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Biomedical subjects

P Strickland

Publications and source records attributed to P Strickland.

At least 19 recordsLinked to original sources

Towards consensus in the long-term management of relapse prevention in schizophrenia.

APPROACH TO DEVELOPING GUIDANCE: When developing guidance for the long-term management of schizophrenia, one approach is to adopt a proactive strategy that sets out clear treatment goals and strategies. This should involve a broad view being taken, embracing overall mental and physical well-being rather than simply the absence of illness. Although relapse prevention is an important goal of any long-term management strategy, there are other aspects that need to be considered, such as reintegration into society, regaining independence and quality of life. CURRENT TREATMENT: To help achieve these goals, a range of interventions can be incorporated into long-term management strategies for schizophrenia, including pharmacological interventions, psychosocial therapies and alliance-building initiatives. The current UK National Institute for Clinical Excellence guidelines already recommend that continuous therapy should be practised using an atypical (second-generation) antipsychotic drug, whenever possible, in preference to older typical drugs. The launch of the first long-acting atypical antipsychotic is an interesting new advance that may benefit many patients with schizophrenia. Psychosocial interventions, particularly family-based therapies, as well as cognitive behavioural and compliance therapies, when used alongside antipsychotics, have been shown to reduce relapse rates dramatically and to assist in social reintegration. In addition, forging collaborative alliances with patients and their carers can help to demystify schizophrenia and empower patients to take responsibility for their illness. CONSENSUS STATEMENT: This article outlines a consensus reached by a panel of leading UK healthcare professionals working with schizophrenia brought together to discuss long-term management strategies.

Antipsychotic Agents↗

catena-Poly[dibromozinc(II)-mu-ethylenediamine-N:N']: resolution of structural anomalies resulting from the interpretation of vibrational spectra.

The title structure, [ZnBr2(C2H8N2)], is made up of infinite -ZnBr2-(en)-ZnBr2-(en)- zigzag chains. Each repeat unit contains a trans ethylenediamine ligand [N-C-C-N -179 (1) degrees ], which bridges two approximately tetrahedral but crystallographically distinct Zn atoms. One Zn atom is bisected by a crystallographic twofold axis, whereas the other has mirror symmetry. Even though the crystal packing does not allow significant interaction between Zn and N atoms on adjacent chains, it does facilitate extensive intermolecular N-H...Br hydrogen bonding (N...H 2.69-2.96 A).

Journal Article↗

Urinary 1-hydroxypyrene and other PAH metabolites as biomarkers of exposure to environmental PAH in air particulate matter.

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) from occupational, environmental, medicinal and dietary sources. PAH metabolites in human urine can be used as biomarkers of internal dose to assess recent exposure to PAHs. The most widely used urinary PAH metabolites are 1-hydroxypyrene (1-OHP) or 1-hydroxypyrene-O-glucuronide (1-OHP-gluc), the major form of 1-OHP in human urine, because of their relatively high concentration and prevalence in urine and their relative ease of measurement. Elevated levels of 1-OHP or 1-OHP-gluc have been demonstrated in smokers, in patients receiving coal tar treatment (vs. pre-treatment), in postshift road pavers or coke oven workers, and in subjects ingesting charbroiled meat. This metabolite is found (at low levels) in most human urine samples, even in persons without apparent occupational or smoking exposure. Recent studies suggest that environmental exposure to PAHs (and air particles) is associated with increased excretion of 1-OHP-gluc or 1-OHP. These findings raise the possibility of using urinary concentration of 1-OHP-gluc, or another PAH metabolite, as a surrogate biomarker of exposure to airborne fine (sooty) particulate matter--the major source of PAHs in polluted air. Reported associations between ambient particulate matter concentrations and health effects among adults and children, including respiratory disease and mortality, indicate the need for biomarkers of fine particle exposure. If validated, such biomarkers would be useful in supplementing and refining exposure information obtained by ambient monitoring.

Adult↗

Is laparoscopy safe and effective for treatment of acute small-bowel obstruction?

BACKGROUND: Acute small bowel obstruction (SBO) has been a relative contraindication for laparoscopic treatment due to the potential for bowel distention and the risk of enteric injury. However, as laparoscopic experience has increased, surgeons have begun to apply minimal access techniques to the management of acute SBO. METHODS: A retrospective review was performed of all patients with acute SBO in whom laparoscopic treatment was attempted. Patients with chronic symptoms and elective admission were excluded. Patients treated by laparoscopy were compared to those converted to laparotomy for differences in morbidity, postoperative length of stay, and return of bowel function as evidenced by toleration of a liquid diet. RESULTS: Laparoscopy was performed in 40 patients for acute SBO. The etiologies of obstruction included adhesions (35 cases), Meckel's diverticulum (two cases), femoral hernia (one case), periappendiceal abscess (one case), and regional enteritis (one case). Laparoscopic treatment was possible in 24 patients (60%), but 13 patients required conversion to laparotomy for inadequate laparoscopic visualization (two cases), infarcted bowel (two cases), enterotomy (four cases), and inability to relieve the obstruction laparoscopically (five cases). There were ten complications-one in the laparoscopic group (pneumonia) and nine in the converted group (prolonged ileus, four cases; wound infection, two cases; pneumonia, two cases; and perioperative myocardial infarction, one case). Respectively, the laparoscopic and converted groups had mean operative times of 68 and 106 min a mean return of bowel function of 1.8 and 6.2 days, and a mean postoperative stay of 3.6 and 10.5 days. Long-term follow-up was available in 34 patients. One recurrence of SBO requiring operation occurred in each group during a mean follow-up of 88 weeks. CONCLUSIONS: Laparoscopy is a safe and effective procedure for the treatment of acute SBO in selected patients. This approach requires surgeons to have a low threshold for conversion to laparotomy. Laparoscopic treatment appears to result in an earlier return of bowel function and a shorter postoperative length of stay, and it will likely have lower costs.

Acute Disease↗

The role of depression in pain, psychophysiological syndromes and medically unexplained symptoms associated with chronic fatigue syndrome.

BACKGROUND: The association between depression and pain, function, medically unexplained symptoms and psychophysiological syndromes such as irritable bowel syndrome has not been explored before in chronic fatigue syndrome. METHODS: Cross-sectional controlled study of the current prevalence of psychophysiological syndromes, pain, function and lifetime prevalence of medically unexplained symptoms in 77 out-patients with chronic fatigue syndrome (CFS) without DSM-III-R depression, 42 CFS out-patients with DSM-III-R depression and 26 out-patient with primary DSM-III-R depression. RESULTS: Both CFS groups differed significantly from the primary depression group but not each other in the prevalence of tension headaches (P < 0.001), reporting of widespread bodily pain (P < 0.001) and the number of lifetime medically unexplained symptoms (P < 0.001). The three groups did not significantly differ in the prevalence of irritable bowel syndrome or fibromyalgia. CFS patients with depression were more impaired in social function than other CFS patients. CONCLUSION: Depression is not associated with the reporting of pain, psychophysiological syndromes and medically unexplained symptoms in CFS patients. Depression is associated with decreased social function in CFS patients. LIMITATIONS: Study depended on recall of symptoms, not confirmed by medical records and current investigations. Patients with depression were taking antidepressants. CLINICAL RELEVANCE: Treating depression in chronic fatigue syndrome is unlikely to diminish reporting of pain and medically unexplained symptoms but may improve social function.

Adult↗

Diesel exhaust exposure among adolescents in Harlem: a community-driven study.

OBJECTIVES: This study sought individual-level data on diesel exhaust exposure and lung function among adolescents in Harlem as part of a community-driven research agenda. METHODS: High school students administered in-person surveys to seventh grade students to ascertain information on demographics, asthma history, and self-reported and maternal smoking. Urine samples were assayed for 1-hydroxypyrene (1-HP), a marker of diesel exhaust exposure, and cotinine, a marker of tobacco smoke exposure. Computer-assisted spirometry was used to measure lung function. RESULTS: Three quarters (76%) of the participating students had detectable levels of 1-HP. Three students (13%) had an FEF25-75 of less than or equal to 80% of their predicted measurements, and 4 students (17%) had results between 80% and 90% of the predicted value, all of which are suggestive of possible lung impairment. CONCLUSIONS: These data suggest that most adolescents in Harlem are exposed to detectable levels of diesel exhaust, a known exacerbator and possible cause of chronic lung disorders such as asthma. Community-driven research initiatives are important for empowering communities to make needed changes to improve their environments and health.

Adolescent↗

A comparison of salivary cortisol in chronic fatigue syndrome, community depression and healthy controls.

BACKGROUND: Previous studies reporting cortisol hyposecretion in chronic fatigue syndrome may have been confounded by venepuncture, fasting and hospitalisation. METHODS: Morning and evening salivary cortisol were obtained on consecutive days in the first 3 days of the menstrual cycle and compared in three samples of women taking no medication and matched for age: 14 patients with chronic fatigue syndrome, 26 community cases of ICD-10 current depressive episodes and 131 healthy community controls. RESULTS: The mean evening cortisol was significantly lower in the chronic fatigue syndrome patients compared to controls with depression (P = 0.02) and healthy controls (P = 0.005). Chronic fatigue syndrome patients without psychiatric disorder had significantly lower morning salivary cortisols compared to controls (P = 0.009). CONCLUSION: Chronic fatigue syndrome patients display cortisol hyposecretion in saliva as well as plasma compared to patients with depression and healthy controls. LIMITATIONS: Small samples of female patients with cortisol estimated at only two time points in the day. Cortisol secretion may be secondary to other neurotransmitter abnormalities or other physiological or lifestyle factors in chronic fatigue syndrome patients. CLINICAL RELEVANCE: Chronic fatigue syndrome is biochemically distinct from community depression.

Adult↗

Altered expression of the WT1 wilms tumor suppressor gene in human breast cancer.

The product of the WT1 Wilms tumor suppressor gene controls the expression of genes encoding components of the insulin-like growth factor and transforming growth factor beta signaling systems. The role of these growth factors in breast tumor growth led us to investigate possible WT1 gene expression in normal and cancerous breast tissue. WT1 was detected by immunohistochemistry in the normal mammary duct and lobule, and the patterns of expression were consistent with developmental regulation. In a survey of 21 infiltrating tumors, 40% lacked immunodetectable WT1 altogether and an additional 28% were primarily WT1-negative. Cytoplasmic, but not nuclear, localization of WT1 was noted in some tumor cells and WT1 was detected, sometimes at high levels, in more-advanced estrogen-receptor-negative tumors. In this highly malignant subset, the tumor suppressor protein p53, which can physically interact with WT1, was also sometimes detected. WT1 mRNA was detected in normal and tumor tissue by reverse transcription-coupled PCR. Alternative splicing of the WT1 mRNA may regulate gene targeting of the WT1 protein through changes either in its regulatory or zinc-finger domains. The relative proportions of WT1 mRNA splice variants were altered in a random sample of breast tumors, providing evidence that different tumors may share a common WT1-related defect resulting in altered regulation of target genes.

Blotting, Southern↗

DNA adducts in urothelial cells: relationship with biomarkers of exposure to arylamines and polycyclic aromatic hydrocarbons from tobacco smoke.

Markers of exposure to polycyclic aromatic hydrocarbons (urinary 1-hydroxypyrene-glucuronide) and aromatic amines (4-aminobiphenyl-hemoglobin adducts), as well as urinary mutagenicity, were measured in 47 healthy smokers and 50 nonsmokers. DNA adducts were determined by P32-postlabeling in the exfoliated bladder cells of 39 healthy subjects. Both 1-hydroxypyrene-glucuronide (1-OHPG) and 4-aminobiphenyl adducts (4-ABP-Hb) were associated with smoking habits, but only 4-ABP-Hb adducts were associated with consumption of black, air-cured tobacco. The levels of 2 DNA adducts (numbers 2 and 4) in urothelial cells were clearly associated with 4-ABP-Hb adducts, in all subjects and in smokers. Levels of one of these DNA adducts (number 2) were also associated with 1-hydroxypyrene-glucuronide in urines, but in smokers the association was not statistically significant. Overall, these observations constitute further evidence of a role of arylamines in tobacco-induced bladder cancer.

Aminobiphenyl Compounds↗

Polycyclic aromatic hydrocarbon metabolites in urine as biomarkers of exposure and effect.

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) from various occupational, environmental, medicinal, and dietary sources. PAH metabolites in human urine can be used as biomarkers of internal dose to assess recent exposure to PAHs. PAH metabolites that have been detected in human urine include 1-hydroxypyrene (1-OHP), 1-hydroxypyrene-O-glucuronide (1-OHP-gluc), 3-hydroxybenzo[a]pyrene, 7,8,9,10-tetrahydroxy-7,8,9, 10-tetrahydrobenzo[a]pyrene, and a number of other hydroxylated PAHs. The most widely used of these is 1-OHP-gluc, the major form of 1-OHP in human urine, by virtue of its relatively high concentration and prevalence in urine and its ease of measurement. This metabolite of pyrene can be measured as 1-OHP after deconjugation of the glucuronide with beta-glucuronidase or directly as 1-OHP-gluc without deconjugation. Elevated levels of 1-OHP or 1-OHP-gluc have been demonstrated in smokers (versus nonsmokers), in patients receiving coal tar treatment (versus pretreatment), after workshifts in road pavers (versus before shifts or versus controls), after shifts in coke oven workers (versus before shift), and in subjects ingesting charbroiled meat (versus preingestion). More importantly, this metabolite is found (at low levels) in most human urine, even in persons without apparent occupational or smoking exposure. Although measurement of these metabolites is useful in assessing recent exposure to PAHs, their value as predictive markers of biological effect or health outcomes has not been rigorously tested and at present can only be inferred by association.

Animals↗

Expression and functional role of E- and P-cadherins in mouse mammary ductal morphogenesis and growth.

Mammary ducts, and the highly mitotic terminal end buds from which they are derived, consist of two layers of ectodermally derived epithelium, forming a tube-within-a-tube structure. We investigated the role of Ca(2+)-dependent cell-cell adhesion molecules in maintaining the integrity of these layers. Immunostaining showed abundant E-cadherin on the lateral membranes of end bud body cells and ductal lumenal cells, but no P-cadherin. The basally located cap cells and their differentiated descendants, the ductal myoepithelial cells, displayed only P-cadherin. We investigated the functional significance of this pattern of cadherin expression in situ by surgically implanting small, slow-release plastic implants releasing function-blocking antibodies. End buds exposed to a monoclonal antibody to E-cadherin showed disruption of the body epithelium, with epithelial cells floating freely in the lumen. Epithelial DNA synthesis, which is normally very high in these growth buds, abruptly declined. That this reduction in growth was not due to cell damage was shown by spontaneous reaggregation of the cells into a normal epithelium, with resumption of DNA synthesis, when the blocking antibody was depleted. A monoclonal antibody to P-cadherin had no effect on the lumenal layer but partially disrupted the basally located cap cell layer. These data indicate that spatially selective expression of E- and P-cadherins is required for mammary tissue integrity, which is in turn a prerequisite for normal rates of DNA synthesis.

Animals↗

Hox genes in normal and neoplastic mouse mammary gland.

Homeobox-containing genes regulate embryonic developmental programs and are expressed in certain adult tissues and cancers. There has been no report of expression in the breast. We amplified homeobox complementary DNA from mouse mammary gland and found expression of members from each of the four major Hox gene clusters. The regulation of expression of two Hox genes was examined in greater depth. Hoxc-6 transcripts were present in the glands of pubescent and mature mice and decreased during pregnancy. Levels were increased substantially following ovariectomy, indicating possible negative regulation by steroid hormones. Hox expression was studied in mammary adenocarcinomas and in transplant lines of the benign, precancerous tissues from which the cancers arose. Hoxc-6 was expressed at low levels in the precancerous tissue but was not expressed in cancers. In contrast, Hoxa-1 was expressed only in cancers, not in normal gland or in precancerous mammary tissues, suggesting that Hox genes may play a role in a late stage in the stepwise development of mammary malignancies.

Amino Acid Sequence↗

Vitamin supplementation and reduced risk of basal cell carcinoma.

A clinic-based case-control study was conducted to determine the association between vitamin supplement use and risk of basal cell carcinoma (BCC) of the skin. The subjects were 131 patients with histopathologically confirmed primary BCC and 200 cancer-free controls with non-premalignant skin disorders. Use of any vitamins (mainly multivitamins and vitamins A, C, and E) was associated with reduced risk of BCC. After controlling for age, sex, cigarette smoking, number of lifetime severe sunburns, and skin actinic elastosis, regular vitamin supplementation was associated with a significantly reduced risk of BCC (odds ratio (OR) = 0.3; 95% confidence interval (CI) = 0.2-0.06). The ORs decreased as the regularity (p < 0.001) and daily doses of supplement used increased, especially for vitamins A (p < 0.005) and E (p < 0.005). Vitamin supplementation was not associated with alterations in cellular DNA repair. These results, however, cannot be considered conclusive because of the relatively low participation rates (131/830 for cases and 200/1406 for controls) due to the requirement of blood donation and more rigorous studies are needed to clarify the effect of supplemental vitamins, particularly of vitamins A and E, on the risk of BCC of the skin.

Adult↗

Correlation between PAH airborne concentration and PAH-DNA adducts levels in coke-oven workers.

In order to evaluate the correlation between peripheral blood leukocyte DNA adducts as an indicator of exposure to polycyclic aromatic hydrocarbons (PAH) and the airborne contamination of PAH at the work places, a survey of a cohort of coke-oven workers has been carried out. In each workplace, total and specific PAH airborne concentrations were measured. Among the job title groups, the highest proportion of subjects with levels of adducts above the detection limit and the highest mean value were observed in the door-operators. The correlation between median values of environmental benzo(a)pyrene concentration and mean values of adducts concentration support the fact that the maintenance workers group has a higher relative risk (RR) to have detectable level of PAH-adducts, which is estimated to be 1.84 for an increase of 1 micrograms/m3 of benzo(a)pyrene.

Air Pollutants, Occupational↗