Fetal bovine serum‐free culture of endothelial progenitor cells—progress and challenges

Two decades after the first report on endothelial progenitor cells (EPC), their key role in postnatal vasculogenesis and vascular repair is well established. The therapeutic potential of EPC and their growing use in clinical trials calls for the development of more robust, reproducible, and safer methods for the in vitro expansion and maintenance of these cells. Despite many limitations associated with its usage, fetal bovine serum (FBS) is still widely applied as a cell culture supplement. Although different approaches aiming at establishing FBS‐free culture have been developed for many cell types, adequate solutions for endothelial cells, and for EPC in particular, are still scarce, possibly due to the multiple challenges that have to be faced when culturing these cells. In this review, we provide a brief overview on the therapeutic relevance of EPC and critically analyse the available literature on FBS‐free endothelial cell culture methods, including xeno‐free, serum‐free, and chemically defined systems.     

Prolactin responses to phenylalanine and tyrosine in phenylketonuria.

In normal subjects, ingestion of tyrosine or phenylalanine stimulates prolactin (PRL) secretion. In patients with phenylketonuria (PKU), we found normal PRL responses to phenylalanine, demonstrating that conversion of phenylalanine to tyrosine is not necessary for PRL stimulation. PKU patients also showed greater PRL responses to tyrosine during dietary phenylalanine restriction than when consuming an unrestricted diet; this finding is consistent with inhibition by phenylalanine of tyrosine transport across the blood-brain barrier. Such competitive inhibition of a normal brain function may serve as a model for some of the neurotoxic effects of phenylalanine in PKU.     

Identifying corpus luteum rupture as the culprit for haemoperitoneum

Corpus luteum rupture presenting as acute abdomen is an underdiagnosed condition. Though a self-limiting entity, its differentiation from other causes is essential to prevent unnecessary surgical procedures. The radiologist should be aware of the possibility of a ruptured haemorrhagic ovarian cyst in a female of reproductive age group presenting with pelvic pain and a large amount of haemorrhagic ascites. Imaging characteristically reveals a thick-walled cystic structure in the adnexa with internal echoes, focal discontinuity or irregularity of its wall with haemoperitoneum. While sonography is usually indicative of corpus luteum rupture, cross-sectional imaging (CT/MRI) can be used to confirm the diagnosis.     

Outcome of low level lasers versus ultrasonic therapy in de Quervain's tenosynovitis

Background:

de Quervain''s tenosynovitis is an inflammation of abductor pollicis longus (APL) and extensor pollicis brevis (EPB) muscle tendon sheaths at the level of radial styloid process. Its conservative management includes nonsteroidal anti-inflammatory drugs, wrist and thumb immobilization, ultrasonic therapy (US Th.) and low level laser therapy (LLLT). Literature is scanty on comparative efficacy of US Th. and LLLT for its management. This prospective study evaluates outcome of US Th. versus LLLT in de Quervain''s disease.

Materials and Methods:

Thirty patients clinically diagnosed de Quervains tenosynovitis were included in the study and randomly assigned to two groups. The average age was 36 years (range: 21-45 years). One group was given LLLT and the other US Th. for a total of 7 exposures on alternate days. The clinical criteria used were Finkelstein''s test, tenderness over radial styloid (Ritchie''s tenderness scale), grip strength, pain (visual analog scale [VAS]) and radiological criteria was ultrasonographic assessment of change in thickness of APL and EPB tendon sheath. They were measured before commencement and at the end of seven sessions of therapy, as per standard procedure.

Results:

Significant improvement was seen within both groups in the following outcome measures assessed: Ritchie''s tenderness scale, grip strength and VAS. Finkelstein''s test was not significantly improved in either groups. Ultrasonographic measurement of tendon sheath diameters, the mediolateral (ML), and anteroposterior (AP) diameters was not found to be significantly different in the US Th. group and the laser therapy group after treatment. On comparing both the groups, no statistically significant difference was found. However, looking at the mean values, the grip strength and VAS showed better improvement in the US Th. group as compared to the laser therapy group.     

Return to sporting activity after Birmingham hip resurfacing arthroplasty: Mid term results

Background:

Hip resurfacing arthroplasty (HRA) is primarily indicated for young, active patients with disabling coxarthrosis who wish to remain active and return to sports after surgery. Relatively few prospective studies have assessed return to sporting activity and impact of gender and age on this.

Materials and Methods:

Seventy-nine consecutive patients treated with HRA were included. Patients were reviewed clinically and radiologically. Function was assessed using the modified University of California Los Angeles (UCLA) activity score. The Oxford, Harris and WOMAC hip scores were calculated.

Results:

Average age at the time of surgery was 54.9 years (range 34.5–73.6 years). Average preoperative and postoperative UCLA scores were 4 and 7.6 respectively. Patients were involved in 2 (0–4) sporting activities preoperatively and 2 (0–5) postoperatively. Preoperative and postoperative Oxford Hip Scores, Harris Hip Score and WOMAC scores were 40, 46 and 51 and 16, 94 and 3 respectively (P < 0.0001). Patients returned to sports at an average of 3 months postoperatively.

Conclusion:

Patients were able to return to sports by 3 months and perform the same number of activities at preoperative intensity. Activity levels are maintained up to the medium term with few complications.     

Mortality in Israeli Jewish patients with Type 1 (insulin-dependent) diabetes mellitus diagnosed prior to 18 years of age: a population based study

Summary A total of 614 Jewish patients under the age of 18 with Type 1 (insulin-dependent) diabetes mellitus, diagnosed in Israel during the period 1 January 1965 to 31 December 1979, were identified by exhaustive screening of all possible sources. Mortality experience of this cohort was updated to 31 March 1988 through the Central Population Registry and 14 deaths were identified. The ascertainment rate for diagnosed cases as well as for deaths is estimated at about 95%. There was a significantly higher (p<0.001) by 3.2-fold excess mortality relative to the age and sex-adjusted mortality as expected the general Jewish population in Israel. This excess was due to three cause-of-death categories: diabetic ketoacidosis (n = 3; p<0.001), cardiovascular diseases (n – 3; p<0.001) and infections (n = 2; p = 0.03). The rate of malignancies (n = 2), external causes (n = 3) and other general causes (n = 1) did not differ significantly from that expected. During the first 15 years of the disease cumulative mortality resembled that of the general population, with a subsequent steep increase so that by 20 years disease duration, the rate was four-fold higher than expected. This mortality pattern was similar irrespective of age at onset, sex and ethnic group (Ashkenazi vs non-Ashkenazi Jews). A factor contributing to the lack of increase in mortality rate in the first 15 years of Type 1 diabetes may be the comprehensive multidisciplinary treatment approach employed for most juvenile diabetic patients in Israel leading to early referral and an overall better metabolic control.The study was supported by a grant from the NIH — National Institute of Diabetes and Digestive and Kidney Diseases, No. 5 RO1 DK3905-04.     

Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease

CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H- RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.