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Biomedical subjects

R Meredith

Publications and source records attributed to R Meredith.

At least 19 recordsLinked to original sources

[Photographs of deceased newborn infants as documentation and as aid in mourning process for parents].

The death of a newborn infant is an extremely emotional event for relatives. Many hospitals provide the parents with support, and in some cases a mourning protocol is available. Some hospitals offer parents photographs of infants which have died around birth. The photographs are often taken by a nurse or doctor on the maternity or paediatric ward. It is advisable to draw up a mourning protocol which allows professional studio photographs to be taken. As a photograph is often the only concrete memento that parents have of their baby, it is important for it to be of good quality. The parents decide what they would prefer, but it is important to point out to them that their wishes and needs immediately following the death may differ to those in the longer term.

Bereavement↗

RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck.

PURPOSE: Patients with recurrent squamous cell cancer of the head and neck (SCH&N) are generally treated with systemic chemotherapy. Improvement in survival has not occurred, despite an increased objective response rate. This study was undertaken to explore the feasibility and toxicity, and estimate the therapeutic impact of, reirradiation (RRT) with concurrent hydroxyurea and 5-fluorouracil. METHODS AND MATERIALS: The eligibility requirements included SCH&N presenting as a second primary or recurrence > or =6 months after definitive RT to > or =45 Gy, with > or =75% of the tumor volume within the previous field. The cumulative spinal cord dose was limited to 50 Gy, and measurable disease was required. Four weekly cycles were given, each separated by 1 week of rest. A cycle consisted of 5 days, Monday through Friday, of 1.5-Gy twice-daily repeated RT, with the fractions separated by > or =6 h, with 1.5 g of hydroxyurea given 2 h and 300 mg/m2 of a 5-fluorouracil IV bolus given 30 min before each second daily fraction. RESULTS: Eighty-six patients were entered; 81 patients were assessable. The median prior radiation dose was 61.2 Gy. The 4 planned cycles were delivered in 79% of patients. Grade 3 mucositis occurred in 14% of patients, and Grade 4 in 5%. Grade 3 acute pharyngeal toxicity was seen in 17%. Grade 3 neutropenia occurred in 9%, Grade 4 in 10%, and Grade 5 in 7%. Six patients died of treatment-related toxicity. Two died of hemorrhage from the tumor site without thrombocytopenia. With a median follow-up of 16.3 months for living patients, the estimated median overall survival was 8.2 months and the estimated 1-year survival rate 41.7%. Patients treated >3 years after the previous RT had a 1-year survival rate of 48% compared with 35% for patients treated within 3 years (p = 0.017). The 1-year survival rate for patients with a second primary was 54% compared with 38% for patients with recurrence (p = 0.083). CONCLUSION: Repeated RT with concurrent chemotherapy as given in this study is a feasible approach for selected, previously irradiated patients with SCH&N and may produce increased median and 1-year survival rates compared with systemic chemotherapy trials reported in the literature. A randomized study should be conducted to compare these two different approaches.

Adult↗

A large-scale evaluation of amnio-PCR for the rapid prenatal diagnosis of fetal trisomy.

OBJECTIVE: Traditional chromosome preparation from amniotic fluid samples often involves lengthy culture procedures in order to obtain cells for analysis. Multiplex quantitative fluorescent polymerase chain reaction (PCR) is a new molecular biological technique capable of quantifying in-situ DNA without the need for cell culture. Our objective was to test the reliability of PCR using fetal DNA from amniotic fluid (amnio-PCR) for the rapid prenatal diagnosis of the common trisomies. DESIGN: This was a large prospective study of 5000 amniocentesis specimens. Multiplex quantitative fluorescent PCR was performed specifically for short tandem repeat sequences within chromosomes 21, 18, 13, X and Y. All amniocentesis samples were subsequently analyzed by traditional karyotyping methods. RESULTS: Amnio-PCR detected all 89 major autosomal trisomies in this cohort. Diagnosis of sex chromosome anomalies was accurate for cases involving first meiotic division nondisjunction. However, further markers were necessary to detect sex chromosome anomalies arising from second meiotic division nondisjunction, highlighting the importance of using specific markers that enable the quantification of both the X and the Y chromosomes simultaneously. CONCLUSIONS: Rapid prenatal diagnosis of trisomies 21, 18, and 13 and the sex chromosome anomalies using amnio-PCR is a reliable technique that aids the clinical management of pregnancy. The speed of the methodology will help to minimize the period of parental anxiety in the wait for a diagnostic test result.

Amniotic Fluid↗

The photography of neonatal bereavement at Wythenshawe Hospital.

A large number of babies are stillborn or die in the neonatal period in Britain every year. This is only a small percentage of births overall, but these babies represent a considerable loss to the parents, and their hopes and ideals both for themselves and for their child. One of the key aids to grieving is memory, and in those cases where babies are born dead or die in utero, a history of the baby needs to be created. Photography can help create this history, and bereaved parents and families have expressed the importance of photographic images in assisting with their grieving process.

Bereavement↗

Effectiveness of prenatal chromosomal analysis using multicolor fluorescent in situ hybridisation.

OBJECTIVE: To evaluate the clinical effectiveness of multicolour fluorescent in situ hybridisation (FISH) analysis in routine prenatal diagnosis. DESIGN: Prospective study. SAMPLE: 3,203 amniotic fluid samples. METHODS: Unique DNA (chromosomes 13 and 21) and alpha satellite centromeric-specific (chromosomes X, Y and 18) probes were used in two mixes to permit the simultaneous analysis of several chromosomes. The performance of multicolour FISH and conventional cytogenetic analysis was compared. RESULTS: Conventional cytogenetic analysis identified 111 chromosomal abnormalities, of which 94 were potentially detectable by the FISH technique and 97 would be typically associated with neonatal phenotypic abnormalities. Multicolour FISH analysis detected 84% (93/111) of all chromosome abnormalities and 99% (93/94) of abnormalities where there was a specific probe. The sensitivity of multicolour FISH analysis was 95% (92/97) for chromosomal abnormalities likely to result in an abnormal postnatal outcome. Multiple ultrasound abnormalities were detected in all five cases of clinically relevant chromosomal abnormalities missed by multicolour FISH. FISH results were available within 48 hours and the sample failure rate was 0 x 1% (3/3,202). CONCLUSION: Multicolour FISH analysis is a sensitive and reliable technique for the rapid prenatal diagnosis of chromosomal abnormalities. Examining only five chromosomes allowed 95% of clinically relevant chromosomal abnormalities to be diagnosed correctly. As routine antenatal screening is targeted at the major autosomal trisomies and sex chromosome aneuploidies, multicolour FISH analysis may potentially replace conventional cytogenetic analysis in routine prenatal diagnosis.

Chromosome Aberrations↗

Ocular injuries due to projectile impacts.

An animal model has been developed using enucleated porcine eyes to evaluate ocular trauma. The eyes were pressurized to approximately 18 mmHg and mounted in a container with a 10% gelatin mixture. The corneas of sixteen pressurized eyes were impacted by a blunt metal projectile (mass of 2.6 gm, 3.5 gm or 45.5 gm) at velocities of 4.0 to 38.1 m/s. The impacted eyes were evaluated by an ophthalmologist. A numerical classification scheme was used to categorize the severity of the ocular injury. A chi-squared test indicates that the injury level is associated with the kinetic energy (KE) and not the momentum of the projectile. The enucleated eyes began to experience lens dislocations when the KE of the projectile was approximately 0.75 Nm, and retinal injuries when the KE was approximately 1.20 Nm.

Acceleration↗

Switch mode power supply for microwave heating based on the Boucherot effect.

This paper describes a new self-resonating switch-mode power-supply for driving CW magnetrons, based on the Boucherot effect. A detailed circuit analysis is given and its performance is evaluated for an 800 W/2450 MHz magnetron, whilst work at high power driving a magnetron up to 40 kW is reported. A comparison of the supply with the conventional power-supply used in microwave ovens is made and the principal features of the new design are found to be: low energy dissipation under short-circuit conditions, low ripple current and voltage waveforms that result in more precise control in the range 20-100% of rated power, high efficiencies and small size and weight.

Hot Temperature↗

Sucralfate for radiation mucositis: results of a double-blind randomized trial.

PURPOSE: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of antacid, diphenhydramine, and viscous lidocaine alone. METHODS AND MATERIALS: A double-blind study was conducted in which nurses and pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of antacid, diphenhydramine, and viscous lidocaine vs. the same solution plus sucralfate. Eligible patients were those receiving >40 Gy at 1.8 Gy/fraction, one fraction/day, five fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. The patients subjective evaluation of throat soreness and relief with medication was elicited as well as physician observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective nonstudy agents was not allowed. The ability to eat various consistency of foods was graded 0-5, with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + SD for food and soreness scores, paired t-test, and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. RESULTS: Over 2 years, 111 patients were entered. Because some withdrew and others did not require medication, results are presented for evaluable patients in each category. Mild adverse effects from the medication solution (usually mouth discomfort) were reported by <10% of patients in each treatment group among 106 patients evaluable for toxicity. There was a comparable incidence of mild-moderate mucositis for the two treatment groups. Severe mucositis was noted in two patients of the standard medication group and none among patients receiving sucralfate. The groups were comparable for indicators including degree of soreness, dietary changes, and objective measures or mucosal irritation or infection. For the head and neck patients there was a significant worsening in soreness and in the ability to eat in both treatment groups, whereas patients treated to the chest had less nutritional change. Multivariate analysis including control for confounding factors did not detect treatment effects for any of the response measures. No patient had occult fungal infection detected by oral pathology evaluation of routine mucosal scrapings. CONCLUSIONS: A trend (that was not statistically significant) of less severe radiation mucositis was noted for patients receiving sucralfate in addition to the combination of viscous lidocaine, diphenhydramine, and antacid for nonulcerative radiation mucositis.

Anti-Ulcer Agents↗

The use of qualitative questionnaires in patients having and being considered for cochlear implants.

Within this study we have examined the particular hearing complaints of patients being considered for a cochlear implant and the specific benefits/shortcomings experienced by implanted patients using open-ended questionnaires. As we expected, the difficulty of hearing general conversation was the most common individual hearing complaint. However, 45% of complaints were concentrated in the 'psychosocial' category, which was significantly higher than that found among general audiological rehabilitation patients. The average number of benefits listed by patients having implants was significantly higher than that of the shortcomings. Moreover, the main benefits listed were focused on the acoustical and psychological factors, e.g. 'environmental sound awareness', 'general conversation easier' and 'feeling of self-confidence'. The main shortcomings were related to the acoustical and practical areas, e.g. hearing difficulty in noisy background, processor being cumbersome.

Cochlear Implants↗

Fractionated radioimmunotherapy of human colon carcinoma xenografts with 131I-labeled monoclonal antibody CC49.

Radiolabeled monoclonal antibodies (MoAbs) have been used for radioimmunotherapy (RIT) of human colon cancer xenografts in an attempt to develop promising clinical approaches to improving therapy success. Several strategies have been investigated to accomplish this task while decreasing toxicity. The CC49 antibody was selected for the present studies because of its relatively high affinity constant (16.2 x 10(9) M-1) for the high molecular weight TAG-72 mucinous antigen secreted by human colon cancer cells. In previous studies, when CC49 was labeled with 131I, it demonstrated a substantial therapeutic advantage over the lower affinity antibody (B72.3) reactive with TAG-72. One of the chief problems in achieving cures with RIT is that hematological toxicity limits the quantity of radionuclide that can be administered. In other studies of dose fractionation using athymic nude mice and 131I-labeled intact MoAbs reactive with human colon cancer xenografts, multiple administrations at approximately 1-week intervals were found to produce more prolonged tumor growth inhibition and less toxicity than single administrations. The purpose of this study was to investigate the therapeutic efficacy and toxicity of 131I-labeled CC49 MoAb administered with short fractionation schedules against human colon cancer xenografts to determine the optimal treatment schedule, with the ultimate aim of applying this approach in clinical trials. The results reported here demonstrate that in an animal colon cancer xenograft model, RIT delivered in a fractionated schedule clearly presents a therapeutic advantage. For example, one administration of 600 microCi 131I-labeled CC49 to LS174T tumor-bearing mice was lethal to approximately 25% of mice but produced no tumor regressions. Fractionation of this dose to two administrations of 300 microCi 131I-labeled CC49 at a 3-day interval resulted in tumor regression in approximately 30% of the animals, accompanied by a similar 25% death rate. The administration of 300 microCi 131I-labeled CC49 at a 7-day interval resulted in 15% animal lethality, but no complete tumor regressions. When three administrations of 300 microCi 131I-labeled CC49 were given over a 1-week period on days 0, 3, and 7, tumor regressions occurred in approximately 40% of the animals, accompanied by a 30% death rate. Moreover, three administrations of 300 microCi 131I-labeled CC49 resulted in 20% tumor recurrence, whereas two administrations of 131I-labeled CC49 resulted in 60% tumor recurrence.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A fetus with an X;1 balanced reciprocal translocation and eye disease.

A 19 week female fetus is described with a de novo X;1 reciprocal balanced translocation, with the breakpoint on the X chromosome at Xp11.4, and eye pathology consistent with the early stages of Norrie disease. The fetus seems to be an example of a female manifesting an X linked recessive disease, and it was shown that the normal X chromosome was completely inactivated in all cells examined. Norrie disease has been mapped to Xp11.3, and fluorescence in situ hybridisation studies showed that the Norrie disease gene had not obviously been disrupted. Mutation screening by SSCP analysis showed no aberrant fragments of the coding region of the gene. Several eye disease genes map to the same region of the X chromosome, but are excluded on grounds of pathology. One possibility is that this fetus has a Norrie-like eye disease caused by the mutation of another gene located at Xp11.4. If this is so, there are implications for prenatal diagnosis.

Abnormalities, Multiple↗

No postural effect on middle ear resonance frequency: a pilot study.

A change in body posture from sitting to reclined is known to cause an increase in intracochlear fluid pressure, if the cochlear aqueduct is patent. Previous studies have shown this increase to have an effect on middle ear dynamics. The aim of this study was to investigate whether such increases in cochlear pressure may affect the stiffness of, and hence the resonance frequency of the middle ear. No consistent group or individual differences were shown between the two postural conditions.

Acoustic Impedance Tests↗

Screening for hearing loss in an at-risk neonatal population using evoked otoacoustic emissions.

The present study examines the performance of a transient evoked otoacoustic emissions hearing screening programme for neonates with risk factors for hearing loss. The programme has run for 5 years, and 772 babies with various risk factors have been screened using the Programmable Otoacoustic Emissions Measurement System (POEMS) designed by the Medical Research Council Institute of Hearing Research. Fourteen cases of significant hearing loss have been detected, with no false negative results. However, a very high false positive rate is reported, especially in babies with a birthweight of less than 1500 g.

Cochlea↗

A phase I clinical trial of murine monoclonal antibody D612 in patients with metastatic gastrointestinal cancer.

In a phase I study, 21 patients with metastatic adenocarcinoma of the gastrointestinal tract received the murine monoclonal antibody D612. This antibody is directed at a M(r) 48,000 antigen restrictively expressed on tumors of the gastrointestinal tract and to a limited degree on normal gastrointestinal mucosa. Patients received total doses of 10-180 mg/m2 administered as single or multiple doses of 1-100 mg/m2 over an 8-day period. Dose-limiting toxicity was secretory diarrhea. A single dose of 100 mg/m2 exceeded guidelines for maximal tolerated dose. Higher total doses were achieved in subsequent patients by using repeated administration of lower doses. Three of five patients receiving 60 mg/m2 for 3 doses (180 mg/m2 total dose) experienced grade 3 diarrhea and could not complete the prescribed course. The dose of 40 mg/m2 administered on days 1, 4, and 8 (total dose, 120 mg/m2) has been selected as the dose for phase II studies. The pharmacokinetics of D612 is best described by a one-compartment model with a mean t1/2 of 48 +/- 3 h (SEM). Eighteen of 21 patients developed human anti-mouse antibody (HAMA). Patients who developed high levels of HAMA demonstrated a more rapid clearance of the day 8 dose than those who developed low levels of HAMA. In all patients studied, a component of HAMA was directed at the D612 variable region. With one exception, serum from all patients with detectable antibody to the D612 variable region demonstrated anti-paratope reactivity. Thirty-four % of known metastatic sites demonstrated uptake of radiolabeled D612. There were no objective antitumor responses in this phase I trial. The antitumor effect of D612 in vitro has been shown to be potentiated by interleukin 2 and recombinant human macrophage colony-stimulating factor. A phase II study of D612 administered in combination with cytokines that enhance human effector function is presently ongoing.

Adenocarcinoma↗

In-the-ear and behind-the-ear hearing aids in the elderly.

A significant proportion of new hearing aid fittings are rejected by elderly patients. One of the reasons for this is their inability to correctly fit the earmould and hearing aid correctly. In this study we compared the ease of fitting of a behind-the-ear hearing aid with a specially modified skeleton earmould with an in-the-ear (ITE) hearing aid, in an elderly subject group. The modified skeleton earmould was found to be easiest to use. However, the ITE hearing aid presented handling problems only in subjects over 75 years of age. Further analysis of the results revealed that the majority of handling problems are found in female subjects in the over-75 age group.

Aged↗

Acceptability of binaural hearing aids: a cross-over study.

Using screening questionnaires we were able to detect individuals aged 50-65 years with hearing disability in a general practice population. Those who had better ear hearing levels of 30 dB or worse were invited to take place in a cross-over study comparing the acceptability of a monaural or binaural hearing-aid fitting. Fifty-five per cent ultimately opted for a binaural fitting and had greater hearing disability and worse mean hearing levels than those who opted for a monaural fitting. They made their choice for acoustical reasons, particularly on the basis of improved localization ability.

Audiometry↗

The desynchrony between complaints and signs of vestibular disorders.

As part of an early intervention study on the acceptability of auditory rehabilitative intervention, we examined patient complaints and clinical findings of balance disorders. Hallam et al. have discussed desynchrony between such findings in hospital patient populations, and the aim of the present study was to investigate these relationships in a general population. The study was conducted in two industrial villages in Wales in which questionnaires were circulated to all individuals in the 50-65 age group. A marked desynchrony between semeions and clinical findings was found. This has been related to the desynchrony between auditory impairment, disability and handicap in this population. Subjects reporting giddiness or vertigo were more disabled but not more impaired in respect of auditory measures than those not reporting such balance problems. Those with abnormal balance test results showed no auditory differences from those with normal results.

Aged↗