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Biomedical subjects

S R Jones

Publications and source records attributed to S R Jones.

At least 73 records · Page 4Linked to original sources

Alpha-foetoprotein heterogeneity: what is its value in managing patients with germ cell tumours?

Alpha-foetoprotein (AFP) is widely used in the diagnosis, therapeutic monitoring and follow-up of patients with germ cell tumours. On occasion, the interpretation of a raised serum AFP measurement in a patient is confounded by the fact that AFP also increases in a variety of liver and gastrointestinal diseases. AFP exists as a number of isoforms, which can be separated by their differential binding to plant lectins. Thus, AFP-concanavalin A (ConA) binding affords a means of distinguishing between a raised AFP of teratoma or liver aetiology and has recently been reported to possess sensitivity and specificity approaching 100%. We present a patient in whom column chromatographic ConA binding was used as a basis for clinical management decisions for treatment for relapsed germ cell testicular tumour. The presumption of high test specificity led to a delay in the diagnosis of cancer recurrence, from which the patient ultimately died. We conclude that the clinical utility of lectin binding assays currently remains uncertain and further evaluation is warranted.

Adult↗

Effects of immersion in water on survival of preimaginal stages of Haematobia irritans (Diptera: Muscidae).

Laboratory studies on effects of immersion and immersion duration on all Haematobia irritans (L.) preimaginal stages revealed a significant disparity in tolerance limits among different developmental stages and in tolerance to different immersion durations (0, 1, 6, 18, and 30 h). Of the 4 preimaginal stages, 2nd instars were most susceptible to immersion of any duration, whereas eggs and pupae were most resistant. All instars were intolerant of immersion durations >6 h, with <10% survival at 6-, 18-, and 30-h immersion durations. Survival of 2nd instars was reduced to 38% by 0-h immersion, when compared with the control group. Adult eclosion was reduced by immersion durations of 18 and 30 h during the pupal stage. Life stage survival was dependent upon immersion duration, with survival generally decreasing as a negative linear function of increasing immersion duration. Immersion durations of 0, 1, 6, 18, and 30 h resulted in overall mortality rates of approximately 30, 37, 53, 61, and 82%, respectively. In wet regions with low elevations, water accumulation may significantly affect horn fly distribution and abundance. In drier regions, where flooding events are sporadic and water accumulation variable, the effect on horn fly populations is uncertain.

Animals↗

Epstein-Barr virus isolates with the major HLA B35.01-restricted cytotoxic T lymphocyte epitope are prevalent in a highly B35.01-positive African population.

An influence of cytotoxic T lymphocyte (CTL) response over Epstein-Barr virus (EBV) evolution was first suggested by the finding that virus isolates from highly HLA-A11-positive Oriental populations were specifically mutated in two immunodominant A11-restricted CTL epitopes. Here we turn to a second HLA allele, B35.01 and show that B35.01-restricted CTL responses in Caucasian donors reproducibly map to a single peptide epitope, YPLHEQHGM, representing residues 458-466 of the type 1 EBV nuclear antigen 3A protein (B95.8 strain). In this case, however, most EBV isolates from a highly B35.01-positive population (in The Gambia) either retained the CTL epitope sequence or carried a mutation (P-->S at position 2) which conserved antigenicity; changes leading to reduced antigenicity (Y-->N at position 1) were found in only a minority of cases. Furthermore, CTL recognizing the YPLHEQHGM epitope could be reactivated from the blood of some B35.01-positive Gambian donors by in vitro stimulation with the synthetic peptide, indicating that epitope-specific immunity does exist in this population. Possible differences between the A11-based and B35.01-based studies are discussed.

Amino Acid Sequence↗

Comparison of dopamine uptake in the basolateral amygdaloid nucleus, caudate-putamen, and nucleus accumbens of the rat.

Regional differences in the kinetics and pharmacological inhibition of dopamine uptake were investigated with fast-scan cyclic voltammetry in both the intact rat brain and a brain slice preparation. The regions compared were the basolateral amygdaloid nucleus, caudate-putamen, and nucleus accumbens. The frequency dependence of dopamine efflux evoked in vivo by electrical stimulation of the medial forebrain bundle was evaluated by nonlinear curve fitting with a Michaelis-Menten-based kinetic model. The Km for dopamine uptake was found to be significantly higher in the basolateral amygdala (0.6 microM) than in the other two regions (0.2 microM), whereas the Vmax value for dopamine uptake in the basolateral amygdala was significantly lower (0.49 microM/s vs. 3.8 and 2.4 microM/s in the caudate and accumbens, respectively). Similar kinetics were also obtained in brain slices. Addition of a dopamine uptake inhibitor, cocaine or nomifensine (10 microM), to the perfusion buffer increased the apparent Km value > 25-fold in slices of both the caudate-putamen and nucleus accumbens. In contrast, neither uptake inhibitor had an observable effect in the basolateral amygdaloid nucleus. Thus, dopamine uptake in the rat brain is regionally distinct with regard to rate, affinity, and sensitivity to competitive inhibition.

Amygdala↗

Fetal mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxycholic acid.

Cholestasis of pregnancy is associated with increased fetal morbidity and mortality and should be treated actively. The significance attached to pruritus in pregnancy is often minimal, but it is a cardinal symptom of cholestasis of pregnancy, which may have no other clinical features. Eight women with previous cholestasis of pregnancy were referred to The Liver Unit within a 12 month period for advice concerning future pregnancies. Thirteen pregnancies had been affected by cholestasis of pregnancy and 12 had been treated expectantly with resultant perinatal morbidity or mortality in 11 (one normal delivery), including; eight stillbirths, two premature deliveries with fetal distress (one died in perinatal period), and an emergency caesarean section for fetal distress. The other pregnancy was treated actively and delivery was uncomplicated. Subsequently, three of these cases with recurrent cholestasis of pregnancy were referred while pregnant. In each, cholestasis developed with severe pruritus, gross increase of serum bile acids, and deranged liver tests. Each was treated with the choleretic agent ursodeoxycholic acid, with rapid clinical improvement and resolution of deranged biochemistry. In conclusion, cholestasis of pregnancy continues to be treated expectantly despite its association with increased morbidity and mortality and evidence suggesting improved prognosis with active treatment and the potential of reducing the associated perinatal mortality. In an uncontrolled series of three patients with cholestasis of pregnancy, ursodeoxycholic acid seemed to provide safe and effective therapy.

Adult↗

Screening for Down's syndrome: the first two years experience in Bristol.

OBJECTIVES: To evaluate the effectiveness of a programme for antenatal screening for Down's syndrome using alpha fetoprotein and total human chorionic gonadotrophin as maternal serum markers. SETTING: A district general hospital providing a screening service to a local purchasing authority and (under contract) to another purchasing authority in the same region. METHODS: Patients were counselled and screened between 15 and 20 weeks gestation and Down's risk estimates calculated using the maternal serum marker results as modifiers of the age related risk. Outcome was determined in collaboration with the Regional Cytogenetics Unit. OUTCOME MEASURES: Detection rate for Down's syndrome, false positive rate, uptake of screening, and uptake of amniocentesis. RESULTS: In two years 22816 women were screened (approximately 84% of population); 32 Down's pregnancies were identified, 19 (59.4%) had a reported risk of > or = 1:250 and 20 (62.5%) a reported risk of > or = 1:300. Of those screened before 17 weeks, 16/20 (80%) had a reported risk of > or = 1: 300 compared with 4/12 (33%) of those screened later (P = 0.008); 4.64% of patients screened had reported risks > or = 1: 250 and 5.87% reported risks of > or = 1:300. Amniocentesis uptake was 70% in patients with reported risks of > or = 1:300. CONCLUSIONS: Overall the screening programme was effective but screening before 17 weeks was very much more effective than screening later.

Adolescent↗

Dopamine supersensitivity and hormonal status in puerperal psychosis.

BACKGROUND: We examine the dopamine receptor supersensitivity hypothesis of puerperal psychosis, and explore puerperal changes in the functional sensitivity of this receptor system. METHOD: Dopamine receptor sensitivity was estimated using growth hormone (GH) response to apomorphine challenge following delivery in 37 control women, and 11 deliveries in 10 women at 'high risk' of puerperal psychosis (previous history of puerperal affective or non-puerperal manic psychosis). Tests were on days 4 or 5, 11 or 12 and at six weeks postpartum. RESULTS: Three women developing puerperal psychosis had subsensitive GH responsiveness on day 4. GH response to 67 challenge tests (in control and 'high risk' women) increased between days 4 or 5 and six weeks postpartum (P < 0.05). GH response at six weeks correlated with free thyroxine levels (P < 0.01). CONCLUSIONS: These three cases do not support the stated hypothesis. Hypothalamic dopamine receptor sensitivity increases during the puerperium; thyroxine might influence this.

Adult↗

Different effects of cocaine and nomifensine on dopamine uptake in the caudate-putamen and nucleus accumbens.

The effects of cocaine and nomifensine on the uptake of dopamine have been compared in the caudate-putamen and nucleus accumbens of rat brain slices. Electrical stimulation of brain slices was used to evoke dopamine efflux and the changes in dopamine concentration in the extracellular fluid were monitored with fast-scan cyclic voltammetry with Nafion-coated, carbon-fiber electrodes. The disappearance of extracellular dopamine after the stimulation fit Michaelis-Menten kinetics in both regions. Cocaine and nomifensine were found to competitively inhibit dopamine uptake in both regions. The competitive mechanism of action was apparent in the primary data because the initial uptake rates were unchanged by low doses of inhibitor, but dopamine uptake was slowed at concentrations near the Km value. In both regions, the apparent Km value increased with higher concentrations of cocaine (0.01-60 microM) or nomifensine (0.01-30 microM) in the perfusion buffer. The apparent Km values were used to obtain inhibition constants (Ki values) for the uptake inhibitors in each region. This analysis showed that cocaine had a Ki of 0.29 microM in both regions. Nomifensine, however, had a significantly higher potency in the caudate-putamen (Ki = 0.09 microM) than in the nucleus accumbens (Ki = 0.21 microM). These results show that there are differential effects of uptake inhibitors in different brain regions, and suggest that the dopamine transporter exhibits cell-specific regulation.

Animals↗

Acute aphasia complicating typhoid fever in an adult.

Motor aphasia complicating bacteriologically confirmed typhoid fever in a 20-year-old adult female is presented. Neither the cause of death nor the aetiology of this isolated neurological deficit could be determined from detailed post-mortem examination. An immune related mechanism is suggested based on the temporal characteristics of this complication and CSF abnormalities.

Acute Disease↗

Interference by pH and Ca2+ ions during measurements of catecholamine release in slices of rat amygdala with fast-scan cyclic voltammetry.

Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to investigate catecholamine release and uptake induced by local electrical stimulation of rat brain slices containing the basolateral amygdaloid nucleus. The amygdala contains less catecholamine than the striatum, and the observed release is proportionately smaller. Stimulus trains of long duration were required to obtain a well-resolved concentration change in the basolateral amygdala. Voltammetric detection of catecholamines under these conditions was complicated by interference from two extracellular ions, H+ and Ca2+. Ion-selective microelectrodes were used in conjunction with carbon-fiber microelectrodes to monitor pH and Ca2+. The magnitude of the pH changes was correlated with stimulation length and followed the pattern of a brief alkaline shift followed by a longer acidic shift. Extracellular Ca2+ concentration decreased during stimulation and returned fairly rapidly to baseline after the stimulation was over. Because it was not possible to account for all of the ionic interferences using information in the voltammograms, other strategies were employed. Exposure of amygdala slices to L-DOPA or DA increased electrically evoked release of catecholamine, but the effect was transient, and uptake rates decreased during continued exposure to these agents. The most successful approach to remove the interferences was to subtract the response obtained after exposure of the slice to the catecholamine depleter, Ro 4-1284. This agent eliminates the catecholamine response but does not appear to alter the ionic changes.

Amygdala↗

Measurement of lamotrigine under conditions measuring phenobarbitone, phenytoin, and carbamazepine using reversed-phase high-performance liquid chromatography at dual wavelengths.

A reverse-phase high-performance liquid chromatographic (HPLC) method for the measurement of lamotrigine (LTG) simultaneously with phenobarbitone (PB), phenytoin (PHT), and carbamazepine (CBZ) is described using hexobarbital as the internal standard. The method uses the chromophore at 307 nm to detect LTG in the presence of interfering CBZ-10,11-epoxide detected at 220 nm, the wavelength used to measure the other drugs. This method requires < 10 min/sample for completion. Simultaneous monitoring of the chromatographs at 220 and 310 nm with a simple calculation allows LTG to be measured virtually identically to a routine method for monitoring of the other anticonvulsants. Between-batch precisions for LTG at 2 and 6 mg/L were < 5%. Accuracy of LTG estimation was assessed by comparison with known values of samples supplied by an external quality assessment scheme.

Anticonvulsants↗

Morphology and infectivity of cultivated Trypanosoma ambystomae.

Cultures of Trypanosoma ambystomae were initiated and maintained in hypo-osmotic biphasic blood-agar medium. Epimastigotes and trypomastigotes occurred in culture and although they were similar in size, epimastigotes predominated with about 70% of all stages. Epimastigotes divided by equal binary fission and occasionally formed rosettes. Cultured trypomastigotes did not divide. Cultures isolated 118 days earlier were infective to all 3 laboratory-reared Ambystoma jeffersonianum and to 2 of 3 Ambystoma mexicanum; the latter is a new host record. Trypanosomes were morphometrically similar in both experimental hosts. Specimens from 20-day-old experimental infections were smaller than those from natural infections. Dividing bloodstream forms were detected in experimental infections. Standard culture conditions should be adopted if the morphology of culture forms is to have taxonomic significance.

Ambystoma↗

Spinal epidural abscess. Optimizing patient care.

The medical literature regarding spinal epidural abscess has two common threads: reports of poor prognosis and appeals for rapid treatment. Spinal epidural abscess is a difficult diagnosis to make because of its rarity--many physicians will never see a case during their careers. Among all patients admitted to hospitals, the incidence is approximately one to two cases per 10,000. Only increased awareness and swift management of spinal epidural abscess will improve outcome. Our goal through this report is to enhance the recognition and treatment of spinal epidural abscess. We present 28 new cases of spinal epidural abscess, giving special attention to the peculiarities of the disease; we compile and analyze comprehensive data from cases from literature; and finally, we present the results of 16 retrospective personal interviews of infected patients.

Abscess↗