Peri-operative medication safety is complex. Avoidance of medication errors is both system- and practitioner-based, and many departments within the hospital contribute to safe and effective systems. For the individual anaesthetist, drawing up, labelling and then the correct administration of medications are key components in a patient's peri-operative journey. These guidelines aim to provide pragmatic safety steps for the practitioner and other individuals within the operative environment, as well as short- to long-term goals for development of a collaborative approach to reducing errors. The aim is that they will be used as a basis for instilling good practice.

Altered frequency and position of meiotic crossovers in infertile men have been linked to spermatogenic arrest and infertility, as well as sperm aneuploidy. However, the mechanisms leading to the meiotic defects observed in this population remain unknown. Recent studies have shed light on the importance of proper telomere function in the progression of meiosis and fertility. This study aims to investigate the distribution of crossovers and the distance between crossovers and telomeres along specific chromosomes in spermatocytes of infertile men with obstructive azoospermia (OA), and non-obstructive azoospermia (NOA). The crossover distributions on Chr 13, 18 and 21 were determined in the pachytene spermatocytes of 20 OA, 14 NOA, and 29 control men. The chromosome arms were divided into 10% intervals with respect to the total length. The frequency of MLH1 foci in each interval was subsequently calculated. Individual infertile men were compared to pooled controls in addition to whole group comparisons. The mean distance of crossovers from telomeres was determined for each infertile man who displayed altered crossover distributions on Chr 13, 18 or 21. This value was given by the average of the distance between each crossover to the end of the long or short chromosome arm being analyzed. Immunostaining was used to observe the synaptomenal complex and MLH1 foci, which localize to crossover sites. Chr 13, 18 and 21 were identified by fluorescence in situ hybridization. Micromeasure V3.3 was used for MLH1 distribution and distance analysis. The Mann-Whitney, χ2 and Fisher tests were used for statistical analysis. Eight out of 20 OA, and 9 out of 14 NOA men showed a significantly altered MLH1 foci distribution on at least one of the chromosome arms studied. The NOA group showed significantly altered MLH1 distribution on Chr 21, while both OA and NOA groups displayed altered distribution on Chr 18 compared to controls. One out of 8 OA and 4 out of 9 NOA men with altered MLH1 distributions also displayed an increased mean distance between crossovers and telomeres on the corresponding chromosomes. Both OA and NOA men exhibit meiotic defects in the form of altered crossover distribution. These men may also display an increased distance between the crossovers and telomeres, which may suggest an inhibition of recombination events near the telomeres, as well as a telomeric role in the increase in recombination errors observed in some infertile men. Our findings may elucidate a new direction for the possible mechanisms involved in male factor infertility.

Pulmonary manifestations of cryoglobulinemia are uncommon and their clinical behaviour is unpredictable, ranging from mild dyspnea to life-threatening presentations. A patient with cryoglobulinemia who presented with hypoxic respiratory failure attributed to pulmonary hemorrhage is reported.

It is well known that men with balanced chromosomal rearrangement are at risk of producing chromosomally unbalanced gametes. However, it is not clear if the meiotic behavior of a balanced chromosomal rearrangement could affect the segregation of chromosomes not involved in the rearrangement (interchromosomal effect), leading to aneuploidy in the gametes. In this study, we investigated the existence of an interchromosomal effect in three heterozygous carriers of structural chromosomal rearrangements. Prospective analysis of the chromosomal complements of spermatozoa by fluorescent in situ hybridization (FISH). All three carriers had abnormal sperm parameters, and history of infertility at least two years. Semen samples were collected from a carrier of a paracentric inversion: inv (5) (q22.1;q23.2); a reciprocal translocation: t (9;22) (p13.1;q13.2); and a Robertsonian translocation: t (13;21) (q10;q10), as well as five normal men. Spermatozoa were prepared for dual FISH for chromosomes 13 and 21, and triple FISH for chromosomes 18, X and Y. 10,000 sperm were scored per patient for each probe set. The Chi-square test was used to compare rates of disomy for each chromosome between the patients and the control men. P<0.05 was considered significant. A total of 152,436 spermatozoa were scored (101,492 controls and 50,944 for patients). Evidence of an interchromosomal effect was observed in the inv(5) carrier, who displayed significantly increased disomy 13, 21, 18, XX and YY (Table 1). The t (9;22) reciprocal translocation carrier showed increased disomy 21, but aneuploidies for all other chromosomes studied were not increased. There was no evidence of an interchromosomal effect in the t (13;21) Robertsonian translocation carrier.Table 1Incidence of sperm disomy for chromosomes 13, 18, 21 X an patients and controlsNo. spermDisomy 13 (%)Disomy 21 (%)No. spermDisomy 38 (%)Sex chromosomes disomy (%)XXYYXYinv 5(q22.1;q23.2)10,14047aP<0.01. (0.46)74aP<0.01. (0.73)10,29627aP<0.01. (0.26)48aP<0.01. (0.47)58aP<0.01. (0.56)14 (0.14)t(9;22)(p13.1;q13.2)10,03316 (0.16)53aP<0.01. (0.53)10,3035 (0.05)2 (0.02)10 (0.10)13 (0.13)t(13;21)(q10;q10)n/an/an/a10,1723 (0.03)0 (0)4 (0.04)11 (0.11)Controls50,75250 (0.10)74 (0.15)50,74035 (0.07)42 (0.08)55 (0.11)99 (0.20)a P<0.01. Open table in a new tab The existence of an interchromosomal effect in carriers of structural rearrangements is contentious, with some studies observing such an effect, and some not. In this study the inversion carrier showed evidence of an interchromosomal effect involving all chromosomes studied, while the t (9;22) carrier showed only an increased aneuploidy for chromosome 21. There was no evidence of an interchromosomal effect in the t (13;21) Robertsonian translocation carrier. Thus, the type of structural abnormality and the chromosomes and breakpoints involved may determine the presence and magnitude of an interchromosomal effect.

Hematopoietic recovery in 115 patients with metastatic breast cancer or metastatic melanoma, enrolled in phase-I studies of recombinant growth factors while undergoing treatment with high-dose chemotherapy with autologous bone marrow support, was examined with assays of bone marrow progenitor cells and peripheral blood progenitor cells, and by evaluation of peripheral blood counts. Groups of patients receiving hematopoietic cytokine support [with interleukin-1 (IL-1), interleukin-2 (IL-2), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or monocyte CSF (M-CSF)] post marrow infusion were compared with contemporaneous control patients not receiving growth factor support. Patients receiving GM-CSF demonstrated statistically significant increases in the growth of granulocyte/macrophage colony-forming units (CFU-GM) in the bone marrow and peripheral blood compared with control patients. The effect of GM-CSF was dose dependent in the early period post marrow infusion (day +6) with bone marrow CFU-GM colonies at doses 8–16 μg/kg/ day 34 times those measured in controls. Significant increases in bone marrow multipotential progenitor cells (CFU-GEMM) were seen in patients receiving GMCSF day + 21 post marrow infusion. Patients receiving IL-1 demonstrated significant increases in bone marrow CFU-GM at day +21, maximal at dosages of 24–32 ng/kg/day. There were no significant increases in burst forming unit-erythroid (BFU-E) among any study group. Patients receiving G-CSF had significantly increased absolute neutrophil counts (ANC) and total white blood cell counts (WBC) by day +11 post transplant compared with control patients. Patients receiving GM-CSF demonstrated significantly increased WBC (greater than 2000/mm3) at day +11 and ANC greater than 500/mm3 at day +16. Optimal dose of GCSF and GM-CSF to stimulate neutrophil recovery post transplant was 4–8 μg/kg/day and 8–16 μg/kg/day, respectively. Platelet recovery did not differ among the six study groups. These data demonstrate accelerated myeloid recovery after high-dose chemotherapy and autologous bone marrow support in patients receiving either G-CSF or GM-CSF. Moreover, GM-CSF and IL-1 stimulate myelopoiesis at the level of bone marrow CFU-GM, while G-CSF causes earlier neutrophil recovery peripherally.