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Biomedical subjects

P Barlow

Publications and source records attributed to P Barlow.

At least 19 recordsLinked to original sources

Treatment limiting decisions in a neurosurgical unit.

In a previous paper on mortality audit we reported on the use of treatment limiting decisions (TLDs) in a neurosurgical unit in the year 1988. In this paper we compare the findings of a similar audit for 1997. It appears that our unit's policy of openly discussing all TLDs in patients who die had led to such decisions being made at a more appropriate stage in the patient's illness. Regular review of TLDs is probably helpful in increasing the confidence of clinicians to make these difficult decisions openly and timeously.

Cause of Death

The influence of mannitol on renal function during and after open-heart surgery.

Mannitol is often included in the priming solution of the heart-lung machine used during cardiopulmonary bypass (CPB). This study was set up to evaluate the effect of different doses of mannitol on human patients. Patients receiving 10 g of mannitol (n = 18) had an increased diuresis only during the bypass period (mean time = 87 min) when compared with a control group (n = 19) who did not receive mannitol. Patients receiving 20 g of mannitol (n = 19) had a significantly greater diuresis than both the control group and the 10 g group and the diuresis continued on throughout the immediate postbypass period (total mean time approximately 3 h). Patients receiving 30 g of mannitol (n = 20) also had a significantly greater diuresis that continued on during the first hour in the intensive care unit (ICU) (total mean time approximately 4 h). After 6 h in the ICU, all three groups of mannitol-treated patients equally demonstrated a trend towards an increased diuresis over the control group, which became a significant increase by 12 h in the ICU (p = 0.001) despite indications that the mannitol had been cleared from the body. These results suggest that there is an improvement of renal function post-CPB if mannitol is included in the CPB prime which may be due to an amelioration of the ischaemic effects of bypass on the kidneys.

Body Water

An economic argument in favour of endoscopic third ventriculostomy as a treatment for obstructive hydrocephalus.

This project was undertaken to examine the health resource implications of performing endoscopic third ventriculostomy as an alternative to CSF shunting in appropriate patients. We carried out a retrospective study of case records and X-rays of patients shunted de novo at the INS, Glasgow for the two year period 1990-1991. We identified all those patients who would have been suitable for endoscopic third ventriculostomy and examined the shunt complications and extra days in hospital required by these patients. A total of 150 new shunts was inserted during the two year period. Of these, 23 patients (15%)were judged suitable for endoscopic third ventriculostomy as an alternative to CSF shunting. Eight out of 23 patients required a total of 29 repeat operations and an extra 230 days in hospital due to shunt complications. Assuming an 80% success (shunt free) rate for endoscopic third ventriculostomy, we calculate that 9 operations and 74 bed days per year could be saved by using this technique. We conclude that in units undertaking a large number of CSF shunt insertions, investment in neuroendoscopic equipment, training, and expertise has the potential to release significant resources for other uses.

Adolescent

[Neonatal screening for hemoglobinopathies in the Brussels region].

We realised this study in order to determine the frequency of abnormal haemoglobins and to appreciate the need for a neonatal screening for haemoglobinopathies in Brussels. Over a two year-period, 9575 cord blood samples were systematically screened. The study disclosed following results : 40% of newborns were from regions at risk for haemoglobinopathies and abnormal haemoglobins were present in 2.5% of the neonates tested. This frequency is similar to those reported elsewhere in North Europe. The most frequent abnormal haemoglobins were the Hb S, Bart's, C, D and E. Three cases of severe forms of sickle cell anaemia were identified. The frequency of abnormal haemoglobins and Hb S traits combined to the high rate of mixed marriages (16%) justifies the need for a universal screening for haemoglobinopathies in Brussels.

Belgium

Point mutations in the herpes simplex virus type 1 Vmw110 RING finger helix affect activation of gene expression, viral growth, and interaction with PML-containing nuclear structures.

Herpes simplex virus type 1 immediate-early protein Vmw110 (also known as ICP0) has been implicated in the control of the balance between the lytic and latent states, but the precise mechanisms by which it exerts its effects are unknown. Vmw110 includes a characteristic zinc binding domain, termed the C3HC4 domain or RING finger, which is essential for its function. The solution structure of a related herpesvirus RING finger domain suggested that an amphipathic alpha helix might be an important functional component of the RING finger. In this paper, we show that the equivalent region of Vmw110 is important for virus growth in tissue culture and for the normal interaction of Vmw110 with nuclear structures which include the PML protein.

Amino Acid Sequence

Structural similarity between the p17 matrix protein of HIV-1 and interferon-gamma.

The human immunodeficiency virus (HIV) matrix protein, p17, forms the outer shell of the core of the virus, lining the inner surface of the viral membrane. The protein has several key functions. It orchestrates viral assembly via targeting signals that direct the gag precursor polyprotein, p55, to the host cell membrane and it interacts with the transmembrane protein, gp41, to retain the env-encoded proteins in the virus. In addition, p17 contains a nuclear localization signal that directs the preintegration complex to the nucleus of infected cells. This permits the virus to infect productively non-dividing cells, a distinguishing feature of HIV and other lentiviruses. We have determined the solution structure of p17 by nuclear magnetic resonance (NMR) with a root-mean square deviation for the backbone of the well-defined regions of 0.9 A. It consists of four helices connected by short loops and an irregular, mixed beta-sheet which provides a positively charged surface for interaction with the inner layer of the membrane. The helical topology is unusual; the Brookhaven protein database contains only one similar structure, that of the immune modulator interferon-gamma.

Amino Acid Sequence

A novel arrangement of zinc-binding residues and secondary structure in the C3HC4 motif of an alpha herpes virus protein family.

A highly conserved, cysteine-rich region plays a crucial role in the function of a family of regulatory proteins encoded by alpha herpes viruses. The so-called C3HC4 motif spans approximately 60 residues and has been predicted to bind zinc. This motif occurs in a number of other viral and cellular proteins, many of which appear to be involved in some aspect of the regulation of gene expression. We have cloned and expressed in bacteria a portion of immediate-early protein Vmw110 of herpes simplex virus type 1 that encompasses the C3HC4 motif, and the equivalent regions from the homologous proteins of varicella zoster virus and equine herpes virus type 1 (EHV-1). All three polypeptides were purified and found to bind zinc stably. None of the three interacted significantly with either DNA or RNA under our assay conditions. The EHV-1 domain yielded interpretable proton nuclear magnetic resonance spectra. Assignment of resonances and analysis of nuclear Overhauser effects revealed its secondary structure. Starting from the N terminus, this consists of an ordered but irregular loop, the first two strands of a triple-stranded antiparallel beta-sheet, two turns of an alpha-helix, a second irregular loop, and the third strand of the beta-sheet. It appears that, taking the cysteine and histidine residues in turn, cysteine residues I, II, IV and V co-ordinate one zinc atom while the histidine residue and cysteine residues III, VI and VII co-ordinate a second zinc atom. This arrangement of secondary structure differs from that found in other characterized zinc-containing proteins.

Amino Acid Sequence

In vitro fertilization, development, and implantation after exposure of mature mouse oocytes to visible light.

Mature mouse oocytes were exposed prior to in vitro fertilization to visible light during 1, 2, or 4 hr at an intensity of 4,000 lux. Compared to controls cultured under identical conditions but protected from light, exposed eggs did not show any significant modification of cleavage speed and rate. After transfer of blastocysts obtained in vitro in uteri of pseudopregnant females, the implantation rate and the proportion of normal fetuses were not found to be different in relation to preliminary light exposure of oocytes fertilized and cultured in vitro.

Animals

Usefulness of partial dissection of the zona pellucida in a human in-vitro fertilization programme.

The influence of partial zona dissection (PZD) on the fertilization rate was studied in 34 couples with a history of fertilization failure and/or severe sperm deficiency. Overall, PZD improved the rate of monospermic fertilization compared to controls (41/254 versus 6/111: P less than 0.001) and fertilization was achieved in 50% of cases. However, the results differed according to the seminal characteristics. In 10 couples with at least two in-vitro fertilization (IVF) trials entailing total fertilization failure and with semen defined as normal, PZD did not significantly improve the monospermic fertilization rate (6/44 in the PZD group versus 2/39 among controls). A benefit related to PZD was evident in 33 attempts with severe sperm deficiency. In this group, only four of 72 unmanipulated control oocytes were fertilized but the monospermic fertilization rate was 14.6% for PZD oocytes. The rates of polyspermy were 40% and 14.6% in the groups with normal and abnormal semen parameters respectively. Of 33 trials with defective spermatozoa, 20 reached the stage of embryo transfer and three pregnancies were obtained, of which one aborted at 9 weeks.

Female

Improvement of fertilizing performance by normal and abnormal mouse semen after zona opening of mature oocytes.

The usefulness of opening the zona pellucida by partial zona dissection (PZD) to enhance fertilization of mature mouse oocytes was studied after insemination with three types of semen: normal and diluted semen and semen from long-term-vasectomized males. Zona opening did not by itself induce parthenogenetic cleavage of mature oocytes and did not significantly increase mono- and polyspermic fertilization of oocytes inseminated with normal semen. While a fertilization rate of 62% was obtained among intact oocytes, of which 4.5% were polyspermic, a 66.8% fertilization rate was observed among PZD oocytes, 6.3% of which were polyspermic. However, after using diluted semen, only 54 of 193 intact oocytes were fertilized (28%), and PZD improved the fertilization rate to 65.4%. Cleavage rate of nonmanipulated oocytes inseminated with abnormal semen from vasectomized males was dramatically decreased in comparison with those inseminated with normal semen (7.6% vs. 65%). PZD induced a moderate but significant improvement of fertilization performance when using this abnormal semen (19.6%).

Animals

Are there predictive criteria of complicated ovarian hyperstimulation in IVF?

Among 599 trials of in-vitro fertilization (IVF) treatment, complicated ovarian hyperstimulation (OHSS) was diagnosed in 14 cases (2.5%) on the basis of heavy abdominal discomfort and echographic findings (ascites, ovarian enlargement with cysts). Among eight hospitalized patients, four presented with a haemoconcentration and/or electrolytic disturbances. OHSS cases were compared with two control groups for a series of criteria: age, aetiology of infertility, total dose of human menopausal gonadotrophin (HMG), day of oocyte collection, oestradiol (E2) peak level, rate of E2 increase, number of oocytes, number of embryos transferred and embryonic vitality scores. Comparison with a random group of normal IVF trials showed a significant difference for the following parameters: E2 peak level and rate of increase, E2/dose of HMG, E2/day of egg collection and number of oocytes. When OHSS cases were compared to another control group consisting only of high E2 responders (peak E2 greater than 2700 pg/ml), no significant difference was found for any of the above-mentioned criteria. In view of this lack of predictive power of individual criteria, stepwise discriminant analysis was applied, showing that this method might provide a predictive mathematical function for evaluating the risk of OHSS before human chorionic gonadotrophin (HCG) administration. Such a formula, however, should be validated by a multicentric study in which a greater number of OHSS cases would be tested.

Adult

Predictive value of classical and automated sperm analysis for in-vitro fertilization.

The fertilization rates observed in 122 attempts at in-vitro fertilization were examined in relation to sperm characteristics assessed by visual and automated screening. Using linear regression analysis, a significant correlation was found between the fertilization rate and (i) evaluations in fresh semen sperm concentration, percentages of sperm motility, vitality and normal morphology and velocity, (ii) measurements in swim-up preparations of percentages of sperm motility, vitality and morphology, velocity and amplitude of lateral head displacement. No significant correlation was found between the fertilization rate and any of the parameters studied in 24-h-old swim-up suspensions. Analysis by multiple variable stepwise linear regression showed an optimal correlation (R6 = 0.62) between the observed fertilization rate and theoretical calculation obtained from the following predictive function: fertilization rate = -0.3 + (0.008 x swim-up motility) + (0.004 x normal sperm morphology in fresh semen). Introduction of kinematic characteristics studied by automated screening improved the multiple correlation between the calculated and observed fertilization rate in cases of normal or mildly defective semen. Because of the limited availability of motile spermatozoa, automated analysis could not supersede classical sperm analysis in cases of more severe sperm defects.

Autoanalysis