Atypical luteinizing hormone rise and associated fertilization failure in non-male factor in vitro fertilization patients

The purpose of this investigation was to analyze fertilization failure in non-male factor infertility in vitro fertilization (IVF) patients. Twenty-five nonfertilized IVF patients were compared with 57 successfully fertilized IVF patients. Patients were matched for age, ovulation-induction protocol, and cycle. The two groups were similar with respect to infertility etiology, peak estradiol, and total oocytes retrieved at laparoscopy. There was a greater incidence of primary infertility (64 versus 49%) and mean years of infertility (5.4 +/- 0.4 versus 4.6 +/- 0.3) in the nonfertilization group, although these differences were not statistically significant. Most important, the nonfertilization patients had a greater incidence of an atypical LH rise prior to hCG administration (60 versus 18%; P less than .001) and fewer mature oocytes (2.0 +/- 0.3 verus 3.4 +/- 0.3; P less than .01). Stepwise linear regression analysis yielded four primary factors for predicting fertilization failure: infertility duration, primary infertility, number of mature oocytes, and presence of LH rise. These findings help characterize several potential factors other than oligozoospermia that are associated with nonfertilization, and support LH monitoring in IVF and gamete intrafallopian tube transport patients.     

Clinical evaluation of a continuous oxygen consumption monitor in mechanically ventilated patients

We measured oxygen consumption using a new noninvasive modular metabolic monitor, M-COVX trade mark, in ventilated critically ill patients. Oxygen consumption was measured continuously as part of routine monitoring for up to 24 h following mechanical ventilation in 27 patients admitted to a general intensive care unit. We explored several possible sources of error. Most errors related to inaccurate tidal volume measurement, which resulted in rejection of a median 14% (interquartile range 8-34%) of data. Water accumulation in the pneumotachograph was responsible and occurred more frequently with water bath humidifiers. After manual removal of erroneous data mean oxygen consumption values were virtually identical to calculated values in 24 of 27 patients. We conclude that in most ventilated patients averaging of continuous oxygen consumption data with the M-COVX module results in small errors.     

P. vivax malaria complicated by shock and ARDS

We report a case of Plasmodium vivax malaria complicated by shock and ARDS. The patient responded to oral chloroquine and primaquine and PCR was positive for P. vivax DNA and negative for P. falciparum DNA. P. vivax may cause severe complications and where the possibility of mixed infections exists, blood should be sent for PCR analysis so that mixed infections can reliably be excluded.     

Allogeneic haemopoietic cell transplants in Australia, 1996--a multi-centre retrospective comparison of the use of peripheral blood stem cells with bone marrow

A retrospective comparison was carried out on adult patients receiving HLA-identical allogeneic haemopoietic stem cell transplants from siblings in Australia in 1996, comparing bone marrow with G-CSF-mobilised peripheral blood stem cells. A total of 131 transplant recipients from nine centres were included in this study, of whom 79 received bone marrow, 44 blood stem cells and eight both. All but three of the 131 patients had cyclosporin and methotrexate as graft-versus-host disease prophylaxis. The minimum follow-up time for surviving patients is 27 months. Comparisons were carried out between the BM and PBSC groups. There were no significant differences between groups in age, sex, diagnosis, donor characteristics or pretransplant conditioning. Median time to neutrophil recovery of 0.5 x 10(9)/l was 14 days for PBSC recipients, compared to 19 days for marrow recipients (P < 0.0005). median time to platelet recovery of 20 x 10(9)/l was 17 days for PBSC recipients, compared to 28 days for marrow recipients (P < 0.0005). there were no significantly increased risks of either acute or chronic GVHD in the PBSC recipients. there were no significant differences between the groups in the incidence of major transplant-related complications, disease-free survival or overall survival.     

Scaphoid interfragmentary motions due to simulated transverse fracture and volar wedge osteotomy

Background

Our goal was to determine 3-dimensional interfragmentary motions due to simulated transverse fracture and volar wedge osteotomy of the scaphoid during physiologic flexion–extension of a cadaveric wrist model.

Methods

The model consisted of a cadaveric wrist (n = 8) from the metacarpals through the distal radius and ulna with load applied through the major flexor–extensor tendons. Flexibility tests in flexion–extension were performed in the following 3 test conditions: intact and following transverse fracture and wedge osteotomy of the scaphoid. Scaphoid interfragmentary motions were measured using optoelectronic motion tracking markers. Average peak scaphoid interfragmentary motions due to transverse fracture and wedge osteotomy were statistically compared (P < 0.05) to intact.

Findings

The accuracy of our computed interfragmentary motions was ± 0.24 mm for translation and ± 0.54° for rotation. Average peak interfragmentary motions due to fracture ranged between 0.9 mm to 1.9 mm for translation and 5.3° to 10.8° for rotation. Significant increases in interfragmentary motions were observed in volar/dorsal translations and flexion/extension due to transverse fracture and in separation and rotations in all 3 motion planes due to wedge osteotomy.

Interpretation

Comparison of our results with data from previous in vitro and in vivo biomechanical studies indicates a wide range of peak interfragmentary rotations due to scaphoid fracture, from 4.6° up to 30°, with peak interfragmentary translations on the order of several millimeters. Significant interfragmentary motions, indicating clinical instability, likely occur due to physiologic flexion–extension of the wrist in those with transverse scaphoid fracture with or without volar bone loss.     

A SYBR green-based real-time PCR method for detection of haemopoietic chimerism in allogeneic haemopoietic stem cell transplant recipients

OBJECTIVE: To develop a reliable and rapid real-time quantitative polymerase chain reaction (Q-PCR) method using SYBR green to quantify chimerism in allogeneic haemopoietic stem cell transplant recipients. METHODS: Twelve specific nucleotide polymorphisms (NPs) were selected to identify informative markers for detecting chimerism in transplant donor/recipient pairs. One informative marker was then used in SYBR green Q-PCR to detect chimerism post-transplantation in each patient. The percentage of donor cells was calculated using a standard curve, constructed using artificially mixed donor/recipient chimeric DNA in 12 serial dilutions (0.01-100%). RESULTS: DNA from 37 donor/recipient pairs was screened for informative markers and 18 post-transplant samples were monitored for chimerism with SYBR green Q-PCR method. The Q-PCR was able to discriminate between recipient and donor genetic profiles in all 18 samples, and quantify the chimerism. These results were confirmed by at least one independent method, such as TaqMan Q-PCR, microsatellite and fluorescent in situ hybridisation (FISH) methods. The detection limit of this method was 0.1%, which was more sensitive than the two currently used microsatellite and FISH methods. CONCLUSION: The new single platform SYBR green Q-PCR method is capable of detecting all haemopoietic chimerism with high accuracy; hence, it may be used to replace the current detection methods.     

Non-comparative evaluation of the safety of aerosolized amphotericin B lipid complex in patients undergoing allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at increased risk for invasive fungal infections (IFIs) over prolonged periods of time. Aerosolized amphotericin B lipid complex (ABLC) has shown promise in lung transplant recipients as a convenient means of delivering protective drug to the upper airways avoiding systemic toxicities. The safety and tolerability of aerosolized ABLC in 40 subjects undergoing allogeneic HSCT was prospectively investigated in an open-labeled, non-comparative study. Subjects received aerosolized ABLC treatment once daily for 4 days, then once weekly for 13 weeks; fluconazole was administered daily as standard of care through post-transplant day 100. Pulmonary mechanics were measured before and after each dose of inhaled ABLC; adverse events (AEs) and the development of IFI were also monitored. Cough, nausea, taste disturbance, or vomiting followed 2.2% of 458 total inhaled ABLC administrations; 5.2% of inhaled ABLC administrations were associated with >or=20% decrease in pulmonary function measurements (forced expiratory volume in 1 second or forced vital capacity) and none required treatment with bronchodilators or withdrawal from study. Four mild AEs were considered possibly or probably related to study treatment; no deaths or withdrawals from treatment were attributed to study drug. Of 3 proven IFIs occurring during the study period, only 1, a catheter-related case of disseminated fusariosis, occurred while the subject was receiving study medication. Aerosolized ABLC was well tolerated in allogeneic HSCT recipients. With only 1 of 40 subjects developing IFI while receiving treatment, the combination of fluconazole and inhaled ABLC warrants further study as antifungal prophylaxis following allogeneic HSCT.     

The activin receptor-like kinase 6 Booroola mutation enhances suppressive effects of bone morphogenetic protein 2 (BMP2), BMP4, BMP6 and growth and differentiation factor-9 on FSH release from ovine primary pituitary cell cultures

Bone morphogenetic proteins (BMPs) have been shown to influence the regulation of FSH synthesis and secretion at the level of the pituitary. Primary pituitary cells were harvested and cultured from Booroola ewes homozygous for a mutation in activin receptor-like kinase 6 (ALK6) also known as BMP receptor IB (BMPRIB), and from wild-type (WT) ewes to determine if the mutation caused alterations in FSH secretion in vitro. The cells were collected 24 h following induction of luteolysis and cultured for 72 h prior to being challenged for 24 h with BMP2, BMP4, BMP6, growth and differentiation factor-9 (GDF9), transforming growth factor-beta 1, activin-A and GnRH. The levels of FSH and LH were measured by RIA and then compared with the untreated controls. Primary pituitary cell cultures from Booroola ewes secreted less FSH than WT cells in the presence of BMP2, BMP4 and BMP6. These BMPs did not affect the FSH stores within the cells, or the levels of LH released. GDF9 appeared to act in a BMP-like manner by suppressing FSH secretion. The ALK6 receptor however, was not found to co-localise with gonadotroph cells in either Booroola or WT pituitary tissues. These findings imply that the increased sensitivity of Booroola cells to BMP2, BMP4, BMP6 and GDF9 cannot be due to the direct action of the ALK6 mutant Booroola receptor in the cells that synthesise FSH.     

New concepts: development of a survivorship programme for patients with a functionally univentricular heart

Children with functionally univentricular hearts are now surviving into their third and fourth decades of life. Although survival alone is a remarkable achievement, a lot must still be done to improve the quality and duration of life after the Fontan operation. Challenges that may be faced by these patients include the impact of the Fontan operation on the liver and the density of bone, protein-losing enteropathy, and plastic bronchitis. Paediatric cardiologists are familiar with the haemodynamic issues inherent in Fontan physiology; however, training in cardiology is often not sufficient to give us a complete understanding of the pathophysiology of the complications or of the options for treatment. Collaboration with other subspecialists including gastroenterologists, endocrinologists, and pulmonologists is essential in order to provide the rigorous and nuanced care that our patients need and deserve. A clinic in which a patient can see multiple subspecialists, and in which the subspecialists, as a group, can discuss each patient, can provide a unique and valuable service for patients with a functionally univentricular heart.     

Multiscale, resurgent epidemics in a hierarchical metapopulation model

Although population structure has long been recognized as relevant to the spread of infectious disease, traditional mathematical models have understated the role of nonhomogenous mixing in populations with geographical and social structure. Recently, a wide variety of spatial and network models have been proposed that incorporate various aspects of interaction structure among individuals. However, these more complex models necessarily suffer from limited tractability, rendering general conclusions difficult to draw. In seeking a compromise between parsimony and realism, we introduce a class of metapopulation models in which we assume homogeneous mixing holds within local contexts, and that these contexts are embedded in a nested hierarchy of successively larger domains. We model the movement of individuals between contexts via simple transport parameters and allow diseases to spread stochastically. Our model exhibits some important stylized features of real epidemics, including extreme size variation and temporal heterogeneity, that are difficult to characterize with traditional measures. In particular, our results suggest that when epidemics do occur the basic reproduction number R(0) may bear little relation to their final size. Informed by our model's behavior, we suggest measures for characterizing epidemic thresholds and discuss implications for the control of epidemics.