Cardiac pacing systems and implantable cardiac defibrillators (ICDs): a radiological perspective of equipment, anatomy and complications.
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Contraindications↗
Biomedical subjects
D Hadley
Publications and source records attributed to D Hadley.
HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival.
Following standard treatment, the prognosis remains poor in patients with high-grade glioma and new therapies are urgently required. Herpes simplex virus 1716 (HSV1716) is an ICP34.5 null mutant that is selectively replication competent and shown to be safe and to replicate following injection into high-grade glioma. We demonstrate that following surgical resection, HSV1716 is safe when injected into the brain adjacent to excised tumour. In all, 12 patients with recurrent or newly diagnosed high-grade glioma underwent maximal resection of the tumour. HSV1716 was injected into eight to 10 sites around the resulting tumour cavity with the intent of infecting residual tumour cells. As clinically indicated, patients proceeded to further radiotherapy or chemotherapy. There has been no clinical evidence of toxicity associated with the administration of HSV1716. Longitudinal follow-up has allowed the assessment of overall survival compared to that of similar patients not treated with HSV1716. Three patients remain alive and clinically stable at 15, 18 and 22 months postsurgery and HSV1716 injection. Remarkably, the first patient in the trial, who had extensive recurrent disease preprocedure, is alive at 22 months since injection of HSV1716 and 29 months since first diagnosis. Imaging has demonstrated a reduction of residual tumour over the 22-month period despite no further medical intervention since the surgery and HSV1716 injection. In this study, we demonstrate that on the basis of clinical observations, there has been no toxicity following the administration of HSV1716 into the resection cavity rim in patients with high-grade glioma. The survival and imaging data, in addition to the lack of toxicity, give us confidence to proceed to a clinical trial to demonstrate efficacy of HSV1716 in glioma patients.
Adult↗
The potential for efficacy of the modified (ICP 34.5(-)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study.
We have previously demonstrated the safety of intratumoural administration of the selectively replication-competent herpes simplex virus mutant HSV1716 in patients with high-grade glioma (HGG). Here we show its potential for efficacy by demonstrating that the virus survives and replicates when injected into the tumours of patients. Since HSV replication is a cytolytic process it must result in tumour cell killing. Twelve patients with biopsy-verified HGG received an intratumoural injection of 10(5) plaque-forming units (p.f.u.) of HSV1716. Four to 9 days after inoculation, tumours were removed and assayed for evidence of viral replication. In two patients, HSV1716, in excess of the input dose was recovered from the injection site. HSV DNA was detected by PCR at the sites of inoculation in 10 patients and at distal tumour sites in four. HSV-specific antigen was detected in tumour tissue from two patients. In five patients an immunological response to HSV1716, as detected by changes in levels of IgG and IgM, was demonstrated. This study demonstrates that HSV1716 replicates in HGG without causing toxicity in both HSV-seropositive and -seronegative patients.
Adult↗
A high-resolution radiation hybrid map of the human genome draft sequence.
We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.
Algorithms↗
Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers.
DNA mismatch repair is of considerable scientific and medical importance because of its essential role in maintaining genomic integrity, and its association with hereditary non-polyposis colon cancer (HNPCC). Germline mutations in five mismatch repair genes (MLH1, MSH2, PMS1, PMS2, and MSH6) have been associated with HNPCC susceptibility. Our laboratory recently identified MLH3, a novel DNA mismatch repair gene. We screened the MLH3 coding sequence in 60 probands with increased genetic risk factors for colorectal cancer susceptibility and no mutations in the other candidate genes. No definite MLH3 germline mutations were found. We subsequently screened 36 colon tumors, and discovered an appreciable frequency of somatic MLH3 coding mutations in MSI-H tumors (25%). In four of six tumors, evidence of biallelic inactivation was noted. Furthermore, MLH3 nonsense mutations were identified in two of 12 microsatellite stable (MSS) tumors with 14q24 loss of heterozygosity. While our analyses do not exclude the existence of germline MLH3 mutations in patients with increased genetic risk factors for colorectal cancer susceptibility, they suggest such mutations are uncommon in this patient population. The finding of an appreciable frequency of somatic MLH3 mutations is consistent with a possible role for this gene in the progression of colorectal cancer tumorigenesis. Hum Mutat 17:389-396, 2001. Published 2001 Wiley-Liss, Inc.
Adaptor Proteins, Signal Transducing↗
Method of determination of three dimensional index finger moment arms and tendon lines of action using high resolution MRI scans.
High-resolution MRI scans, in conjunction with CAD software, were used to determine the three-dimensional moment arms and force vector direction cosines for 11 structures passing the interphalangeal and metacarpophalangeal joints of the index finger. The results are presented for five different angles of joint flexion for a single subject. The moment arm data obtained differ from previous studies, where results have been derived from tendon excursion techniques or geometrical models. These dissimilarities have been accounted for by the differences in experimental techniques.
Adult↗
Unusual renal features of Lowe syndrome in a mildly affected boy.
The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, mental retardation, and renal tubular dysfunction. The gene responsible for OCRL was identified by positional cloning and encodes a lipid phosphatase, phosphatidylinositol 4,5, bisphosphate [PtdIns(4,5)P2]5-phosphatase, which localizes to the Golgi apparatus and is suspected to play a role in Golgi vesicular transport [Suchy et al., 1995]. In addition to the ocular and renal manifestations, most boys with OCRL have cognitive problems and maladaptive behaviors including tantrums and stereotypies. We report a boy with a history of congenital cataracts and mild developmental delay who was also found to have hematuria with proteinuria but minimal signs of renal tubular dysfunction. Subsequent renal biopsy was compatible with a diagnosis of a noncomplement fixating chronic glomerulonephritis. Despite the atypical renal findings, skin fibroblast analysis for PtdIns (4,5)P2 5-phosphatase was performed, and enzyme activity was low, consistent with the diagnosis of OCRL. Western blot analysis from cell lysates showed the ocrl protein was decreased in size and amount. Our report shows atypical renal features of OCRL in a mildly affected boy. The possibility of OCRL should be considered in boys with cataracts and glomerular disease, even in the absence of renal tubular defects and frank mental retardation usually associated with the syndrome. Am. J. Med. Genet. 95:461-466, 2000. Published Wiley-Liss, Inc.
Acidosis, Renal Tubular↗
Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma.
The herpes simplex virus (HSV) ICP34.5 null mutant 1716 replicates selectively in actively dividing cells and has been proposed as a potential treatment for cancer, particularly brain tumours. We present a clinical study to evaluate the safety of 1716 in patients with relapsed malignant glioma. Following intratumoural inoculation of doses up to 10(5) p.f.u., there was no induction of encephalitis, no adverse clinical symptoms, and no reactivation of latent HSV. Of nine patients treated, four are currently alive and well 14-24 months after 1716 administration. This study demonstrates the feasibility of using replication-competent HSV in human therapy.
Adult↗
PCR detection of bacteria in seven minutes.
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Bacteria↗
Racial differences in testing motivation and psychological distress following pretest education for BRCA1 gene testing.
OBJECTIVES: We conducted a randomized trial to investigate racial differences in response to two alternate pretest education strategies for BRCA1 genetic testing: a standard education model and an education plus counseling (E + C) model. MATERIALS AND METHODS: Two hundred twenty-eight Caucasian women and 70 African American women with a family history of breast or ovarian cancer were contacted for a baseline telephone interview to assess sociodemographic characteristics, number of relatives affected with cancer, and race before pretest education. Outcome variables included changes from baseline to 1-month follow-up in cancer-related distress and genetic testing intentions, as well as provision of a blood sample after the education session. RESULTS: African American women were found to differ significantly from Caucasian women in the effects of the interventions on testing intentions and provision of a blood sample. Specifically, in African American women, E + C led to greater increases than education only in intentions to be tested and provision of a blood sample. These effects were independent of socioeconomic status and referral mechanisms. In Caucasian women, there were no differential effects of the interventions on these outcomes. Reductions in cancer-specific distress were evidenced in all study groups. However, this decrease, although not significantly different, was smallest among African American women who received E + C. CONCLUSIONS: In low- to moderate-risk African American women, pretest education and counseling may motivate BRCA1 testing. Further research is needed to explore the mechanisms of impact of the alternate pretest education strategies and to increase the cultural sensitivity of education and counseling protocols.
Adolescent↗
Regional cerebral perfusion and amytal distribution during the Wada test.
UNLABELLED: The distribution of sodium amytal and its effect on regional cerebral perfusion during the intracarotid amytal (Wada) test were investigated using high-resolution hexamethyl propyleneamine oxime (HMPAO) SPECT coregistered with the patient's MRI dataset. METHODS: Twenty patients underwent SPECT after intravenous HMPAO injection, and 5 patients had both intravenous and intracarotid injections in a double injection-acquisition protocol. RESULTS: All patients had hypoperfusion in the territories of the anterior and middle cerebral arteries. Basal ganglia perfusion was preserved in 20 of 25 patients. Hypoperfusion of the entire mesial temporal cortex was seen in 9 of 25 patients. Partial hypoperfusion of the whole mesial cortex or hypoperfusion of part of the mesial cortex was seen in 14 of 25 patients. In 2 of 25 patients, mesial temporal perfusion was unaffected. In 5 patients, the double acquisition showed a distribution of HMPAO delivery matching that of hypoperfusion, except for the following: (a) HMPAO was delivered to the basal ganglia and insula, where there was no hypoperfusion; (b) HMPAO was not delivered to the contralateral cerebellum, which did show hypoperfusion; and (c) in 1 patient, perfusion of the mesial temporal cortex was preserved despite intracarotid delivery of HMPAO. CONCLUSION: Some degree of hypoperfusion of medial temporal structures occurs in the great majority of patients during the Wada test. Partial inactivation of memory structures is therefore a credible mechanism of action of the test. The double acquisition protocol provided no evidence that mesial temporal structures are inactivated remotely by diaschisis. Perfusion in the basal ganglia and insular cortex is not affected by amytal.
Adult↗
A miniature analytical instrument for nucleic acids based on micromachined silicon reaction chambers.
In this paper, we describe a miniature analytical thermal cycling instrument (MATCI) to amplify and detect DNA via the polymerase chain reaction in real-time. The MATCI is an integrated, miniaturized analytical system that uses silicon-based, high-efficiency reaction chambers with integrated heaters and simple, inexpensive electronics to precisely control the reaction temperatures. Optical windows in the silicon and solid-state, diode-based detection components are employed to perform real-time fluorescence monitoring of product DNA production. The entire system fits into a briefcase and runs on rechargeable batteries. The applications of this miniaturized nucleic acid analysis system include clinical, research, environmental, and agricultural analyses as well as others which require rapid, portable, and accurate analysis of biological samples for nucleic acids. This paper describes the MATCI and presents results from ultrafast thermal cycling and real-time PCR detection. Examples include human genes and pathogenic viruses and bacteria.
Actins↗
Single photon emission computed tomography in the identification of new variant Creutzfeldt-Jakob disease: case reports.
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Adult↗
Face processing impairments after encephalitis: amygdala damage and recognition of fear.
Face processing and facial emotion recognition were investigated in five post-encephalitic people of average or above-average intelligence. Four of these people (JC, YW, RB and SE) had extensive damage in the region of the amygdala. A fifth post-encephalitic person with predominantly hippocampal damage and relative sparing of the amygdala (RS) participated, allowing us to contrast the effects of temporal lobe damage including and excluding the amygdala region. The findings showed impaired recognition of fear following bilateral temporal lobe damage when this included the amygdala. For JC, this was part of a constellation of deficits on face processing tasks, with impaired recognition of several emotions. SE, YW and RB, however, showed relatively circumscribed deficits. Although they all had some problems in recognizing or naming famous faces, and had poor memory for faces on the Warrington Recognition Memory Test, none showed a significant impairment on the Benton Test of Facial Recognition, indicating relatively good perception of the face's physical structure. In a test of recognition of basic emotions (happiness, surprise, fear, sadness, disgust and anger), SE, YW and RB achieved normal levels of performance in comparison to our control group for all emotions except fear. Their results contrast with those of RS, with relative sparing of the amygdala region and unimpaired recognition of emotion, pointing clearly toward the importance of the amygdala in the recognition of fear.
Aged↗
Early 1H magnetic resonance spectroscopy of acute head injury: four cases.
In an attempt to examine in vivo the early metabolic consequences of severe acute head injury, 1H MRS was performed in four patients from 8 to 25 h (mean 15 h) following trauma. In three of these patients, decompressive surgery was performed 4-5 h prior to the MRS. High levels of lactate (area of lactate peak >50% of the mean areas of the NAA, choline-containing, and creatine-containing compound peaks) were found at 8 h posttrauma in the one patient who was not operated on and at 10 h posttrauma in one of the patients who underwent surgery. In the other two postoperative patients, at 18 and 25 h after trauma, lactate levels were found to be low (lactate peak <20% of the mean area of the other three peaks). In the one patient who had a follow-up at 6 days and who had the largest initial lactate levels, these remained high. These findings suggest that high levels of lactate may not be an inevitable consequence of severe head injury and that similar MRS studies should be performed on each individual patient before therapies to reduce lactate are considered. There appeared to be no correlation between the relative amounts of lactate and outcome.
Acute Disease↗
Rapid pathogen detection using a microchip PCR array instrument.
An array of PCR microchips for rapid, parallel testing of samples for pathogenic microbes is described. The instrument, called the Advanced Nucleic Acid Analyzer (ANAA), utilizes 10 silicon reaction chambers with thin-film resistive heaters and solid-state optics. Features of the system include efficient heating and real-time monitoring, low power requirements for battery operation, and no moving parts for reliability and ruggedness. We analyzed cultures of Erwinia herbicola vegetative cells, Bacillus subtilis spores, and MS2 virions, which simulated pathogenic microbes such as Yersinia pestis, Bacillus anthracis spores, and Venezuelan equine encephalitis, respectively. Detection of microbes was achieved in as little as 16 min with detection limits of 10(5)-10(7) organisms/L (10(2)-10(4) organisms/mL).
Bacillus subtilis↗
Ictal regional cerebral blood flow in frontal lobe seizures.
99mTC (single photon emission computed tomography) (HMPAO SPECT) was carried out during 16 frontal-lobe seizures in 15 patients. Focal changes in regional cerebral blood flow were seen during all seizures. In 9 of 16 seizures SPECT showed hyperperfusion localized to one frontal lobe. In 1 of 16 seizures ictal hypoperfusion was seen in one frontal lobe. In 2 of 16 seizures there was hyperperfusion in both frontal lobes, and in 4 of 16 seizures hyperperfusion involved the frontal lobe or lobes plus other lobes of the brain. These changes were accompanied by hyperperfusion of subcortical structures in 13 seizures. SPECT thus localized to one frontal lobe in 10 of 16 seizures, and localized to the frontal lobes without lateralizing in two further seizures. No seizure showed a pattern of perfusion similar to that reported in mesial-temporal-lobe seizures. We conclude that ictal SPECT may provide useful localizing information in frontal-lobe seizures.
Adolescent↗
Errors in MR stereotaxy due to undetected extraneous metal objects.
MR stereotaxic procedures are being increasingly used, particularly in functional neurosurgery where very high levels of localization accuracy are required. Whilst many studies have investigated intrinsic causes of non-linearity, potential errors due to an extrinsic cause are not generally appreciated. It is not uncommon to find objects such as hair clips, paper clips and pins inside high-field magnets. They can remain undetected for long periods because they can reach positions not open to visual inspection and because they often do not produce observable deterioration in routine image quality. In this study we measured the maximum absolute positional shifts caused by such objects and found that these can be significant (> 1 mm, even up to 200 mm from one such object). Additional measurements were performed using an MR compatible Leksell stereotaxic frame to calculate actual stereotaxic coordinate errors. The encompassing nature of the frame is such that some degree of compensation for such nonlinearities is inherent, and so errors for areas of the brain more proximal to the object are found to be reduced but not eliminated. Stereotaxic coordinate errors will not be reduced in nonencompassing designs and in frameless stereotaxy. The prevalence of such objects in clinical systems and the measures required to detect their presence are discussed. The need for quality control testing before each stereotaxic procedure is highlighted.
Biophysical Phenomena↗