Y chromosome microdeletions in azoospermic patients with Klinefelter＇s syndrome

Aim： To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter＇s syndrome （KFS）. Methods： Blood and semen samples were collected from azoospermic patients with KFS （n = 14） and a control group of men of proven fertility （n = 13）. Semen analysis was done according to World Health Organization （WHO） guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization （FISH） and measurement of plasma follicle stimulating hormone （FSH） by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction （PCR） of 16 sequence tagged sites （STS） and three genes （DFFRY, XKRY and RBM1 Y） was performed on isolated genomic DNA. Testicular fine needle aspiration cytology （FNAC） was done in selected cases. Results： Y chromosome microdeletions spanning the azoospermia factor （AZF）a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. Conclusion： Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques. （Asian JAndrol 2006 Jan; 8： 81-88）     

Fluid resuscitation in major burns

BACKGROUND: The Parkland formula is established as the "gold standard" for initial fluid resuscitation for major burns. The purpose of this study was to review our fluid resuscitation practice for major burns to determine whether anecdotal observations of significant variations from the Parkland formula were wide spread and whether any difference could be used as a basis for a revision of fluid resuscitation in major burns. METHODS: A retrospective review of 127 presentations to The Alfred Burns Unit with total body surface area (TBSA) affected > or =15% was conducted. A retrospective review of the resuscitation data from these patients was compared with the Parkland formula as well as other studies. RESULTS: A total of 49 patients with complete data on fluid administration and uncomplicated burns were included in the analysis. Significantly larger volumes of fluid (5.58 mL/kg per %TBSA) were given to these patients in the first 24 h than predicted by the Parkland formula. Mean arterial pressure, pulse rate and urine output were at satisfactory levels. Clinically evident complications from fluid administration were minimal. Mortality was similar to that in other centres. CONCLUSION: Fluid resuscitation volumes significantly higher than those predicted by the Parkland formula were given, without adverse consequences. This retrospective review supports a prospective, multicentre, randomized, controlled study comparing this study with the Parkland formula, resulting in a better guide to initial fluid resuscitation in major burns.     

Shape imposed by secondary structure of a polypeptide affects its free diffusion through liquid-filled pores

The purpose of the present study was to investigate the effect of secondary structure of three model polypeptides on their apparent permeability (P(app)) across a synthetic, microporous membrane. Poly-L-lysine (PL), poly-L-glutamate (PGlu), and poly-L-lysine-L-phenylalanine (1:1) (PLP) were selected because a solution environment in which their predominant secondary structure is random coil (RC), alpha-helix, and beta-sheet, respectively, is easily achieved. The conformation of each polypeptide was verified by circular dichroism (CD). Diffusion studies were conducted under sink conditions at 25 degrees C across a microporous polyester membrane using a donor concentration of 0.02 mM for each model polypeptide. NMR was utilized to obtain a second estimation of the diffusion coefficient for each polypeptide. The equivalent hydrodynamic radii (R(e)) of the three model polypeptides were calculated using the values of the diffusion coefficient obtained by both NMR and the classic in vitro diffusion studies. The viscosity of each polypeptide solution was also determined to investigate the effect of viscosity on the aqueous diffusion coefficient. Statistical analysis demonstrated a significant (P < 0.05) difference in both P(app) and the aqueous diffusion coefficient (D(aq)), as well as the calculated R(e) values, between all three model polypeptides and there was no significant (P > 0.05) difference in the viscosity of the polypeptide solutions. Values of D(aq) and R(e) calculated from the diffusion studies were in relatively close agreement to those obtained using NMR. The logarithm of P(app) was highly correlated (r = -0.961) with the values of R(e) calculated from NMR (R(e (NMR))) rather than the mw of the polypeptides (r = 0.681). Values of the Perrin or shape factor which deviate substantially from unity are suggestive of a non-spherical or ellipsoid shape and were 1.22 +/- 0.20, 1.55 +/- 0.11, and 2.38 +/- 0.20 for PGlu, PL, and PLP, respectively. In conclusion, the observed difference in the membrane transport/diffusion of the three model polypeptides is suggested to be due to the shape associated with the secondary structure of each macromolecule, rather than the polypeptide's mw or the viscosity of the dilute polypeptide solution.     

Clinical and immunological assessment of Mycobacterium vaccae (SRL172) with chemotherapy in patients with malignant mesothelioma

The objectives of this study were to determine the toxicity of intratumoural/intrapleural SRL172 in addition to intradermal SRL172 and standard chemotherapy (mitomycin-C, vinblastine and cisplatin) in patients with malignant mesothelioma. Patients received chemotherapy (mitomycin-C: 8 mg m(-2), vinblastine: 6 mg m(-2), cisplatin 50 mg m(-2)) on a 3-weekly basis for up to six courses. IP SRL172 injections were given 3-weekly prior to chemotherapy and escalated in groups of three patients from 1 microg to 1 mg bacilli in 10-fold increments. Patients were also given ID SRL172 at a dose of 1 mg bacilli 4-weekly. Patients were assessed for toxicity after each course of chemotherapy and for response by CT imaging. Immuno-haematological parameters were analyzed pre-treatment and 1 month after completion of treatment. There was no dose limiting toxicity with IP SRL172 although there was greater toxicity at the highest dose (n=13). There were six out of 16 partial responses (37.5%). Haemato-immunological parameters, measured in seven patients pre and post-therapy, revealed that response rate correlated with a decrease in platelet count and there was an increase in activation of natural killer cells and a decrease in the percentage of IL-4 producing T cells in all tested patients post-treatment. SRL172 can be given safely into tumour deposits and the pleural cavity in patients with malignant mesothelioma and we have established the dose for phase II testing.     

MRI simulation: effect of gradient distortions on three-dimensional prostate cancer plans

PURPOSE: To quantify the dosimetric consequences of external patient contour distortions produced on low-field and high-field MRIs for external beam radiation of prostate cancer. METHODS AND MATERIALS: A linearity phantom consisting of a grid filled with contrast material was scanned on a spiral CT, a 0.23 T open MRI, and a 1.5 T closed bore system. Subsequently, 12 patients with prostate cancer were scanned on CT and the open MRI. A gradient distortion correction (GDC) program was used to postprocess the MRI images. Eight of the patients were also scanned on the 1.5 T MRI with integrated GDC correction. All data sets were fused according to their bony landmarks using a chamfer-matching algorithm. The prostate volume was contoured on an MRI image, irrespective of the apparent prostate location in those sets. Thus, the same target volume was planned and used for calculating the anterior-posterior (AP) and lateral separations. The number of monitor units required for treatment using a four-field conformal technique was compared. Because there are also setup variations in patient outer contours, two different CT scans from 20 different patients were fused, and the differences in AP and lateral separations were measured to obtain an estimate of the mean interfractional separation variation. RESULTS: All AP separations measured on MRI were statistically indistinguishable from those on CT within the interfractional separation variations. The mean differences between CT and low-field MRI and CT and high-field MRI lateral separations were 1.6 cm and 0.7 cm, respectively, and were statistically significantly different from zero. However, after the GDC was applied to the low-field images, the difference became 0.4 +/- 0.4 mm (mean +/- standard deviation), which was statistically insignificant from the CT-to-CT variations. The mean variations in the lateral separations from the low-field images with GDC would result in a dosimetric difference of <1%, assuming an equally weighted four-field 18-MV technique for patient separations up to approximately 40 cm. CONCLUSIONS: For patients with lateral separations <40 cm, a homogeneous calculation simulated using a 1.5 T MRI or a 0.23 T MRI with a gradient distortion correction will yield a monitor unit calculation indistinguishable from that generated using CT simulation.