How the immune system works and why it causes autoimmune diseases.
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Animals↗
Biomedical subjects
D Adams
Publications and source records attributed to D Adams.
Peroperative endoscopic sphincterotomy during laparoscopic cholecystectomy for choledocholithiasis.
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Cholecystectomy, Laparoscopic↗
Contribution of nerve biopsy findings to the diagnosis of disabling neuropathy in the elderly. A retrospective review of 100 consecutive patients.
Peripheral neuropathy is an important factor of disability in the elderly. In order to learn more on the usefulness of intensive evaluation of patients over 65 years of age with subacute or chronic disabling peripheral neuropathy, we reviewed the clinical and nerve biopsy findings of the last 100 patients of this age group who suffered from a peripheral neuropathy severe enough to justify performance of a nerve biopsy for a diagnostic or prognostic purpose. Normal nerve biopsy findings led to the diagnosis of lower motor neuron disease in three patients and pointed to lesions of the spinal roots in six other patients. Necrotizing arteritis was demonstrated in the biopsy specimens of 23 patients, and non-necrotizing vasculitis in five. In five additional patients the diagnosis of vasculitic neuropathy was kept in spite of non-contributive biopsy findings. In two diabetic patients who had a multifocal neuropathy the biopsy also revealed the presence of vasculitis. Thus 35% of the patients included in this series had one form or another of vasculitic neuropathy. Fourteen patients had a chronic inflammatory demyelinating polyneuropathy. In 11 patients the neuropathy was associated with monoclonal gammopathy, which was benign in nine and associated with malignant plasma cell dyscrasia in two. Among the six patients with diabetes mellitus, two patients who presented with a multifocal neuropathy were found to have vasculitis in the nerve specimen; in the others the biopsy was performed because of uncommonly severe pains or motor involvement due to an extremely severe diabetic neuropathy. Six patients suffered from a long-lasting disability secondary to a drug-induced neuropathy. The remaining 15% had neuropathies of different origin, including amyloidosis, lepromatous leprosy, carcinomatous neuropathy and alcoholic neuropathy. Six patients had a mild, non-progressive or slowly progressive axonopathy of unknown origin, ageing of the peripheral nervous system may have played a role in its development. Our findings show that vasculitis is an important and treatable cause of disabling neuropathy in the elderly and that the proportion of patients with severe neuropathy of unknown origin is small.
Aged↗
Flow cytometry of neonatal platelet RNA.
PURPOSE: Serious disorders of hemostasis occur more often in the small, stressed preterm infant, partly due to immaturity of the newborn hemostatic mechanism. Information regarding the maturational development of platelets in infants has been limited by the large amounts of blood historically needed for platelet studies. The objective of this study was to determine differences between platelets in adults and infants by flow cytometric analysis of "reticulated" platelets. PATIENTS AND METHODS: Eighteen normal adults, 42 healthy term infants, and 27 preterm infants were studied. The infants were subdivided by mode of delivery: vaginal or Caesarean section. Platelet-rich plasma from adult whole blood and infant cord blood samples was divided into aliquots containing 5 X 10(6) platelets, fixed with 1% paraformaldehyde, and stained with thiazole orange for RNA content. The percentage of RNA positive "reticulated" platelets in each aliquot was then determined by flow cytometry. RESULTS: Group comparisons using ANOVA statistical analysis showed a significant difference (p<0.05) for platelet RNA content between adults and term infants, the adults having a higher percentage of reticulated platelets. Although the difference was smaller, adults also had a higher percentage of reticulated platelets than preterm infants. There was no significant difference in reticulated platelet values between infants within one gestational age group compared by type of delivery. CONCLUSION: There are demonstratable differences in adult and infant platelet RNA content that may reflect developmental differences in megakaryocytic/platelet kinetics.
Adult↗
The effect of chlorhexidine on defined, mixed culture oral biofilms grown in a novel model system.
In order to develop an improved method to evaluate antimicrobial agents for use in clinical dentistry, a constant-depth film fermenter (CDFF) has been used to generate biofilms of fixed depth comprising nine species of bacteria commonly found in dental plaque in health and disease. These bacteria were grown together initially in a conventional chemostat which was used to inoculate the CDFF over an 8 h period. Medium was then supplied directly to the CDFF and biofilms allowed to develop. The biofilms were then challenged with eight short pulses of two concentrations of chlorhexidine (0.0125 and 0.125% w/v). The lower concentration had a limited effect on the composition of the biofilms while a differential and substantial inhibition was obtained with a higher concentration. Actinomyces naeslundii was lost from the biofilm, and the viable counts of streptococci, Fusobacterium nucleatum and Porphyromonas gingivalis were inhibited by over three orders of magnitude by 0.125% chlorhexidine, whereas Veillonella dispar was only transiently affected. The findings were consistent with those from clinical studies of dental plaque, suggesting that this model would have a predictive value when evaluating novel antiplaque or antimicrobial inhibitors.
Anti-Infective Agents, Local↗
Professionalism behaviors of hospital nurse executives and middle managers in 10 western states.
What is the level of professionalism of nurse managers? These leaders of nurses are expected to establish a climate in which professional practice can flourish. In this study, the authors used the Professionalism Inventory to determine professional behaviors of 144 nurse executives and 135 middle managers. Nurse executives performed at consistently higher levels except for the categories concerning autonomy and knowledge of the Code for Nurses.
Adult↗
Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.
Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.
Alzheimer Disease↗
Haplotype analysis of French, British and other European patients with familial amyloid polyneuropathy (met 30 and tyr 77).
Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder originally and most frequently described in Portugal. The usual constituent amyloid fibril protein is transthyretin (TTR) and the most frequent mutation in the TTR gene associated with FAP (including all Portuguese cases) is that at position 30 (met 30). Three different TTR haplotypes have been described in association with the met 30 mutation in European patients. We studied the haplotypes of 27 families (24 French, 2 British and 1 Greek) with FAP met 30 by analysing three polymorphisms in introns of the TTR gene. We also studied 6 families (2 British, 3 French and 1 Spanish) with FAP tyr 77. There were two main haplotypes in French patients with FAP met 30, one most commonly seen in the French families of Portuguese descent which was the same haplotype as previously described in Portuguese patients (haplotype I) and another haplotype (III) detected in most informative French families not of Portuguese origin. The age of onset of symptoms was consistently later in French than in Portuguese patients and in patients with haplotype III as the disease-associated haplotype rather than haplotype I. British and French patients with the tyr 77 mutation had different haplotypes. The most likely explanation of these findings is multiple founders of both mutations.
Amyloid Neuropathies↗
Transthyretin gene analysis in European patients with suspected familial amyloid polyneuropathy.
We investigated 99 patients from 64 European families (51 French, 11 British, one Italian and one Spanish) with suspected familial amyloid polyneuropathy (FAP) for transthyretin (TTR) gene mutations. Thirty-nine families were found to have point mutations causing the following amino acid substitutions: Met30 (28 families), Tyr77 (five), Arg 50 (one), Ala49 (one), Gln89 (one), Ala60 (one) and one each with previously undescribed mutations at Asn35 and Gys54. The clinical picture in the patients with new and known mutations were typical of FAP, without any specific features for a particular mutation. Onset of symptoms was late (over 50 years) in many French and British patients with the Met30 and Tyr77 mutations, and only 30% of all index cases had affected relatives. We propose an approach to molecular diagnosis in European patients with FAP, apart from members of families with known mutations, based on the frequency of TTR mutations observed in this and and other studies of FAP in Europe. It is logical to screen for the Met30 and Tyr77 mutations and Ala60 in the UK, using restriction enzyme analysis. If these are absent, the TTR gene should be sequenced directly to detect less common or unknown mutations.
Adult↗
Dentine hypersensitivity: uptake of toothpastes onto dentine and effects of brushing, washing and dietary acid--SEM in vitro study.
Toothpastes are commonly used in the treatment of dentine hypersensitivity. One mode of action could be to block patent dentinal tubules with toothpaste ingredients or by abrasion to form a smear layer. Studies in vitro have shown that toothpaste abrasives have variable affinity for the dentine surface but retention may be limited. This SEM study extended previous work and determined the uptake in vitro of toothpaste ingredients onto the dentine surface and their retention when challenged by washing with water or orange juice. All products were seen to leave variable residues on the surface of etched or unetched dentine specimens, furthermore brush application produced some smearing with closure of previously open tubules. Washing with water and more particularly orange juice removed most residues and orange juice etched the dentine to open previously closed tubules. One product with an artificial silica abrasive was relatively resistant to both water and orange juice washings and in a pilot experiment showed some penetration into tubules not seen with another desensitizing product. These findings suggest that some abrasives may be usefully employed in desensitizing products, but without consideration of erosive factors in the aetiology of dentine hypersensitivity recurrences of the condition will be common.
Acid Etching, Dental↗
Multifocal motor neuropathy with conduction block: a study of 24 patients.
Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment.
Adult↗
Managing meningitis in children: audit of notifications, rifampicin chemoprophylaxis, and audiological referrals.
Important aspects of the management of meningitis in children include notification to local officers for control of communicable diseases; chemoprophylaxis for index cases and close contacts in cases of meningococcal or Haemophilus influenzae meningitis; and a formal hearing assessment for all survivors. A retrospective audit of these aspects of management was carried out for children admitted with meningitis in 12 months from 1 September 1990 to 31 August 1991 at the Royal Belfast Hospital for Sick Children. Only 20 of 36(56%) cases were notified by medical staff. Chemoprophylaxis was arranged for all close family contacts but to only five of the 23(22%) index cases for whom it was indicated. Appointments for audiological testing were arranged for only 19 of the 32(59%) survivors. Subsequently all doctors, including each intake of junior doctors, were given written information on the importance of notification and locally agreed guidelines for chemoprophylaxis and hearing assessments for survivors before discharge. Guidelines were also displayed prominently in each ward. A repeat audit from January 1992 to December 1992 showed significant improvement in these aspects of care. Twenty eight of 32 cases (88%) were notified, chemoprophylaxis was given to 20 of 22(91%) index cases for whom it was indicated, and 25 of 29(86%) survivors had hearing assessments arranged before discharge. Correct management of some aspects of care cannot be assumed, even if statutory (notification), nationally agreed (chemoprophylaxis), or generally agreed good practice (hearing assessments). These aspects of care improved after the first audit but the authors conclude that the notification rate remains below 100% and a repeat audit is necessary.
Adolescent↗
Impact of cardiopulmonary bypass and cardioplegic arrest on myocardial lymphatic function.
Cardioplegic arrest (CPA) is associated with interstitial myocardial edema, which has been shown to impair myocardial function. The accumulation of interstitial myocardial edema may be enhanced by impaired myocardial lymph flow. The purpose of this study was to investigate the effects of CPA on myocardial lymphatic function. In nine anesthetized dogs, we cannulated a prenodal cardiac lymphatic and measured myocardial lymph flow rate (QL), myocardial lymph driving pressure (PL), and myocardial lymph hyaluronan (Hya) concentration. We determined left ventricular function using pressure-volume curves derived by sonomicrometry and micromanometry. The dogs were placed on cardiopulmonary bypass (CPB) (28 degrees C) and subjected to 60 min of hypothermic, crystalloid CPA. With the onset of asystole both QL and PL decreased significantly from 70.7 +/- 31.8 (SD) to 3.3 +/- 4.0 microliters/min and from 19.9 +/- 8.0 to 10.4 +/- 1.8 mmHg, respectively (P < 0.01). Following return of sinus rhythm after separation from CPB, QL and PL increased significantly to 135.4 +/- 28.0 microliters/min and 27.3 +/- 7.5 mmHg, respectively (P < 0.01). Post-CPA myocardial edema was demonstrated by gravimetric wet-to-dry weight determination of 3.67 +/- 0.20 (normal 2.90 +/- 0.20, P < 0.001) and was associated with significantly decreased left ventricular function. Myocardial Hya turnover rate was 1.3 +/- 1.0% per day under baseline conditions and increased significantly to 2.7 +/- 0.9% per day post-CPA (P < 0.01). We conclude that organized myocardial contraction is the major determinant of myocardial lymph flow. Myocardial lymph flow impairment during CPA may contribute to post-CPA myocardial edema and left ventricular dysfunction.
Animals↗
Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm.
Stress represents a complex stimulus to neuroendocrine systems regulating homeostasis. By and large, stress effects are mediated by stress-integrative corticotropin-releasing hormone (CRH) neurons present in the medial parvocellular division of the hypothalamic paraventricular nucleus (PVN). These neurons summate a large variety of neuronal and hormonal signals to eventually yield a physiologically meaningful level of circulating glucocorticoids. In the present experiments, we examined the effects of a chronic variable-stressor paradigm on indices of adrenocorticotropic hormone (ACTH) secretagogue biosynthesis in the PVN and adrenocorticosteroid receptor mRNA expression in the hippocampal formation, PVN and cortex. The variable-stressor paradigm produces a syndrome consistent with chronic stress, including baseline hypersecretion of corticosterone, ACTH and prolactin, and adrenal hypertrophy. CRH mRNA levels in the PVN are increased some 61%, consistent with the observed hypothalamo-pituitary-adrenal (HPA) up-regulation. There was a small but significant increase in arginine vasopressin (AVP) mRNA expression in individual parvocellular PVN neurons (16%), and no demonstrable increase in the number of AVP mRNA-containing neurons. No change in AVP expression was seen in the magnocellular PVN, supraoptic or suprachiasmatic nuclei. In all, these data highlight the importance of CRH in maintaining HPA up-regulation in the face of prolonged challenge. To investigate effects of chronic stress on the regulation of glucocorticoid receptivity, mineralocorticoid receptor (MR) and glucocorticoid receptor mRNA expression was assessed in the hippocampus, frontoparietal cortex and PVN. Chronic stress significantly down-regulated MR mRNA expression in subfields CA1, CA3 and the dentate gyrus (DG), and GR mRNA expression in subfields CA1, the DG and frontoparietal cortex. The reduction in receptor biosynthesis suggests the capacity for stress to modulate the impact of glucocorticoid on hippocampal cell physiology at the genomic level, potentially influencing processes ranging from cognition to feedback regulation of the HPA axis. At the level of the parvocellular PVN, GR mRNA expression was decreased to 60% of control values. GR mRNA expression was negatively correlated with PVN CRH mRNA expression, suggesting a relationship between elevated CRH gene expression and down-regulation of GR at the level of the PVN.
Adrenocorticotropic Hormone↗
Buy materials management systems, or pray you can swim.
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Computer Communication Networks↗
[Hereditary amyloid neuropathies].
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Amyloid Neuropathies↗
Phase I/II study of paclitaxel plus cisplatin as first-line chemotherapy for advanced non-small cell lung cancer: preliminary results.
From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). Nine patients had stage IIIB disease and 23 had stage IV disease. The first four dose levels of paclitaxel were 135, 175, 200, and 225 mg/m2 given with a fixed cisplatin dose of 100 mg/m2; at level 5, paclitaxel 225 mg/m2 was again given, and the cisplatin dose was increased to 120 mg/m2. Cycles were given every 3 weeks. Paclitaxel was administered as a 3-hour infusion followed by cisplatin, with standard premedication and hyperhydration. The maximum tolerated dose for the first cycle was not reached. Grades 3 and 4 neutropenia occurred in 24% and 16% of cycles (two cases with fever), respectively. Grades 2 and 3 peripheral axonal neurotoxicity occurred in two and 16 patients, respectively; the neurotoxicity appeared to be dose dependent and cumulative after a median total paclitaxel dose of 1,300 mg/m2. Of the 29 patients evaluable for efficacy, 11 (38%) had a partial response; efficacy was superior at paclitaxel doses of at least 200 mg/m2, with eight (47%) of 17 evaluable patients responding at these levels. In conclusion, at these doses of paclitaxel and cisplatin, the dose-limiting neurologic toxicity is dose dependent and cumulative after a total paclitaxel dose of approximately 1,300 mg/m2. This combination is highly active, with a total objective response rate of 38% and an objective response rate of 47% at paclitaxel doses of 200 mg/m2 or higher. Further evaluation is warranted.
Adenocarcinoma↗