Gene/Protein Disease Symptom Drug Enzyme Compound
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 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We prospectively determined the prevalence of morbidity from the various forms of diabetic neuropathy over one year in a population of 800 patients with diabetes mellitus (336 type 1, 464 type 2 DM). Symptoms documented were: pain/paraesthesia in the feet, loss of feeling and the restless legs syndrome. We also documented the prevalence of: neuropathic ulcers, amyotrophy, foot drop, and oculomotor palsy. Autonomic symptoms documented were: impotence, postural hypotension and diarrhoea. The only symptoms reported by 100 non-diabetic control subjects were: loss of feeling in 2% and restless legs syndrome in 7%. In the diabetics; pain/paraesthesia was present in 13%, feeling loss in 7% and neuropathic ulcers in 2%. The prevalence of Diabetic amyotrophy (proximal femoral neuropathy) was 0.8%, oculomotor palsy 0.1% and peroneal nerve palsy 0.1%. Erectile impotence was present in 20%, symptomatic postural hypotension in 1% and diabetic diarrhoea in 1%. Overall; 22.9% of the population was afflicted by one or more problems resulting from neuropathy. Neuropathy was associated with older age (p < 0.001), and serious retinopathy (p < 0.001) in both groups of diabetics and with duration of diabetes, proteinuria (p < 0.02), hypertension (p < 0.01) and ischaemic heart disease (p < 0.02) in type 1 diabetics.
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PMID:Prevalence and forms of neuropathic morbidity in 800 diabetics. 820 Jul 77

Sphingolipid biosynthesis begins with the condensation of L-serine and palmitoyl-CoA catalyzed by the PLP-dependent enzyme serine palmitoyltransferase (SPT). Mutations in human SPT cause hereditary sensory autonomic neuropathy type 1, a disease characterized by loss of feeling in extremities and severe pain. The human enzyme is a membrane-bound hetereodimer, and the most common mutations are located in the enzymatically incompetent monomer, suggesting a "dominant" or regulatory effect. The molecular basis of how these mutations perturb SPT activity is subtle and is not simply loss of activity. To further explore the structure and mechanism of SPT, we have studied the homodimeric bacterial enzyme from Sphingomonas paucimobilis. We have analyzed two mutants (N100Y and N100W) engineered to mimic the mutations seen in hereditary sensory autonomic neuropathy type 1 as well as a third mutant N100C designed to mimic the wild-type human SPT. The N100C mutant appears fully active, whereas both N100Y and N100W are significantly compromised. The structures of the holoenzymes reveal differences around the active site and in neighboring secondary structure that transmit across the dimeric interface in both N100Y and N100W. Comparison of the l-Ser external aldimine structures of both native and N100Y reveals significant differences that hinder the movement of a catalytically important Arg(378) residue into the active site. Spectroscopic analysis confirms that both N100Y and N100W mutants subtly affect the chemistry of the PLP. Furthermore, the N100Y and R378A mutants appear less able to stabilize a quinonoid intermediate. These data provide the first experimental insight into how the most common disease-associated mutations of human SPT may lead to perturbation of enzyme activity.
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PMID:The external aldimine form of serine palmitoyltransferase: structural, kinetic, and spectroscopic analysis of the wild-type enzyme and HSAN1 mutant mimics. 1937 77

About 60 to 70 percent of people with diabetes have some neuropathy. Diabetic neuropathy can be classified as peripheral, autonomic, proximal, focal and multifocal or mixed. Peripheral neuropathy, the most common type of diabetic neuropathy, causes pain and/or loss of feeling in the toes, feet, legs, hands, and arms; extreme sensitivity to touch, loss of balance and coordination; muscle weakness and loss of reflexes, especially at the ankle, leading to changes in the way a person walks. The aim of this study is to underline the importance of drug and rehabilitative approach in the therapy of peripheral neuropathy, that frequently influences both diabetes mellitus type 1 and diabetes mellitus type 2.
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PMID:[Diabetic peripheral neuropathy: reflections and drug-rehabilitative treatment]. 1972 72

The aims of this study were to evaluate the impact of cosmetic and functional outcomes after breast-conserving surgery (BCS) and radiation on quality of life (QOL). In this exploratory analysis; baseline, 5 and 10 years data of patient's assessment of breast cosmesis, arm swelling/pain, limitation of movement, loss of feeling in fingers and breast sensitivity/tenderness were dichotomized and their impact on QOL (QLQ-C30) were assessed. Multivariable modelling was also performed to assess associations with QOL. The St. George and Wollongong randomized trial randomized 688 patients into the boost and no boost arms. 609, 580, and 428 patients had baseline, 5 and 10 years cosmetic data available, respectively. Similar numbers had the various functional assessments in the corresponding period. By univariate analysis, cosmesis and a number of functional outcomes were highly associated with QOL. Adjusted multivariate modelling showed that cosmesis remained associated with QOL at 5 and 10 years. Breast sensitivity, arm pain, breast separation, age and any distant cancer event were also associated with QOL on multivariate modelling at 10 years. This study highlights the importance of maintaining favorable cosmetic and functional outcomes following BCS. In addition, the clinically and statistically significant relationship between functional outcomes and QOL shows the importance for clinicians and allied health professionals in identifying, discussing, managing, and limiting these effects in women with breast cancer in order to maintain QOL.
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PMID:The impact of breast cosmetic and functional outcomes on quality of life: long-term results from the St. George and Wollongong randomized breast boost trial. 2358 69

Fibromyalgia is a diffuse chronic pain condition that occurs predominantly in women and may be under-reported in men. Symptoms include a loss of feeling of well-being and generalized widespread flu-like muscle aches and pain that fail to resolve due to central sensitization of nociceptive neurons. It has commonalities with a myriad of other chronic pain conditions which include PTSD, "Gulf War Syndrome", and various stress-induced conditions caused, for example, by viral infection, emotional or physical stress, trauma, combat, accident or surgery. It is not understood why some individuals are susceptible to this condition and others are not. White et al., elsewhere in this issue, present a clinical feasibility study designed to test the hypothesis that 1) low or deficient testosterone serum levels are linked to a high risk for an inflamed nociceptive nervous system and resultant chronic pain states, and 2) a testosterone transdermal gel applied once a day by fibromyalgia patients can be an effective therapeutic against chronic pain. Here, a short profile of fibromyalgia is provided along with a brief summary of best practices currently recommended by clinical specialists. The link between testosterone and pain is then discussed, with an overview of scientific studies that lay the foundation for testosterone as a possible important additional therapeutic that has the potential to be safely administered and effective but also avoid the adverse effects of other therapeutics. Finally, novel mechanisms by which testosterone therapy is likely to down-modulate pain signaling are proposed.
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PMID:A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients. 2600 14

Pain and a loss of feeling in your thumb, index finger, middle finger, and part of your ring finger may be a sign of carpal tunnel syndrome. This syndrome and the pain, numbness, tingling, and weakness in your hand that result from it are caused by pressure on the median nerve as it travels through the carpal tunnel. Guidelines published in the May 2019 issue of JOSPT make recommendations, based on best practices from the published literature, for evaluating, diagnosing, and treating carpal tunnel syndrome. For you as a patient, these guidelines outline the best rehabilitation treatment options based on the scientific research. Ultimately, the best care is a combination of the leading science, the clinical expertise of your health care provider, and your input as the patient. These guidelines help inform the first step in that process. J Orthop Sports Phys Ther 2019;49(5):361. doi:10.2519/jospt.2019.0502.
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PMID:Carpal Tunnel Syndrome: Treating Hand Pain and Numbness. 3103 89