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D Adams

Publications and source records attributed to D Adams.

At least 73 records · Page 4Linked to original sources

Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14 loop splice hybrids at N and P/Q-type calcium channels.

The omega-conotoxins are a set of structurally related, four-loop, six cysteine containing peptides, that have a range of selectivities for different subtypes of the voltage-sensitive calcium channel (VSCC). To investigate the basis of the selectivity displayed by these peptides, we have studied the binding affinities of two naturally occurring omega-conotoxins, MVIIA and MVIIC and a series of 14 MVIIA/MVIIC loop hybrids using radioligand binding assays for N and P/Q-type Ca2+channels in rat brain tissue. A selectivity profile was developed from the ratio of relative potencies at N-type VSCCs (using [125I]GVIA radioligand binding assays) and P/Q-type VSCCs (using [125I]MVIIC radioligand binding assays). In these peptides, loops 2 and 4 make the greatest contribution to VSCC subtype selectivity, while the effects of loops 1 and 3 are negligible. Peptides with homogenous combinations of loop 2 and 4 display clear selectivity preferences, while those with heterogeneous combinations of loops 2 and 4 are less discriminatory. 1H NMR spectroscopy revealed that the global folds of MVIIA, MVIIC and the 14 loop hybrid peptides were similar; however, several differences in local structure were identified. Based on the binding data and the 3D structures of MVIIA, GVIA and MVIIC, we have developed a preliminary pharmacophore based on the omega-conotoxin residues most likely to interact with the N-type VSCC.

Amino Acid Sequence↗

Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability.

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sudden deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42+/-12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36+/-0.26 versus 1.98+/-0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, without correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evaluate the extent of cardiac sympathetic denervation in FAP patients.

3-Iodobenzylguanidine↗

A comparison of the interpretation of digitized and videotape recorded echocardiograms.

Conventional echocardiograms are typically recorded on videotape and later reviewed and interpreted by a physician. Although videotape recording is an excellent medium for this purpose, it does have several disadvantages, which may be overcome by digital storage. This study compared the diagnostic accuracy of digitized and videotape recorded echocardiograms. Echocardiographic examinations (n = 110) were recorded simulta-neously on videotape and were digitized with a commercially available frame grabber system. Images were transmitted by an Ethernet link to the network-based computer system and compressed with a nondestructive compression algorithm. Images were reviewed on a personal computer. Images were interpreted by 3 observers, and differences in interpretation were documented. There were 274 findings in 110 patients. Exact agreement in interpretation was found in 83%. A major discrepancy occurred in 2%, and a minor discrepancy occurred in 15%. Most discrepancies occurred in the setting of valvular heart disease. When compared with a consensus interpretation, no significant difference was seen in the number of errors between the digital and videotape interpretation. We conclude that the interpretation of a properly recorded digitized echocardiographic examination yields interpretations equivalent to those of videotape recordings.

Echocardiography↗

Domino liver transplants for metabolic disorders: experience with familial amyloidotic polyneuropathy.

BACKGROUND: Shortage of liver donors means that new methods of liver procurement must be explored. In domino transplantation, organs explanted during transplantation in one patient are transplanted into a second patient. Domino procedures can be performed with livers from patients having transplantation for hepatic metabolic disorders that cause systemic disease without affecting other liver functions. Familial amyloidotic polyneuropathy (FAP) type I is one of these. STUDY DESIGN: We reviewed the Paul Brousse experience with a domino liver transplant program for FAP, hoping to extend the approach to other metabolic disorders. RESULTS: Livers from 10 patients transplanted for FAP type 1 were used for domino transplants to patients with unresectable primary or metastatic liver cancers. There was no perioperative mortality. Neuropathy or cardiomyopathy did not increase the morbidity of the domino liver explant and transplant procedures. Morbidity for the domino recipients did not appear to be increased. Variant transthyretin was detected in the serum in FAP liver recipients, with no immediate clinical consequences. CONCLUSIONS: The domino approach is feasible and requires careful planning of the surgical procedures for liver explantation, particularly for the nature and site of vascular anastomoses. Domino transplantation of metabolically dysfunctional livers creates new categories of potential donors and potential recipients. It raises new ethical, technical, and societal issues. The domino approach could be used in several genetic or biochemical disorders now treated by liver transplantation. It has the potential to increase the number of liver grafts available for transplantation.

Adult↗

Effects of smoking on local delivery of controlled-release doxycycline as compared to scaling and root planing.

This paper examines the effects of smoking on the treatment outcomes of two nonsurgical therapies: (1) scaling and root planing alone (SRP) or (2) controlled-release of subgingivally delivered doxycycline hyclate in a polylactic acid based polymer gel. Subjects from 2 9-month multicenter studies were classified as nonsmokers (never smoked: 100 subjects), former smokers (137 subjects), and current smokers (> or = 10 cigarettes/day: 121 subjects). Clinical parameters were analyzed for treated sites with baseline probing depths > or = 5 mm and for a subset of treated sites with baseline probing depths of > or = 7 mm. Clinical parameters (plaque levels, clinical attachment levels, pocket depths, and bleeding on probing) were analyzed at baseline, 4, 6, and 9 months. In the doxycycline treated group in general, there were neither marked significant differences in clinical attachment gain nor differences in probing depth reduction among the 3 smoking groups. On the other hand, in the scaling and root planing treated group in general, there were significant differences in clinical attachment gain and pocket depth reduction, with non-smokers responding better than former smokers and current smokers at 6 and 9 months. These differences in clinical response between scaling and root planing alone versus controlled-release of locally-delivered doxycycline hyclate among these 3 smoking groups are discussed in relation to treatment implications for smokers.

Administration, Topical↗

5-hydroxytryptamine stimulation of phospholipase D activity in the rabbit isolated mesenteric artery.

1. The involvement of phospholipase D (PLD) in the 5-hydroxytryptamine 5-HT1B/5-HT1D-signalling pathway was assessed in the rabbit isolated mesenteric artery. 2. RT-PCR analysis of mesenteric smooth muscle cells revealed a strong signal corresponding to mRNA transcript for the 5-HT1B receptor. The PCR fragment corresponded to the known sequence for the 5-HT1B receptor. No signal corresponding to 5-HT1D mRNA was detected. 3. Neither 5-HT (3 microM) nor KCl (45 mM) individually stimulated any significant increase in the smooth muscle concentration of [33P]-PtdBut to reflect PLD activity. However, in the presence of KCl (45 mM), 5-HT evoked a concentration-dependent increase in [33P]-PtdBut, to a maximum of 84% with 5-HT (3 microM). 4. [33P]-PtdBut accumulation evoked by 5-HT in the presence of KCl was abolished in nominally calcium-free Krebs-Henseleit Buffer (KHB) or with the selective protein kinase C inhibitor, Ro-31 8220 (10 microM, 20 min). 5. 5-HT (3 microM) in the presence of KCl (45 mM) failed to increase either the accumulation of [33P]-phosphatidic acid in the presence of butanol, or total [3H]-inositol phosphates ([3H]-InsP) in the presence of LiCl (10 mM). 6. 5-HT (0.1-1 microM) abolished forskolin (1 microM) stimulated increases in cyclic AMP (15 fold increase), an action which was pertussis toxin-sensitive. 7. Therefore, in the presence of raised extracellular potassium 5-HT can stimulate PLD via 5-HT1B receptors in the rabbit mesenteric artery. This action requires extracellular calcium and the activation of protein kinase C. These characteristics are identical to the profile for 5-HT1B/5-HT1D-receptor evoked contraction in vascular smooth muscle cells, suggesting a role for PLD in this response to 5-HT.

Animals↗

Managing alcohol withdrawal in the acutely ill hospitalized adult.

Managing individuals with acute illness who are at high risk for alcohol withdrawal presents multiple challenges to the treatment teams caring for them. Following realization that management of this group was often characterized by severe withdrawal symptoms (delirium tremens, seizures and the need for leather restraints), a Task Force developed protocols to guide care. Its principal goal was to avoid cardiorespiratory and neurologic morbidities associated with severe withdrawal. The first 441 episodes of care treated after protocol implementation are described in this report. There were no instances of oversedation requiring pharmacological reversal or intubation, few individuals suffered seizures outside of the emergency department and the use of leather restraints declined dramatically. Outstanding issues arising from analysis include the necessity of subjecting the symptom severity instrument to rigorous psychometric study and reconsideration of the appropriateness of a symptom-triggered approach in treating this population. Our experience suggests that use of a nonprescriptive approach by educated and motivated nursing and medical staffs can reduce serious morbidity in this at-risk population.

Acute Disease↗

Clinicopathologic findings and prognosis of chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: To evaluate the clinicopathologic features and prognostic factors of 100 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Comparison of clinical and biopsy findings with functional score evaluated an average of 6 years after referral. RESULTS: CIDP followed a relapsing course in 14% of the patients and a progressive course in 45%. After progressive onset, little change was noted during follow-up in the others. Five patients had symptomatic involvement of the CNS. Teased fiber preparations of nerve biopsy specimens showed that 68 patients had purely demyelinative lesions, 20 had mixed axonal and demyelinative lesions, and 5 had predominantly axonal lesions. Axonal loss was a common finding, with 47% of the patients retaining less than half of the normal density of fibers. Inflammatory infiltrates, found in 18 samples, were prominent only in 4. Of the 83 patients evaluated an average of 6 years after onset, 56 were in good condition; 24 had deteriorated and failed to respond to treatment, including 9 patients who died as a consequence of their neurologic deficit. Progressive course, CNS involvement, high proportion of fibers showing active demyelination on nerve biopsy, and axonal loss overall correlated with higher disability. CONCLUSION: Axonal loss is the major long-term pejorative prognostic factor in CIDP.

Adolescent↗

Trends in indications and outcomes in the Whipple procedure over a 40-year period.

There have been increasing changes in the role of pancreatoduodenectomy (PD) in the management of benign and malignant pancreatic disease. The aim of this paper was to compare the current role of PD with that of our earlier experience. The records of patients undergoing PD at our institution between 1983 and 1996 (Group A) were reviewed and compared with cases between 1956 and 1982 (Group B). Student's t test was used to analyze differences between groups. A total of 153 PDs were performed with 98 (64%) in Group A (88% of these in the last 6 years) and 55 (36%) in Group B. Carcinoma of the head of the pancreas was the most common indication for surgery in both periods (43% and 47% for Groups A and B, respectively). In Group A, the next most common indication was chronic pancreatitis, accounting for 28 per cent versus 13 per cent in Group B. Carcinoma of ampulla of Vater was also a common indication, making up 21 per cent of the cases in Group A and 20 per cent in Group B. Preoperative biliary drainage was performed in 62 per cent of Group A and 3 per cent of Group B patients (P < 0.001). Postoperative complications were comparable in both groups: delayed gastric emptying (22%), wound infection (17%), pancreatic fistula (13%), gastrointestinal bleeding (8%), and intestinal obstruction (3%). The perioperative mortality rate was significantly different between the two groups: 1 per cent in Group A versus 16 per cent in Group B (P < 0.001). Mean postoperative length of stay was 17 days in Group A (22 days for benign disease) and 25 days for Group B (P < 0.01). In the last 40 years, there has been a rise in the use of PD for chronic pancreatitis and a significant decrease in postoperative mortality and hospital length of stay. These data support the safety of PD in the management of patients with both benign and malignant periampullary disease.

Adult↗

Increased lower denture security using the Myoloc system.

PURPOSE OF THE STUDY: To assess whether the Myoloc System. Improves the stability of the mandibular complete denture. METHOD: Unstable dentures move during function causing pain and discomfort to patients resulting in decreased denture security. Improvement in patients' perceived denture security was used to assess if the Myoloc System improved the stability of the mandibular complete denture. Complete dentures were constructed for 27 patients (20 female and seven male) by conventional methods. Patients were asked to mark a point on a visual analogue scale to indicate their denture security. Following this, copies of the mandibular dentures were made and Myoloc wings added to the dentures. Denture security was recorded once again. The two responses were statistically analysed for significant improvement. RESULT: A statistically significant improvement in denture security was found to occur after addition of the Myoloc wings to the mandibular denture. CONCLUSION: The Myoloc System improves the stability of the mandibular complete denture and may prove useful when conventional methods fail to provide adequate denture stability and the patient is not a candidate for surgery.

Aged↗

The Wisconsin Card Sorting Test in stroke rehabilitation: factor structure and relationship to outcome.

The present study attempted to replicate the findings of previous factor analytic studies of the Wisconsin Card Sorting Test (WCST) in a homogeneous sample of patients suffering recent cerebrovascular accidents and being treated in a comprehensive inpatient physical rehabilitation program. In addition this study examined the relationship of the WCST to standard measures of functional ability used in many rehabilitation programs. The results confirmed the previously reported three-factor structure and replicated past findings concerning the test's construct validity. A small but significant relationship was noted between the WCST and functional status, though the WCST did not make a unique contribution to the prediction of functional status at discharge. This study highlights the similarities and differences in WCST factor structure in a stroke sample compared to a more general neurological sample and raises questions about the utility of the WCST in stroke rehabilitation.

Journal Article↗

Assessing priorities for allocation of donor liver grafts: survey of public and clinicians.

OBJECTIVES: To compare the priorities of the general public, family doctors, and gastroenterologists in allocating donor livers to potential recipients of liver allograft. DESIGN: Representative quota sampling of 1000 members of the general public and 200 family doctors, and a postal questionnaire of 100 gastroenterologists. SUBJECTS: Respondents were given eight hypothetical case histories (based on real patients) and asked to select recipients for four donor livers. Cases were selected to identify controversial areas such as extremes of age, misuse of alcohol, and intravenous drugs. Respondents were also asked to select the least deserving case and which of seven possible factors (time on waiting list, outcome, age, value to society, return to work, previous use of illicit drugs, and involvement of alcohol in the liver damage) should be used to select patients already listed for transplantation. Focus groups were also held to explore further the reasons for the choices given. RESULTS: There were considerable differences between the three groups in the choice of the recipients, although alcohol use and antisocial behaviour always rated low. For selection of recipients the general public thought that, in decreasing order of importance, age, outcome, and time on the waiting list were the most important factors in selecting recipients; family doctors rated outcome, age, and likely work status after transplantation and the gastroenterologists outcome, work status, and non-involvement of alcohol in the cause of the liver disease as the most important factors. CONCLUSIONS: The views of the public are at variance with those of clinicians. Further debate is required to ensure an equitable and appropriate distribution of a scarce resource.

Adolescent↗

New transthyretin variants SER 91 and SER 116 associated with familial amyloidotic polyneuropathy. Mutations in brief no. 151. Online.

Mutations of the transthyretin (TTR) gene are associated with familial amyloidotic polyneuropathy (FAP). Two new mutations were detected in French patients with TTR amyloidosis. The first patient was a 72 year old man who presented with severe and rapidly evolving sensory motor polyneuropathy of the 4 limbs, a bilateral carpal tunnel syndrome and a restrictive cardiomyopathy. His father died after a clinical history suggestive in retrospect of TTR amyloidosis. The second patient was a 75 year old man who presented with axonal sensory neuropathy of the 4 limbs and a bilateral carpal tunnel syndrome. In both cases immunohistochemistry performed on a nerve biopsy reveled TTR positive amyloid. Direct genomic sequencing of the full TTR gene coding region indicated two heterozygous transversions encoding Ser for Ala 91 substitution in the third exon of the gene in patient 1 and Ser for Tyr 116 substitution in the fourth exon of the gene in patient 2. The mutations were confirmed by digesting PCR products with restriction enzymes and were not found in a control population of 100 unrelated individuals. The Ser 116 substitution was also detected in the daughter and the 70 year old sister of the proband. However the absence of symptomatology suggestive of TTR amyloidosis may be related to the late onset of the disease. The clinical immunohistochemical and molecular studies in both patients are highly suggestive of an association between the Ser 91 and Ser 116 TTR variants with amyloidosis.

Aged↗

Evaluation of 31P metabolite differences in human cerebral gray and white matter.

31P NMR is commonly used to study brain energetics in health and disease. Due to sensitivity constraints, the NMR measurements are typically made in volumes that do not contain pure gray or white matter. For accurate evaluation of abnormalities in brain metabolite levels, it is necessary to consider the differences in normal levels of 31P metabolites in gray and white matter. In this study, voxels from a three-dimensional spectroscopic image acquisition were analyzed for their dependence on tissue type to assess differences in metabolite levels between gray and white matter. Specifically, gray matter was found to have significantly higher ratios of phosphocreatine (PCr) to gamma-ATP and PCr to the total 31P metabolite signal, whereas pH and the ratio of PCr to inorganic phosphate (Pi) were found to differ insignificantly between gray and white matter. Thus, tissue type can be an important factor to consider for alterations in bioenergetics by 31P NMR spectroscopic studies of the brain.

Adenosine Triphosphate↗

Rapid, fluorometric DNA determination for chick limb-bud mesenchymal-cell microcultures.

Micromass cultures of chick and mouse limb-bud mesenchymal cells are commonly used for in vitro studies of cellular differentiation. Previously, adaptation of these cultures to 96-well plates facilitated analyses of various aspects of cellular behavior and the effects of different media components in these cultures. These adjustments allowed development of a serum-free medium for chick limb-bud mesenchymal cells and substantially decreased costs associated with media and reagents. Here we report a further development for this model system; a Hoechst 33342-based in situ DNA assay that provides reliable data much more quickly and with considerably less effort than had been feasible in the past. Because it allows quantitation of products of cellular differentiation and DNA in the same cultures, the number of cultures needed to provide the same data is essentially halved and the accuracy of normalized values for quantitative estimates of markers of differentiation is improved. Studies of the effects of retinoic acid on chick limb-bud mesenchymal cells were performed to document the usefulness of this method.

Animals↗

Platelet and neutrophil activation during cardiac surgical procedures: impact of cardiopulmonary bypass.

BACKGROUND: Platelet and neutrophil activation plays a crucial role in reperfusion injury. To determine whether platelet and neutrophil activation occurs in the coronary circulation after cold cardioplegic arrest and reperfusion, we studied 22 patients undergoing coronary artery bypass or valve procedures, or both procedures. METHODS: Blood was sampled from the coronary sinus and the radial artery (A) before bypass; (B) immediately after cross-clamp release; and (C) 5 minutes after cross-clamp release; and was analyzed for surface markers of platelet (CD62P) and neutrophil (CD11b) activation. RESULTS: During bypass, platelet activation increased significantly (p < 0.01) over prebypass values, but no difference was seen between arterial and coronary sinus samples. Neutrophil activation also increased significantly (p < 0.001) during bypass, but there was no difference between arterial and coronary sinus samples. CONCLUSIONS: Cellular activation occurs locally in the coronary circulation during bypass, but no more so after cold cardioplegic arrest and reperfusion.

Aged↗

Migraine-like symptoms triggered by occipital lobe seizures: response to sumatriptan.

BACKGROUND: The relationship of ictal and post-ictal cephalic pain to migraine remains debatable. We hereby report 2 patients, a 27-year-old woman and 41-year-old man were referred for assessment of migraine of 10 years and 4 years duration, respectively. The man described a recent episode of "vacant stare" and the woman has sensitivity to bright colours and light. Neurological examination, visual field testing, CAT scan, MRI scan, and prolonged EEG recordings were accomplished for each patient. RESULTS: The man had a spontaneous seizure with ictal discharge arising from the right occipital lobe. Bilateral occipital spikes, associated with palinopsia was triggered in the woman by photic stimulation. Both patients developed post-ictal headaches with symptoms similar to their migraines. The symptoms subsided following treatment with oral sumatriptan. CONCLUSION: Migraine-like symptoms occurring following occipital lobe seizures may share similar pathophysiological substrates with idiopathic migraine. Serotonergic mechanisms may be implicated.

Adult↗