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Biomedical subjects

H Jackson

Publications and source records attributed to H Jackson.

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

Depression in young people. A growing challenge for primary care.

BACKGROUND: Recent research indicates that 27% of young people aged 18-24 have a mental health problem involving mood, anxiety, personality and/or substance abuse disorders and 15-40% report depressive symptomatology. A proportion of these young people will suicide. The morbidity associated with depressive illness in this age group is high, with those experiencing a depressive episode having reduced vocational and life prospects and being highly vulnerable to further episodes in later life. OBJECTIVE: To outline the clinical features of depression in young people and to provide strategies for appropriate management. DISCUSSION: Presentation of depression in young people is likely to vary from accepted diagnostic criteria with non specific symptoms such as boredom, anxiety, failing adjustment and sleep disturbance predominating. Management includes attending to key social problems, ensuring a safe environment and counselling, which may be supportive counselling or more specific treatments of cognitive behavioural therapy or interpersonal psychotherapy. Medication is indicated for more severe depression or with failure of response to psychological strategies. Early case identification and intensive treatment of first episodes of depression is important in reducing prevalence, cost and morbidity.

Adolescent↗
PubMed2000

Oral oseltamivir in human experimental influenza B infection.

Oseltamivir is the prodrug of Ro64-0802 (GS4071), a potent and selective inhibitor of influenza A and B virus neuraminidases. Three randomized, double-blind, placebo-controlled, parallel-group studies evaluated oral oseltamivir for early treatment (75 or 150 mg twice daily for 5 days) or prevention (75 mg once or twice daily for 7 days) of experimental influenza B virus infection in healthy susceptible adults. Treatment study A (n=60) demonstrated similar trends to treatment study B (n=117), in which 75 mg doses of oseltamivir introduced 24 h after inoculation reduced median area under curve (AUC) virus titre (oseltamivir, 22.7; placebo, 131.1 log10 TCID50 x h/ml; P=0.002) and duration of viral shedding (oseltamivir, 23.9 h; placebo, 95.8 h; P=0.0005). In prevention study C (n=58), oseltamivir did not reduce infection rates (85 versus 84%) but significantly reduced median AUC virus titre (10.0 versus 66.9 log10 TCID50 x h/ml; P=0.03) and duration of viral shedding (36 versus 84 h; P=0.03) compared with placebo. Oseltamivir was well tolerated. No emergence of drug-resistant variants was detected by testing last-day isolates (n=112) in neuraminidase inhibition assays. These results indicate that oseltamivir has significant antiviral activity in experimental human influenza B virus infection when used for prophylaxis or early treatment.

Acetamides↗
PubMed1999

The molecular basis of transferase galactosaemia in South African negroids.

Transferase galactosaemia is an autosomal recessively inherited disorder caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT). Manifestations include jaundice, vomiting, cataracts, mental retardation, speech abnormalities and poor growth. The GALT gene has been mapped and sequenced. The S135L mutation accounts for approximately 48% of galactosaemia alleles in African Americans and has been found to account for about 91% of galactosaemia alleles in negroid South African patients which suggested that the mutation had an African origin. We have calculated the S135L allele frequency (+/- 1SE) in a sample of healthy unrelated negroid South Africans to be 0.0067 (+/- 0.0024). The S135L mutation was also detected in negroid populations from other regions of Africa confirming its African origin.

Alleles↗
PubMed1999

Transscleral diode laser in the treatment of retinopathy of prematurity.

PURPOSE: To assess the outcome of contact transscleral diode laser (TSDL) in the treatment of threshold retinopathy of prematurity (ROP). METHOD: TSDL was performed in 14 eyes of 8 babies who presented to the paediatric ophthalmic service at King's College Hospital between 1996 and 1997 with threshold ROP (median post-conceptual age 26 + 1 weeks, median birthweight 835 g) by a single surgeon. Follow-up ranged from 9 to 41 weeks (median 21 weeks). RESULTS: In 11 eyes (79%) regression of ROP occurred after a single laser treatment with a good anatomical outcome. In 3 eyes (21%) there was an unfavourable response with the development of traction retinal detachment. These include both eyes of one baby who rapidly progressed to stage IV ROP. One other eye developed a fibrotic band a few months after treatment. No significant complications of laser treatment were observed. CONCLUSION: These initial results indicate that TSDL photocoagulation is an effective and technically straightforward alternative to cryotherapy in the treatment of ROP.

Follow-Up Studies↗
PubMed1999

Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia.

Thebcl-2oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18), and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly valuated by MIB1, a monoclonal antibody to Ki67 proliferation antigen. Immuno-histochemical (IHC) staining expression of bcl-2 and Ki67 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas according to the avidin-biotin-complex method. The aim of the study was twofold: 1) to investigate any correlation between MIB1 and bcl-2 immunostaining expression in colonic adenomas and carcinomas, 2) to identify any relationship between either marker and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angio-lymphatic invasion, tumor grade and differentiation in colon carcinomas. Bcl-2 was consistently higher in adenomas than in carcinomas. There were 44/56 (78.6%) adenomas, and 27/52 (51.9%) carcinomas positive for bcl-2 (p=0.004). The mean Ki67 labeling index (LI) was 30.05+/-7.6 and 38.12+/-11.01 in adenomas and carcinomas, respectively (p=0.0001). Expression of bcl-2 in carcinoma was significantly associated with a lower mean Ki67 LI and with favorable histopathologic parameters. We conclude that bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with a favorable clinical course. Furthermore, an inverse relationship exists between bcl-2 and Ki67 in colonic neoplasia. Evaluation of bcl-2 and Ki67 IHC expression in colonic carcinoma should be performed prospectively to determine if their expression is of value in predicting the clinical course in these patients.

Adenocarcinoma↗
PubMed1999

An investigation of attributional style in first-episode psychosis.

OBJECTIVE: The present study investigated covert and overt attributional styles in individuals experiencing a first episode of psychosis. It was hypothesized that those individuals experiencing paranoia, as operationalized by higher scores on the suspiciousness item of the Brief Psychiatric Rating Scale (BPRS) would perform differently on both covert and overt measures of attributional style when compared to those individuals who scored lower on the BPRS suspiciousness item. DESIGN AND METHODS: A cross-sectional design was used. The sample consisted of 62 participants (50 males and 12 females) from the Early Psychosis Prevention and Intervention Centre. The Pragmatic Inference Task (PIT) was used to measure covert attributional style, whereas the Attributional Style Questionnaire (parallel form; ASQpf) measured overt attributional style. The Rosenberg Self-Esteem Questionnaire measured global self-esteem. Participants' positive, negative, and depressive symptoms were assessed by means of the BPRS, the Scale for the Assessment of Negative Symptoms, and the Beck Depression Inventory, respectively. RESULTS: Regression analyses found that less suspiciousness (p = .02) and more depression (p = .02) predicted higher internal attributions for negative events scores on the ASQpf. There was a trend (p = .07) for more suspicious individuals to endorse the self-serving bias (SSB) on the PIT, even despite the SSB not being large enough to be considered defensive. Verbal IQ emerged as a significant predictor of covert attributional style (p = .04). CONCLUSIONS: The findings suggest that increasing suspiciousness does predict attributional style in the early stages of psychosis, although the relationship appears weaker than in reports with more chronic psychotic patient samples. Longitudinal research is needed to ascertain whether attributional style is a stable characteristic in psychosis, or whether it fluctuates between periods of remission and active psychosis.

Acute Disease↗
PubMed1998

Flow cytometric apoptosis assays indicate different types of endonuclease activity in haematopoietic cells and suggest a cautionary approach to their quantitative use.

Two flow cytometric apoptosis assays, the terminal deoxynucleotidyl transferase (TdT) assay and in situ nick translation (ISNT) assay, were assessed for their ability to quantitate drug-induced apoptosis in CLL lymphocytes. In contrast to HL60 cells, biotinylated dUTP could not be effectively incorporated into apoptotic CLL lymphocytes using exogenous TdT. This suggested that CLL lymphocytes possess a different type of endonuclease that cleaves DNA, leaving blunt or 3' recessed DNA breaks, which are poor substrates for TdT. This possibility was tested using lambda exonuclease, which can convert a blunt or 3' recessed DNA break into a 3' overhang. Apoptotic CLL lymphocytes pre-treated with lambda exonuclease demonstrated increased nucleotide incorporation with TdT. Single-strand DNA breaks are also present in apoptotic CLL lymphocytes, as labelled nucleotides could be incorporated using the in situ nick translation assay. This study suggests that the efficiency of tailing reactions may be limited by the nature of the endonuclease activity in certain cell types and that validation with other parameters is an essential prerequisite to their quantitative use.

Apoptosis↗
PubMed1998

Spontaneous T cell responses to melanoma differentiation antigens from melanoma patients and healthy subjects.

The spontaneous cytotoxic T cell responses to melanoma differentiation antigens and influenza matrix peptide were compared in 20 HLA-A2+ melanoma patients and 17 healthy A2+ individuals. Cytotoxic T lymphocyte (CTL) responses were determined by mixed lymphocyte peptide culture (MLPC) involving two stimulations of unfractionated peripheral blood lymphocytes (PBLs) with peptide in vitro. CTL responses to Melan-A 9-mer (amino acids 27-35, AAGIGILTV) peptide were detected in 4 out of 16 normal individuals, but in none of the melanoma patients. CTL specific for influenza matrix peptide were frequently found in both normal individuals and melanoma patients, suggesting that generalized immuno-suppression was not responsible for this difference. No significant responses were observed in either normal individuals or melanoma patients to Melan-A 10-mer (26-35, EAAGIGILTV), two gp1OO epitopes (280-288, YLEPGPVTA; 457466, LLDGTATLRL) and two tyrosinase epitopes (1-9, MLLAVLYCL; 368-376, YMDGMSQV). Melan-A (27-35)-specific CTL cells generated by normal individuals and melanoma patients recognized both synthetic peptide-pulsed T2 cells and two HLA-A2+, Melan-A+ melanoma cell lines (ME272, LAR1) in an antigen-specific, MHC class I restricted manner. T cells generated against Melan-A 9-mer were also able to recognize Melan-A 10-mer-pulsed target cells. Spontaneous CTL responses to Melan-A 9-mer from three known responder normal individuals were further evaluated over a prolonged time course (6-11 months). All 3 subjects demonstrated specific Melan-A 9-mer responses throughout the study period, although lytic activity fluctuated over time for a given individual. We found the MLPC assay to be reliable and easy to perform for monitoring T cell responses, although it may still not be sufficiently sensitive to detect low numbers of precursor T cells.

Adjuvants, Immunologic↗
PubMed1998

Antigen specificity and tumour targeting efficiency of a human carcinoembryonic antigen-specific scFv and affinity-matured derivatives.

We have examined the biological properties of CEA6, a human carcinoembryonic antigen (CEA)-specific single-chain Fv (scFv) isolated by phage display, and five related clones derived by affinity maturation and selected for improved off-rate (Koff). All clones bind strongly and specifically to CEA-positive human tumours by immunocytochemistry and show negligible cross-reactivity with normal colon. Flow cytometry of scFv on human liver cells indicates a shift in fine epitope specificity resulting from mutagenesis. All monomeric scFv have been radioiodinated, retaining effectively full binding activity. A single intravenous injection into nude mice bearing human colon tumour xenografts confirms tumour targeting in all cases. As reported in other studies, the kidney is the main route of elimination of scFv at early time points. Tumour binding of the parental antibody CEA6 consistently gives the highest tumour-blood ratios at 24 h (mean 16:1). Clone TO6D11, which has a sevenfold reduced Koff relative to CEA6, showed no difference in tumour uptake at 24 h but persisted at the tumour site for longer than CEA6. This study demonstrates a possible correlation between binding affinity and tumour residence time when examined in this model.

Animals↗
PubMed1998

The cost of home-based care for HIV/AIDS patients in Zimbabwe.

From a study on the cost and quality of community home-based care (CHBC) for HIV/AIDS patients in Zimbabwe, programme and household costs were estimated. Interviews, using a structured questionnaire, were held with 60 patients and caregivers sampled from six types of established CHBC schemes. Detailed cost information was collected from four home care programmes, two urban and two rural. The cost of a home visit in the two urban programmes studied was estimated to be Z$129 (US$16) in one, and Z$183 (US$23) in the other. In one of the two rural schemes, the cost of a home visit was Z$313 (US$38), in the other this was Z$343 (US$42). A large proportion of these costs were not of direct benefit to the patients, as approximately 56-75% of the total cost per home visit was spent getting to the patient. The costs of a home visit in a rural home-based care programme corresponded to the costs of 2.7 inpatient days in a district hospital. The family cost of caring for a bedridden AIDS patient over a three-month period was estimated to be between Z$556-841. Caregivers spent as much as 2.5-3.5 hours a day on routine patient care. The programme costs are high, and schemes do not generally assess effectiveness, nor cost-effectiveness. The high cost of home visits leads to less frequent visits, leaving a larger part of both the burden and the cost of care to the families and the patients.

Cost of Illness↗
PubMed1998

Cognitively-oriented psychotherapy for early psychosis (COPE). Preliminary results.

BACKGROUND: The present study describes the results of the pilot testing of a therapy we have developed for people with first-episode psychosis. Cognitively-oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. METHOD: Eighty people formed three groups: those who were offered and accepted COPE (COPE subjects); those who refused COPE (refusal subjects); and those who were offered neither COPE nor any other continuing treatment from our service (control subjects). The individuals were assessed prior to, and at the end of, COPE treatment (a 12-month period) on the Integration/Sealing Over, Explanatory Model, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, Quality of Life, SCL-90-R, and Beck Depression Inventory measures. RESULTS: People who received COPE obtained significantly superior scores (P < 0.05) to the control group on four of the seven measures but only significantly out-performed the refusal group on one of the seven measures (P < 0.05). The COPE group performed significantly worse on the BDI than the refusal group (P < 0.05). Effect sizes are also provided for each measure. CONCLUSIONS: There seems to be a place for psychological therapy in this group of people but our results need to be replicated in a more definitive randomised controlled trial and such a study is now in progress.

Adult↗
PubMed1997

Use of pulsed irrigation evacuation in the management of the neuropathic bowel.

Management of the neuropathic bowel is one of the major issues in the treatment of patients with severe spinal cord injury (SCI). Pulsed irrigation evacuation (PIE) has been evaluated in several small studies for the clearing of fecal impactions in patients with a neuropathic bowel. We evaluated our experience with 398 PIE procedures performed on inpatients and outpatients at our facility. It has proven to be both safe and effective in a wide variety of patients with this disorder, and is a useful addition to traditional methods in the management of the neuropathic bowel.

Adult↗
PubMed1997

Covert poisoning with difenacoum: clinical and toxicological observations.

1. The coumarin anticoagulant difenacoum was detected by high performance liquid chromatography (HPLC) with multi-wavelength UV detection in plasma from a 41 years old man who presented with a severe deficiency of vitamin K-dependent clotting factors of unknown aetiology. A longitudinal toxicological study of the consequent coagulopathy is described. 2. Plasma concentrations of difenacoum declined from 0.97 to 0.11 mgl-1 in 47 days with a terminal half life of 11.7 days. Rifampacin (300 mg bd) had no apparent effect on the terminal half life of the drug. Subsequently plasma concentrations of difenacoum and descarboxyprothrombin (DCP) unexpectedly increased. 3. Seven months after exposure clotting times were prolonged. The patient continued to have episodes of epistaxis, haematoma, purpurae and bruising and he required frequent treatment with Fresh Frozen Plasma in additional to oral phylloquinone (200 mg day-1). 4. Intermittent and unexpected increases in plasma concentrations of difenacoum and descarboxypro-thrombin suggested that covert, repeated ingestion of the anticoagulant was the most likely cause of the poisoning. The measurement of low concentrations of plasma phylloquinone except following supervised ingestion of the vitamin indicated that as an outpatient, the subject was not compliant with treatment despite his protestations to the contrary. He continued to deny this even when confronted by laboratory findings and at no time did he ever admit to self-poisoning.

4-Hydroxycoumarins↗