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Biomedical subjects

G Forster

Publications and source records attributed to G Forster.

At least 19 recordsLinked to original sources
PubMed2004

Comparison of the pathology of cerebral white matter with post-mortem magnetic resonance imaging (MRI) in the elderly brain.

White matter lesions (WML) on magnetic resonance imaging (MRI) brain scans are associated with ageing. They are unrelated to specific disorders, and their impact on cognitive and other brain functions is poorly characterized. Pathological studies often omit systematic survey of WML because of the need to study multiple full coronal tissue blocks, and uncertainty over the significance of lesions identified in periventricular and deep subcortical regions. Post-mortem MRI provides a means of mapping WML but the sensitivity and specificity of the method are unresolved. In this study post-mortem MRI of WML in fixed brain slices was compared with pathology in 33 brains donated to the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). This study shows that MRI detection of WML was less sensitive than pathology: periventricaular lesions (PVL) sensitivity = 95% (87-99%), specificity = 71% (44-90%); deep subcortical lesions (DSCL) sensitivity = 86% (79-93%), specificity = 80% (72-88%). False negative MRI was associated with milder pathology, but lesions detected by myelin attenuation alone showed both microglial and endothelial activation. Therefore post-mortem MRI of formalin-fixed brain slices is a reliable method to obtain systematic data on the severity and distribution of cerebral white matter disease, and appears to detect those WML most likely to have clinical impact.

Aged↗
PubMed2003

Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS.

OBJECTIVE: Examining the unresolved relationship between the lower motor neuron disorder progressive muscular atrophy (PMA) and ALS is important in clinical practice because of emerging therapies. METHODS: Spinal and brainstem tissues donated from patients with ALS/motor neuron disorder (n = 81) were examined. Using retrospective case note review, the authors assigned patients into three categories: PMA (12), PMA progressing to ALS (6), and ALS ab initio (63). Conventional stains for long tract degeneration and immunocytochemistry for ubiquitin and the macrophage marker CD68 were examined. RESULTS: Rapid progression and typical ubiquitinated inclusions in lower motor neurons were present in 77 (95%) of the cases. Immunocytochemistry for CD68 was a more sensitive marker of long tract pathology in comparison with conventional stains. Half of the cases with PMA showed corticospinal tract degeneration by CD68. CONCLUSION: Patients with PMA frequently have undetected long tract pathology and most have ubiquitinated inclusions typical of ALS. A patient presenting with PMA with rapid clinical evolution likely has the pathology and pathophysiology of ALS whether or not upper motor neuron signs evolve.

Aged↗
PubMed2003

National guideline for the management of suspected sexually transmitted infections in children and young people.

The Children Act 1989 defines a child as "a person who has not yet reached 18 years of age." In England, Wales, and Scotland the present age of consent for heterosexual and homosexual sex is 16 years and in Northern Ireland it is 17 years. The proportion of young people who report heterosexual intercourse before the age of 16 years increased in the 1990s compared with the previous decade.

Adolescent↗
PubMed2002

Heterogeneity of O6-alkylguanine DNA-alkyltransferase expression in human breast tumours.

An important determinant of cellular resistance to chemotherapeutic O6-alkylating agents, which comprise methylating and chloroethylating agents, is the ability of cells to repair alkylation damage at the O6-position of guanine in DNA. This is achieved by a specific DNA repair enzyme O6-alkylguanine DNA-alkyltransferase. In this study O6-alkylguanine DNA-alkyltransferase expression was measured in human breast tumours using both biochemical and immunohistochemical techniques. O6-alkylguanine DNA-alkyltransferase activity was then compared with known clinical prognostic indices to assess the potential role of O6-alkylguanine DNA-alkyltransferase in predicting the behaviour of this common malignancy. The application of both biochemical and immunohistochemical techniques was feasible and practical. Most breast tumours expressed high levels of O6-alkylguanine DNA-alkyltransferase. Immunohistochemical analysis showed marked variation in expression not only between individuals but also within individual tumours, and in the same patient, between metastases and between primary tumour and metastatic site. O6-alkylguanine DNA-alkyltransferase activity in tissue extracts significantly correlated not only with immunohistochemical staining intensity determined by subjective quantitation, but also with measures of protein levels using a computerised image analysis system including mean grey (P<0.001), percentage of cells positive for O6-alkylguanine DNA-alkyltransferase (P<0.001), and integrated optical density (P<0.001). O6-alkylguanine DNA-alkyltransferase expression did not correlate with any of the established clinical prognostic indicators for current treatment regimens. However, immunohistochemical offers a rapid and convenient method for assessing potential utility of O6-alkylating agents or O6-alkylguanine DNA-alkyltransferase inactivating agents in future studies of breast cancer treatment.

Adenosine Triphosphatases↗
PubMed2001

M5 muscarinic receptors are needed for slow activation of dopamine neurons and for rewarding brain stimulation.

Mesopontine cholinergic neurons (Ch5 and Ch6 cell groups) activate the cerebral cortex via thalamic projections, and activate locomotion and reward via dopamine neurons in the substantia nigra and ventral tegmental area (VTA). Nicotinic receptors in VTA activate dopamine neurons quickly, and are needed for the stimulant and rewarding effects of nicotine in rats. Muscarinic receptors in VTA activate dopamine neurons slowly, and are needed for the rewarding effects of hypothalamic stimulation, but do not increase locomotion. Antisense oligonucleotides targetting M5 mRNA, when infused into the VTA, inhibited M5 receptor binding and rewarding hypothalamic stimulation. Mutant mice with truncated M5 muscarinic receptor genes drank more water than wild-type controls. Spontaneous locomotion and locomotor responses to amphetamine and scopolamine were unchanged. Electrical stimulation near Ch6 induced dopamine release in the nucleus accumbens in two phases, an early phase (0-2 min after stimulation) dependent on nicotinic and gluatamatergic receptors in VTA, and a late phase (8-50 min after stimulation) dependent on muscarinic receptors in VTA. The late phase was lost in M5 mutant mice, while the early phase was unchanged. M5 muscarinic receptors bind slowly to muscarinic ligands, and appear to mediate slow secretions.

Acetylcholine↗
PubMed2001

Adherence to highly active antiretroviral therapy in the real world: experience of twelve English HIV units.

In order to describe how human immunodeficiency virus (HIV) clinics in and around London are trying to optimize their patients' adherence to highly active antiretroviral therapy (HAART), we performed a survey of practice and policy in the clinics using a postal questionnaire. Clinics were also asked to review up to 10 randomly selected case notes of patients receiving HAART and complete a questionnaire on each about how adherence was encouraged and assessed. Twelve clinics took part in the project and surveyed the notes of 89 patients. The results show that several clinics define adequate adherence as taking more than 95% of prescribed doses although there was no uniform definition across the participating units. Adherence was encouraged through simplifying HAART regimens, providing dose-dispensing boxes and alarms, arranging early follow-up for patients starting treatment, and offering continuing support through specific health care workers. Adequate discussion and provision of written information was seen as an important aid to adherence but the case note survey showed evidence of deficiencies in this area in approximately 40% of patients. Assessed levels of adherence were less than 95% in 27% of patients. The main reasons for suboptimal adherence were found to be lack of motivation to take treatment by the patients, high pill burden, and drug side effects although there were several other contributing factors. This study shows that the HIV units take HAART adherence seriously but there are several deficiencies in putting policy into practice.

Ambulatory Care Facilities↗
PubMed2001

Graded challenge in an aciclovir allergic patient.

An immunocompetent woman presented with a hypersensitivity skin reaction following suppressive therapy with aciclovir for recurrent culture proved genital herpes simplex virus infection. She developed a similar reaction when treatment was changed to famciclovir. Without antiviral suppression her recurrences were frequent and distressing. Graded challenge was performed and she became tolerant to aciclovir. She successfully continued suppressive therapy for 1 year with no further hypersensitivity reactions or recurrences.

Acyclovir↗
PubMed2001

Management of chronic prostatitis in Genitourinary Medicine clinics in the United Kingdom's North Thames Region 2000.

Twenty-two Genitourinary Medicine (GUM) clinics in North Thames participated in a survey of policies and case notes audit of chronic prostatitis managed within the past 2 years, compared with the UK National Guideline. For 32/33 cases notes reviewed (97%) chronic abacterial prostatitis/chronic pelvic pain syndrome (CAP/CPPS) were diagnosed. Of these, 14/32 cases (44%) were following non-chlamydial non-gonococcal urethritis (NGU), 1/32 cases (3%) followed Chlamydia trachomatis infection and for 17/32 cases (53%) no predisposing cause was identified. The single case of chronic bacterial prostatitis (CBP) was caused by prostatic infection with Staphylococcus spp. All cases were prescribed antibiotics, initial follow-up appointments coinciding with completion of antibiotics. Fourteen cases (42%) were discharged following GUM clinic management; only 7 of these cases (50%) were asymptomatic, the others having residual problems. Nine cases (27%) were referred to a specialist. Ten cases (30%) defaulted follow-up appointments; 7 of these did not attend their first follow-up appointments.

Adult↗
PubMed2001

Screening for sexually transmitted infections in children and adolescents in the United Kingdom: British Co-operative Clinical Group.

Our objectives were (1) to assess the number of young people aged under 16 years attending genitourinary medicine (GUM) departments in the UK in 1998; (2) to identify clinical activity and policy; (3) to determine the knowledge and training needs of healthcare professionals within GUM providing care for this client group. In July 1999 a questionnaire was circulated via the 18 regional British Co-operative Clinical Group (BCCG) representatives to the consultants in charge of all 197 main GUM departments in the UK. One hundred and sixty out of 197 (81%) completed questionnaires were returned and analysed. The reported number of under-16-year-olds attending in 1998 varied considerably between clinics; for females ranging from 0 to 256 and for males between 0 and 50, with a male to female ratio of 1:4.4. The majority of responding clinics, 139/160 (87%) had been involved in the screening of abused children/adolescents for sexually transmitted infections (STIs). Most clinics were prepared to screen for STI (86%), HIV test (79%) and assess contraceptive needs (50%) in this age group. Staff involved in care included health advisers (74), nurses (59), and doctors (138) in the responding clinics. Only 31/160 clinics (19%) had a written policy for the management of children/adolescents attending their clinic. The majority of respondents were aware of their child protection policy [122/154 (79%)] and designated child sexual abuse doctor, [125/157 (80%)] in their district. When questioned on previous and current training needs, 134/160 (84%) respondents identified their need for further training in the area of adolescent sexual health and 124/160 (78%) in child sex abuse. The publication Physical Signs of Sexual Abuse in Children, was known to 112/160 (70%) respondents, of whom 58/112 (52%) who answered this question had read the publication. Genitourinary physicians in the UK are aware of the increasing number of children and adolescents accessing their services, and recognize the need to identify those in abusive situations. Written policies dealing with children and adolescents in GUM clinics in the UK are lacking. This needs to be rectified urgently. This survey identifies that further training in the field of child sexual abuse and adolescent sexual health would be welcomed by the respondents.

Adolescent↗
PubMed2001

The detection of Chlamydia trachomatis by DNA amplification methods in urine samples from men with urethritis.

Our objective was to compare 3 deoxyribonucleic acid (DNA) amplification methods for the diagnosis of chlamydial infection with an enhanced enzyme immunoassay (EIA) method for antigen detection in urine samples, from men with non-gonococcal urethritis (NGU) attending a busy inner city genitourinary medicine centre. Urethral swabs and urine samples were collected from 346 male patients with NGU attending the clinic. All swabs and urines were tested for chlamydial infection (CT) using the EIA (Dako PCE immunoassay). Three aliquots of the urine samples were stored immediately at -70 degrees C for subsequent testing by: Amplicor polymerase chain reaction (PCR) (Hoffmann-La Roche, Switzerland); the amplified Chlamydia trachomatis assay (AMP CT) using transcription mediated amplification (TMA) (GenProbe, USA); and BDProbeTecET using the strand displacement assay (SDA) (Becton Dickinson, USA). The positive rate for the 3 amplified assays PCR, TMA and SDA (on urine) was 88/346 (25.4%), 80/346 (23.1%) and 88/346 (25.4%), respectively compared to 56/346 (16.2%) by EIA on urethral swabs, the current means of diagnosis in this laboratory. Thirty-one samples were positive in 2 or more of the amplification assays but negative in the EIA, 50 positives (53% sensitivity) detected in the urine samples by the EIA assay were detected by all 3 of the amplified assays. Three samples were positive by PCR only, 5 were positive by TMA only and 7 were positive by SDA only. DNA amplification assays are superior to standard immunoassays for the diagnosis of C. trachomatis infections in urine samples. Urine samples are suitable for use in these amplified assays to detect C. trachomatis. Freezing of samples before testing reduces the rate of inhibition reported in other published studies.

Chlamydia Infections↗
PubMed2000

4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer.

OBJECTIVES: To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer. METHODS: We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only. RESULTS: 'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41). CONCLUSIONS: In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.

Antineoplastic Agents, Hormonal↗
PubMed1999

Rape attitudes amongst British medical students.

OBJECTIVES: To examine the rape attitudes of a sample of 252 British medical students. DESIGN: A 20-item questionnaire was used. SETTING: A London medical school. SUBJECTS: Fourth-year medical students. RESULTS: In general, students were well informed on legal and factual issues regarding rape and sexual assault. However, significant differences were found in the attitudes to rape between males and females. Female students were significantly more positive in their responses to victims. CONCLUSIONS: These results support findings from previous studies of rape attitudes in other professional groups. Better knowledge and enlightened attitudes amongst health care staff can have a significant impact on the management of sexual assault and influence the likelihood of victims presenting for treatment. In conclusion, this study emphasizes the importance of teaching about sexual violence in British medical schools.

Adult↗
PubMed1999

Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors.

We have analyzed a panel of 14 cases of childhood adrenocortical tumors unselected for family history and have identified germline TP53 mutations in >80%, making this the highest known incidence of a germline mutation in a tumor-suppressor gene in any cancer. The spectrum of germline TP53 mutations detected is remarkably limited. Analysis of tumor tissue for loss of constitutional heterozygosity, with respect to the germline mutant allele and the occurrence of other somatic TP53 mutations, indicates complex sequences of genetic events in a number of tumors. None of the families had cancer histories that conformed to the criteria for Li-Fraumeni syndrome, but, in some families, we were able to demonstrate that the mutation had been inherited. In these families there were gene carriers unaffected in their 40s and 50s, and there were others with relatively late-onset cancers. These data provide evidence that certain TP53 alleles confer relatively low penetrance for predisposition to the development of cancer, and they imply that deleterious TP53 mutations may be more frequent in the population than has been estimated previously. Our findings have considerable implications for the clinical management of children with andrenocortical tumors and their parents, in terms of both genetic testing and the early detection and treatment of tumors.

Adaptor Proteins, Signal Transducing↗