Thromboembolic disease associated with ovarian stimulation and assisted conception techniques

Thromboembolic disease, as a complication of ovarian stimulation and assisted conception techniques, is generally considered to be a rare complication of ovarian hyperstimulation syndrome and, by implication, lower limb in origin. Sporadic cases of unusually sited thromboses, both venous and arterial, have been reported. This paper aims to draw attention to the relatively large number of such thromboses reported in the world literature compared with those cited in previous commentaries, and to emphasize how little is known about their pathogenesis. It is believed that this is an issue which requires to be addressed in order to understand the background pathology to such incidents and if possible to identify women at greatest risk from such potentially debilitating or fatal complications, such that appropriate prophylactic measures can be taken.      

Identification of ovarian antibodies by immunofluorescence, enzyme- linked immunosorbent assay or immunoblotting in premature ovarian failure

The development of new techniques for the detection of ovarian antibodies has challenged early concepts about the rarity of ovarian antibodies in idiopathic premature ovarian failure (POF), but few attempts have been made to compare results between assays. We have sought to define the prevalence of ovarian autoimmunity in a group of 30 idiopathic POF patients compared to a group of 12 patients with POF plus an associated autoimmune disease and a group of 38 controls, using an enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IFL). Ovarian antibodies were detected in 27% of idiopathic POF patients by ELISA (not significantly different compared to POF patients with associated autoimmune disease; P < 0.0003 compared to controls) but only 7% of these patients were positive by IFL. In a further, pre-selected group of individuals, all positive for ovarian antibodies by IFL, 53% had measurable antibodies by ELISA. Some overlap was therefore demonstrated between the two techniques but many POF patients had ovarian antibodies detectable by only one method. Immunoblotting studies revealed that no consistent pattern of binding could be demonstrated for these patients. These results call into question the specificity of ovarian antibodies as a marker for autoimmune POF.      

ototoxicity after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin followed by stem cell transplantation in patients with breast cancer

Our purpose was to determine the risk of ototoxicity in breast cancer patients receiving a myeloablative regimen consisting of cyclophosphamide 6000 mg/m², thiotepa 500mg/m² and carboplatin 800mg/m² (CTCb) followed by stem cell transplantation. Fourteen consecutive patients with breast cancer were treated with high dose chemotherapy consisting of the CTCb regimen followed by stem cell transplantation. A pretransplant complete hearing study was obtained which consisted of hearing case history, audiometry and tympanometry. In addition, DPOAE (Distortion Product Otoaccoustic Emissions) was done to evaluate measurable changes in the cochlear (outer hair cell) functioning. Pre-transplant, all patients had no clinical evidence of hearing impairment and hearing studies were normal. Eleven patients had hearing studies and a telephone interview posttransplant. One patient was lost to follow-up and two patients died. One of the 11 patients tested had an abnormal post-transplant hearing study but none of them had clinically detectable hearing impairment. In our prospective study of breast cancer patients treated with the CTCb regimen, we did not observe clinically detectable hearing impairment in any of the patients tested.     

The bare bones of object recognition: implications from a case of object recognition impairment

Three experiments were designed to investigate the performance of a patient (RK) who could name objects when presented in conventional views but showed catastrophic failures in identification from unconventional views. The aim of all three experiments was to assess the properties of the central representations that allow recognition of objects presented in conventional but not unconventional views. All three experiments showed that RK had problems in object identification not apparent from his naming performance. In the first experiment, RK was found to be extremely impaired at recognising the parts of objects even though he could name the whole object. In the second experiment, alterations in colour, shape and parts of objects were undetected in stimuli that he could name. In the third experiment, RK showed considerable difficulty with mirror-images and inversion tasks. The explanation for RK's impaired object recognition could not be attributed to defects to his early visual processing. We argue that RK's recognition is achieved through abstract (object-centred) representations that are global rather than local, and quite independent of their spatial framework. These abstract representations we take to be the essential bare bones for object recognition.     

The use of gel dosimetry for verification of electron and photon treatment plans in carcinoma of the scalp

In recent years there has been a large amount of research into the potential use of radiation sensitive gels for three-dimensional verification of clinical radiotherapy doses. In this paper we report the use of a MAGIC gel dosimeter (Fong et al 2001 Phys. Med. Biol. 46 3105) for the verification of a specific patient's radiation therapy dose distribution. A 69-year-old male patient presented with a squamous cell carcinoma extending approximately 180 degrees across the top of the scalp (anterior to posterior) and from just over midline to 90 degrees left of the skull. The patient's treatment was commenced using two electron fields. For gel dosimetry, phantoms were produced in which the outer surface spatially corresponded to the outer contours of the patient's anatomy in the region of irradiation. The phantoms were treated with either electrons or intensity modulated radiation therapy (IMRT) with photons. The results identified a hot spot between the matched electron fields and confirmed the more homogeneous dose distribution produced by the IMRT planning system. The IMRT plan was then clinically implemented. The application of a clinical dose to a phantom shaped to a specific patient as well as the ability to select a slice at will during phantom imaging means that gel dosimetry can no longer be considered to simply have potential alone, but is now in fact a useful dosimetric tool.     

The reproducibility of polyacrylamide gel dosimetry applied to stereotactic conformal radiotherapy

The reproducibility of polyacrylamide gel (PAG) dosimetry has been evaluated when used to verify two radiotherapy treatment plans of increasing complexity. The plans investigated were a three-field coplanar arrangement, using the linac jaws for field shaping, and a four-field, conformal, non-coplanar plan using precision-cast lead alloy shielding blocks. Each treatment was performed three times using phantoms and calibration gels manufactured in-house. Two phantoms were specially designed for this work to aid accurate positioning of the gels for irradiation and imaging. All gels were imaged post-irradiation using a Siemens Vision 1.5T MR scanner. T2 relaxation images were calibrated to absorbed dose distributions using a number of smaller calibration vessels to produce distribution maps of relative dose. The relative dose distributions were found to be reproducible, with the standard deviation on the mean areas enclosed by the > or = 50% isodose lines measured in three orthogonal planes being 6.4% and 4.1% for the coplanar and non-coplanar plans respectively. The measured distributions were also consistent with those planned, with isodose lines generally agreeing to within a few millimetres. However, the measured absolute doses were on average 23.5% higher than those planned. Although the polyacrylamide gel dosimetry technique has some limitations, particularly when calibrating distributions to absolute dose, the ability to resolve sharp dose gradients in three dimensions with millimetre precision is invaluable when verifying complex conformal treatment plans, where avoidance of proximal, critical structures is a treatment criterion.     

Production of migration inhibition factor (MIF) by purified human T cell subpopulations.

T cells possessing suppressor activity (TG) were isolated from normal human peripheral blood by rosetting with IgG-coated ox red blood cells (OxRBC) as shown by their ability to inhibit pokeweed mitogen (PWM) induced proliferation and Ig synthesis in vitro. The suppressor activity of the intact T cell and Tg cell fractions was enhanced by concanavalin A (Con A) stimulation for 48 hr and supernatants from these Con A-treated cell cultures, after removal of mitogen, contained migration inhibition factor (MIF). Its release appeared to be primarily a function of the TG cells. The bulk of the MIF activity was present in a gel filtration fraction of mol. wt approx. 25,000, similar to that found in previous studies of Con A- or antigen-induced MIF in man.     

Cognitive abnormalities in multiple sclerosis: a psychometric and MRI study

This study reports the cognitive abnormalities of a group of 58 patients with definite multiple sclerosis (MS). The psychometric functions measured were: 'IQ deficit', verbal and visual memory, abstracting ability, visual and auditory attention and naming ability. The presence of brain pathology was investigated using magnetic resonance imaging (MRI). A group of 46 physically disabled controls without significant brain disease was used for comparison. Normative MRI data were obtained from a group of 40 normal volunteers. The psychometric performance of the MS group was compared to the previously reported findings in patients with clinically isolated syndromes. MS patients had widespread cognitive deficits sparing naming ability and affecting verbal memory less severely than other intellectual functions. The overall performance on psychometric tests was related to the severity of the MRI abnormalities and to the duration of the illness, but was not significantly influenced by the presence of psychiatric morbidity or the degree of physical disability. Patients with clinically isolated syndromes occupied an intermediate position between MS patients and disabled controls in terms of cognitive and MRI abnormalities.     

Is subclinical ovarian failure an autoimmune disease?

Young women with unexplained infertility who exhibit elevated basal serum follicle stimulating hormone (FSH) concentrations (>10 IU/l) have poor outcomes in in-vitro fertilization. A subgroup of these women has regular menses, representing 'subclinical' ovarian failure, which may have an autoimmune basis and could potentially be treated by immunosuppression. To investigate this further, a range of immunological markers was used to assess autoimmune activity in 14 women aged <40 years with elevated FSH compared with 15 infertile women with normal FSH and 10 pre-menopausal, healthy controls. All samples were taken during natural menstrual cycles. Organ-specific antibodies against ovary, endometrium and thyroid, and non-organ-specific antibodies against histones and cardiolipin, were not significantly increased in elevated FSH patients compared with other control groups. Soluble CD23 and soluble intercellular adhesion molecule concentrations were not elevated in the sera of the women tested, and circulating T cell subsets remained unaltered. Significantly, increased concentrations of the complement breakdown product C3a and terminal complement complexes were detected in the elevated FSH group compared with the normal FSH group, although the latter also had significant complement activation compared with laboratory controls. Autoimmunity appears as an infrequent cause of 'subclinical' ovarian failure, but there is evidence of activation of complement in the sera of infertile women.