Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen patients who had bilateral mediofrontal hypoactivity and 30 control subjects without this SPECT anomaly underwent Tc-99m HMPAO brain SPECT imaging. Bilateral mediofrontal hypoactivity was found in various neurologic disorders, including subcortical arteriosclerotic encephalopathy, lacunar state, chronic alcoholism, progressive nonvascular dementia, carbon monoxide poisoning, and diabetes mellitus. This SPECT abnormality was, however, specifically associated with three clinical signs: motor disabilities predominating in the lower limbs, urinary incontinence, and akinetic mutism.
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PMID:Bilateral cerebral mediofrontal hypoactivity in Tc-99m HMPAO SPECT imaging. 780 20

We have investigated the effect of long-term strict glycaemic control on peripheral and autonomic nerve function in 45 IDDM patients (age 18-42 years, diabetes duration 7-23 years) without clinical signs of neuropathy or other neurological disease. They were randomly assigned to treatment either with continuous insulin infusion, multiple injections (4-6 times daily), or conventional treatment (twice daily) for 4 years and followed prospectively for 8 years. Motor and sensory nerve conduction velocities were measured at the start and after 8 years. Autonomic nerve function tests were performed only once, after 8 years. A significant reduction of nerve conduction velocity was observed during 8 years in patients with mean HbA1 more than 10% (n = 12, group mean 10.9%, range 10.1-13.2%) compared to patients with HbA1 less than 10% (n = 33, group mean 9.0%, range 7.5-9.9%). Change of motor nerve conduction velocity in the peroneal nerve was: -4.8 +/- 4.9 (SD) vs -2.2 +/- 5.3 m/s (p < 0.01). Change of motor nerve conduction velocity in the posterior tibial nerve was: -6.8 +/- 5.7 vs- 3.9 +/- 5.1 m/s (p < 0.05). No significant changes were observed in the ulnar nerve. Change of sensoric nerve conduction velocity in the sural nerve was: -8.9 +/- 8.0 vs -4.6 +/- 5.3 m/s (p < 0.05). Multiple regression analysis showed that a change in HbA1 of 1% resulted in a 1.3 m/s change in nerve conduction velocity during 8 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of 8 years of strict glycaemic control on peripheral nerve function in IDDM patients: the Oslo Study. 792 42

The aim of the present study was to elucidate the connection between yersiniosis and chronic inflammation. During the period 1974-83, Yersinia enterocolitica infection was diagnosed in 458 hospitalized patients by antibody response, or isolation. The patients were followed for 4-14 years (1987); 160 were readmitted with chronic disease. Fifty-three patients had persistent joint complaints, 18 developed ankylosing spondylitis, 14 rheumatoid arthritis, and 17 iridocyclitis. Thirty-eight patients suffered from chronic abdominal pain, and another 28 from chronic diarrhoea. Two who underwent proctocolectomy microscopically had ulcerative colitis. Eleven patients developed neurological disease; others developed conditions such as chronic nephritis, thyroid disease, insulin-dependent diabetes, etc. Chronic hepatitis, found in 22 patients, was significantly correlated with positive test for antinuclear antibody and rheumatoid factor, and with death. Several patients developed chronic multiorgan disease, probably with chronic hepatitis as pivot. Regarding the whole material, the difference between observed and expected cumulative survival rates remained significant for 8 years (0.9189 < 0.9456; p < 0.025), indicating a substantial impact on long-term survival exerted by chronic yersiniosis.
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PMID:Yersinia enterocolitica: an inducer of chronic inflammation. 796 May 1

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the CNS, taking part in processes which are now relatively well understood but also in processes which are remarkable progress has been achieved. The most thoroughly studied field of GABA operation is its role of inhibitory neurotransmitter realized through the mediation of GABA-A and GABA-B receptors. There are at least 40 per cent of synaptic inhibitory events in the CNS in which the neurotransmitter action of GABA is involved. The action of GABA on GABA-A receptor, a Cl- channel, is influenced by benzodiazepines, barbiturates and other substances, suggesting that some neurological and psychiatric diseases are connected with the function of GABA-A receptor. In addition to synaptic inhibition, GABA has several metabolic regulatory functions. GABA is produced not only in neurons but also in beta cells of the pancreas and in tubular cells of the kidney cortex. Its role in these parenchymatous cells is not sufficiently understood. Similarly as GABA, glutamic acid decarboxylase (GAD), an enzyme catalysing GABA formation from glutamate, has also been intensively studied. GAD structure, its function in various parts of the CNS and in some parenchymatous cells, and the regulation of GAD activity are still in the focus of interest. Recently GAD has been demonstrated to act as autoantigen in the rare neurological disease "stiff man syndrome" (SMS) and in insulin-dependent diabetes mellitus (IDDM). In the presented paper a short review of GABA functions, GAD properties and of the antigenic feature of GAD are given. (Fig. 7, Ref. 41.)
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PMID:[Gamma-aminobutyric acid and glutamate decarboxylase]. 800 82

Glutamic acid decarboxylase (GAD) is the enzyme that synthesizes the neurotransmitter gamma-aminobutyric acid (GABA) in neurons and in pancreatic beta cells. It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus. The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes. GAD-67 and GAD-65 are very similar to each other in amino acid sequence and differ substantially only at their NH2-terminal region. We have investigated the reactivity of autoantibodies of 30 Stiff-Man syndrome patients to GAD. All patient sera contained antibodies that recognize strongly GAD-65, but also GAD-67, when tested by immunoprecipitation on brain extracts and by immunoprecipitation or immunocytochemistry on cells transfected with either the GAD-65 or the GAD-67 gene. When tested by Western blotting, all patient sera selectively recognized GAD-65. Western blot analysis of deletion mutants of GAD-65 demonstrated that autoantibodies are directed predominantly against two regions of the GAD-65 molecule. All SMS sera strongly recognized a fragment contained between amino acid 475 and the COOH terminus (amino acid 585). Within this region, amino acids 475-484 and 571-585 were required for reactivity. The requirement of these two discontinuous segments implies that the epitope is influenced by conformation. This reactivity is similar to that displayed by the monoclonal antibody GAD 6, suggesting the presence of a single immunodominant epitope (SMS-E1) in this region of GAD-65. In addition, most SMS sera recognized at least one epitope (SMS-E2) in the NH2-terminal domain of GAD-65 (amino acids 1-95). The demonstration in SMS patients of a strikingly homogeneous humoral autoimmune response against GAD and the identification of dominant autoreactive target regions may help to elucidate the molecular mechanisms of GAD processing and presentation involved in GAD autoimmunity. Moreover, the reactivity reported here of GAD autoantibodies in SMS partially differs from the reactivity of GAD autoantibodies in insulin-dependent diabetes mellitus, suggesting a link between the pattern of humoral autoimmunity and the clinical condition.
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PMID:Identification of a dominant epitope of glutamic acid decarboxylase (GAD-65) recognized by autoantibodies in stiff-man syndrome. 824 84

We report the findings of a total population survey of Thugbah community in the Eastern Province of Saudi Arabia (SA) to determine its point prevalence of neurological diseases. During this two-phase door-to-door study, all Saudi nationals living in Thugbah were first screened by trained interviewers using a pretested questionnaire (sensitivity 98%, specificity 89%) administered at a face-to-face interview. Individuals with abnormal responses were then evaluated by a neurologist using specific guidelines and defined diagnostic criteria to document neurological disease. The questionnaire was readministered blind by a neurologist to all those with abnormal responses and a 1-in-20 random sample of those without abnormal responses, respectively. The family members of an individual with an abnormal response were also screened to improve accuracy. A total of 23,227 Saudis (98% of the eligible subjects) were screened and those residing in Thugbah on the reference date (22,630) were used to calculate the point prevalence rates. Forty-two percent of those screened were in the first decade of life and only 1.5% were more than 60 years old. There were marginally more females (50.2%) than males (49.8%). Consanguineous marriages especially between first cousins were present in 54.6%. The demographic characteristics of Thugbah community were similar to those in other parts of SA. The overall crude prevalence ratio (PR) for all forms of neurological disease was 131/1,000 population. All subsequent PRs are per 1,000 population. Headache syndromes were the most prevalent disorder (PR 20.7). The PR for all seizure disorders was 7.60, and the epilepsies (6.54) were more frequent than febrile convulsions (0.84). Mental retardation, cerebral palsy syndrome, and microcephaly were common pediatric problems with PRs of 6.27, 5.30 and 1.99, respectively. Stroke, Parkinson's disease, and Alzheimer's disease were uncommon with respective PRs of 1.8, 0.27 and 0.22. Central nervous system (CNS) malformations (0.49) such as hydrocephalus and meningomyelocele were more prevalent than spinal muscular atrophy (0.13), congenital brachial palsy (0.13) and narcolepsy (0.04). Multiple sclerosis was rare (0.04). Osteoarthritis and low back pain syndromes were the main non-neurological conditions seen. The major medical diseases that may be neurologically relevant were diabetes mellitus, hypertension, and connective tissue disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A community survey of neurological disorders in Saudi Arabia: the Thugbah study. 827 77

This report describes an age-related clinical study of detrusor muscle function using urodynamic data obtained from 1391 women and 324 men of different age groups who were free from overt neurological disease and diabetes. Isometric detrusor function during unstable activity was assessed by integrating the calculated force of unstable detrusor activity during filling of the bladder. Isotonic voiding activity was measured by calculating the velocity constant Q*, which reflects the speed of detrusor muscle shortening. In addition, the change in detrusor pressure on initiation of voiding and the post-micturition residual urine volume were recorded. Older patients of both sexes had higher residual urine volumes. Older women showed lower detrusor shortening velocities. There were no age-related differences in isometric detrusor function. Older women showed a tendency for the detrusor contraction to fail on initiation of voiding, whereas older men did not demonstrate this difference. Voiding dysfunction in late life was more marked amongst women and seemed to be related to a failure of isotonic detrusor function with no related changes in isometric function.
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PMID:Characterisation of detrusor contractile function in relation to old age. 830 49

We prospectively evaluated autonomic function in 50 patients with clinical and manometric features of a neuropathic form of chronic intestinal pseudo-obstruction (CIP). In 26 patients, there were underlying disease processes that may have affected extrinsic neural control to viscera: diabetes mellitus (n = 16), previous gastric surgery (n = 5), and other neurologic disorders (n = 5). Our aim was to characterize autonomic function in these patients, and those 24 with CIP unassociated with a known underlying neurologic disorder (idiopathic group). We assessed vagal function and sympathetic cholinergic and adrenergic function by means of standardized autonomic tests and quantitated postprandial antral pressure activity. We also measured postprandial levels of pancreatic polypeptide and neurotensin as indicators of vagal function and of the delivery of nutrients to the distal small bowel. Among the idiopathic group (n = 24), two had evidence of a generalized sympathetic neuropathy and five abdominal vagal dysfunction (one had both). Among diabetic patients, three had sympathetic adrenergic failure, six had orthostasis with normal plasma noradrenaline, ten had signs of generalized sympathetic neuropathy and eight had abdominal vagal dysfunction. Vagal dysfunction was identified in all three patients who underwent vagotomy as part of their previous gastric surgery. In the other neurologic syndromes, vagal function was abnormal in three of the five patients. Thus, autonomic and, particularly, vagal dysfunction are confirmed in a majority of patients with CIP associated with known diabetes or neurologic disorders; however, a previously unrecognized autonomic (chiefly vagal) neuropathy of undetermined cause has been identified in five of the 24 'idiopathic' CIP patients.
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PMID:Autonomic dysfunction in patients with chronic intestinal pseudo-obstruction. 832 79

In idiopathic thrombocytopenic purpura, a known immune-mediated disorder, intravenous IgG is the treatment of choice. Success and the lack of side effects of intravenous IgG in the treatment of idiopathic thrombocytopenic purpura have encouraged consideration of its use in the treatment of neurologic disorders of presumed autoimmune pathogenesis. In this report, we describe two patients who developed acute renal failure following intravenous IgG treatment. The first patient had chronic inflammatory demyelinating polyneuropathy and was treated with intravenous IgG instead of prednisone because of preexisting diabetes. The second patient had idiopathic thrombocytopenic purpura and received intravenous IgG treatment as part of standard care. The patient with idiopathic thrombocytopenic purpura had unrelated bilateral high-grade renal artery stenosis. Both patients had a creatinine level of 140 mumol/L (1.6 mg/dL) prior to treatment. Renal biopsies performed during acute renal failure in each patient demonstrated marked swelling and vacuolization of the proximal tubular epithelial cytoplasm typical of high-solute-load-induced damage (similar to that associated with the use of mannitol). This report draws attention to the importance of screening for impaired renal function before intravenous IgG therapy is initiated. The patients we describe received standard doses of intravenous IgG at the recommended infusion rate yet developed oliguric renal failure. Awareness of serious side effects and recognition of predisposing factors provide means of avoiding known life-threatening complications of intravenous IgG therapy.
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PMID:Acute renal failure resulting from intravenous immunoglobulin therapy. 843 Nov 31

Although much has been learned about cerebral physiology during CPB in the past decade, the role of alterations in CBF and CMRO2 during CPB and the unfortunately common occurrence of neuropsychologic injury still is understood incompletely. It is apparent that during CPB temperature, anesthetic depth, CMRO2, and PaCO2 are the major factors that effect CBF. The systemic pressure, pump flow, and flow character (pulsatile versus nonpulsatile) have little influence on CBF within the bounds of usual clinical practice. Although cerebral autoregulation is characteristically preserved during CPB, untreated hypertension, profound hypothermia, pH-stat blood gas management, diabetes, and certain neurologic disorders may impair this important link between cerebral blood flow nutrient supply and metabolic demand (Figure 5). During stable moderate hypothermic CPB with alpha-stat management of arterial blood gases, hypothermia is the most important factor altering cerebral metabolic parameters. Autoregulation is intact and CBF follows cerebral metabolism. Despite wide variations in perfusion flow and systemic arterial pressure, CBF is unchanged. Populations of patients have been identified with altered cerebral autoregulation. To what degree the impairment of cerebral autoregulation contributes to postoperative neuropsychologic dysfunction is unknown. It must be emphasized that not the absolute level of CBF, but the appropriateness of oxygen delivery to demand is paramount. However, the assumption that the control of cerebral oxygen and nutrient supply and demand will prevent neurologic injury during CPB is simplistic. A better understanding of CBF, CMRO2, autoregulation and mechanism(s) of cerebral injury during CPB has lead to a scientific basis for many of the decisions made regarding extracorporeal perfusion.
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PMID:Cerebral blood flow and metabolism during cardiopulmonary bypass. 846 2


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