Biomedical subjects

J J Walker

Publications and source records attributed to J J Walker.

At least 55 records · Page 3Linked to original sources

PubMed1999

The influence of donated gametes on the incidence of hypertensive disorders of pregnancy.

Pregnancies achieved from oocyte, sperm or embryo donation are unique, since they have resulted from donor gametes that are immunologically foreign to the mother. Thus, studying the obstetric outcome of such pregnancies may shed some light on the pathophysiology of preeclampsia, particularly in women conceiving with donated embryos, since the entire fetal genome is allogenic in these pregnancies. In this retrospective cohort study, a total of 144 women were studied. Of these, 72 were infertility patients who had conceived as a result of sperm, ovum or embryo donation and the other 72 women were age- and parity-matched control patients who became pregnant with their own gametes, either spontaneously, or following intrauterine insemination with their partner's spermatozoa. Study patients were divided into three groups depending on the origin of the donated gametes. Group 1 consisted of pregnancies achieved by intrauterine insemination with washed donor spermatozoa (n = 33). Group 2 included women who conceived using donated oocytes (n = 27) and group 3 consisted of women who conceived as a result of embryo donation (n = 12). The incidence of pregnancy-induced hypertension in the donated gametes study group was 12.5% (9/72) compared with 2.8% (2/72) in the control group. In addition, pre-eclampsia was diagnosed in 18.1% (13/72) of the donated gametes study group compared to 1.4% (1/72) in the age- and parity-matched controls. The increased incidence of gestational hypertension in pregnancies resulting from donated gametes gives evidence for a maternal genetic component, with an equally strong fetal influence, in the complicated aetiology of gestational hypertension, and pre-eclampsia in particular.

Cohort Studies↗

PubMed1999

Menopausal changes in the myometrium: an investigation using a GnRH agonist model.

Thirty-four premenopausal women were randomized to receive 3.75 mg of leuprorelin acetate depot or placebo for 8 weeks before hysterectomy. Postoperatively, the myometrium was examined by two independent pathologists and the pathologic features were graded. Computer analysis was used to assess myometrial cellularity and arterial wall structure (on hematoxylin and eosin-stained sections) and vascularity (on sections immunostained for Factor VIII-related antigen). The cellularity of the gonadotrophin-releasing hormone agonist-treated myometrium was higher than the controls with less stromal edema. Focal myometrial hyalinization was present in a minority of cases, all in the gonadotrophin-releasing hormone agonist-treated cases. The arteries in the gonadotrophin-releasing hormone agonist-treated uteri underwent atrophy of the tunica media and had significantly more perivascular fibrosis. The number of vessels per 100 myocytes also was decreased. Hypoestrinism secondary to leuprorelin treatment leads to myocyte atrophy, decreased stromal edema, atrophy of the arcuate arteries, and decreased myometrial vascularity.

Arteries↗

PubMed1999

Intramuscular opioids for maternal pain relief in labour: a randomised controlled trial comparing pethidine with diamorphine.

OBJECTIVE: To compare the pain relief and side effects of intramuscular pethidine with intramuscular diamorphine in labour. DESIGN: Double-blind randomised controlled trial. SETTING: The labour ward in a UK teaching hospital. PARTICIPANTS: Sixty-nine nulliparous women and 64 multiparous women in labour who requested narcotic analgesia and remained undelivered one hour after trial entry. METHODS: Nulliparous women were randomised to receive either 150 mg intramuscular pethidine or 7.5 mg intramuscular diamorphine. Multiparous women were randomised to receive either 100 mg intramuscular pethidine or 5 mg intramuscular diamorphine. All participants received the anti-emetic prochloroperazine at the same time as the trial drugs. MAIN OUTCOME MEASURES: Maternal analgesia assessed by a visual analogue score and verbal scales of pain intensity and pain relief, maternal sedation and vomiting, neonatal outcome assessed by Apgar scores and the need for resuscitation. RESULTS: More women allocated to receiving pethidine than to diamorphine reported slight or no pain relief at 60 minutes after administration of these drugs (P = 0.03). This trend was repeated in most of the other measures for maternal analgesia. There was no difference in maternal sedation, but the incidence of vomiting within 60 minutes was lower for women who received diamorphine (P = 0.02). Pethidine was associated with lower Apgar scores at 1 minute (P < 0.05). CONCLUSION: Intramuscular diamorphine in labour appears to have some benefits, compared with intramuscular pethidine, but the trial was small and further research, particularly into alternative opioids and long term effects on the infants is still needed.

Analgesics, Opioid↗

PubMed1999

Modern management of eclampsia.

Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains an important cause of maternal mortality and morbidity. Despite being recognised since antiquity, consistent management practices are still lacking. Given that the aim of good care is to prevent seizures, it is disappointing that in the majority of cases the first eclamptic convulsion occurs after admission to hospital. This indicates that either the women who are likely to have a convulsion were not identified accurately, or the treatment given was ineffective. The answer to poor management of eclampsia lies in better education and training of all obstetricians, anaesthetists, midwives, and general practitioners in the diagnosis and treatment of severe pre-eclampsia and eclampsia. Protocols for the management of fluid balance, antihypertensive and anticonvulsant therapies should be available and reviewed regularly. The universal adoption of such guidelines in all obstetric units would substantially reduce elements of substandard care which have repeatedly been identified in the triennial reports of the confidential enquiries into maternal deaths in the UK.

Delivery, Obstetric↗

PubMed1999

1H NMR as a non-invasive probe of amniotic fluid in insulin dependent diabetes mellitus.

Ten amniotic fluid samples obtained from third trimester pregnant women suffering from insulin dependant diabetes mellitus were analysed by 1H-NMR and compared to ten samples from a group of normal volunteers. A subset of the metabolites identified; valine, lactate, alanine, acetate, citrate and glucose were quantitated using standard addition methods. Apart from valine and citrate, a general diminution in the concentration of each of these species was found, especially glucose, in the diabetic group. The abnormally low glucose levels in the diabetic group are suggestive of infection in the patient group. However, the depressed lactate levels in the diabetic group suggest that in these cases the fetus was not subjected to stress.

Acetates↗

PubMed1999

GnRH analogue in everyday gynecology: is it possible to rationalize its use?

BACKGROUND: The study was an audit of patients who attended the Menstrual Disorders Clinic at Glasgow Royal Infirmary over a five year period, and received gonadotrophin-releasing hormone analog (GnRHa). We aimed to identify the clinical indications for the use of GnRHa, and the effect of the latter in terms of symptom resolution and ultimate outcome. We aim to use this information to formulate a strategy for the use of GnRHa by targeting this expensive therapy to those situations where maximum benefit will be achieved. METHODS: A retrospective case review analysis of 201 patients. RESULTS: Thirty-eight percent of women presented with pelvic pain, 33% with disordered menstruation and 26% with premenstrual symptomatology. Overall, 74% of patients reported a beneficial effect of GnRHa. In the non-cyclical pelvic pain group, those patients with adhesions constituted a much greater proportion of those who did not derive benefit from GnRHa than those who did (43% vs. 16%; p<0.05; data not shown). In those patients with disordered menses, there was no difference between the diagnosis in those who did or did not derive benefit from GnRHa. Also with the exception of endometrial preparation prior to ablation and in the correction of anemia, the ultimate outcome was no different in the two groups. Of the patients with premenstrual symptomatology, the greatest proportion of those deriving benefit from GnRHa (41%) ultimately had an operative resolution. CONCLUSIONS: Our results enable us to use GnRHa as a first line in those clinical situations where maximum benefit will be achieved, either in terms of symptom resolution or as a tool to identify the most appropriate therapeutic option. We can therefore rationalize our prescribing both to the benefit of the patient and to our budget.

Adult↗

PubMed1998

Oxidation of erythrocyte glutathione by monocytes stimulated with interleukin-6. Analysis by 1H spin echo NMR.

1H spin echo NMR was used to follow the release of reactive oxygen species (ROS) from human monocytes by monitoring erythrocyte glutathione status, which is sensitive to applied oxidative stress. This allowed the ability of the cytokine interleukin-6 (IL-6) to stimulate release of ROS from monocytes to be assessed in terms of oxidative damage to other cells, providing an estimation of its importance in vivo. It was found that incubation of monocytes with erythrocytes in the presence of IL-6 resulted in oxidation of the erythrocyte glutathione pool, indicating that oxidants are released in sufficient amounts to cause oxidative stress. High levels of IL-6 occurring in plasma of women with severe pre-eclampsia could therefore be responsible for depleted plasma antioxidants and haemolysis. The oxidation of erythrocyte glutathione was inhibited by the presence of the cyclooxygenase inhibitor indomethacin, suggesting that this may be of value in the treatment of oxidative pathologies.

Erythrocytes↗

PubMed1998

Erythrocyte glutathione balance and membrane stability during preeclampsia.

This study aimed to determine whether oxidative damage to the erythrocyte occurs in preeclampsia, and relates to disease severity. The oxidative status of intact erythrocytes from preeclamptic patients and normal pregnant women was determined using spin echo 1H-NMR, which measures both the concentration and redox state of intracellular glutathione. Previous studies of preeclampsia have only measured total glutathione levels. Membrane fragility was determined from the degree of lysis caused by incubation in hypotonic saline. Erythrocytes from moderate-severe preeclamptic patients underwent more lysis than erythrocytes from control pregnant women (p < .05) or mild preeclamptic patients. It is suggested that increased lysis results from oxidative damage to the erythrocyte membrane, causing a decrease in membrane fluidity and reducing its ability to withstand osmotic changes. Intracellular glutathione was more oxidized in erythrocytes from pregnant women compared to nonpregnant controls (p < .05), and there was a less significant trend toward more oxidized glutathione with increasing severity of preeclampsia. The moderate-severe group showed a clear division in glutathione redox status: some patients had very oxidized glutathione while others had a normal redox balance. This novel finding suggests that some patients may be unusually susceptible to erythrocyte glutathione oxidation, possibly leading to general cellular damage, in particular HELLP Syndrome.

Erythrocyte Membrane↗

PubMed1998

Antioxidants and inflammatory cell response in preeclampsia.

There is widespread evidence of inflammatory cell and antioxidant activity in preeclampsia. However, it is difficult to disentangle the pathological changes from the normal physiological responses to the pathological process. The site at which the measurements are taken, and the severity of disease, alter the results. The interaction between the mother and the fetus needs to be considered separately, especially when the genetics of preeclampsia is considered. It is clear that within the placenta, there is an increase in tumor necrosis factor-alpha (TNF-alpha) and lipid peroxide production. These changes are associated with a reduction in the various placental antioxidants. This suggests there may be a failure of the normal fetal protection systems. Lipid peroxidation is also increased in the peripheral blood, as well as IL-6, IL-8, and TNF-alpha, which are of monocytic origin. Stimulated monocytes produce free radicals, which can cause oxidative damage. Maternal cells protect themselves with both plasma and intracellular antioxidants. There is an imbalance between oxidant and antioxidant activity in preeclampsia. Changes in membrane oxidation can lead to changes in the membrane stability. Genetic difference in the production of TNF-alpha and nitric oxide may also modify the disease process, demonstrating the role for "moderator genes."

Antioxidants↗

PubMed1998

A comparison of a Patient Enablement Instrument (PEI) against two established satisfaction scales as an outcome measure of primary care consultations.

OBJECTIVES: We aimed to compare a new primary care outcome measure-the Patient Enablement Instrument (PEI)-against two established satisfaction measures [the Medical Interview Satisfaction Scale (MISS) and the Consultation Satisfaction Questionnaire (CSQ)]. Specifically, we sought (i) to test whether enablement and satisfaction are related or separate concepts; and (ii) to assess whether the internal consistency of the PEI might be enhanced by the inclusion of items from the satisfaction instruments. METHODS: Questionnaire forms containing the three instruments in a variety of combinations were distributed to a total of 818 patients attending for routine surgery consultations in three urban general practices of varying socio-economic mix. The main outcome measures were: scores on the PEI; scores on the CSQ, the MISS and their individual components; rank correlations between scores on the PEI and scores on the CSQ, the MISS and their component subscales; and Cronbach's alpha coefficient for the PEI. RESULTS: Overall mean scores, expressed as percentages of maximum scores attainable, were 44.1% for the PEI, 76.9% for the CSQ and 77.6% for the MISS. Rank correlations between PEI scores and scores for the complete CSQ and MISS instruments were 0.48 (P < 0.01) and 0.47 (P < 0.01), respectively. Correlations of PEI scores with individual component scores on the CSQ were generally lower and ranged from 0.14 to 0.53; correlations of PEI scored with MISS component scores were also generally lower and ranged from 0.21 to 0.53. Internal consistency of the PEI items (assessed by Cronbach's alpha coefficient) was lowered when items from the CSQ or MISS were added. CONCLUSIONS: The study shows that 'enablement' is a primary care outcome measure which is related to but is different from general satisfaction.

Family Practice↗

PubMed1998

Evidence for the existence of a novel pregnancy-associated soluble variant of the vascular endothelial growth factor receptor, Flt-1.

Angiogenesis is essential in physiological processes including ovulation, implantation and pregnancy. One of the most potent regulators is the cytokine vascular endothelial growth factor (VEGF). We provide evidence for a novel pregnancy-associated soluble variant of the VEGF receptor Flt-1. VEGF ranged from undetectable to 157.3 pg/ml (mean 49.9 pg/ml, SD 48.4 pg/ml) in plasma samples from normal volunteers (n = 10), but was undetectable in plasma from pregnant women (n = 12) and amniotic fluid (n = 10). Recoveries of spiked VEGF were poor in pregnancy-related samples, indicating the presence of VEGF-binding activity which was confirmed using biosensor and chromatographic techniques. Partial purification and protein sequencing indicated a novel soluble form of Flt-1 with a subunit size of 150 kDa. Normally present as a multimeric structure of approximately 400-550 kDa, complexes of 600-700 kDa were formed following binding of multiple VEGF molecules. Reverse transcriptase polymerase chain reaction of Flt-1 in placenta, amnion, chorion, human umbilical vein endothelial cells and cord blood samples produced bands of the predicted sizes but failed to identify any additional RNA species, and possible reasons for this are discussed. Soluble Flt-1 may be important in regulating the actions of VEGF in angiogenesis and trophoblast invasion and may have therapeutic implications in diseases with inappropriate angiogenesis such as proliferative retinopathies and cancer.

Amino Acid Sequence↗

PubMed1998

Sympathetic nerve discharge in normal pregnancy and pregnancy-induced hypertension.

BACKGROUND: Microneurographic assessment of processed bursts that represent multi-unit nerve discharge has suggested that sympathetic hyperactivity occurs in pregnancy induced hypertension and pre-eclampsia in comparison with normal pregnancy. OBJECTIVE: To examine the differences between peripheral sympathetic outputs in pregnancy-induced hypertension and normal pregnancy by directly measuring single impulses of neural discharge. DESIGN: We compared the sympathetic neural discharge at rest and its reflex responses in subjects with pregnancy-induced hypertension and normal pregnancy and re-examined their progress at least 6 weeks post partum. The patients with pregnancy-induced hypertension were hospital in-patients for whom the diagnosis could be strictly defined and the normally pregnant women were recruited to match the former. METHODS: Standard microneurography was performed to quantify single impulses of action potentials, together with the processed multi-unit bursts from fibres innervating the leg muscles. We measured neural discharge with vascular vasoconstrictive properties, heart rate and finger arterial blood pressure at rest and their responses to standard isometric hand-grip exercise and cold pressor tests. RESULTS: As expected, patients with pregnancy-induced hypertension (n = 13) had higher levels of finger arterial blood pressure than did women with normal pregnancies (n = 11). The number of single impulses of action potentials (per min and per 100 cardiac beats) in resting patients with pregnancy-induced hypertension was more than three times greater than that in resting women with normal pregnancies, and the number of multi-unit bursts was twofold greater. After delivery of their child, sympathetic activity and heart rate in nine patients decreased, but finger arterial blood pressure decreased in patients with pregnancy-induced hypertension only. CONCLUSIONS: From results of cross-sectional and longitudinal studies, pregnancy-induced hypertension is associated with a greater resting sympathetic output than that of women with normal pregnancies. Follow-up data after parturition suggest that this hyperactivity is not the only cause of hypertension.

Electrophysiology↗

PubMed1998

Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia.

OBJECTIVE: To compare the efficacy and acceptability of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia. DESIGN: A randomised comparative parallel group study. SETTING: Gynaecology outpatient clinic in a teaching hospital. PARTICIPANTS: Forty-four women with heavy regular periods and a measured menstrual blood loss exceeding 80 ml. METHODS: Twenty-two women had a levonorgestrel intrauterine system inserted within the first seven days of menses, and 22 women received norethisterone (5 mg three times daily) from day 5 to day 26 of the cycle for three cycles. MAIN OUTCOME MEASURES: The main outcome measure was the change in objectively assessed menstrual blood loss after three months of treatment. RESULTS: When menstrual blood loss at three months was expressed as a percentage of the control, the levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the women in the levonorgestrel intrauterine system group wished to continue with the treatment, compared with only 22% of the norethisterone group. CONCLUSIONS: Both the levonorgestrel intrauterine system and oral norethisterone in this regimen provided an effective treatment for menorrhagia in terms of reducing menstrual blood loss to within normal limits. The levonorgestrel intrauterine system was associated with higher rates of satisfaction and continuation with treatment, and thus offers an effective alternative to currently available medical and surgical treatments for menorrhagia.

Adult↗

PubMed1998

The rise in caesarean section rate: the same indications but a lower threshold.

OBJECTIVE: To investigate the reasons for the rise in caesarean section rate and note any change in indications. DESIGN: A retrospective, descriptive study comparing the years 1962 and 1992. SETTING: A large city centre teaching hospital. RESULTS: There was an overall increase in the caesarean section rate from 6-8% in 1962 to 18.1% in 1992. No single cause contributed more than 30% towards this increase. The main indications in both years were similar: failure to progress (42.2% vs 36.7%) and fetal indications (18.1% vs 18.9%). The largest relative increases were in the malpresentation group (10.8% vs 16%) and previous caesarean section (4.5% vs 15.2%). CONCLUSIONS: These results suggest that there has been a lowering in the overall threshold concerning the decision to carry out a caesarean section rather than changes in obstetric management. Obstetricians and the women in their care have to decide whether the current balance between risk and benefit is acceptable or whether they wish to alter the underlying philosophy if any significant reduction is to be sustained.

Adult↗

PubMed1998

How should we approach the management of pelvic pain?

Pelvic pain is a common debilitating condition. Most investigations are invasive, expensive and usually negative. Although a positive diagnosis of endometriosis justifies a recognized treatment programme, the majority of women with negative investigations are left without a diagnosis and often accused of psychological abnormalities. The reasons for the negative investigations are just as likely to be due to the inadequate techniques of the operator as the lack of pathological signs. The early use of menstrual suppression with GnRH analogue allows pain relief sooner in the majority of sufferers and separates those with pain related to the menstrual cycle, from whatever cause, from those whose pain is not related to pelvic physiology and who would not benefit from further medication or operative therapy. The majority, who have obtained relief from the analogue therapy, then have time to discuss alternative long-term treatments without the feeling of desperation that chronic monthly pelvic pain can produce.

Endometriosis↗

PubMed1998

Trends in incidence of and mortality from invasive cancer of the uterine cervix in Scotland (1975-1994).

OBJECTIVE: I. To identify major trends in the incidence of and mortality from invasive cancer of the cervix uteri in Scotland during the twenty year period 1975-1994; II. to consider the extent to which these trends may have been shaped by the introduction of systematic cervical screening. DESIGN: Analysis of annual age standardised and age specific rates for incidence and mortality, based on data collected by the Scottish Cancer Registry and the General Register Office for Scotland. SETTING: Scotland. SUBJECTS: Women registered with the Scottish Cancer Registry as having developed invasive cancer of the cervix during the period of interest. RESULTS: Annual all ages incidence rates of invasive cervical cancer show little overall change over the period 1975-1989, but exhibit a pronounced decline from 1990 onwards. All-ages mortality rates show clear evidence of decline during the period 1975-1994, the rate for 1994 being some 30% lower than that for 1975. Annual age-specific incidence rates show different patterns by age group, with clear evidence of decreasing trends in the age range 50-64 years but different patterns in younger and older age groups. Most age groups show steep declines in incidence from 1990 onwards. Age specific mortality rates for 1975-1994 exhibit the most pronounced decreasing trends in the age range 50-64 years. The trends identified are broadly similar to those experienced in England and Wales over an approximately comparable period. CONCLUSIONS: The overall (all ages) incidence of invasive cervical cancer in Scotland changed little during the period 1975-1989, but declined sharply from 1990 onwards. The most pronounced decline in incidence across the period 1975-1994 appears to have taken place in the age range 50-64 years. This decline has been accompanied by a commensurate fall in mortality in the same age range. These reductions in incidence and mortality may be attributable in part to increased coverage of cervical screening programmes during the period of interest. Evidence from other studies suggest that, without the increased coverage of cervical screening achieved during this period incidence rates in Scotland might have been seen to increase.

Adult↗

PubMed1997

Transabdominal cervico-isthmic cerclage in the management of cervical incompetence.

The use of transabdominal cervico-isthmic cerclage is described in 13 patients with a diagnosis of cervical incompetence. The patients were recruited from seven Scottish Maternity Units over a period of 10 years. The 13 patients have had a successful pregnancy in 86.6% of pregnancies with this procedure compared with a success rate of 16% in their previous pregnancies. In carefully selected cases transabdominal cervico-isthmic cerclage is a worthwhile procedure in patients with cervical incompetence when the cervix is so damaged that it would be impossible to insert a vaginal suture or when a vaginal suture has previously failed.

Adult↗

PubMed1997

Altered interleukin 12 and nitric oxide levels in recurrent miscarriage.

The causes of recurrent miscarriage are not fully understood. Recent studies have suggested that whilst a TH 2 type immune response may be associated with a healthy pregnancy, miscarriage may be associated with a TH 1 type response. Serum levels of nitric oxide (NO) and Interleukin 12 (IL 12) were measured in; healthy non-pregnant women; healthy pregnant women; women suffering spontaneous abortion; pregnant women with a history of recurrent miscarriage; non-pregnant women with a history of recurrent miscarriage. Normal pregnancy was associated with a significant decrease in serum levels of nitrite (13.0 vs. 22.0 P < 0.0001). In women admitted with spontaneous abortion there was a significant increase in the levels of nitrite (16.0 vs. 13.0 P < 0.05), but no change in IL 12 compared to normal pregnant women. In pregnant women with a history of recurrent miscarriage levels of nitrite (16.0 vs. 13.0 P < 0.05) and IL 12 (10.0 vs. 6.0 P < 0.0006) were significantly elevated compared to normal pregnancy. When these women were sampled prior to becoming pregnant the levels of NO were found to be significantly lower than those in the non-pregnant control group (13.1 vs. 22.0 P < 0.05) although levels of IL 12 were unchanged. No correlation was found between serum nitrite and IL 12 levels. This report further supports the idea that polarisation of the immune response during pregnancy may predispose to recurrent miscarriage.

Abortion, Habitual↗