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Biomedical subjects

J Newton

Publications and source records attributed to J Newton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38alpha.

Endothelial cell (EC) apoptosis is important in vascular injury, repair, and angiogenesis. Homocysteine and/or adenosine exposure of ECs causes apoptosis. Elevated homocysteine or adenosine occurs in disease states such as homocysteinuria and tissue necrosis, respectively. We examined the intracellular signaling mechanisms involved in this pathway of EC apoptosis. Inhibition of protein tyrosine phosphatase (PTPase) attenuated homocysteine- and/or adenosine-induced apoptosis and completely blocked apoptosis induced by the inhibition of S-adenosylhomocysteine hydrolase with MDL-28842. Consistent with this finding, the tyrosine kinase inhibitor genistein enhanced apoptosis in adenosine-treated ECs. Adenosine significantly elevated the PTPase activity in the ECs. Mitogen-activated protein kinase activities were examined to identify possible downstream targets for the upregulated PTPase(s). Extracellular signal-regulated kinase (ERK) 1 activity was slightly elevated in adenosine-treated ECs, whereas ERK2, c-Jun NH(2)-terminal kinase-1, or p38beta activities differed little. The mitogen-activated protein kinase-1 inhibitor PD-98059 enhanced DNA fragmentation, suggesting that increased ERK1 activity is a result but not a cause of apoptosis in adenosine-treated ECs. Adenosine-treated ECs had diminished p38alpha activity compared with control cells; this effect was blunted on PTPase inhibition. These results indicate that PTPase(s) plays an integral role in the induction of EC apoptosis upon exposure to homocysteine and/or adenosine, possibly by the attenuation of p38alpha activity.

Adenosine↗
PubMed2000

Depo provera discussion paper on clinical care, effectiveness and side effects

Recent changes to the health services have led to an increased provision of clinical care in family planning clinics. While some women may only require contraceptive services, others may demand advice on a breadth of lifestyle issues, including diet and nutrition. Obesity affects 17% of women of childbearing age in Scotland and being overweight during pregnancy has significant health risks. A postal survey of 227 nurses identified as working in family planning clinics in Scotland was conducted in 1998. After a mail shot and one reminder, a net response rate of 64% (n = 145) was achieved. Overall, it was found that obesity was perceived as the most extensive problem in women of childbearing age. Seventy nurses (48%) reported that, in addition to offering family planning services, they gave dietary advice 'frequently' or 'always' to their clients without being asked. There were differences in nutrition-related activities in consultations between nurses offering family planning services only and those who routinely offered nutritional advice. Over half (61%) of the nurses reported that they would give advice regarding weight management even if the patients were not seeking help, although there was no significant difference between the two comparison groups. In some cases, the nutritional advice offered to clients highlighted a deficit in training. Most nutrition education came from diploma and/or training courses and scientific literature, followed by 'experience'. Those nurses already embracing a nutritional advice and guidance role were more interested in further nutrition training (p = 0.018) than the other nurses. However, overall, 67% of the nurses wished to train further in nutrition and weight management. The findings suggest that family planning nurses should be supported to develop nutritional advice and guidance skills, and that there is a pressing need for training in public health nutrition and weight management for nurses working in family planning services.

Journal Article↗
PubMed1999

Community care. Flexible friends.

A scheme that trains students to become part-time community support workers to people with mental health problems has proved popular with clients. A third of the carers had felt unsafe on at least one occasion and the service requires a high level of supervision. Professionals considered the service particularly useful for clients who felt isolated, and those at risk of self-neglect.

Community Mental Health Services↗
PubMed1999

Quantitative determination of an extremely polar compound allantoin in human urine by LC-MS/MS based on the separation on a polymeric amino column.

Quantitative determination of allantoin in biological matrix poses a challenge to bioanalysis due to the extreme polarity of allantoin. The molecule exhibits virtually no retention on any of the available hydrophobic HPLC packing materials. In this study, an assay was developed for the LC-MS/MS quantitation of allantoin in human urine using a polymeric amino column to achieve the necessary separation. The urine samples were prepared by a single-step solid phase extraction (SPE) procedure. The extracted samples were analyzed on a jordi-gel DVB polyamine column (operated under an acetonitrile/water gradient with water as the stronger mobile phase) interfaced with a Finnigan TSQ 7,000 mass spectrometer. Negative electrospray ionization (ESI) was employed as the ionization source. Allantoin and its internal standard (13C1, 15N1-allantoin) were detected by use of single reaction monitoring (SRM) mode. The method was validated in the concentration range of 14.6-213 microg/ml(-1), with within and between run accuracy and precision both < 7%. The method has been successfully applied to clinical sample analysis.

Acetonitriles↗
PubMed1999

CD8+ T cell-mediated enhancement of tumour necrosis factor-alpha (TNF-alpha) production and HIV-1 LTR-driven gene expression in human monocytic cells is pertussis toxin-sensitive.

HIV replication and LTR-mediated gene expression can be modulated by CD8+ T cells in a cell type-dependent manner. We have previously shown that supernatants of activated CD8+ T cells of HIV-infected individuals greatly enhanced p24 levels in human macrophages infected with NSI or SI primary isolates of HIV-1. Here we have examined the effect of culture with CD8+ T cell supernatants on HIV-1 LTR-mediated gene expression in monocytic cells. CD8+ T cell supernatants enhanced LTR-mediated gene expression in U38 cells activated with Tat in the absence or presence of phorbol myristate acetate (PMA) and ionomycin or TNF-alpha. Further, enhancement of LTR-mediated gene expression and virus replication in U38 cells and U1 cells, respectively, was pertussis toxin-sensitive. The enhancement of gene expression and virus replication was associated with increased levels of TNF-alpha and was significantly abrogated by antibody to TNF-alpha. In contrast, the suppression of LTR-mediated gene expression by CD8+ T cell supernatants in Jurkat T cells was not pertussis toxin-sensitive and TNF-alpha levels were not affected. These results demonstrate that factors produced by CD8+ T cells utilize different cellular pathways to mediate their effects on HIV transcription and replication in different cell types.

CD8-Positive T-Lymphocytes↗
PubMed1999

Depo Provera. Position paper on clinical use, effectiveness and side effects.

Depo Provera (medroxyprogesterone acetate, DMPA) when given as 150 mg by deep intramuscular injection every 12 calendar weeks (84 days+5 days), is a highly effective contraceptive with a very low failure rate comparable to modern copper IUDs and lower than many other methods. It should be available as a first line method to all who wish to make an informed choice about reversible methods of contraception. Pre-use counselling is essential to minimise the effect of menstrual change which occurs in most patients. However there is great patient variability. Use of DMPA is independent of intercourse and also independent of the user's memory (and thus of continuing motivation), other than remembering the 12 weekly appointments. For many women this is a great advantage. Oral contraceptive methods involve remembering to take a pill each day, in the case of the progestogen only pill within the same three hours each day. This places considerable strain on women who lead irregular lifestyles, who are very busy or travel frequently. Such women often describe a constant 'fear of forgetting', especially with the POP. The main potential disadvantage of DMPA in this country are likely to be menstrual disturbance and weight gain. The combined oral contraceptive pill gives the appearance of excellent cycle control because it removes the natural cycle altogether and replaces it with an artificial one. All progestogen-only methods, whether low or high dose, lead to menstrual disturbances, so in this respect DMPA is not unique. Although troublesome, the menstrual disturbances which occur in DMPA users very rarely require operative medical intervention, and can often be improved simply by short courses of oestrogen or shorter injection intervals. Again, women need to know what can be done so that they are aware that they should seek advice early, rather than miserably waiting.for their 12 week appointment. DMPA has no appreciable effects on blood pressure or thrombosis risk. In this it has an advantage over the combined oral contraceptive pill, and provides a simple, effective alternative for women who cannot use the pill for these reasons. Similarly, it has been suggested that women who suffer from focal migraine and are therefore advised against use of the combined oral contraceptive pill can still use progestogen-only contraceptives. Although the POP is medically safe in these circumstances, in young women it is less effective, and involves strict time keeping, which will be disadvantageous for some women. Side effects, long term use and schedules of administration are also discussed. The use of local protocols to allow nurse administration is to be supported both in general practice and the clinic situation. Perhaps the most important issue surrounding the use of DMPA is that of patient information. The method has had a particularly bad public image, which naturally makes potential users anxious and subject to misinformation from poorly informed or biased sources. Also, it is temporarily irreversible during its three months duration, so the duration of any problems or anxieties resulting from side effects may be longer than for other methods. It is of paramount importance that easily understood, accurate patient information leaflets are available, since biased and inaccurate information is readily available from women's magazines, perpetuating the myths surrounding the method.

Adolescent↗
PubMed1998

High throughput liquid chromatography/mass spectrometry bioanalysis using 96-well disk solid phase extraction plate for the sample preparation.

The 96 well solid phase extraction (SPE) operated by robot in the LC/MS/MS bioanalysis offered rapid sample preparation for drugs and metabolites in biological matrices, based on simultaneous extraction of 96 samples. The use of a disk as sorbent in the 96 well plate further improved the performance of SPE and allowed for small elution volumes, making it possible to 'dilute and shoot" after SPE elution. In this study, a 96 well plate (Empore) was developed, characterized and optimized for several pharmaceutical compounds. In addition, a robot (MultiProbe) was modified to automate the 96 well plate operation. Examples were given to illustrate the major differences of using 96 well disk plate SPE in the method development as compared to the traditional SPE. This technology has been successfully used to support many clinical studies. Typically, a batch of 96 samples were prepared in 1-1.5 hours unattended (except for the replacement of a collection plate). Considerable savings in disposable supplies were also noted.

Anti-Asthmatic Agents↗
PubMed1998

Twenty-four month comparison of apolipoproteins A-1, A-II and B in contraceptive implant users (Norplant and Implanon) in Birmingham, United Kingdom.

A 2-year prospective, randomized study of 60 implant users was performed to evaluate fasting serial serum apolipoprotein A-I, A-II, and B levels before insertion and every 3 months in users of two contraceptive implants releasing levonorgestrel (Norplant) and 3-ketodesogestrel/etonogestrel (Implanon) in Birmingham, United Kingdom. All changes in serum apolipoprotein concentrations, irrespective of an increase or decrease, were smaller than one standard deviation of the mean concentration at baseline and did not exceed the normal range for the laboratory, thus implying no evidence of an increased risk of coronary heart disease.

Adolescent↗
PubMed1998

Contraceptives: regional perspectives, issues, and unmet needs--the European perspective.

Existing methods of contraception clearly do not meet all the needs of European women. Studies have shown that women continue to want contraceptive methods with the lowest possible risks and highest possible health care benefits. In addition to offering health benefits, these methods must have extremely low failure rates and permit good compliance. Studies reflect high rates of non-compliance and discontinuation with the combined OC and the progestogen-only contraceptive pill. Methods, such as the IUDs, subdermal implants, and injectable contraceptives offer significant advances in continuation of contraception coupled with low failure rates. In the past, the use of injectable contraceptive methods in Europe was low because only the progestogen-alone methods were available - Depo-Provera and Noristerat. Both methods have been linked with extensive menstrual cycle disturbance, which has not been noted with the combined injectable methods, as reviewed by Newton et al.. The author believes that combined injectable methods should be added to the list of contraceptive methods freely available to women in Europe, not only because of their lack of disruption of the menstrual cycle, but also because of their high efficacy, good cycle control, and other health benefits. This method may prove extremely useful over the next 10-20 years. Market surveys will determine whether combined monthly injectables are perceived by potential contraceptive users as having health benefits, and focus group discussions will allow an appropriate range of contraceptive products to be available. These should increase patient choice and allow clinicians to make available a wider range of products for those seeking contraception.

Abortion, Legal↗
PubMed1998

Nosocomial acute-onset postoperative endophthalmitis survey. A 10-year review of incidence and outcomes.

OBJECTIVE: The purpose of the study was to evaluate the incidence of acute-onset (within 6 weeks after surgery) postoperative endophthalmitis and to assess the visual acuity outcomes after treatment over a 10-year period at one institution. PATIENTS AND METHODS: This retrospective study reviews all surgical cases performed between January 1, 1984 and December 30, 1994 at the Anne Bates Leach Eye Hospital, Bascom Palmer Eye Institute, University of Miami Medical Center, for the occurrence of nosocomial acute-onset postoperative endophthalmitis. RESULTS: The overall 10-year incidence of acute-onset postoperative endophthalmitis after intraocular surgery was 0.093% (54/58, 123). The incidences of culture-proven acute-onset postoperative endophthalmitis by surgical category were as follows: cataract surgery with or without intraocular lens (IOL) (0.082%, 34/41, 654), pars plana vitrectomy (PPV) (0.046%, 3/6557), penetrating keratoplasty (0.178%, 5/2805), secondary IOL placement (0.366%, 5/1367), glaucoma surgeries (0.124%, 4/3233), combined trabeculectomy and cataract surgery (0.114%, 2/1743), and combined penetrating keratoplasty and cataract surgery (0.194%, 1/515). The median visual acuity after endophthalmitis treatment was 20/200. The median visual acuities after endophthalmitis treatment by procedure were as follows: cataract surgery with or without IOL (20/133), PPV (no light perception), penetrating keratoplasty (2/200), secondary IOL implantation (20/40), glaucoma surgery (20/80), and combined trabeculectomy and cataract surgery with or without IOL (20/150). CONCLUSIONS: The overall incidence of endophthalmitis after intraocular surgery was 0.093%. The incidence of endophthalmitis was higher after secondary IOL implantation than after cataract extraction (P = 0.008, Fisher's exact test). After treatment, the visual acuity outcomes were worse in the patients who developed endophthalmitis after PPV than after cataract extraction, glaucoma procedures, or secondary IOL implantation (P < 0.05, analysis of variance, Duncan's multiple range test). Acuity outcomes after treatment of endophthalmitis were better among the patients with secondary IOL implantation than after penetrating keratoplasty or PPV (P < 0.05, analysis of variance, Duncan's multiple range test). The results of this 10-year review from a large teaching center may serve as a source of comparison for other centers and future studies.

Acute Disease↗
PubMed1998

A 2-year comparative study of endometrial histology and cervical cytology of contraceptive implant users in Birmingham, UK.

The objectives of this study were to evaluate the endometrial histology and cervical cytology of users of two contraceptive implants releasing etonogestrel/3-keto-desogestrel (Implanon) and levonorgestrel (Norplant) in West Midlands (UK) users. A 2-year prospective randomized design was used to study 60 implant users. Endometrial histology and cervical cytology were compared before insertion and after 12 and 24 months. At the end of 12 months, the majority of samples were inactive/weakly proliferative in both groups. At the end of 24 months, this remained unchanged in the Implanon group whereas the pattern was more diverse in the Norplant group. Endometrial thickness was significantly reduced in both groups during treatment. Cervical cytology remained unchanged. It is concluded that, after 2 years, there was no evidence of an increasing risk of endometrial hyperplasia, endometrial carcinoma, cervical intra-epithelial neoplasia or cervical carcinoma in either of the two groups of implant users.

Adolescent↗
PubMed1998

A novel method for the visualization of the in situ mucus layer in rat and man.

1. The observed thickness of the gastric mucus barrier varies widely, even appearing discontinuous, depending on the methods used. Here we describe the development and application of a modified periodic acid Schiff/Alcian Blue staining technique for use on cryostat sections of gastric mucosa. This technique for the first time enables the preservation and visualization of the full thickness of the adherent gastric mucus layer and the underlying mucosa. 2. In designing this novel method we have selected those procedures which would result in the least alteration to the mucus layer. The methods used were snap freezing, cryostat sectioning of the whole stomach followed by brief ethanol pretreatment (10 min in 100% ethanol), a prolonged staining with periodic acid Schiff/Alcian Blue (15 min and 2.5 h respectively), a gentle post-fixation (45 min paraformaldehyde vapour at 37 degreesC) and the use of a water-soluble mountant. 3. A continuous, adherent mucus layer was observed over the surface of the rat gastric mucosa (periodic acid Schiff/Alcian Blue stained) and human gastric antral biopsies (periodic acid Schiff stained). In the rat the mean (S.D.) mucus thickness measurements along the antrum to oesophageal axis (which was divided histologically into four regions, A to D) were: A, 166 (47) micrometer; B, 179 (48) micrometer; C, 184 (50) micrometer; D (the non-glandular stratified epithelium at the top of the stomach), Absent. In human gastric antral biopsies the mean (S.D.) mucus thickness was 144 (52) micrometer. 4. This new technique has enabled the visualization and precise measurement of thickness of the gastric mucus layer in rat and man. The adherent gastric mucus layer was observed to be continuous in the rat glandular stomach and human antrum. In validation experiments in rat the mean mucus thickness measurements were found to be twice those measured by conventional histological techniques, in which the mucus layer appeared discontinuous and patchy. However, they were within the range of thickness values seen in unfixed tissues and in the rat in vivo preparation.

Aged↗
PubMed1997

Diurnal variation in the effect of chronic mild stress on sucrose intake and preference.

Diurnal variation (depression worse in the morning) is one of the diagnostic criteria for the melancholic subtype of major depression. This study examined diurnal variation in the effects of chronic mild stress (CMS), an animal model of depression, by testing Wistar rats at different phases of the light-dark cycle. CMS decreased sucrose intake and sucrose preference in animals tested at the start of the dark phase (the most active period in this nocturnal species), but not in animals tested during the light phase. CMS also decreased body weight in both groups; however, the effects of CMS on sucrose intake in the dark phase were not secondary to body weight changes. On the contrary, loss of body weight led to underestimates in the magnitude of the effects of CMS on sucrose intake. The results support the validity of the CMS procedure as a model of melancholia. The discussion addresses criticisms of this position that have been raised in two recent publications.

Animals↗
PubMed1997

Spontaneous regression of granulomatous mycosis fungoides in an HIV positive patient.

The development of mycosis fungoides in HIV-positive patients is uncommon. We describe the granulomatous type of mycosis fungoides in an HIV-positive patient whose cutaneous lesions regressed without treatment. In addition to HIV seropositivity and mycosis fungoides, he had a long history of pulmonary sarcoidosis. Immunophenotyping of the cutaneous lymphoid infiltrates revealed a predominance of CD4+ T cells, and monoclonality was demonstrated by T-cell gene rearrangement studies. The regression of mycosis fungoides in this patient was associated with a falling peripheral blood CD4 T-cell count.

Adult↗