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Biomedical subjects

J M Graham

Publications and source records attributed to J M Graham.

At least 19 recordsLinked to original sources

A comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy--a systematic review and meta-analysis of randomized trials.

Epidural analgesia is considered by many to be the best method of pain relief after major surgery. It is used routinely in many thoracic surgery centres. Although effective, side-effects include hypotension, urinary retention, incomplete (or failed) block, and, in rare cases, paraplegia. Paravertebral block (PVB) is an alternative technique that may offer comparable analgesic effectiveness and a better side-effect profile. We undertook a systematic review and meta-analysis of all relevant randomized trials comparing PVB with epidural analgesia in thoracic surgery. Data were abstracted and verified by both authors. Studies were tested for heterogeneity, and meta-analyses were done with random effects or fixed effects models. Weighted mean difference (WMD) was used for numerical outcomes and odds ratio (OR) for dichotomous outcomes, both with 95% CI. We identified 10 trials that had enrolled 520 thoracic surgery patients. All of the trials were small (n<130) and none were blinded. There was no significant difference between PVB and epidural groups for pain scores at 4-8, 24 or 48 h, WMD 0.37 (95% CI: -0.5, 121), 0.05 (-0.6, 0.7), -0.04 (-0.4, 0.3), respectively. Pulmonary complications occurred less often with PVB, OR 0.36 (0.14, 0.92). Urinary retention, OR 0.23 (0.10, 0.51), nausea and vomiting, OR 0.47 (0.24, 0.53), and hypotension, OR 0.23 (0.11, 0.48), were less common with PVB. Rates of failed block were lower in the PVB group, OR 0.28 (0.2, 0.6). PVB and epidural analgesia provide comparable pain relief after thoracic surgery, but PVB has a better side-effect profile and is associated with a reduction in pulmonary complications. PVB can be recommended for major thoracic surgery.

Analgesia, Epidural↗

How we do it: patient participation in cochlear implant selection.

. Involving patients and parents in the choice of their cochlear implant encourages an active role in the process and facilitates 'bonding' and 'ownership' of the device. . The most frequent reasons given by patients for selecting a device included cochlear implant comfort and appearance. . We describe the Implant Programme based at the Royal National Throat, Nose and Ear Hospital, London, and also examine patient satisfaction with the scheme.

Adult↗

The adult phenotype in Costello syndrome.

We report clinical findings in 17 adults with Costello syndrome ranging in age from 16 to 40 years. Two patients in this series have had bladder carcinoma, the only malignancy reported to affect adults with Costello syndrome. Benign tumors included multiple ductal papillomata in two women, and a fourth ventricle mass in one man, thought to be a choroid plexus papilloma. Endocrine problems in this series were osteoporosis, central hypogonadism, and delayed puberty. Other health problems were symptomatic Chiari malformations in three patients. Four patients had adult-onset gastro-esophageal reflux, three of whom had Chiari malformations. Fourteen adults had mild to moderate intellectual disability with three individuals having severe intellectual disability; 15 individuals attained some reading and writing skills and 14 showed ongoing acquisition of new skills into adulthood. On the basis of this data, we recommend that neuro-imaging be considered in adults with Costello syndrome if they develop symptoms suggestive of a Chiari malformation. In the event of pubertal delay, endocrine investigations are indicated and hormone treatment may be required. Bone density assessments should be performed in adults with Costello syndrome, particularly in those with pubertal abnormalities. Screening for microscopic hematuria as a marker for bladder carcinoma may be indicated, although this requires further evaluation.

Abnormalities, Multiple↗

A prospective randomized controlled trial evaluating alcohol on loudness perception in cochlear implant users.

AIM: The aim of this study was to determine the effects of alcohol on the psychophysical responses in patients with cochlear implants. This has not been previously studied. It was also hoped to provide information that could suggest possible sites of action of the known effects of alcohol on the auditory pathway. DESIGN: A prospective randomized placebo-controlled trial, with full ethical approval. PARTICIPANTS: Eight successful cochlear implant users were selected, of whom two had bilateral implants which were tested separately. In total 10 cochlear implants were tested. INTERVENTION: Alcohol was given in the form of vodka (50% alcohol, 1 mL/kg body weight) with 500 mL of orange and cranberry juice. The placebo control was given in the form of 500 mL of orange and cranberry juice alone. OUTCOME MEASUREMENT: The 'comfort level' (C level) was recorded before, and 1 h after alcohol or placebo ingestion for each patient's cochlear implant. Blood alcohol concentration was determined prior to alcohol or placebo consumption and then repeated after 45, 60, 90 and 180 min. RESULTS: The mean blood alcohol concentration 1 h after ingestion was 50 mg/dL. In the 'alcohol' arm the mean electrical unit increase in the C level was 19.9 with a standard deviation of 2.2. In the control arm the mean change in C level was 0.10 with a standard deviation of 0.3. CONCLUSIONS: In this first prospective randomized control study of the effect of alcohol on sound perception in cochlear implant users, alcohol significantly increased the upper end of the dynamic range (C levels) in comparison with placebo (P = <0.0001 using paired t-test analysis). This effect is likely to be the result of change in the auditory pathways proximal to the cochlea.

Adult↗

The relationship between oxygenator exhaust P(CO2) and arterial P(CO2) during hypothermic cardiopulmonary bypass.

During cardiopulmonary bypass the partial pressure of carbon dioxide in oxygenator arterial blood (P(a)CO2) can be estimated from the partial pressure of gas exhausting from the oxygenator (P(E)CO2). Our hypothesis is that P(E)CO2 may be used to estimate P(a)CO2 with limits of agreement within 7 mmHg above and below the bias. (This is the reported relationship between arterial and end-tidal carbon dioxide during positive pressure ventilation in supine patients.) During hypothermic (28-32 degrees C) cardiopulmonary bypass using a Terumo Capiox SX membrane oxygenator, 80 oxygenator arterial blood samples were collected from 32 patients during cooling, stable hypothermia, and rewarming as per our usual clinical care. The P(a)CO2 of oxygenator arterial blood at actual patient blood temperature was estimated by temperature correction of the oxygenator arterial blood sample measured in the laboratory at 37 degrees C. P(E)CO2 was measured by connecting a capnograph end-to-side to the oxygenator exhaust outlet. We used an alpha-stat approach to cardiopulmonary bypass management. The mean difference between P(E)CO2 and P(a)CO2 was 0.6 mmHg, with limits of agreement (+/-2 SD) between -5 to +6 mmHg. P(E)CO2 tended to underestimate P(a)CO2 at low arterial temperatures, and overestimate at high arterial temperatures. We have demonstrated that P(E)CO2 can be used to estimate P(a)CO2 during hypothermic cardiopulmonary bypass using a Terumo Capiox SX oxygenator with a degree of accuracy similar to that associated with the use of end-tidal carbon dioxide measurement during positive pressure ventilation in anaesthetized, supine patients.

Blood Gas Analysis↗

Severe uncontrolled pain in buttock in a patient on naltrexone: a diagnostic challenge.

A 26-year-old woman with a history of intravenous drug use was admitted to hospital with worsening pain in the right buttock radiating to the lateral part of the thigh and to the calf with no suspicion of cauda equina compression. Eventually, a diagnosis of sacroiliitis was made and appropriate antibiotics were administered. Provision of analgesia for this patient was difficult. On admission her medications included naltrexone, venlafaxine and tramadol. Initially naltrexone was continued and analgesia provided by epidural local anaesthetic and clonidine, intravenous ketamine and oral agents. After several days, naltrexone was ceased and opioids were used in addition to the other analgesics. The epidural analgesia was only partially effective, perhaps because of inadequate blockade of the L4-S1 nerve roots, which carry sensation from the sacroiliac joint. Naltrexone is a long-acting opioid antagonist. If opioid analgesia is planned, it is necessary to cease naltrexone for 24 to 72 hours. In an emergency, if non-opioid techniques prove ineffective, short-acting opioids can be titrated to effect in a monitored environment.

Adult↗

Diffusion tensor imaging for the assessment of upper motor neuron integrity in ALS.

BACKGROUND: High angular resolution diffusion tensor imaging (HARD) is an MRI technique that exploits the mobility of water molecules to yield maps of structural order and directionality of white matter tracts with greater precision than six-direction diffusion tensor imaging (DTI) schemes. OBJECTIVE: To assess whether HARD is more sensitive than conventional MRI or neurologic assessment in detecting the upper motor neuron (UMN) pathology of patients with ALS. METHODS: Twenty-five patients with definite UMN clinical signs and 23 healthy volunteers underwent conventional MRI. HARD datasets were collected from a subset of these participants plus four patients with isolated lower motor neuron (LMN) signs. ALS symptom severity was assessed by a neurologist, the conventional MR images were reviewed by neuroradiologists, and the DTI maps were subject to quantitative region of interest analysis. RESULTS: Motor cortex hypointensity on T2-weighted images and corona radiata hyperintensity on proton density-weighted images distinguished patients with UMN involvement from volunteers with 100% specificity, but only 20% sensitivity. Fractional anisotropy (FA) was reduced in the posterior limb of the internal capsule in patients with UMN involvement compared to volunteers. A FA threshold value with a sensitivity of 95% to detect patients with ALS (including those with isolated LMN signs) had a specificity of 71%. CONCLUSIONS: High angular resolution diffusion tensor imaging may be more sensitive than conventional MRI or neurologic assessment to the upper motor neuron (UMN) pathology of ALS, but it lacks the specificity required of a diagnostic marker. Instead, it is potentially useful as a quantitative tool for monitoring the progression of UMN pathology.

Adult↗

Incidence of meningitis and of death from all causes among users of cochlear implants in the United Kingdom.

BACKGROUND: During 2002, there was an increase in reports of bacterial meningitis among people with cochlear implants in Europe and North America. One model of implant, which included a space-occupying 'positioner', was recalled. Implantation of a positioner was shown to be a risk factor for meningitis among children in the United States. The situation in the United Kingdom was not known. METHODS: We ascertained the cohort of people who had received cochlear implants with intra-cochlear electrodes in UK hospitals prior to 1 October 2002 and were permanently resident in the United Kingdom. We compared the incidence of meningitis, and the causes and incidence of death from all causes, between the cohort and reference populations. RESULTS: Of 1851 children (66 with positioners), none had contracted meningitis. Neither the incidence rate of meningitis, nor the cumulative mortality from all causes, differed significantly between implanted children and values expected for the general population. Of 1779 adults (139 with positioners), five had contracted meningitis with three fatalities. No case of meningitis involved a positioner and four of the cases, including the fatalities, possessed risk factors unrelated to implantation. Although the incidence rate of meningitis was significantly higher in implanted adults than the general population, cumulative mortality from all causes was never higher, and was significantly lower at some time points after implantation. CONCLUSION: Specific evidence of the association between bacterial meningitis and implantation with a positioner that arose in the United States and mainland Europe during 2002 has not been found in the United Kingdom.

Adolescent↗

Seasonal dynamics of phytoplankton and planktonic protozoan communities in a northern temperate humic lake: diversity in a dinoflagellate dominated system.

Species diversity and richness, and seasonal population dynamics of phytoplankton, planktonic protozoa, and bacterioplankton sampled from the epilimnion of Crystal Bog in 2000, were examined in order to test the hypothesis that these groups' diversity and abundance patterns might be linked. Crystal Bog, a humic lake in Vilas County, Wisconsin, is part of the North Temperate Lakes Long-Term Ecological Research Site. Phytoplankton and planktonic protozoa were identified and enumerated in a settling chamber with an inverted microscope. Bacterial cells were enumerated with the use of fluorescence 4', 6'-diamidino-2-phenylindole (DAPI)-staining procedures, and automated ribosomal intergenic spacer analysis (ARISA) was used to assess bacterioplankton diversity. Bacterial cell counts showed little seasonal variation and averaged 2.6 x 10(6) cells/mL over the ice-free season. Phytoplankton and planktonic protozoan numbers varied by up to two orders of magnitude and were most numerous in late spring and summer. Dinoflagellates largely dominated Crystal Bog throughout the ice-free period, specifically Peridiniopsis quadridens in the spring, Peridinium limbatum in summer, and Gymnodinium fuscum and P. quadridens in fall. Brief blooms of Cryptomonas, Dinobryon, and Synura occurred between periods of dinoflagellate domination. The dominant dinoflagellate, Peridinium limbatum, was calculated to have a growth rate of 0.065 day(-1) and a doubling time of 10.7 days. Heterotrophic nanoflagellates (HNFs) were a consistent component of the planktonic protozoa; seasonal patterns were determined for three genera of HNFs (Monosiga, Bicosoeca, and Desmarella moniliformis). Three genera of ciliates (Coleps, Strobilidium, and Strombidium) comprised the greater part of the planktonic protozoa in Crystal Bog. The number of species of planktonic protozoa was too low to calculate a diversity index. Shannon-Weaver diversity indices for phytoplankton and bacterioplankton in the epilimnion followed very similar seasonal patterns in this lake, supporting the hypothesis that in freshwaters, diversity patterns of these groups are linked.

Animals↗

Annual patterns in bacterioplankton community variability in a humic lake.

Bacterioplankton community composition (BCC) was monitored in a shallow humic lake in northern Wisconsin, USA, over 3 years using automated ribosomal intergenic spacer analysis (ARISA). Comparison of ARISA profiles of bacterial communities over time indicated that BCC was highly variable on a seasonal and annual scale. Nonmetric multidimensional scaling (MDS) analysis indicated little similarity in BCC from year to year. Nevertheless, annual patterns in bacterioplankton community diversity were observed. Trends in bacterioplankton community diversity were correlated to annual patterns in community succession observed for phytoplankton and zooplankton populations, consistent with the notion that food web interactions affect bacterioplankton community structure in this humic lake. Bacterioplankton communities experience a dramatic drop in richness and abundance each year in early summer, concurrent with an increase in the abundance of both mixotrophic and heterotrophic flagellates. A second drop in richness, but not abundance, is observed each year in late summer, coinciding with an intense bloom of the nonphagotrophic dinoflagellate Peridinium limbatum. A relationship between bacterial community composition, size, and abundance and the population dynamics of Daphnia was also observed. The noted synchrony between these major population and species shifts suggests that linkages across trophic levels play a role in determining the annual time course of events for the microbial and metazoan components of the plankton.

Bacterial Physiological Phenomena↗

Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus.

BACKGROUND: Insulin therapy may influence cardiovascular disease (CVD) and lipid metabolism in type 2 diabetes (T2D). Exaggerated postprandial lipaemia (PPL) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress (OS) and endothelial dysfunction. We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty (17 M) T2D patients were studied (mean Hba1c 8.4%) at baseline, following 6 weeks of insulin lispro (0.2 Iu kg-1) and vitamin C 1-g daily. Eight-h lipid and glucose profiles were measured following a fatty meal. Endothelial function (flow-mediated vasodilatation: FMD) and OS were measured at fasting, 4 h and 8 h. MATERIALS AND METHODS: Glucose, body mass index, and total and LDL cholesterol remained unchanged. FMD improved. Placebo group: fasting, 1.1 +/- 1.2 to 4.2 +/- 1.1% (P < 0.001); 4-h, 0.3 +/- 1.2 to 3.1 +/- 0.9% (P < 0.01); 8-h, 0.7 +/- 1.1 to 3.76 +/- 1.1% (P < 0.001). Vitamin C group: fasting, 0.9 +/- 1.1 to 6.1 +/- 1.3% (P < 0.001); 4-h, 0.7 +/- 1.5 to 4.9 +/- 2.1% (P < 0.001); 8-h, 0.8 +/- 0.9 to 5.8 +/- 0.6% (P < 0.01). Post-prandial lipaemia was attenuated: TG area-under-curve (mmol L-1 8 h-1), 52.6 +/- 11 to 39.1 +/- 12.5 (placebo group), P < 0.02; and 56.9 +/- 8 to 40.1 +/- 10.3 (vitamin C group), P < 0.02. Oxidative stress was reduced, with greater changes in the vitamin C group. CONCLUSION: Insulin may thus exert vascular benefits in T2D, by modifying fasting and postprandial lipid metabolism resulting in reduced OS and improved EF. Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF.

Adult↗

A novel retractor for use in cochlear implantation.

A new self-retaining scalp retractor is described, which elevates the scalp away from the skull to allow better access and vision in preparing the bony recess for a cochlear implant and protect the pericranium from surgical trauma. It is designed for use with the present generation of small vertical scalp incisions in cochlear implant surgery. In these incisions, the part of the skull drilled to create the implant bed is not directly under the wound; instead, it extends under a flap of scalp and pericranium for 5 cm or more. The retractor is simple to use, and the authors believe that it represents a new type of retractor, which may have other uses in the fields of orthopedic; ear, nose, and throat, cosmetic, and plastic surgery. Photographs demonstrate the instrument in use. A cochlear implant company has agreed to manufacture the instrument.

Cochlear Implantation↗

Cochlear implantation in Jervell and Lange-Nielsen syndrome.

A case of familial prolonged QT interval and congenital sensorineural hearing loss is described emphasising the diagnostic and management implications. Jervell and Lange-Nielsen syndrome is important because of its potential association with sudden death in children with congenital sensorineural deafness. It is known to be associated with mutations of the genes KCNQ1 (KVQTI) and KCNE1 (Isk). The underlying molecular abnormality leads to cardiac and cochlear dysfunction through a potassium channel defect. All children with congenital sensorineural hearing loss who have suffered unexplained syncopal attacks or convulsions should be screened for this syndrome. There is also a strong case for including a 12 lead ECG as part of the investigative work up of all children with congenital sensorineural deafness in whom a firm aetiology has not been established.

Adolescent↗

Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy.

Cerebro-oculo-facio-skeletal (COFS) syndrome is a recessively inherited rapidly progressive neurologic disorder leading to brain atrophy, with calcifications, cataracts, microcornea, optic atrophy, progressive joint contractures, and growth failure. Cockayne syndrome (CS) is a recessively inherited neurodegenerative disorder characterized by low to normal birth weight, growth failure, brain dysmyelination with calcium deposits, cutaneous photosensitivity, pigmentary retinopathy and/or cataracts, and sensorineural hearing loss. Cultured CS cells are hypersensitive to UV radiation, because of impaired nucleotide-excision repair (NER) of UV-induced damage in actively transcribed DNA, whereas global genome NER is unaffected. The abnormalities in CS are caused by mutated CSA or CSB genes. Another class of patients with CS symptoms have mutations in the XPB, XPD, or XPG genes, which result in UV hypersensitivity as well as defective global NER; such patients may concurrently have clinical features of another NER syndrome, xeroderma pigmentosum (XP). Clinically observed similarities between COFS syndrome and CS have been followed by discoveries of cases of COFS syndrome that are associated with mutations in the XPG and CSB genes. Here we report the first involvement of the XPD gene in a new case of UV-sensitive COFS syndrome, with heterozygous substitutions-a R616W null mutation (previously seen in patients in XP complementation group D) and a unique D681N mutation-demonstrating that a third gene can be involved in COFS syndrome. We propose that COFS syndrome be included within the already known spectrum of NER disorders: XP, CS, and trichothiodystrophy. We predict that future patients with COFS syndrome will be found to have mutations in the CSA or XPB genes, and we document successful use of DNA repair for prenatal diagnosis in triplet and singleton pregnancies at risk for COFS syndrome. This result strongly underlines the need for screening of patients with COFS syndrome, for either UV sensitivity or DNA-repair abnormalities.

Abnormalities, Multiple↗

Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3.

A unique type of craniofacial dysostosis, Crouzon syndrome with acanthosis nigricans (CAN), has been attributed to a specific substitution (Ala391Glu) in the fibroblast growth factor receptor 3 (FGFR3) gene. At birth, individuals with this disorder have craniosynostosis, ocular proptosis, midface hypoplasia, choanal atresia, hydrocephalus, and they experience the onset of acanthosis nigricans during childhood. We report three cases and compare the clinical characteristics of our cases with the previously reported cases of this disorder. Since the Ala391Glu substitution in FGFR3 is close to the substitutions in the transmembrane domain that result in achondroplasia, we carefully reviewed the skeletal findings in six patients. We identified subtle radiographic findings of achondroplasia in all six cases including narrow sacrosciatic notches, short vertebral bodies, lack of the normal increase in interpediculate distance from the upper lumbar vertebrae caudally, and broad, short metacarpals and phalanges. Even before acanthosis nigricans appears, the presence of choanal atresia and hydrocephalus in an individual with features of Crouzon syndrome should suggest the diagnosis of CAN, and subtle skeletal findings can lend further support to this diagnosis.

Acanthosis Nigricans↗