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Biomedical subjects

M Black

Publications and source records attributed to M Black.

At least 19 recordsLinked to original sources
PubMed1998

Overexpression of p53 protein does not predict local-regional control or survival in patients with early-stage squamous cell carcinoma of the glottic larynx treated with radiotherapy.

PURPOSE: Nonfunctional or mutated p53 protein (m-p53) is found in a myriad of solid tumors in humans. m-p53 is believed to confer radioresistance through inhibition of radiation-induced apoptosis. This study was carried out to determine if the overexpression of p53 in squamous cell carcinomas (SCC) of the glottic larynx treated with radiation therapy alone carried a poorer prognosis than normal wild-type p53 (w-p53) and could, therefore, be used as a marker of radioresistance in glottic SCC. METHODS & MATERIALS: Eighty-six patients with early-stage glottic SCC (64 T1N0, 25 T2N0 by TMN stage) treated with contemporary radiotherapy techniques to doses of 50-70 Gy were analyzed. Aberrant p53 protein was detected by immunohistochemical (IHC) staining on archival tissue samples containing original tumor specimens. Analysis of prognostic factors and treatment outcome to expression of p53 was performed. All patients were carefully selected to have comparable sites of disease, histology, early-stage disease, and treatment delivered, thus increasing the power of this study by controlling for other independent factors affecting outcome. RESULTS: Sixty percent of patients demonstrated overexpression of p53 in tissue samples. Accumulation of p53 was not predictive of tumor grade, stage, or smoking status prior to diagnosis. p53 status was not predictive of treatment outcome parameters including local-regional failure rate and disease-free survival rate. Factors significantly affecting treatment outcome were stage and dose of radiotherapy in T2 patients (50 Gy vs. > 62 Gy). CONCLUSION: m-p53 protein detected by IHC staining was not predictive as a prognostic factor for clinical outcome following radiation therapy for early-stage glottic SCC. This is in general agreement with other recently published studies of laryngeal carcinoma patients treated with radiation or surgery. At the present time, p53 status should not be used as a marker for prognosis and clinical outcome in laryngeal SCC.

Adult↗
PubMed1998

The role of professional diagnostic delays in the prognosis of upper aerodigestive tract carcinoma.

Despite the belief that cancer mortality can be reduced if lesions are detected, diagnosed and treated at an early stage, only one study, among a number concerning cancers of the upper aerodigestive tract (UADT), has found any relationship between such delays and prognosis for this population of cancer patients. The aim of this study was, therefore, to investigate the relationship between patient and professional diagnostic delays and patient prognosis in a group of UADT cancer patients. Patients diagnosed with squamous cell carcinoma of oral cavity sites (ICD-9 141, 143-5)oro-, naso- and hypopharynx (ICD-9 146-8) and larynx (ICD-9 161) were included in the study. Stepwise multiple logistic regression was used to calculate the odds ratio (OR) of late versus early stage disease for selected study variables. The sample comprised 188 subjects. Multivariate analysis found that having a pharyngeal cancer (OR 9.26; 95% CI 4.02-21.32; P: 0.0001) a professional delay > 1 month (OR 2.28; 95% CI 1.13-4.64; P: 0.022) and age > or = 65 years (OR: 0.45; 95% CI: 0.22-0.91; P: 0.024) were predictive of late stage disease. A dose-response relationship between professional delay and OR for late stage disease for the whole sample (P for trend 0.03) and among those with oral cancer (P for trend 0.0001) was found. The results of this study suggest that, among patients with an UADT cancer, professional delays > 1 month are contributing to an increased risk for being diagnosed with late stage disease.

Adult↗
PubMed1998

Relationship between biochemical and virological responses to interferon therapy in chronic hepatitis C infection. Consensus Interferon Study Group.

We have investigated the relationship between serum alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA in the assessment of responses to interferon (IFN) therapy in chronic HCV infection. Data from 704 patients with HCV infection who were randomized to receive consensus IFN-alpha (CIFN) 3 micrograms (n = 232 patients) or 9 micrograms (n = 232 patients), or IFN-alpha 2b 3 million units (MU) (n = 240 patients), were used for these analyses. All patients were treated three times weekly. Hepatitis C viral RNA (HCV RNA) was determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with a lower limit of detection of 100 copies ml-1. Of patients with normal serum ALT concentrations, 53% (120/225) had undetectable HCV RNA at the end-of-treatment period and 47% (51/109) had undetectable HCV RNA at the end of the post-treatment observation period. In contrast, of the patients with undetectable HCV RNA, 75% (120/161) and 84% (51/61) had normal serum ALT activities at the end-of-treatment and post-treatment observations periods, respectively. The majority of patients with undetectable HCV RNA had normal ALT values. In contrast, only half of the patients with normal ALT values were negative for HCV. End-of-treatment HCV RNA response also better predicted sustained virological response than did end-of-treatment ALT response.

Adult↗
PubMed1998

Uptake, toxicity and radiation effects of the boron compounds DAAC-1 and DAC-1 in cultured human glioma cells.

PURPOSE: To study the uptake, toxicity and radiation effects in vitro of a diol-amino acid-carborane (DAAC-1) and make comparisons with the previously studied diol-amine-carborane (DAC-1). MATERIALS AND METHODS: Toxicity and radiation effects were studied with clonogenic survival, uptake by measuring the cellular boron content and the subcellular distribution was investigated after organelle separation with centrifugation. The studied cell line was human glioma U343. RESULTS: DAAC-1 showed an accumulation of 1-1.5 times, compared with the culture medium, and was non-toxic up to 47 microg boron/ml. The accumulation of DAC-1 was about 90 times, but toxic effects were detectable already at the concentration 5 microg boron/ml. None of the compounds was localized in the cell nucleus. Following irradiation with thermal neutrons, DAC-1 was about 2.5 times more effective than DAAC-1 and about 4.9 times more effective than neutrons alone, at the survival level 0.2. The dose modifying factors, when compared with the neutron beam alone, were for both DAAC-1 and DAC-1 about 1.5 and about 5 when compared with 60Co-gamma-radiation. CONCLUSIONS: DAAC-1 was less toxic than DAC-1 but gave less accumulation of boron. Both substances gave significant boron-dependent cell inactivation when the test cells were exposed to thermal neutrons.

Boranes↗
PubMed1998

In vivo comparison of esophageal varices at and above the diaphragmatic high pressure zone using high resolution endoluminal sonography.

Our objective in this study was to use high resolution endoluminal sonography to compare the size of esophageal varices within 5 cm of and at the esophageal high pressure zone. We carried out the study in 36 patients with endoscopically proven esophageal varices. A 20-MHz 6.2F ultrasound catheter was passed through a 34F endoscope and used to image esophageal varices as it was slowly withdrawn through the high pressure zone (the level at which the diaphragm was imaged) and into the body of the esophagus approximately 5 cm above the high pressure zone. All images were captured on videotape and reviewed by one of the investigators. The mean, total, and percent cross-sectional surface areas occupied by varices were calculated and then compared within 5 cm and at the esophageal high pressure zone. Six of 36 (17%) patients had no varices imaged at the high pressure zone but did have varices imaged in the distal esophagus. The mean cross-sectional surface area per varix at the high pressure zone (0.036+/-0.006 cm2) was significantly less (p < or = 0.0001) than the mean cross-sectional area per varix 5 cm above the high pressure zone (0.142+/-0.018 cm2). The average total cross-sectional surface area occupied by varices at the high pressure zone (0.137+/-0.034 cm2) was significantly less (p < 0.0001) than the average cross-sectional surface area occupied by varices 5 cm above the high pressure zone (0.672+/-0.080 cm2). The mean percent esophageal wall cross-sectional surface area occupied by varices at the high pressure zone (16%) was significantly less (p < or = 0.0001) than 5 cm above the high pressure zone (49%). We conclude that the mean, total, and percent cross-sectional surface areas of esophageal varices at the high pressure zone are significantly less than those 5 cm above the high pressure zone.

Endosonography↗
PubMed1998

The palm print as a sensitive predictor of difficult laryngoscopy in diabetics.

BACKGROUND: Grading of the ink impression made by the palm of the hand has been proposed as a means of screening diabetic patients in whom tracheal intubation may be difficult because of glycosylation of both metacarpal and cervical joints. The current study was designed to test the predictability of the palm print and other airway evaluation indices in a diabetic population. METHOD: 83 adult, diabetic patients scheduled for surgery under general anesthesia were evaluated preoperatively using 4 physical examination indices predictive of difficult laryngoscopy and intubation: Mallampati classification, thyromental distance, head extension, and palm print. Following induction of anesthesia and neuromuscular relaxation, laryngoscopy was performed and the laryngoscopic view scored. The sensitivity, specificity and positive predictive value of each airway evaluation index was calculated. RESULTS: The palm print had the highest sensitivity of all indices (100%). The other 3 indices failed to detect 9 to 13 difficult laryngoscopies. CONCLUSION: We believe that in the diabetic population, the palm print index may be a sensitive marker of difficult intubation. It is possible that other airway evaluation indices would prove more sensitive, and have greater utility, in distinct populations as compared to when they are applied to all patients.

Adult↗
PubMed1997

Patients' views on their discharge from follow up in outpatient clinics: qualitative study.

OBJECTIVES: To discover the views of patients about their discharge from outpatient clinics, to detect any change in these perceptions over time, and explore how the discharge process might be improved for the patient. DESIGN: A qualitative study comprising in-depth or semistructured interviews with patients 2 weeks and 3 months after discharge from an outpatient clinic. SUBJECTS: 45 patients who had attended outpatient clinics on three or more occasions. SETTING: Five general medical outpatient clinics from a Manchester provider trust. MAIN OUTCOME MEASURES: Aspects of the discharge consultation valued by patients included confidence that the doctor knew and understood their case; clarity of the discharge process; an explanation of the reasons for discharge; information about treatment, future care, and the mechanism for re-referral; and being seen by doctors who sought their views and allowed time for questions and reflection. CONCLUSIONS: Patients' views about their discharge changed over time and varied in relation to several factors, which included patients' perceptions of the discharge process, patients' expectations, the way in which the outpatient clinics were organised, and patients' relationships with, and confidence in, their general practitioners.

Attitude to Health↗
PubMed1997

Genetic and biochemical analysis of development in Toxoplasma gondii.

Toxoplasma gondii has recently come under intense study as a model for intracellular parasitism because it has a number of properties that facilitate experimental manipulation. Attention is now being turned towards understanding the developmental biology of this complex parasite. The differentiation between the two asexual stages, the rapidly growing tachyzoites and the more slowly dividing, encysted bradyzoites, is of particular interest. Progression from the former to the latter is influenced by the host's immune response. This paper describes current progress on a number of research fronts, all aimed at understanding the triggers that push the tachyzoite-bradyzoite equilibrium in one or other direction and the changes that occur in gene expression (and ultimately metabolism and function). Chief among the techniques used for these studies are genetics and molecular genetics. Recent progress in these areas is described.

Acetylglucosamine↗
PubMed1997

Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group.

This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-alpha2b). Patients were randomized to receive CIFN at doses of 3 microg or 9 microg, or 15 microg IFN-alpha2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-microg dose than the 3-microg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-microg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-microg IFN-alpha2b cohort. However, patients receiving 9 microg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 microg IFN-alpha2b over the course of treatment (P < .01). Similarly, analysis of patients infected with HCV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-microg CIFN group when compared with the 15-microg IFN-alpha2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 microg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-microg IFN-alpha2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 microg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.

Adult↗
PubMed1997

Long-term follow-up in outpatient clinics. 1: The view from general practice.

BACKGROUND: Nearly three-quarters of patients seen in specialist outpatient clinics in England are in follow-up. It has been suggested that the care of many of these patients could be transferred to general practice. OBJECTIVES: We aimed to estimate the proportion of patients in general practice who are in long-term outpatient follow-up, and to identify GPs' perspectives on the appropriateness and implications of the discharge of their patients to primary care. METHOD: Prevalence data were collected by identifying correspondence from outpatient clinics to GPs in four Manchester practices (population 29,000). GPs were asked to assess the suitability for discharge of their patients who were seen in medical outpatient clinics. Semi-structured interviews were carried out with 15 of these GPs, and with 11 GPs who had patients recently discharged from medical clinics. RESULTS: At least 4.5% of the practice populations were in long-term outpatient follow-up (median duration 25 months). These patients had consulted their GP a median of seven times during the previous year. GPs were willing to take over the care of 48% of patients in medical clinics, and in many cases did not expect that this would lead to an increase in their workload. Some resource needs were identified in general practice, and improvements to the process of discharge were suggested. CONCLUSION: The need for continued follow-up in outpatient clinics should be reviewed. Many patients could be discharged without increasing GPs' workload. For more complex cases, additional resources may be needed to provide co-ordinated care within general practice. When patients are discharged, GPs need information quickly and need access to specialist advice for their patients when necessary without long delays.

Ambulatory Care Facilities↗
PubMed1997

Long-term follow-up in outpatient clinics. 2: The view from the specialist clinic.

BACKGROUND: Most of the patients seen in outpatient clinics are in follow-up. Waiting times for patients requiring first appointments would be shorter if more patients were discharged to the care of their GPs. OBJECTIVE: To identify opportunities and barriers to discharge of patients from follow-up in medical outpatient clinics and describe the use of discharge criteria to facilitate discharge. METHOD: General medical clinics held by five consultants in a district general hospital in Manchester were observed by the research team. Discussion groups were held with specialists to explore their views on barriers to and opportunities for discharge from outpatient care. Data from the hospital information system were used to compare discharge rates before, during and after the introduction of discharge criteria. RESULTS: Discharge consultations were inconsistently handled, and patients were not always aware that they had been discharged. Specialists were ambivalent about discharging patients, and uncertain about the care these patients would receive in general practice. Use of structured discharge criteria appeared to improve the quality of discharge consultations, and may have increased the proportion of patients discharged. Specialists were concerned about the work involved in giving detailed feedback to patients and GPs about patients' management needs after discharge. CONCLUSIONS: There are a number of issues arising from the findings of our study concerning the discharge of patients from long-term outpatient follow-up which purchasers of outpatient services may wish to consider. Referral letters should spell out clearly reasons for referral and the expectations of the GP. Discharge consultations should be accorded higher priority, and allocated sufficient time. It may sometimes be appropriate to prepare a patient for discharge at the previous visit. The reason for discharge should be made clear to patients. All discharges should be accompanied by a management plan for the GP, including arrangements for gaining further access to specialist care when needed in the future. Providing written information for patients in lay language would improve the process of discharge, and would allow patients to share the responsibility for their on-going care.

Ambulatory Care↗
PubMed1997

Specialist outreach clinics in general practice: what do they offer?

BACKGROUND: Specialist outreach clinics in general practice, in which hospital-based specialists hold outpatient clinics in general practitioners' (GPs) surgeries, are one example of a shift in services from secondary to primary care. AIM: To describe specialist outreach clinics held in fundholding general practices in two specialties from the perspective of patients, GPs, and consultants, and to estimate the comparative costs of these outreach clinics and equivalent hospital outpatient clinics. METHOD: Data were collected from single outreach sessions in fundholding practices and single outpatient clinics held by three dermatologists and three orthopaedic surgeons. Patients attending the outreach and outpatient clinics, GPs from practices in which the outreach clinics were held, and the consultants all completed questionnaires. Managers in general practice and hospital finance departments supplied data for the estimation of costs. RESULTS: Initial patient questionnaires were completed by 83 (86%) outreach patients and 81 (75%) outpatients. The specialist outreach clinics sampled provided few opportunities for increased interaction between specialists and GPs. Specialists were concerned about the travelling time resulting from their involvement in outreach clinics. Waiting times for first appointments were shorter in some outreach clinics than in outpatient clinics. However, patients were less concerned about the location of their consultation with the specialist than they were about the interpersonal aspects of the consultation. There was some evidence of a difference in casemix between the dermatology patients seen at outreach and those seen at outpatient clinics, which confounded the comparison of total costs associated with the two types of clinic. However, when treatment and overhead costs were excluded, the marginal cost per patient was greater in outreach clinics than in hospital clinics for both specialties studied. CONCLUSION: The study suggests that a cautious approach should be taken to further development of outreach clinics in the two specialties studied because the benefits of outreach clinics to patients, GPs and consultants may be modest, and their higher cost means that they are unlikely to be cost-effective.

Ambulatory Care Facilities↗
PubMed1996

Study of potency, kinetics of block and toxicity of NMDA receptor antagonists using fura-2.

NMDA receptor antagonists reduced NMDA-triggered increases in [Ca2+]i measured by fura-2 and showed qualitative differences in the potency and kinetics of block. High potency antagonists produced a slow block which allowed an initial increase in [Ca2+]i that was greater than the steady-state level, while compounds with moderate to low potency produced a rapid block that was at steady-state from the first measurement. The more potent antagonists showed the slowest unblocking rates. Using this simple method, novel NMDA antagonists can be screened to ascertain potency, kinetics of block and relative toxicity, prior to animal testing.

Animals↗
PubMed1996

Delivery of DNA-cationic liposome complexes by small-particle aerosol.

Aerosol delivery of gene therapy for treatment of lung diseases allows topical treatment of the airways with DNA concentrations not obtainable by systemic administration. We have investigated delivery of cationic liposomes complexed to plasmid DNA in a small particle aerosol. Plasmid cDNA-DMRIE/DOPE complexes were nebulized using either an Aerotech II or Puritan-Bennett 1600 (PB1600) nebulizer. Reservoir sampling showed that DNA-DMRIE/DOPE complexes were damaged to a significant degree during nebulization, such that activity of transfected gene was diminished. Of the nebulizers analyzed, DNA-DMRIE/DOPE complexes were more stable in the PB1600. The loss of effective transfection by DNA-DMRIE/DOPE, as detected by decreased reporter gene activity in A549 lung cells, was consistent with denaturation of the DMRIE/DOPE. In contrast, nebulized DNA-DOSPA/DOPE complexes retained complete ability to transfect. Adjustments to flow rate and reservoir volume of the PB1600 allowed a longer period of delivery of active DNA-DMRIE/DOPE particles. DNA-DMRIE/DOPE was radiolabeled with Technetium-99m (99mTc), nebulized, and the output captured in either an Andersen Sampler (AS) (Andersen, 1958) cascade impactor particle size analyzer or an all glass impinger. cDNA-cationic lipid complexes were detected in size ranges of 0.4-10 microns, with most particles found between 1-2 microns. Aerosol output was consistent from 0 to 5 min. These results show the feasibility of aerosol delivery of DNA-cationic lipids for the purposes of gene therapy to the lung.

Aerosols↗
PubMed1996

Lung tumours immunoreactive for parathyroid hormone related peptide: analysis of serum calcium levels and tumour type.

Secretion by tumours of parathyroid hormone-related peptide (PTHrP) in quantities sufficient to raise circulating levels results in the syndrome of humoral hypercalcaemia of malignancy (HHM). Since HHM is commonly associated with squamous carcinoma of lung and rarely with adenocarcinoma or lung neuroendocrine tumours, immunopositivity was related to tumour type, to assess whether this difference was due to a low general incidence of PTHrP expression in the latter two groups. Seventy-six of 82 tumours were immunopositive: 22 of 22 squamous carcinomas, 21 of 25 small cell lung carcinomas, 14 of 15 carcinoids, and 19 of 20 adenocarcinomas. These data confirm and extend previous observations on squamous and neuroendocrine tumours but are in contrast with previous findings in adenocarcinoma, which have suggested that only a small proportion of cases express the peptide. They suggest that the differences in incidence of HHM in the various tumour types are due to patterns of secretion, rather than differences in expression of PTHrP. The second aim of this study was therefore to assess whether tumours immunopositive for PTHrP, but not associated with HHM, might secrete PTHrP at levels which might result in more subtle changes in calcium metabolism. Preoperative calcium levels were analysed in a series of 56 patients with immunopositive lung tumours of all types. One small cell carcinoma was associated with hypercalcaemia, but there was no evidence of any other alteration in serum calcium. These data indicate that the majority of tumours expressing PTHrP do not secrete it in amounts sufficient to alter calcium metabolism.

Adenocarcinoma↗
PubMed1996

Comparison of high-resolution endoluminal sonography to video endoscopy in the detection and evaluation of esophageal varices.

High-resolution endoluminal sonography (HRES) was used to image and measure esophageal varices in control subjects and patients with portal hypertension and compared with endoscopic findings. Nine control patients and 68 patients with known cirrhosis or noncirrhotic portal hypertension underwent videotaped HRES and videotaped esophagoscopy (EGD). Two blinded investigators reviewed the videotapes to determine the presence and size of the largest esophageal varix in each patient. The largest varix by HRES was measured with the esophagus at rest at a point where the varix appeared most circular. The largest varix seen on EGD was graded on a 5-point scale. All nine of the control patients were correctly identified by both EGD and HRES as grade I (no varices). Eight of the 10 patients with no varices seen on EGD had varices identified by HRES. The interobserver correlation for HRES was r = .88 and for EGD was r = .79. The correlation between EGD and HRES was r = .50. High resolution endoluminal sonography allows quantitative measurement of variceal size, is a more sensitive and reproducible imaging modality than esophagoscopy for the detection and sizing of esophageal varices. There is poor correlation between monographic measurement and endoscopic grading of esophageal varices. Assessment of esophageal variceal presence and the measurement of variceal size by high resolution endoluminal sonography is an accurate, reproducible method of determining the size of esophageal varices.

Adult↗