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Biomedical subjects

P Hammond

Publications and source records attributed to P Hammond.

At least 37 records · Page 2Linked to original sources

Mucinous cystic neoplasms of the pancreas: imaging features and diagnostic difficulties.

AIMS: To review the imaging features of mucinous cystic neoplasms (MCNs) of the pancreas and to highlight difficulties in differentiating these lesions from pancreatic pseudocysts. MATERIALS AND METHODS: The imaging investigations, case notes and histopathology of 13 patients who underwent surgery for an MCN of the pancreas, were reviewed. RESULTS: An erroneous diagnosis of a pancreatic pseudocyst had been made in five of the 13 cases and in two patients cystenterostomy had been performed. Only one patient had a documented history of acute pancreatitis although mildly elevated serum amylase levels were identified in a further five cases. CT and US correctly diagnosed a cystic pancreatic mass in all 13 patients, however cross-sectional imaging features of neoplasia, such as septae, cyst wall calcification, focal thickening of the cyst wall and papillary projections, were absent in five (38%) cases. Coexistent imaging features of chronic pancreatitis were present in five of the 13 patients and in six resected specimens. Cyst wall calcification occurred only in malignant lesions and there was no relationship between cyst size and the degree of malignancy. While ERCP, angiography, and percutaneous needle aspiration may provide additional information, the majority of these examinations were either unhelpful or even misleading. CONCLUSION: MCNs of the pancreas are frequently diagnosed and mismanaged as pancreatic pseudocysts with an associated increase in patient morbidity and mortality. Diagnostic imaging can help to distinguish MCNs from pseudocysts when there are features of neoplasia present, however, no imaging investigation can reliably differentiate the two conditions in all cases. If clinical doubt remains, it is preferable to err on the side of safety and either employ a 'wait and watch' strategy or to resect a cystic pancreatic lesion rather than drain a potentially malignant MCN.

Adult↗

An evaluation of active shape models for the automatic identification of cephalometric landmarks.

This paper describes an evaluation of the application of active shape models to cephalometric landmarking. Permissible deformations of a template were established from a training set of hand-annotated images and the resulting model was used to fit to unseen images. An evaluation of this technique in comparison to the accuracy achieved by previous methods is presented. Sixty-three randomly selected cephalograms were tested using a drop-one-out method. On average, 13 per cent of 16 landmarks were within 1 mm, 35 per cent within 2 mm, and 74 per cent within 5 mm. It was concluded that the current implementation does not give sufficient accuracy for completely automated landmarking, but could be used as a time-saving tool to provide a first-estimate location of the landmarks. The method is also of interest because it provides a framework for a range of future improvements.

Adolescent↗

Safety and computer-aided design of chemotherapy plans.

Previously, generic principles were derived empirically from examples of reasoning about the efficacy and safety of chemotherapy. Some of the principles were used in a prototype decision-support system for managing patients through chemotherapy. It reminded clinicians which, how, and when drugs were to be given; suggested treatment modifications as a result of detected adverse events; and warned how unplanned actions undermine efficacy or exacerbate hazardous side effects. Here, we investigate the reuse of these safety principles to generate symbolic and textual representations of new chemotherapy plans. In clinical trials of chemotherapy, a written protocol is essential, especially in obtaining ethical approval. The symbolic representation, from which textual extracts are derived, can be used in conjunction with software for managing chemotherapy.

Antineoplastic Agents↗

Developmental expression of acetyl- and butyrylcholinesterase in the rat: enzyme and mRNA levels in embryonic dorsal root ganglia.

Dorsal root ganglia (DRG) in the adult rat contain acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes implicated in neural morphogenesis. We used quantitative histochemistry, reverse transcription-PCR (RT-PCR), and in situ hybridization histochemistry to study cholinesterase expression during embryogenesis. Longitudinal sections of rat embryos, embryonic day 9 (E9), E11-E17, and E19, were studied by video microscopy of the stained enzyme reaction products. Both enzymes were detectable in the early DRG (E11-E12), with BChE being most prominent. There was a spatiotemporal change in expression of each cholinesterase within the DRG. From E13 on, AChE expression predominated, especially in the neuronal cell bodies, while BChE was more highly expressed in the surrounding neuropil and the ganglionic roots. This distribution resembled the pattern in adult DRG. AChE mRNA levels, as determined by RT-PCR from DRG collected at days E12-E17, and E19, varied in parallel with the intensity of enzyme stain in the DRG. Overall, these results demonstrate temporally regulated ganglionic expression of cholinesterases, which may be important in the development of the sensory nervous system.

Acetylcholinesterase↗

Acetylcholinesterase immunolesioning: regional vulnerability of preganglionic sympathetic neurons in rat spinal cord.

Rats given antibodies against acetylcholinesterase (AChE) develop sympathetic dysfunction stemming from losses of preganglionic neurons in spinal cord. Central effects of AChE antibodies are surprising since IgG does not readily cross the blood-brain barrier, and lesions of peripheral terminals should not cause cell death. This study was designed to explore the distribution of central neural damage and to investigate features that might account for vulnerability. Rat spinal cord and brainstem were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) immunoreactivity. Four months after administration of AChE antibodies, ChAT-positive neurons in the intermediolateral nucleus (IML) were 61-66% fewer throughout the thoracolumbar cord (T1, T2, T8, T12, L1). NOS-positive neurons in these loci were affected to the same extent by antibody-treatment, although they were only two-thirds as numerous. By contrast, neurons in the central autonomic nucleus of the thoracolumbar cord were scarcely affected. These results point to immunochemical differences in the central autonomic outflow, which may partially explain the puzzling selectivity of neural damage in AChE immunolesioning. Different results were obtained after guanethidine sympathectomy, which ablated nearly all neurons in the superior cervical ganglion without any effect on preganglionic neurons in the IML. Therefore, if the central effects of antibodies are indirectly mediated by loss of trophic support from the periphery, this support cannot arise from adrenergic neurons but must come from other ganglionic cells.

Acetylcholinesterase↗

Cystic tumours of the pancreas.

BACKGROUND: Cystic pancreatic tumours may be misdiagnosed as pseudocysts. METHODS: From August 1990 to January 1998, 21 patients (16 women) with a median age of 60 years underwent operation for a cystic mass in the pancreas with histological confirmation of neoplasia (six serous cystadenoma (SCA), three mucinous cystic adenoma (MCA), ten mucinous cystadenocarcinoma (MCAC), one ductal adenocarcinoma with cystic degeneration, one cystic islet cell tumour). RESULTS: While the lesion had been labelled as a pseudocyst in eight patients, only one patient (MCA in the pancreatic head) had had acute pancreatitis previously. In seven patients the computed tomogram (CT) lacked suspicious neoplastic features, while endoscopic retrograde cholangiopancreatography, angiography and percutaneous cyst fluid analysis were unhelpful or misleading in 16 of 18 investigations with respect to differentiating tumour from pseudocyst. Attempted operation for cure was performed in 18 patients despite diagnostic delays of up to 6 years and initial treatment with cystenterostomy in two cases. CONCLUSION: Retrospective review revealed that all 21 cystic neoplasms could be diagnosed before operation by a history excluding previous pancreatitis (20 of 21 patients) or a CT suspicious for neoplasia (14 of 21). The diagnosis relies more on absence of previous pancreatitis and a suspicious clinician who errs on the side of resecting a pseudocyst rather than watching or draining a cystic neoplasm.

Adenoma↗

Testing times.

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Female↗

Transient expression of acetylcholinesterase messenger RNA and enzyme activity in developing rat thalamus studied by quantitative histochemistry and in situ hybridization.

The molecular basis for transient expression of acetylcholinesterase in noncholinergic regions of the early postnatal rat brain was studied by in situ hybridization histochemistry. A 33P-labelled 63-mer DNA oligonucleotide was used to probe acetylcholinesterase messenger RNA in the brains of rat pups at one, two, six, nine, 12, 16 and 21 days of age (birth = day 0). Cryostat brain-sections were hybridized with probe and exposed to X-ray film or emulsion coatings. Acetylcholinesterase messenger RNA was quantitated by counting silver grains and by measuring X-ray film density with video imaging and computer-based densitometry. Adjacent sections were stained histochemically for acetylcholinesterase activity, also quantitated by video densitometry. Overall there was a significant correlation between apparent levels of acetylcholinesterase activity and acetylcholinesterase messenger RNA. Increases in message tended to accompany the surges of acetylcholinesterase activity that marked the maturation of thalamocortical sensory relay pathways. Acetylcholinesterase expression in the youngest rats was generally sparse but it increased markedly during the first postnatal week, especially in the sensory relay nuclei of the thalamus. Levels of message and enzyme activity in the medial and dorsolateral geniculate and the ventral posteromedial and ventral posterolateral nuclei rose to a peak, typically about day 9. Beyond this time there was a gradual decline. By day 21 the staining and in situ hybridization patterns resembled those in adult brains, whose thalamic relay nuclei are impoverished in acetylcholinesterase activity and messenger RNA. Thus, acetylcholinesterase expression is strongly modulated in certain thalamic systems as they undergo neural morphogenesis.

Acetylcholinesterase↗

The acquisition and validation of removable partial denture design knowledge. I. Methodology and overview.

The authors report on the eliciting of the partial denture design expertise of teachers of prosthetic dentistry. Their approach was to identify 125 design rules and then to sample expert reaction by surveying 10 experts individually and by surveying the prosthetic departments in all 17 dental schools in the British Isles. The surveys achieved a return of 100% and revealed an unsuspected consensus concerning the rules. A majority of schools were in agreement on whether or not 111 (89%) of the rules could be supported. This design expertise will be disseminated through RaPiD, a knowledge-based assistant for the design of removable partial dentures. It is expected that by incorporating into this design assistant rules which have been shown to be widely supported, the acceptability and usefulness of RaPiD for clinical education and practice will be increased.

Artificial Intelligence↗

Role of suppression in shaping orientation and direction selectivity of complex neurons in cat striate cortex.

1. Single binocularly driven complex neurons in cat striate cortex were recorded extracellularly under nitrous oxide-oxygen-halothane anesthesia and muscle relaxant. Orientational/directional tuning was initially derived for each eye in turn, with sine wave gratings of optimal spatial frequency and velocity, while the other eye viewed a uniform field. 2. For the dominant eye, previously concealed suppression was revealed against elevated levels of firing induced with a conditioning grating, drifting continuously in the preferred direction, simultaneously presented to the nondominant eye. During steady-state binocular conditioning, orientational/directional tuning was reestablished for the dominant eye. In a subset of cells, tuning curves during conditioning were also derived for the reverse configuration, i.e., nondominant eye tuning, dominant eye conditioning: results were qualitatively identical to those for conditioning through the nondominant eye. 3. Neurons were initially segregated into five groups, according to the observed suppression profiles induced at nonoptimal orientations/directions during conditioning: Type 1, suppression centered on orthogonal directions; Type 2, suppression around null directions; Type 3, null suppression combined with orthogonal suppression; Type 4, lateral suppression, maximal for directions immediately flanking those inducing excitation; and Type 5, the residue of cells, totally lacking suppression or showing complex or variable suppression. 4. Sharpness of (excitatory) tuning was correlated with directionality and with class of suppression revealed during binocular conditioning. Direction-biased neurons were more sharply orientation tuned than direction-selective neurons; similarly, neurons exhibiting lateral or orthogonal suppression during conditioning were more sharply tuned than neurons with null suppression. 5. Application of suboptimal directions of conditioning weakened the induced suppression but altered none of its main characteristics. 6. The relationship between excitation, suppression, and spatial frequency was investigated by comparing tuning curves for the dominant eye at several spatial frequencies, without and during conditioning. End-stopped neurons preferred lower spatial frequencies and higher velocities of motion than non-end-stopped neurons. Confirming previous reports, suppression in some neurons was still present for spatial frequencies above the cutoff frequency for excitation, demonstrating the tendency for suppression to be more broadly spatial frequency tuned than excitation. 7. Scatterplots of strength of suppression, in directions orthogonal and opposite maximal excitation, partially segregated neurons of Types 1-3. Clearer segregation of Types 1-4 was obtained by curve-fitting to profiles of suppression, and correlating half-width of tuning for suppression with the angle between the directions of optimal suppression and optimal excitation in each neuron. 8. Two interpretations are advanced-the first, based on three discrete classes of inhibition, orthogonal, null and lateral; the second, based on only two classes, orthogonal and null/lateral--in which null and lateral suppression are manifestations of the same inhibitory mechanism operating, respectively, on broadly tuned direction-selective or on sharply tuned direction-biased neurons. Orthogonal suppression may be untuned for direction, whereas lateral and null suppression are broadly direction tuned. Within each class, suppression is more broadly spatial frequency tuned than excitation. 9. It is concluded that orientational/directional selectivity of complex cells at different spatial frequencies is determined by the balance between tuned excitation and varying combinations of relatively broadly distributed or untuned inhibition.

Animals↗

Accumulation of enkephalin, proenkephalin mRNA, and neuropeptide Y in immunologically denervated rat adrenal glands: evidence for divergent peptide regulation.

To investigate transsynaptic effects on peptides of adrenal chromaffin cells in the rat, presynaptic sympathetic terminals were destroyed by intravenous injection of monoclonal antibodies to acetylcholinesterase. At several times thereafter, neuropeptide Y (NPY)-like immunoreactivity (NPY-IR) and methionine-enkephalin-like immunoreactivity (Met-Enk-IR) were measured by radioimmunoassay. Within 2 days of antibody injection, adrenal Met-Enk-IR increased five- to 10-fold and NPY-IR increased 50%. These effects were accompanied by large increases in proenkephalin A mRNA assayed by polymerase chain reaction. The peptide responses could reflect either an acute activation, as presynaptic terminals degenerated, or a chronic synaptic inactivation after terminal degeneration. To test the possibilities, muscarinic and nicotinic receptors were inhibited by repeated injection of atropine (1 mg/kg) and chlorisondamine (5 mg/kg). Measurements of urinary free catecholamine excretion showed that this treatment prevented the paroxysmal release of norepinephrine and reduced the release of epinephrine that normally followed injection of acetylcholinesterase antibodies. When the drugs were given alone for 2 or 4 days, adrenal Met-Enk-IR increased modestly and NPY-IR remained steady or declined. When given together with acetylcholinesterase antibodies, the cholinergic antagonists blocked the increase of NPY-IR but not Met-Enk-IR. Adding naloxone (1 mg/kg) to the treatment regimen enhanced the blockade of epinephrine excretion and largely prevented the antibody-induced increase in Met-EnK-IR. These findings indicate that adrenal NPY and enkephalin are not regulated identically. Adrenal NPY behaves as though controlled by transsynaptic cholinergic input. On the other hand, adrenal enkephalin may be regulated by additional or different mechanisms, possibly involving peptidergic transmission or synaptic inactivation.

Acetylcholinesterase↗