Hydatidiform molar pregnancy following assisted reproduction.

INTRODUCTION: The use of assisted reproduction techniques (ART) is increasing; however, reports of molar pregnancy following ART remain scarce. Currently, the Human Fertility and Embryology Authority (HFEA) collates data on the molar pregnancies that have resulted through the use of ART. Recently, they have indicated that they will no longer collect these data. AIM: This paper aimed to examine the incidence of molar pregnancy amongst patients undergoing assisted reproduction. METHODS: We contacted HFEA and placed a request under the Freedom of Information Act (2000) for the number of molar pregnancies that resulted from fresh/frozen embryo transfer since HFEA started collecting data in 1991 to February 2018. We also asked how many patients who had suffered a molar pregnancy went on to have a normal pregnancy and how many had subsequent molar pregnancies, in subsequent treatment cycles. RESULTS: Between 68 and 76 molar pregnancies occurred within this period using ART (n = 274,655). The incidence of molar pregnancy using fresh intracytoplasmic sperm injection (ICSI) (1/4302) and fresh in vitro fertilisation (IVF) (1/4333) was similar. The risk of recurrence of molar pregnancy following a previous molar was higher following ART compared to spontaneous conceptions. CONCLUSION: The use of ICSI should be protective against triploidy; however, the retrospective data suggests that molar pregnancy is not eliminated with the use of ART. It is pertinent to continue to record this data, through the gestational trophoblastic disease centres, in order to ensure no further increase in incidence, appropriate follow-up, and transparency in communication.

Identification of circulating microRNAs as diagnostic biomarkers for use in multiple myeloma.

BACKGROUND: Multiple myeloma is a plasma cell disorder that is characterised by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal paraprotein in the blood or urine and associated organ dysfunction. It accounts for approximately 1% of cancers and 13% of haematological cancers. Myeloma arises from an asymptomatic proliferation of monoclonal plasma cells termed monoclonal gammopathy of undetermined significance (MGUS). METHODS: MicroRNA expression profiling of serum samples was performed on three patient groups as well as normal controls. Validation of the nine microRNAs detected as promising biomarkers was carried out using TaqMan quantitative reverse transcription PCR. MicroRNA levels in serum were normalised using standard curves to determine the numbers of microRNAs per µl of serum. RESULTS: Three serum microRNAs, miR-720, miR-1308 and miR-1246, were found to have potential as diagnostic biomarkers in myeloma. Use of miR-720 and miR-1308 together provides a powerful diagnostic tool for distinguishing normal healthy controls, as well as patients with unrelated illnesses, from pre-cancerous myeloma and myeloma patients. In addition, the combination of miR-1246 and miR-1308 can distinguish MGUS from myeloma patients. CONCLUSION: We have developed a biomarker signature using microRNAs extracted from serum, which has potential as a diagnostic and prognostic tool for multiple myeloma.

The marker of alkyl DNA base damage, N7-methylguanine, is associated with semen quality in men.

Sperm DNA contains a range of DNA base damage that can arise, in part, from exposure to methylating agents. However, the effects are not fully characterized and so the aim of this study was to investigate associations between semen quality and the levels of N7-methyldeoxyguanosine (N7-MedG), a marker of exposure to methylating agents, and other markers of DNA damage and DNA methylation. Sperm samples were collected from 105 men attending an assisted reproduction clinic as part of a couple undergoing treatment for infertility and semen quality assessed manually according to WHO guidelines. Semen levels of N7-MedG, quantified by immunoslotblot, were significantly higher in men with sperm concentration < 15 × 106/ml (p ≤ 0.01), semen volume < 1.5 ml (p ≤ 0.05) and also in men with any aspect of semen quality below WHO reference levels (p ≤ 0.001). Measures of neutral Comet DNA damage were correlated with semen quality in a univariate analysis but not after adjustment for N7-MedG levels. Sperm concentration was negatively associated with % methylation at the gene for DAZL but no other marker of global or gene-specific DNA methylation. Results support the hypothesis that the known toxic and DNA damaging properties of alkylating agent exposure may have direct deleterious consequences on semen quality.

Alkylation of sperm DNA is associated with male factor infertility and a reduction in the proportion of oocytes fertilised during assisted reproduction.

Approximately one-third of IVF cases in the UK are attributed to male factor infertility and in the majority of cases the origin of male infertility is unknown. The integrity of sperm DNA is important both for the success of assisted reproduction and the implications for the off-spring. One type of DNA damage that has not been investigated with respect to fertility outcomes is the adduct N7-methyldeoxyguanosine (N7-MedG), a biomarker for exposure to alkylating agents. A prospective cohort of couples attending for IVF had their N7-MedG levels in sperm measured using an immunoslot blot technique to examine whether sperm N7-MedG levels are associated with male factor infertility, semen quality measures or assisted reproduction outcomes. Sufficient DNA for analysis was obtained from 67/97 couples and N7-MedG was detected in 94% of sperm samples analysed. Men diagnosed with male factor infertility had significantly higher mean levels of N7-MedG in their sperm DNA (P=0.03). Logistic regression analysis showed that N7-MedG levels were significantly negatively associated with the proportion of oocytes successfully fertilised irrespective of the method of fertilisation used (IVF or intra-cytoplasmic sperm injection; ICSI, P<0.001). Therefore exposure to DNA alkylating agents is significantly associated with male infertility and the proportion of oocytes fertilised during assisted reproduction. Reducing such exposure may improve male fertility but further work is required to determine the relative importance of exogenous and endogenous sources of exposure.

A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease.

In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two patients were randomly assigned to either arm. Treatment 'successes' was the primary end point, defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end points were 24-month treatment 'successes', molecular response and progression at 12 and 24 months, comparison of IM levels, and achievement of blood HCQ levels >2000 ng/ml. At 12 months, there was no difference in 'success' rate (p = 0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p = 0.21). At 24 months, the 'success' rate was 20.8% higher with IM/HCQ (p = 0.059). No patients progressed. Seventeen serious adverse events, including four serious adverse reactions, were reported; diarrhoea occurred more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.

Implantation, clinical pregnancy and miscarriage rates after introduction of ultrasound-guided embryo transfer.

The purpose of this study was to compare the reproductive outcome of ultrasound-guided (USG) embryo transfers versus clinical touch embryo transfers. A statistically powered retrospective analysis of women undergoing fresh and frozen embryo transfers in a National Health Service-based tertiary referral centre in the Department of Reproductive Medicine, St Mary's Hospital, Manchester was carried out. A total of 1723 embryo transfers were included in the analysis. The implantation rate was significantly higher in the USG embryo transfer group compared with the non-USG embryo transfer group (fresh: 19.9 versus 9.5%, P < 0.0001; frozen: 13.1 versus 7.3%, P < 0.0004). The clinical pregnancy rate was also significantly higher in the former group (fresh: 26.9 versus 12.5%, P < 0.0001; frozen: 15.6 versus 8.9%, P < 0.0015). For the frozen embryos, the miscarriage rate was significantly elevated among the USG embryo transfer group [unadjusted rate ratio (RR) = 1.65, 95% CI: 1.04, 2.62], but this was of borderline significance when the model was adjusted for the potential confounders (adjusted RR = 1.56, 95% CI: 0.997, 2.45). There was no difference in the ectopic pregnancy rates between the two groups. The findings of this study show that the practice of USG embryo transfer is associated with statistically higher implantation and clinical pregnancy rates in IVF.

Islet cell antibodies predict insulin-dependent diabetes in United States school age children as powerfully as in unaffected relatives.

Islet cell antibodies (ICA) in the sera of nondiabetic relatives of patients with insulin-dependent diabetes (IDD) are predictive of the disease, a finding that permits the design of intervention strategies to prevent it. However, 85% or more of patients with new onset IDD have no affected relative. We therefore screened 9,696 schoolchildren between the ages of 5 and 18 yr (mean age 10.7 yr) in Pasco County, Florida for ICA in three surveys during 1984/5, 1987/8, and 1990/1 and have followed them prospectively. Approximately 4,000 of these children have been followed for nearly 8 yr. ICA titers > or = 10 Juvenile Diabetes Foundation units on replicate tests were detected in 57 of the children (0.59%). 10 children have developed diabetes so far, and all had ICA detected beforehand. The likelihood of developing IDD among the ICA-positive children was compared with 2,959 age-matched nondiabetic first degree relatives of IDD probands who were screened for ICA by our laboratory during the same time period and also followed prospectively. Of 103 (3.5%) ICA-positive relatives, 31 have developed IDD. Life table analysis reveals no statistically significant differences in the probability of developing IDD between the ICA-positive schoolchildren and ICA-positive first degree relatives (P = 0.3). The estimated risk of developing IDD by 7 yr in the ICA-positive schoolchildren was 45% (95% confidence interval 15-74%) compared with 43% (confidence interval 22-63%) in the relatives. We conclude that ICA appear to be as predictive of IDD in low-risk schoolchildren as they are in high-risk relatives. These data suggest that it is feasible to predict IDD by screening a general population of schoolchildren for ICA and that those found to be positive could be considered, in addition to relatives, for intervention protocols to prevent the disease.

Comparative analysis of epicuticular lipid profiles of sympatric and allopatric field populations of Anopheles gambiae s.s. molecular forms and An. arabiensis from Burkina Faso (West Africa).

We analysed by gas chromatography-mass spectrometry (GC-MS) and Gas Chromatography-Flame Ionization Detector (GC-FID) the epicuticular lipid profiles of field females of the major Afro-tropical malaria vector, Anopheles gambiae. The samples were collected in three villages in Burkina Faso (West Africa), where An. gambiae M and S molecular forms and An. arabiensis live sympatrically. The aim was to compare the cuticular hydrocarbon (CHC) composition of individual field specimens of these three taxa, to highlight possible differences among them. All the samples analysed by GC-MS (55 individuals and eight pools) were characterized by the same 48 CHCs and 10 oxygenated compounds. The 19 most abundant CHCs were quantified in 174 specimens by GC-FID: quantitative intra-taxon differences were found between allopatric populations of both An. arabiensis and S-form. Inter-taxa quantitative differences in the relative abundances of some hydrocarbons between pairs of sympatric taxa were also found, which appear to be mainly linked to local situations, with the possible exception of diMeC(35) between An. arabiensis and S-form. Moreover, MeC(29) shows some degree of differentiation between S- and M-form in all three villages. Possible causes of these differences are discussed.

Multimodal immunosuppressant therapy in steroid-refractory common variable immunodeficiency sprue: a case report complicating cytomegalovirus infection.

Immunodeficient patients can develop malabsorption, mimicking celiac disease clinically and histologically. Such individuals may also occasionally require immunosuppressive therapy for autoimmune disorders. We have identified a patient with common variable immunodeficiency (CVID)-associated sprue complicated by duodenal cytomegalovirus (CMV) infection following corticosteroid and ancillary immunomodulatory therapy. Ganciclovir and a modification of the immunosuppressant regimen improved both clinical symptoms and villous atrophy. To our knowledge, this is original documentation of duodenal CMV infection secondary to immunomodulatory therapy for steroid-refractory CVID-sprue.

Reevaluation of Neptunium-Nitric Acid Radiation Chemistry by Multiscale Modeling.

Multiscale modeling has been used to quantitatively reevaluate the radiation chemistry of neptunium in a range of aerated nitric acid solutions (0.1-6.0 mol dm-3). Exact calculation of initial radiolytic yields accounting for changes in radiation track chemistry was found to be crucial for reproducing experimental data. The γ irradiation induces changes in the Np(VI)/Np(V) oxidation-state distribution, predominantly driven by reactions involving HNO2, H2O2, NO2•, and NO3• from the radiolysis of aqueous nitric acid. Oxidation of Np(V) by NO3• (k = 8.1 × 108 dm3 mol-1 s-1) provides the initial increase in Np(VI) concentration, while also delaying net reduction of Np(VI) by consuming HNO2. Reduction of Np(VI) is dominated by thermal reactions with HNO2 (k = 0.7-73 dm3 mol-1 s-1) and H2O2 (k = 1.9 dm3 mol-1 s-1). A steady state is eventually established once the concentration of Np(V) is sufficiently high to be oxidized by NO2• (k = 2.4 × 102-3.1 × 104 dm3 mol-1 s-1). An additional thermal oxidation reaction between Np(V) and HNO3 (k = 2.0 × 103 dm3 mol-1 s-1) is required for nitric acid concentrations >4.0 mol dm-3. For 0.1 mol dm-3 HNO3, the rate of Np(VI) reduction is in excess of that which can be accounted for by radiolytic product mass balance, suggesting the existence of a catalytic-acid-dependent reduction process.

Control of an outbreak of respiratory syncytial virus infection in immunocompromised adults.

Respiratory syncytial virus (RSV) is increasingly recognized as an important pathogen in immunocompromised adults, particularly those receiving bone marrow transplants, and, given the ease with which it spreads, represents a significant nosocomial problem. We describe an outbreak of RSV infection involving eight patients on a haematology/oncology ward which was controlled by early screening of patients and staff. Positive patients were cohort nursed on a separate ward and basic infection control measures including use of gowns and gloves were enforced. Children under age 12 were denied ward access. All patients with lower respiratory tract infection, and bone marrow transplant recipients with upper respiratory symptoms, were treated with nebulized ribavirin. There were no deaths. We conclude that awareness of the risk of RSV infection in immunocompromised patients coupled with rapid diagnosis and treatment, screening of symptomatic patients and staff, cohort nursing of cases and basic infection control procedures can prevent spread of RSV infection and reduce morbidity.

Spondylo-epiphyseal dysplasia tarda. The X-linked variety in three brothers.

Three brothers with the X-linked variety of spondylo-epiphyseal dysplasia tarda are presented. Their clinical courses differed: one was relatively free of symptoms, the second had slowly progressive osteoarthritis of the hip, and the third had an acute, disabling arthritis necessitating total hip arthroplasty. The clinical features of this disorder are reviewed.

Preoperative assessment of the acetabulum.

Preoperative assessment of the acetabulum requires a good knowledge of the normal acetabular anatomy, good plain radiographs, and a knowledge of the various defect patterns that may influence the surgeon's ability to achieve secure fixation of the component at surgery. In certain situations, special radiographic techniques are advantageous.

Hip fractures: an increasing health care cost.

Studies in several countries have indicated that there is likely to be a dramatic increase in the number of hip fractures in the early part of the 21st century. At a time when health care costs are coming under close scrutiny internationally, the added financial burden of the increasing number of fractures is of concern. This study analyzes the cost of treating hip fractures in New Zealand in 1990 and projects forward the costs of treatment and the percentage of that portion of the government's health budget for the years 2001 and 2011.

Air cushion mower foot injuries.

AIMS: This study was undertaken to identify significant physical, social and psychological problems resulting from injuries caused to the feet by air cushion mowers. METHODS: Thirty-four patients seen with air cushion mower injuries were reviewed, either by personal assessment, or by questionnaire. RESULTS: A large number of patients had significant symptoms relating to their soft tissue or bone injuries, the majority experiencing some pain, and those who had amputations difficulty in some aspects of walking. CONCLUSIONS: Better education of the dangers of the misuse of these mowers may reduce the incidence of significant forefoot injuries.

Avascular necrosis of the femoral head in neurosurgical patients: a report of two cases.

Two patients having subarachnoid haemorrhage due to cerebral aneurysms were given betamethasone postoperatively. Both developed avascular necrosis of the head of the femur, three and four years later.

Pneumococcal osteomyelitis of the superior pubic ramus: case report.

A patient with osteomyelitis of the superior pubic ramus is reported. Computed tomography was helpful in making the diagnosis.

Indoor cricket finger injuries.

Indoor cricket is a popular winter sport, but injuries sustained in the game have not been previously reported. The Accident Compensation Corporation statistics showed that in 1987 520 injuries were sustained in indoor cricket. This paper reports 33 finger and thumb injuries sustained in two seasons of indoor cricket. The majority of patients had some residual stiffness, deformity or loss of function as a result of the injuries.

Albumin levels and mortality in patients with hip fractures.

AIM: The aim of the study was to examine the serum albumin levels of patients admitted with hip fractures to see whether there was any relationship between serum albumin and subsequent mortality. METHODS: A group of 39 consecutive patients with hip fractures was followed for a period of 12 months. The serum albumin was determined preoperatively. No patient was lost to follow up. RESULTS: Ten patients died at 12 months. Those who died had a significantly lower serum albumin level than those alive at the end of the follow up period. CONCLUSIONS: The results of this study show that preoperative serum albumin determination in patients with hip fractures is a useful guide to postfracture mortality.

Enoxaparin prophylaxis for deep vein thrombosis in orthopaedic surgery.

Seventeen patients undergoing elective total hip or knee joint replacement were given enoxaparin prophylaxis against deep vein thrombosis. Four patients developed clinical evidence of deep vein thrombosis, confirmed by venography. Two patients developed disseminated intravascular coagulation.