Biomedical subjects

J J Walker

Publications and source records attributed to J J Walker.

At least 19 recordsLinked to original sources

PubMed2000

Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen.

The assessment of angiogenesis in breast cancer is of importance as a key indicator of survival and response to therapy. Circulating vascular endothelial growth factor (VEGF) measurements may provide a less subjective analysis than microvessel density (MVD) or immunohistochemical analysis of VEGF expression; however, most studies have used serum, which is now known to largely reflect platelet-derived VEGF concentrations. This study examined for the first time both plasma (VEGFp) and serum (VEGFs) VEGF concentrations in 201 blood samples from pre- and postmenopausal healthy controls and from patients with benign breast disease, localized breast cancer, breast cancer in remission, or metastatic breast cancer and related these to other clinicopathological markers. VEGFp but not VEGFs concentrations of patients with localized disease were significantly elevated compared with normal controls (P = 0.016). Patients with metastatic disease had higher VEGFp and VEGFs levels than normal controls (P < 0.001, P = 0.044 respectively), and higher VEGFp, but not VEGFs, than patients with benign disease (P = 0.009) and patients with localized disease (P = 0.004). However, the highest VEGFp and VEGFs concentrations were seen in patients in remission compared with normal controls (P < 0.001 and P = 0.008, respectively). VEGFp concentrations in patients in remission were also higher than in patients with benign disease (P = 0.01) or patients with localized disease (P = 0.005). Tamoxifen treatment was significantly associated with higher circulating and platelet-derived VEGF levels. Circulating VEGF did not correlate with any clinicopathological factor, including MVD or VEGF expression. VEGF expression was significantly correlated with estrogen receptor status and inversely correlated with tumor grade. MVD correlated with tumor size. Tamoxifen-induced increases in VEGF may be important in clinical prognosis or associated pathologies.

Adult↗

PubMed2000

Ectopic pregnancy.

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Abortifacient Agents, Nonsteroidal↗

PubMed2000

Evidence of a T(H) 1 type response associated with recurrent miscarriage.

OBJECTIVE: To determine whether the T(H) 1 cytokine interferon (IFN)-gamma is associated with miscarriage whereas the T(H) 2 cytokine interleukin (IL)-10 is associated with successful pregnancy. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic setting. PATIENT(S): Group 1 comprised 10 nonpregnant women; group 2, 10 first-trimester primigravid women; group 3, 10 first-trimester primigravid women suffering spontaneous abortion; and group 4, 10 first-trimester pregnant women with a history of miscarriage. All women were pregnant at the time of sampling, but 5 miscarried later in the first trimester. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Serum levels of IL-10 and IFN-gamma. RESULT(S): Levels of IL-10 were significantly raised in normal pregnancy. Levels of IFN-gamma were raised in the recurrent-miscarriage group as compared with normal pregnancy. When patients in group 4 were divided into those whose pregnancies went to term and those who miscarried, we found that successful pregnancy was associated with a statistically significant increase in IL-10, whereas miscarriage was associated with significantly increased levels of IFN-gamma. CONCLUSION(S): These results support the view that miscarriage is associated with a T(H) 1 type response.

Abortion, Habitual↗

PubMed2000

Severe pre-eclampsia and eclampsia.

The mainstay of the management of severe pre-eclampsia is early referral, stabilization of the mother with antihypertensive therapy and anticonvulsants if required, full assessment of the mother and the baby, and delivery on the best day in the best way. It is to be remembered that delivery is the long-term cure, but most women get worse after delivery and most maternal deaths occur postpartum. It is important that doctors have the training to be aware of the dangers of this condition, guidelines to follow and senior support. Lowering blood pressure has been associated with a reduction in the mortality from cerebrovascular accident and early use of antihypertensive agents is beneficial to both mother and baby. The main cause of death is now pulmonary oedema, with renal failure a rare complication. It is important that, after delivery, vigilance is maintained and fluid replacement is given with care. It is better to 'run them dry' than to give fluid replacement that may encourage pulmonary oedema. Followup is required with counselling about what has happened and the prospects of recurrence.

Anticonvulsants↗

PubMed2000

The Drosophila melanogaster sex determination gene sisA is required in yolk nuclei for midgut formation.

During sex determination, the sisterlessA (sisA) gene functions as one of four X:A numerator elements that set the alternative male or female regulatory states of the switch gene Sex-lethal. In somatic cells, sisA functions specifically in sex determination, but its expression pattern also hints at a role in the yolk cell, a syncytial structure believed to provide energy and nutrients to the developing embryo. Previous studies of sisA have been limited by the lack of a null allele, leaving open the possibility that sisA has additional functions. Here we report the isolation and molecular characterization of four new sisA alleles including two null mutations. Our findings highlight key aspects of sisA structure-function and reveal important qualitative differences between the effects of sisA and the other strong X:A numerator element, sisterlessB, on Sex-lethal expression. We use genetic, expression, clonal, and phenotypic analyses to demonstrate that sisA has an essential function in the yolk nuclei of both sexes. In the absence of sisA, endoderm migration and midgut formation are blocked, suggesting that the yolk cell may have a direct role in larval gut development. To our knowledge, this is the first report of a requirement for the yolk nuclei in Drosophila development.

Alleles↗

PubMed2000

A double-blind randomised trial of leuprorelin acetate prior to hysterectomy for dysfunctional uterine bleeding.

OBJECTIVE: To evaluate the use of pre-operative leuprorelin acetate for reducing the morbidity from hysterectomy for nonfibroid menorrhagia. DESIGN: A double-blind, randomised, placebo-controlled trial. SETTING: Gynaecology department in a large university teaching hospital. SAMPLE: Fifty-one women without uterine fibroids awaiting abdominal or vaginal hysterectomy for dysfunctional uterine bleeding. METHODS: Participants received leuprorelin acetate or placebo for eight weeks prior to hysterectomy. MAIN OUTCOME MEASURES: Operative blood loss, operative difficulty, first day morphine use, speed of return to 'normal health'. RESULTS: The study and control groups were similar as regards prognostic factors. Two women in the study group withdrew because of side-effects. Although a 34% reduction in uterine volume was seen in those treated with leuprorelin, there were no significant differences in operative blood loss (183 mL in the study group vs 285 mL in controls, P = 0.27), operation time (39 vs 49 min, P = 0.64) or operative difficulty (visual analogue scale 3.0 vs 4.0, P = 0.09). Furthermore, there was no difference between the groups in post-operative morbidity or rate of recovery. CONCLUSIONS: Treating women with leuprorelin acetate for 8 weeks prior to surgery for nonfibroid menorrhagia has no significant operative or post-operative benefits.

Adult↗

PubMed2000

Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team.

OBJECTIVE: To test the postulated preventive effects of dietary n-3 fatty acids on pre-term delivery, intrauterine growth retardation, and pregnancy induced hypertension. DESIGN: In six multicentre trials, women with high risk pregnancies were randomly assigned to receive fish oil (Pikasol) or olive oil in identically-looking capsules from around 20 weeks (prophylactic trials) or 33 weeks (therapeutic trials) until delivery. SETTING: Nineteen hospitals in Europe. SAMPLES: Four prophylactic trials enrolled 232, 280, and 386 women who had experienced previous pre-term delivery, intrauterine growth retardation, or pregnancy induced hypertension respectively, and 579 with twin pregnancies. Two therapeutic trials enrolled 79 women with threatening pre-eclampsia and 63 with suspected intrauterine growth retardation. INTERVENTIONS: The fish oil provided 2.7 g and 6.1 g n-3 fatty acids/day in the prophylactic and therapeutic trials, respectively. MAIN OUTCOME MEASURES: Preterm delivery, intrauterine growth retardation, pregnancy induced hypertension. RESULTS: Fish oil reduced recurrence risk of pre-term delivery from 33% to 21% (odds ratio 0.54 (95% CI 0.30 to 0.98)) but did not affect recurrence risks for the other outcomes (OR 1.26; 0.74 to 2.12 and 0.98; 0.63 to 1.53, respectively). In twin pregnancies, the risks for all three outcomes were similar in the two intervention arms (95% CI for the three odds ratios were 0.73 to 1.40, 0.90 to 1.52, and 0.83 to 2.32, respectively). The therapeutic trials detected no significant effects on pre-defined outcomes. In the combined trials, fish oil delayed spontaneous delivery (proportional hazards ratio 1.22; 1.07 to 1.39, P = 0.002). CONCLUSIONS: Fish oil supplementation reduced the recurrence risk of pre-term delivery, but had no effect on pre-term delivery in twin pregnancies. Fish oil had no effect on intrauterine growth retardation and pregnancy induced hypertension, affecting neither recurrence risk nor risk in twin pregnancies.

Delivery, Obstetric↗

PubMed2000

Ectopic pregnancy.

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Abortifacient Agents, Nonsteroidal↗

PubMed2000

Malignant primary hypertension in pregnancy treated with lisinopril.

OBJECTIVE: To report a case of a patient treated with an angiotensin-converting enzyme (ACE) inhibitor with a good neonatal outcome. CASE REPORT: A 39-year-old African-Caribbean patient who had chronic hypertension presented at 18 weeks' gestation with acute hypertension. She was being treated for chronic hypertension with lisinopril, but had self-discontinued treatment. Attempts to control her hypertension with labetolol, nifedipine, and methyldopa were ineffective. She was therefore offered termination of pregnancy so treatment with lisinopril could be restarted. The patient elected to continue with the pregnancy in spite of the fetal risks associated with the use of an ACE inhibitor. She was delivered of a girl at 26 weeks' gestation. The baby initially had renal failure and also developed acute necrotizing enterocolitis. The renal failure improved simultaneously with the latter complication, and it is postulated that there was enteric excretion of lisinopril. The baby was discharged home on day 102 with no further complications. DISCUSSION: ACE inhibitors are acceptable medications to use in the first trimester of pregnancy; however, fetal malformations and neonatal complications have been associated with their use later in pregnancy, and they have a perinatal mortality rate of 97/1000. Lisinopril is excreted in urine and feces unchanged, and its half-life is prolonged in anuric neonates. Peritoneal dialysis eliminates lisinopril; however, this neonate improved after treatment for necrotizing enterocolitis and simultaneous improvement in bowel function. CONCLUSIONS: ACE inhibitors should not be used in pregnancy beyond the end of the first trimester. In exceptional cases, they may be indicated for the control of severe hypertension when the patient is refractory to other medications. The patient should be fully counseled about the adverse effect profile and neonatal outcome. This case report documents a successful outcome for mother and baby in these circumstances.

Adult↗

PubMed1999

Quality at general practice consultations: cross sectional survey.

OBJECTIVES: To measure quality of care at general practice consultations in diverse geographical areas, and to determine the principal correlates associated with enablement as an outcome measure. DESIGN: Cross sectional multipractice questionnaire based study. SETTING: Random sample of practices in four participating regions: Lothian, Coventry, Oxfordshire, and west London. PARTICIPANTS: 25 994 adults attending 53 practices over two weeks in March and April 1998. MAIN OUTCOME MEASURES: Patient enablement, duration of consultation, how well patients know their doctor, and the size of the practice list. RESULTS: A hierarchy of needs or reasons for consultation was created. Similar overall enablement scores were achieved for most casemix presentations (mean 3.1, 95% confidence interval 3.1 to 3.1). Mean duration of consultation for all patients was 8.0 minutes (8.0 to 8.1); however, duration of consultation increased for patients with psychological problems or where psychological and social problems coexisted (mean 9.1, 9.0 to 9.2). The 2195 patients who spoke languages other than English at home were analysed separately as they had generally higher enablement scores (mean 4.5, 4.3 to 4.7) than those patients who spoke English only despite having shorter consultations (mean 7.1 (6. 9 to 7.3) minutes. At individual consultations, enablement score was most closely correlated with duration of consultation and knowing the doctor well. Individual doctors had a wide range of mean enablement scores (1.1-5.3) and mean durations of consultation (3. 8-14.4 minutes). Doctors' ability to enable was linked to the duration of their consultation and the percentage of their patients who knew them well and was inversely related to the size of their practice. At practice level, mean enablement scores ranged from 2.3 to 4.4, and duration of consultation ranged from 4.9 to 12.2 minutes. Correlations between ranks at practice level were not significant. CONCLUSIONS: It may be time to reward doctors who have longer consultations, provide greater continuity of care, and both enable more patients and enable patients more.

Adult↗

PubMed1999

Uterine ultrasonographic changes with gonadotropin-releasing hormone agonists.

OBJECTIVES: Our purpose was to assess the changes in uterine volume and uterine artery pulsatility index in response to gonadotropin-releasing hormone agonist treatment in women undergoing hysterectomy for nonfibroid-related uterine bleeding. STUDY DESIGN: A double-blind, placebo-controlled randomized trial of 51 women awaiting hysterectomy in a gynecology outpatient clinic was conducted. The women were treated for 8 weeks with either leuprolide acetate depot or placebo. Vaginal ultrasonographic examinations were performed before and after treatment. The paired t test was used for statistical analysis. RESULTS: In those allocated to therapy with gonadotropin-releasing hormone agonist the mean uterine volume decreased by 34% and the uterine artery pulsatility index increased from 2.25 to 2.7. No significant changes were seen in the placebo group. The intersonographer variability was low and there was a high correlation between uterine size as measured by ultrasonography before hysterectomy and that measured postoperatively. CONCLUSIONS: Treatment with gonadotropin-releasing hormone agonists leads to uterine shrinkage and an increase in the uterine artery pulsatility index even in the absence of uterine fibroids.

Adult↗

PubMed1999

Decreasing estrogen in nonpregnant women lowers uterine myometrial type I nitric oxide synthase protein expression.

OBJECTIVE: Our purpose was to study the effect of estrogen on myometrial nitric oxide synthase. STUDY DESIGN: Twenty-four women were randomly assigned to treatment with gonadotropin-releasing hormone agonist or placebo for 8 weeks before hysterectomy, at which time samples of myometrium were collected and the serum levels of estrogen, nitrate, and nitrite measured. Myometrial nitric oxide synthase was measured with the arginine-citrulline assay. The levels of endothelial nitric oxide synthase and neuronal nitric oxide synthase were determined by Western blot analysis. RESULTS: Myometrial nitric oxide synthase was 88% calcium dependent but only partially calmodulin dependent. Women treated with gonadotropin-releasing hormone agonist had postmenopausal levels of estradiol and had significantly lower levels of myometrial neuronal nitric oxide synthase than those in the control group. Total, endothelial, and inducible nitric oxide synthase levels in the myometrium were unchanged, as were serum nitrite and nitrate levels. CONCLUSION: Neuronal nitric oxide synthase is regulated in the myometrium by estrogen. Myometrial nitric oxide synthase is not all calmodulin dependent; this may represent the activity of a novel nitric oxide synthase isoform.

Adult↗

PubMed1999

Thyroid antibody titer and avidity in patients with recurrent miscarriage.

OBJECTIVE: To determine whether the titer and avidity of the thyroid peroxidase antibody differs between pregnant women in their first trimester who have a history of recurrent miscarriage and whose pregnancies continue to term and those whose pregnancies fail again later in the first trimester. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Pregnant women in their first trimester who had a history of recurrent miscarriage (> or = 3 miscarriages) and who were known to be positive for the thyroid peroxidase antibody. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Thyroid peroxidase antibody titer and avidity (i.e., the net binding strength between antibody and antigen). RESULT(S): At the time of presentation, thyroid peroxidase antibody titer and avidity was significantly higher in those women who later miscarried compared with those whose pregnancies continued. In those whose pregnancies continued to term, titer and avidity declined as the pregnancy progressed. CONCLUSION(S): Autoimmunity plays a role in recurrent miscarriage. Among a group of patients who had had recurrent miscarriages, there appeared to be differences in the humoral response to the pregnancy between those whose pregnancies continued to term and those whose pregnancies failed again.

Abortion, Habitual↗

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

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↗