell acute lymphoblastic leukemia (T‐ALL) has a poor prognosis derived from its genetic heterogeneity, which translates to a high chemoresistance. Recently, our workgroup designed thrombospondin‐1‐derived CD47 agonist peptides and demonstrated their ability to induce cell death in chronic lymphocytic leukemia. Encouraged by these promising results, we evaluated cell death induced by PKHB1 (the first‐described serum‐stable CD47‐agonist peptide) on CEM and MOLT‐4 human cell lines (T‐ALL) and on one T‐murine tumor lymphoblast cell‐line (L5178Y‐R), also assessing caspase and calcium dependency and mitochondrial membrane potential. Additionally, we evaluated selectivity for cancer cell lines by analyzing cell death and viability of human and murine non‐tumor cells after CD47 activation. In vivo, we determined that PKHB1‐treatment in mice bearing the L5178Y‐R cell line increased leukocyte cell count in peripheral blood and lymphoid organs while recruiting leukocytes to the tumor site. To analyze whether CD47 activation induced immunogenic cell death (ICD), we evaluated damage‐associated molecular patterns (DAMP) exposure (calreticulin, CRT) and release (ATP, heat shock proteins 70 and 90, high‐mobility group box 1, CRT). Furthermore, we gave prophylactic antitumor vaccination, determining immunological memory. Our data indicate that PKHB1 induces caspase‐independent and calcium‐dependent cell death in leukemic cells while sparing non‐tumor murine and human cells. Moreover, our results show that PKHB1 can induce ICD in leukemic cells as it induces CRT exposure and DAMP release in vitro, and prophylactic vaccinations inhibit tumor establishment in vivo. Together, our results improve the knowledge of CD47 agonist peptides potential as therapeutic tools to treat leukemia.     

HIV/AIDS selective infectivity–report of two peculiar cases

We report two peculiar cases that were observed in two communities of Anambra State, South East Nigeria. The first case was a woman of 44 with a history of blood transfusion from a donor of questionable HIV status. A pint of blood was transfused in a private Hospital on the 15 th January, 2000. She has had no form of antiviral therapy until 22nd April, 2008 when she came to the hospital for routine medical check up. Her HIV result came out confirmed positive while that of her husband came out negative. She has had active sexual life with her husband in the previous eight years as they have had some difficulties in getting their desired extra two children having earlier gotten a boy and a girl. The second case involves a family of six. A couple with four children of ages about 6 months, 2 years, 3 years and 5 years. The youngest, a female presented with fever and multiple lymphadenopathy. She tested HIV positive and so was her mother and her second sibling. But her father and two other siblings remained negative at post three and six months intervals from their very first test date with us. These reported cases appear to go contrary to earlier formed opinion on HIV transmission. We support the opinion on a naturally, occurring substance, APOBEC3G which possibly confers permanent immunity against the HIV virus. We recommend clinical trials of the characterized APOBEC3G as a vaccine for non HIV infected persons of all ages and to people living with as a therapeutic drug.     

The associations of parity and maternal age with small-for-gestational-age,preterm, and neonatal and infant mortality: a meta-analysis

Background

Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).

Methods

Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.

Results

Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.

Conclusions

Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.

Funding

Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

     

Oral fungal and bacterial infections in HIV-infected individuals: an overview in Africa

Oral opportunistic infections developing secondary to human immunodeficiency virus (HIV) infection have been reported from the early days of the epidemic and have been classified by both the EC-Clearinghouse and the World Health Organisation (WHO). Among the fungal infections, oral candidiasis, presenting in African HIV-infected patients has been sporadically documented. We review the literature with respect to candidal carriage, oral candidiasis prevalence and the predictive value of oral candidiasis for a diagnosis of underlying HIV disease in African HIV-infected patients. The use of oral candidiasis as a marker of disease progression, the species of yeasts isolated from the oral cavity in Africa and the resistance of the yeasts to antifungal agents and treatment regimens are discussed. Orofacial lesions as manifestations of the systemic mycoses are rarely seen in isolation and few cases are reported in the literature from Africa. In spite of the high incidence of noma, tuberculosis, chronic osteomyelitis and syphilis in Africa, surprisingly there have been very few reported cases of the oral manifestations of these diseases in HIV-positive individuals. Orofacial disease in HIV-infected patients is associated with marked morbidity, which is compounded by malnutrition. The authors indicate specific research areas, initially directed at the most effective management strategies, which would complete data in this important area.     

De novo 16p13.11 microdeletion identified by high-resolution array CGH in a fetus with increased nuchal translucency

Objective  We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT).
Design  Case study.
Setting  Tertiary referral obstetrics unit.
Sample  Pregnant woman attended the antenatal clinic.
Methods  Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.
Main outcome measures  Detection of chromosomal abnormality.
Results  Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.
Conclusions  This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.