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D Adams

Publications and source records attributed to D Adams.

At least 91 records · Page 5Linked to original sources

Modulation of spasmogen-stimulated Ins(1,4,5)P3 generation and functional responses by selective inhibitors of types 3 and 4 phosphodiesterase in airways smooth muscle.

1. The effects of isoenzyme-selective inhibitors of phosphodiesterases PDE3 and PDE4 on cyclic AMP concentration, two indices of phosphoinositide hydrolysis, and contractile responses to spasmogens have been investigated in bovine tracheal smooth muscle (BTSM). 2. Neither the PDE3-selective inhibitor ORG 9935, nor the PDE4-selective inhibitor rolipram increased cyclic AMP levels in BTSM. However, rolipram addition in the presence of PDE3 inhibition (ORG 9935; 1 microM) concentration-dependently (-log EC50 (M), 6.55+/-0.15; n = 3) increased cyclic AMP levels to about 70% of the maximal response to the beta-adrenoceptor agonist isoprenaline. 3. Rolipram per se inhibited histamine-stimulated [3H]-inositol (poly)phosphate ([3H]-InsP(X)) accumulation by > 80% (-log EC50 (M), 6.92+/-0.11; n = 3). Although ORG 9935 (1 microM) had little effect on histamine-stimulated [3H]-InsP(X) accumulation alone it greatly facilitated the inhibitory action of rolipram (-log EC50 (M), 8.82+/-0.39; n = 3). The effects of PDE3 and/or PDE4 inhibition on [3H]-InsP(X) accumulation stimulated by muscarinic acetylcholine (mACh) receptor activation were less marked. However, combined PDE3/4 inhibition significantly decreased this response at a submaximal concentration of mACh receptor agonist (carbachol; 1 microM). 4. The greater-than-additive effect of combined PDE3/4 inhibition was also observed at the level of contractile responses to histamine and carbachol. In experiments designed to investigate the effects of PDE3 and/or 4 inhibitors on the carbachol-mediated phasic contraction, additions of rolipram (10 microM) or ORG 9935 (1 microM) were without effect, whereas added together the inhibitors caused a significant (P < 0.01) 40% reduction in the peak phasic contractile response. 5. The effect on contraction correlated with a substantial inhibitory effect of PDE3/4 inhibition on the initial increase in inositol 1,4,5-trisphosphate (InsP3) accumulation stimulated by spasmogen. Thus, in the presence of ORG 9935 (1 microM) rolipram concentration-dependently inhibited carbachol-stimulated InsP3 accumulation by > or = 50% (-log EC50 (M), 6.77+/-0.21; n = 4). 6. Carbachol (100 microM) addition caused a rapid decrease (by 67% at 10 s) in BTSM cyclic AMP level in the presence of PDE3/4 inhibition. However, omission of Ca2+ from the incubation medium prevented the carbachol-evoked decrease in cyclic AMP and this coincided with a greater inhibition (> or = 80%) of the carbachol-stimulated InsP3 response. 7. These data indicate that combined PDE3 and PDE4 inhibition has greater-than-additive effects on second messenger and functional responses to spasmogens in BTSM. Furthermore, the ability of PDE3/4 inhibition significantly to attenuate mACh receptor-mediated contractile responses, may be, at least in part, attributed to an effect exerted at the level of InsP3 generation.

Animals↗

The delirious cardiac surgical patient: theoretical aspects and principles of management.

Delirium, an etiologically nonspecific disorder of consciousness characterized by prominent deficits in attention, cognition, and perception, affects more than one-third of adult cardiac surgical patients. Despite the frequency of occurrence and the increased morbidity and mortality associated with it, the diagnosis is commonly late or missed, and management is less than optimal. This article addresses the recognition and management of delirium. Nurses who develop an index of suspicion for the diagnosis and acquire the diagnostic and interventional skills required to address this cerebral complication of cardiac surgery may well decrease its incidence and severity.

Antipsychotic Agents↗

Apical mural thrombus: technical pitfalls.

A left ventricular thrombus can occur in a variety of clinical settings and, when small, may be difficult to document. Understanding the clinical scenarios of when these thrombi form and how to optimise echocardiographic scanning techniques will increase the sensitivity and specificity of the examination (tables 1 and 2).

Diagnosis, Differential↗

Ultrastructural characterisation of the M protein in nerve biopsy of patients with POEMS syndrome.

To learn more about the mechanisms of nerve lesions in POEMS syndrome, nerve specimens from four patients were studied with an immunogold method at the ultrastructural level to detect and localise the M protein in the different nerve compartments. An indirect immunolabelling technique was applied on 4% PFA fixed and LR White embedded nerve specimens. Antisera against IgG, IgA, IgM, and lambda and kappa light chains were used as primary antisera. Morphological studies disclosed an important axonal loss in association with the demyelinative process. Endoneurial deposits of immunoglobulins were found in all cases. In the patient with the most severe form of neuropathy, diffuse deposits were present in the endoneurial space, especially in the subperineurial area. In the other patients, occasional deposits of the M protein were found in the myelin sheath (n=2); or between cells (n=1). No deposit was found in the axons. The class of the M protein labelled in the nerve corresponded to that detected in the serum in three of four patients, with labelling of two heavy chains in one patient. Immunolabelling of the M protein on the myelin sheath, Schwann cells, and in the endoneurial space favour a direct role of the M component in the lesions of nerve fibres, and justify active treatment of the plasmacytic proliferation.

Biopsy↗

Cell adhesion and migration. IV. Lymphocyte trafficking in the intestine and liver.

Naive lymphocytes patrol continuously between the blood and different lymphatic tissues to sample the whole body for foreign antigens. During inflammation, leukocyte recruitment into tissue is enhanced to promote the recruitment of a range of effector cells into the affected area. The complex recirculatory pathways that underlie this process are governed by adhesion receptors on blood-borne leukocytes and by their specific ligands expressed on the luminal aspect of endothelial cells lining the vessels. Gut-associated lymphatic tissues are positioned strategically at the major port of entry for foreign antigens. They form a functionally unified entity that utilizes both the afferent and efferent arms of the immune response to respond to the large array of antigens entering via the gut under normal conditions as well as during inflammation. Once antigens have been absorbed from the gut, they may enter the portal vein and the liver where the immune response can be further regulated by the resident immune cells of the liver. Thus the gut and liver form an important barrier to enteral antigens, and leukocyte recruitment to these sites will need to be carefully regulated to ensure effective immune surveillance. In this article, we describe the current concepts of lymphocyte adhesion in these two organs as revealed by animal models. Subsequently, we discuss how well these principles apply to the lymphocyte-endothelial cell interactions in humans and what additional insights can be obtained from human studies.

Cell Adhesion↗

Genotypic-phenotypic variations in a series of 65 patients with familial amyloid polyneuropathy.

OBJECTIVE: To investigate the genotypic-phenotypic variations in a series of patients with familial amyloid polyneuropathy (FAP). BACKGROUND: Progress in molecular genetics has led to the identification of point mutations in the transthyretin (TTR) gene in FAP--a dominantly inherited neuropathy with a fatal outcome. These findings have modified the management of patients with small-fiber neuropathy and allow genetic counseling. METHODS: We performed a clinical and molecular genetic study with screening of the TTR gene mutations and associated haplotypes in 65 patients from 29 unrelated families of French ancestry. RESULTS: We detected nine heterozygous point mutations segregating with FAP. Fourteen families (48%) carried the common methionine (Met) 30 substitution. Seven kindreds (24%) had previously unreported TTR variants, namely asparagine 35, serine (Ser) 91, phenylalanine (Phe) 77, and Ser 116. At least two different haplotypes were associated with each of the following: Met 30, Phe 77, and valine 107, suggesting that multiple founders occurred for each variant. Only 35% of the index patients had affected relatives. Other patients had a sporadic presentation. All progressed to a severe sensorimotor and autonomic neuropathy with frequent cardiac involvement (80%). On average, a late age at onset (54.3 +/- 13.3 years) and a disease duration shorter than 10 years were observed for virtually all variants. CONCLUSION: The heterogeneity of the TTR variants, the late age at onset, and the short duration of the disease found in our patients contrast with the presentation of FAP in Portugal. These findings must be taken into account in the management of both patients and asymptomatic carriers.

Adult↗

The swing-lock removable partial denture in clinical practice.

The authors of this article consider that the swing-lock partial denture has a useful place in contemporary clinical dental practice and offers many advantages compared with conventional removable partial dentures in terms of retention and stability, especially in the extremely compromised dentitions. Here they describe the concept of the swing-lock removable partial denture, together with the indications, contraindications, technical and clinical considerations.

Dental Abutments↗

Painful proximal diabetic neuropathy: inflammatory nerve lesions and spontaneous favorable outcome.

Proximal diabetic neuropathy is a disabling neuropathy that occurs predominantly in non-insulin-dependent diabetic patients over the age of 50. Inflammatory lesions have been found in nerve biopsy specimens of diabetic patients with severe proximal neuropathy or with other patterns of multifocal neuropathy. Some of these patients respond dramatically to treatment with corticosteroids or with other immunomodulators. In this article we report on our findings in 4 additional patients with painful proximal diabetic neuropathy and different patterns of inflammatory nerve lesions whose condition improved spontaneously shortly after performance of a nerve biopsy, without additional treatment.

Aged↗

Higher doses of alpha-interferon do not increase the activity of the weekly cisplatin-interferon combination in advanced malignant mesothelioma.

Management of advanced malignant mesothelioma (MM) still requires innovative systemic therapy as its prognosis is poorly affected by currently available chemotherapy. The combination cisplatin and alpha-interferon (alpha-INF) has synergistic antitumoral activity in preclinical models and interesting activity in phase I-II clinical trials. Weekly CDDP (60 mg/m2) and alpha-IFN (3 MUI/d: d1-d4) in combination was tested in a previous phase I-II study in 23 MM patients, with a 36% objective response rate (ORR). A trial with higher doses of alpha-IFN in the same combination schedule was conducted to explore an incrementalist hypothesis. Thirty patients with MM received the same CDDP dose (60 mg/m2/w) and doubled doses of alpha-IFN (6 MUI/d: d1-d4). The treatment protocol consisted of two cycles of 4 weeks on/4 weeks off followed by two shorter cycles of 3 weeks on/3 weeks off, in the absence of life-threatening toxicity or progressive disease. All patients were evaluable for toxicity. The main treatment-limiting side-effects were digestive intolerance (nausea, vomiting) and severe asthenia. Antitumoral efficacy was not increased (ORR = 27%). Haematological and neurological toxicities were moderate and manageable. The antitumoral activity of the CDDP-alpha-IFN combination with higher doses of the latter is similar to our previous experience, but tolerance issues make it a poorer choice for eventual comparative trials, or as a standard therapeutic indication.

Adult↗

Maternal and professional assessment of breastfeeding.

This study explored the relationships among maternal and professional breastfeeding assessments and maternal reports of satisfaction with breastfeeding. Participants were 35 first-time breastfeeding mothers. The LATCH Breastfeeding Documentation Tool was used for data collection. This tool was used in its original version for professional assessment and in a modified version for maternal reporting. Results show high percentages (85.7 to 100) of agreement among lactation consultants using the LATCH tool which supports the reliability of the tool. Correlation coefficients between professional scores and maternal scores ranged from 0.18 for "A" (Audible swallowing) to 0.67 for "L" (Latch). It appears that, unlike lactation consultants, new mothers evaluate breastfeeding based upon their somatic experience rather than observation of infant behavior.

Adult↗

Perinatal social work with childbearing adolescents.

Issues relating to adolescent childbearing have rapidly moved to the forefront of this nation's agenda. The implications of an adolescent's decision to have a baby have health, social and economic consequences for the adolescent, her offspring, partner and family and for all of society. This article will discuss the health, social and developmental consequences of adolescent childbearing and provide an overview of social work practice with childbearing adolescents.

Adolescent↗

Pharmacological management of post-traumatic stress disorder: clinical summary of a five-year retrospective study, 1990-1995.

Beginning in 1990, the Department of Psychiatry. Tripler Army Medical Center developed a formal treatment program for post-traumatic stress disorder (PTSD). Between 1990 and 1996, 632 patients, the vast majority of whom suffered from combat-related PTSD, were treated. Historically, many PTSD patients were treated with benzodiazepines, often in high dosages. The risks attendant to benzodiazepine management of PTSD, coupled with poor clinical outcome, prompted the staff to explore treatment alternatives. This paper describes the role of pharmacotherapy in the management of PTSD. The medications described in this paper have other primary uses in clinical practice (e.g., hypertension, insomnia, seizure control, depression, and anxiety). Medications were selected for use based on the putative modes of action and the degree of symptom relief. The therapeutic rationale was to decrease hyperarousal and sleep disturbance to permit the patients to engage in other psychotherapeutic efforts.

Adrenergic alpha-Antagonists↗

[Multifocal motor neuropathies with conduction blocks. 39 cases].

Clinical, biological and electrophysiological features from a cohort of 39 multifocal motor neuropathies with conduction blocks (NMM with CB) have been studied. There were 29 males and 10 females with an average of 47.3. At the first evaluation, the mean duration of the symptoms was of 8 years with extremes between 1 and 28. Pain and paresthesias were present in respectively 10 and 18 p. 100 of the patients. Fasciculations and cramps were observed in more than 2/3 of the cases. Three patients had tremor at rest. Upper limb muscular weakness was the predominant initial symptom (84.6 p. 100). The weakness always affected distal and unilateral muscles. Radial and cubital nerve distribution are mainly affected and in half of the cases an unilateral motor deficit in the lower limb was associated. Muscle atrophy was frequent (74 p. 100) and rapidly developed in the first 2 years. Reflexes were decreased or absent in 64 p. 100. In 78 p. 100 of cases, biological study showed normal serum immunoelectrophoresis and CSF. IgM anti-GM1 antibodies were found in 24/36 patients. Very high titres were found in 5 cases. All patients had CB in upper limbs. The preferential localizations of the CB were equally at the median and ulnar nerves. Only 7 patients had CB localized to the lower limbs. In many cases, marked reduction of the motor amplitude prevented the detection of CB, marked reduction of the motor amplitude prevented the detection of CB. Moderate fibrillation potentials were found in 28 p. 100 of patients. Giant muscular unit potentials were frequent (21/39). F-waves in nerve with CB were always abnormal with marked increased latencies. Late responses sometimes seemed to be repeater F-waves. Axon reflexes were detected in 5 cases. The late responses abnormalities could precede the block. Clinical, biological and electrophysiological described arguments could may distinguish NMM with CB from motor neuron disease and relate them to the group of chronic demyelinating neuropathies.

Adult↗

Quantitative 1H spectroscopic imaging of human brain at 4.1 T using image segmentation.

Metabolic differences in the content of N-acetylaspartate (NAA), creatinine (CR), and choline (CH) in cerebral gray and white matter can complicate the interpretation of 1H spectroscopic images. To account for these variations, the gray- and white-matter content of each voxel must be known. To provide these data, a T1-based image segmentation scheme was implemented at 4.1 T. The tissue composition of each voxel was determined using the point-spread function of the spectroscopic imaging acquisition and the segmented anatomical image. Pure gray- and white-matter values for CR/NAA and CH/NAA, and the content of CR, CH, and NAA, were determined using a linear-regression analysis of 984 voxels acquired from 10 subjects using white-matter CR as an internal standard. This information was used to establish means and confidence intervals for CR/NAA and CH/NAA from a voxel of arbitrary tissue composition. Using a single-tailed t test, the extent and locations of the metabolic abnormalities (P < 0.05) in a patient with multiple sclerosis were identified.

Aspartic Acid↗

Ultrastructural immunolabelling of amyloid fibrils in acquired and hereditary amyloid neuropathies.

Both acquired and familial amyloid neuropathies carry a poor prognosis. In addition, amyloid is sometimes difficult to visualise in nerve biopsy specimens, and the pathogenesis of nerve lesions is still a matter of controversy. In order to learn more on the subject, we studied nerve specimens from seven patients with proven amyloid neuropathy by ultrastructural immunocytochemistry in order to better understand their pathogeny and to evaluate the reliability of the method for detection of amyloid antigens in the endoneurium. An indirect immunolabelling technique using protein A-gold complex (pA-g) was applied. Polyclonal antisera against human IgG, IgM, lambda and kappa light chains and prealbumin were assayed. Amyloid fibrils were labelled in six of seven cases: in four cases with anti-transthyretin (TTR) antibodies and in two with anti-lambda light chain antibodies. The type of immunolabelling correlated with the biochemical type of the amyloidosis as defined by TTR gene analysis and serum immunoelectrophoresis. The amyloid fibrils and gold labelling were always located in the endoneurial space. No intracellular deposit or labelling was found. The immunolabelling was highly specific, gold particles being detected only near to amyloid fibrils with no background gold labelling. Ultrastructural immunolabelling with pA-g could be used for detection of amyloid in progressive axonal neuropathy of unknown origin, with important therapeutic implications.

Adult↗