A giant renal artery aneurysm diagnosed post partum

We report a case of a 5.8 cm. right renal artery aneurysm diagnosed intact 8 weeks post partum. Rupture of a renal arterial aneurysm during pregnancy is a rare but well described catastrophic event. There are no previous reports of an intact renal artery aneurysm diagnosed either ante partum or post partum. To our knowledge, this also represents the largest reported renal artery aneurysm. The aneurysm was repaired successfully with kidney salvage and closure of the fistulous connection to the renal vein.     

Investigating the role of heparin sulfate proteoglycans in hereditary multiple exostoses (HME) tumourigenesis

Introduction Heparin sulfate (HS) has long been implicated in the bone deformity hereditary multiple exostoses (HME), and it is now clear that HME is associated with mutations in the HS biosynthetic genes EXT1 and EXT2. Interestingly, HME is also associated with an increased risk of chondro‐ and osteo‐sarcomas. Methods and results Preliminary analysis of GAG samples purified from fibroblasts of both HME and isolated non‐HME exostoses patients reveal a dramatic shift in the ratio of CS : HS, with the HME and isolated cases having a much higher proportion of CS relative to normal controls. This is true in the case of both shed and cell surface material but is far more extreme in the latter, with the HS reducing from approximately 45% in the controls to less than 10% in HME patients. Initial analysis also reveals shortened chain length within these samples; indeed they often have two populations of chains present. Simple analysis of the total disaccharide composition of these samples demonstrates no significant differences against controls. However, detailed analysis of the subpopulations of chains (as determined by chain length) within these samples as well as cartilaginous samples from exostoses patients may provide further insight into the changes that occur within the biosynthetic pathway following disrupted EXT function. We are also carrying out immunocytochemistry with a variety of HS‐specific antibodies with the aim to further investigate normal HS structure and localization. This is being carried out on human primary chondrocytes isolated from normal patients and also adult mesenchymal stem cells as they undergo differentiation into chondrocytes. HS has been identified in both these cell types, and it is hoped that the manipulation of these cells through RNAi of different enzymes of the HS biosynthetic pathway will provide a suitable model for studying what changes may occur in cellular HS structures over the initial differentiation process in the growth plate. Discussion Together, these investigations should provide a good model to allow us to determine the role of HS in chondrocyte differentiation and maturation in both normal and diseased states.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

Toxicity but not arthritogenicity of Mycoplasma arthritidis for mice associates with the haplotype expressed at the major histocompatibility complex.

The use of inbred and congenic mouse strains established that toxicity and death induced by Mycoplasma arthritidis associates with the haplotype expressed at the murine major histocompatibility complex. Mice bearing H-2k and H-2d are susceptible, whereas those bearing H-2b are much more resistant. Mice susceptible to toxicity exhibited massive peritoneal adhesions and a decreased ability to clear organisms from the peripheral circulation. However, the severity of acute arthritis developing over a 3-month period was not statistically related to the haplotype expressed at the major histocompatibility complex. Lymphocyte activation in vitro by a soluble T-cell mitogen is also dependent on a similar haplotype expression.     

Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system

Recently, in-vitro maturation (IVM) of immature human oocytes recovered from non-stimulated follicles has been applied in the treatment of infertility. However, in previous reports, very few embryos cultured in conventional medium have reached the expanded blastocyst stage following in-vitro maturation and fertilization (IVM/IVF). The objective of this study was to investigate whether the developmental competence of human embryos following IVM/IVF could be enhanced by the use of a human ampullary cell co-culture system. Immature human oocytes were aspirated from small follicles at Caesarean section and then cultured in medium containing human menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes were randomly cultured either in conventional culture medium alone or in the co-culture system. Of 48 embryos cultured in conventional medium alone, all arrested at the 2-16- cell stage on day 3 after insemination. Of 46 embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at the 2-16-cell stage. Six embryos (13%) developed to the morula stage. Fourteen embryos (30.4%) developed to expanded blastocysts and two blastocysts were hatching on day 7 after insemination. We conclude that co-culture significantly enhances the development of blastocysts in embryos resulting from IVM/IVF.