Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
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Undernutrition is a frequent complication of evolutive and chronic HIV (human immunodeficiency virus) infection characterized by bodyweight loss and changes in body composition. The Centers for Disease Control and Prevention define AIDS wasting as involuntary loss of more than 10% of body weight, plus more than 30 days of either diarrhea, or weakness and fever. Wasting syndrome has been considered as a case definition of the AIDS disease since 1987. Wasting syndrome is clearly linked to disease progression and death. Despite the progress under the era of highly active antiretroviral therapy (HAART), wasting is still a problem for people with AIDS. A small part of the weight lost is fat. More important is the loss of "lean body mass", which is mostly muscle. Body composition changes during HIV infection are different from those observed in food deprivation. Under the era of HAART, a HIV-associated adipose redistribution syndrome (HARS) was described that associates subcutaneous lipoatrophy and abdominal obesity linked to various metabolic disorders. Several factors contribute to wasting syndrome. Not only low food intake and poor nutrient absorption, but mainly altered metabolism (increased resting energy expenditure) and specific disturbances in protein turnover, which is also increased. Nutritional evaluation of HIV-infected patients should include the measurement of body composition and analysis of nutritional parameters, including albumin, transthyretin and C-reactive protein. Transthyretin seems to be particularly useful to follow the recovery period of malnutrition.
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PMID:Body composition and nutritional parameters in HIV and AIDS patients. 1255 39

We report a 21-year-old-man, with myositis as a manifestation of chronic graft-versus-host-disease (GVHD). He was diagnosed as having acute myelogenous leukemia at the age of 18 years, and had bone marrow transplantation (BMT) two years after the onset of the disease. Cutaneous manifestation of acute GVHD appeared on the twelfth day following BMT, which responded to prednisolone. Thereafter, GVHD has been well-controlled except for mild liver dysfunction which was thought to be a sign of chronic GVHD. Eleven months after BMT, he enjoyed snowboarding for two days from morning till night. Two days later, he experienced muscle swelling with pain and fever, which gradually worsened for which he was admitted to our hospital. Neurological examination revealed severe proximal and distal muscle swelling with fever and tenderness in all extremities. Mild, symmetrical, proximal weakness was observed in all four limbs. Severity of muscle swelling and its generalized nature restricted the movements of shoulder-, elbow- and ankle-joints and he was unable to walk. Laboratory investigations revealed creatine kinase (CK) of 7,860 IU/L, C-reactive protein (CRP) of 21.5 mg/dL and raised biliary enzymes. MRI generated high intensity signals from the swollen muscles. Muscle biopsy examination of involved areas showed severe interstitial edema and mononuclear cells infiltration. Macrophages were scattered through out the perimysium and endomysium. On the other hand, T cells and B cells were localized to the endomysium. Although a lot of CD8 positive T cells were seen adjacent to non-necrotic fibers, none of them was obviously invading the non-necrotic fibers. Perifascicular atrophy was not seen. Symptoms gradually worsened over two weeks or so when prednisolone was started to which he responded rapidly. While tapering steroids, the symptoms relapsed on resuming aggressive exercise. Resumption of the treatment regime promptly controlled the symptoms. The cause of myositis as a manifestation of chronic GVHD is unclear. T-cell or B-cell dysfunction, collagen-vascular-like processes, viral infection and direct damage by radiation or chemotherapy have been supposed to involve in the disease process. Our case suggests that aggressive muscular exercise could play as a initiator of myositis as a manifestation of chronic GVHD.
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PMID:[A case with myositis as a manifestation of chronic graft-versus-host-disease (GVHD) with severe muscle swelling developed after aggressive muscular exercise]. 1282 May 56

Positron emission tomography (PET) has emerged as a powerful tool in clinical oncology which allows to detect pathological changes in the metabolic characteristics of different tissues. In recent years the PET with the radiopharmakon 18F-2-fluoro-2-deoxyglucose has proved to be valuable for the diagnostic approach in inflammatory diseases. We report the case of a 69 year old female patient who was admitted for the diagnostic evaluation of a single pulmonary nodule in the right upper lobe which was suspicious for malignancy in the CT scanning. In the last three month the patient lost 13 kg weight, and was complaining about weakness, fatigue, enhanced body temperature up to 101 degrees F and night sweets. In the laboratory findings a microcytic anemia (80 g/L, 74,4 fL), an enhanced C-reactive protein (133 mg/L) and an accelerated ESR of 100 mm Hg/h was remarkable. The pulmonary nodule located in the second segment of the right upper lobe was not accessible in the bronchoscopic examination. Abdominal and cerebral CT scannings showed no pathological findings. In the positron emission tomography an enhanced accumulation of 18F-2-fluoro-2-deoxyglucose could be detected in the complete aorta and the large-sized arteries of the aortic arch consistent with the diagnosis of a giant-cell arteritis. The suspicious pulmonary nodule of the CT scanning showed no metabolic activity as provable with the PET. The 18F-FDG PET which is used in the initial staging of newly diagnosed lung cancer and known to be superior to CT in the evaluation of lymph node and distant metastases, is applicable in the diagnostic assessment of chronic inflammatory diseases. As the diagnostic approach in patients presenting with clinical symptoms as fatigue, weight loss, night sweets and fever is often arduous and time-consuming, the PET might become a more central role in the future.
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PMID:[PET-imaging proves giant-cell arteritis as the cause of FUO in a patient with a pulmonary nodule of unknown malignancy]. 1286 94

Carnitine is a small water-soluble molecule that is present in almost all animal species. It plays an indispensable role in fatty acid metabolism, where it is involved in the transport of activated fatty acids between different cellular compartments. Uremic patients, as well as patients with chronic renal failure, appear to have abnormal renal handling of carnitine leading to dyslipidemia, lethargy, muscular weakness, hypotension, cardiac dysfunction and arrhythmias, and recurrent cramps. It often is difficult to distinguish these symptoms from similar ones related to uremia and dialysis. Many investigators have advocated L-carnitine supplementation in an attempt to alleviate carnitine deficiencies, and good results from this therapy have been reported. Moreover, several studies have shown that L-carnitine supplementation improves the response to erythropoietin. Chronic inflammation is another particular aspect affecting these patients. Anti-inflammatory properties of L-carnitine in hemodialysis patients have been shown by our group. Treatment with L-carnitine (20 mg/kg, given intravenously at the end of each dialysis session for 6 mo), significantly decreased serum C-reactive protein (CRP) levels, a proinflammatory cytokine known to inhibit erythropoiesis. Moreover, data from published literature are indicative of L-carnitine modulation of the immune system by the activation of glucocorticoid receptors and the modulation of the transcription of glucocorticoid-responsive genes. Our study showed that in these patients, treatment with L-carnitine has been able to improve their body mass index, likely by promoting a positive protein balance. This aspect is strictly correlated with the status of insulin resistance, which is well described in patients with renal diseases. Many studies showed that carnitine allowed mitochondrial fatty acid usage to link to the rate of glucose usage, thus improving insulin resistance. In conclusion, clinical beneficial effects of L-carnitine treatment on patients suffering from renal diseases are supported by molecular evidence involving both inflammatory and metabolic aspects of the disease.
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PMID:Carnitine system in uremic patients: molecular and clinical aspects. 1549 Apr 12

Deep soft-tissue infection occurs infrequently after rotator cuff repair surgery. We retrospectively reviewed the clinical presentation in 14 patients whose rotator cuff repair was complicated by an early deep infection (<6 weeks). The functional outcome after treatment in 12 of these patients was analyzed at a mean follow-up of 37.5 months (range, 11-122 months). The diagnosis of infection was most often made within 3 weeks from the date of surgery (mean, 18 days; range, 3-41 days). Common presenting symptoms included localized wound erythema and drainage. The blood leukocyte counts were usually normal, but the erythrocyte sedimentation rates and C-reactive protein levels were elevated. A mean of 2.6 surgical debridements were required to clean the wound effectively in each case. Eight of twelve patients were dissatisfied at final assessment. Most patients reported reasonably good relief of pain, but they had residual shoulder stiffness and weakness. Retention of suture anchors in the humeral head did not preclude successful eradication of the infection.
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PMID:Management of early deep infection after rotator cuff repair surgery. 1572 6

A 15-year-old, unmarried female presented to our dermatology department for an intensely pruritic skin rash that had appeared abruptly 3 days earlier. She had a remarkable medical history for a case of allergic rhinitis and several attacks of asthma in her early childhood. The condition waxed and waned initially but had improved in recent years. Physical examination revealed several erythematous plaques, papules studded with scattered pustules having diameters less than 0.3 mm. Conspicuous scratch marks had caused erythematous wheal-like indurations also studded with pustules in a linear distribution across the waist, forearms (Fig. 1), and back (Fig. 2). Discrete papulopustules were present on the face, nape and neck. The patient was otherwise healthy. There were no other symptoms such as fever, malaise, weakness, or lymphadenopathy Laboratory results were normal for hepatic and renal functions, serum electrolytes, glucose, protein, erythrocyte sedimentation rate (8 mm/h), and C-reactive protein (0.355 mg/l). A human immunodeficiency virus (HIV) antibody screen test was negative. Serum was positive for herpes simplex virus (HSV)-1 and HSV-2 IgG (in low titers), but negative for HSV-1 and HSV-2 IgM. White blood cell count revealed leukocytosis (11.2 x 10(3)/l), with a differential count of 68% neutrophils, 27% lymphocytes, and 8% eosinophils. Serum IgA, IgG, and IgM were within normal limits, but the IgE level was elevated (677 mg/dl). Cultures from peripheral blood and pustules were negative. A Tzank smear performed on the pustules showed no multinucleated giant cells. Fungal testing of skin scrapings from the initial lesion site gave negative results. Routine stool tests, including common pathogen and parasite screens, were negative, and urinalysis results were unremarkable. A biopsy specimen obtained from a skin pustule showed subcorneal eosinophilic and neutrophilic pustules in the follicular infundibulum with marked spongiosis of the follicular epithelium. (Fig. 3). There was a moderately dense superficial and deep perivascular mixed inflammatory cell infiltrate comprising eosinophils, neutrophils and lymphocytes. Migration of eosinophils and neutrophils through the vessel wall with variable luminal intramural fibrin deposition, histologically indicative of vasculopathy, was seen. There was concomitant slight perivascular dermal necrosis. (Fig. 4). Based on the clinical presentation and light microscopic findings on biopsy, a diagnosis of eosinophilic pustular folliculitis with pathergy was made. Systemic prednisolone 30 mg in divided doses was given. After 1 week of systemic corticosteroid therapy, the patient's condition was significantly improved and the patient was subsequently discharged. Two months later she had a relapse, upon which corticosteroid therapy was commenced leading to lesional resolution. The foci of eosinophilic folliculitis healed with areas of hyperpigmentation with variable scarring.
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PMID:Pathergy in atypical eosinophilic pustular folliculitis. 1580 26

Polymyalgia rheumatica is a disorder that affects people over 50 years of age. The etiology of the disease has not been hitherto clarified exactly. Its incidence among people over 50 is in the range of 0.1-0.5%. The incidence rate peaks in the age group of 60-70 years. It is also found in younger people, but far less frequently. The diagnosis is based primarily on locomotor complains--namely on pronounced pain, morning stiffness of the shoulder girdle, pelvic girdle and neck. Complaints relating to the arms and legs (such as muscular weakness, oedema, tendonitis etc.) are also observed, however, in one third of the cases. The diagnostic criteria are defined empirically. Polymyalgia rheumatica was formerly considered to be a form of elderly onset rheumatoid arthritis. The progressive erosion process is absent in the case of polymyalgia rheumatica unlike in the case of rheumatoid arthritis. Numerous factors are known, which point to a link between polymyalgia rheumatica and giant cell vasculitis, arthritis, but the precise nature of this relationship remains unknown. Both conditions affect the same age group in the general population and they are even found--not infrequently--in the same patient. Polymyalgia rheumatica can be found in 40% of the patients suffering from arthritis while the histological examination detected mild vasculitis in approximately 10% of the patients suffering for "isolated" polymyalgia rheumatica. The response to be given to the acute phase is similar in both disorders. Scandinavian authors consider polymyalgia rheumatica as the appearance of generalised arthritis. Arthroscopic, nuclear magnetic resonance imaging as well as isotopic studies show unequivocally, that in the background of the osteo-muscular symptoms, complaints, inflammation is to be found partly of the joints but primarily that of the periarticular synovial structures. The above mentioned--dominant--proximal symptoms can often mask the distal locomotor disorders (pitting oedema of the hands and feet, tendonitis, tendosynovitis, carpal tunnel syndrome). The disorder may be accompanied by atypical generalised symptoms (loss of appetite, weight loss, fever, fatigue). An excellent indicators of the acute phase reactions are erythrocyte sedimentation rate, C-reactive protein and interleukin-6. These are suitable for monitoring the effectiveness of the therapy, for indicating a relapse/recurrence. It should be noted, that polymyalgia rheumatica may also be present if the erythrocyte sedimentation rate and C-reactive protein values are low. This disorder is also characterised by fast and effective response to corticosteroid, which should be administered for 1-2 years. In some individual cases a different dosage regime may be necessary: steroid administered in low dosage over a longer period of time. Administration of methotrexate and anti-tumor necrotic factor-alpha may also be considered as alternative or adjuvant therapy for lowering the quantity of corticosteroid. Further multicenter, double blind studies should, however, be performed on large number of patients in this regard.
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PMID:[Polymyalgia rheumatica]. 1713 99

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.
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PMID:Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. 1792 97

The majority of men with prostate cancer are aged > or =65 years. Men, as they age, are more likely to suffer from impaired physical function. The standard treatment for recurrent prostate cancer is androgen-deprivation therapy (ADT). Well-established toxicities from ADT include lean weight loss or sarcopenia, muscle weakness, fatigue, and reduced activity levels. Frailty is a term from geriatrics that describes older individuals with limited physiologic reserve who are at significant risk for adverse outcomes, including falls, disability, hospitalization, and death. An increasingly accepted definition of frailty is a syndrome in which > or =3 of the following are present: unintentional (lean) weight loss > or =10 pounds in the past year, weakness (measured by grip strength), slow walking speed, self-reported exhaustion, and low physical activity. This clinical syndrome overlaps closely with the known toxicities of ADT. In addition, alterations in the inflammatory system, neuroendocrine system, and energy production are associated with this syndrome, as evidenced by biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. For this article, the authors reviewed the evidence for the effect of ADT on each of the 5 frailty components plus the identified biomarkers, and the evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer. Given the association of frailty with important clinical outcomes such as hospitalization and death, this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer.
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PMID:Does androgen-deprivation therapy accelerate the development of frailty in older men with prostate cancer?: a conceptual review. 1796 Jun 9

To determine the peculiarities of clinical presentations of vertebrobasilar transient ischemic attacks in elderly and aged patients (42 patients aged 61-90 years) have been studied using clinical, laboratory, neuroimaging and ultrasound methods. Hemodynamically significant stenosis of vertebral or basilar arteries caused by atherosclerosis was found in 16 patients. It was associated with hypoplasia or kinking of vertebral arteries in 4 patients. Six patients had atrial fibrillation, 15 isolated arterial hypertension and 4 an unspecified type of the disease. Transient ischemic attacks in patients with hemodynamically significant stenosis of vertebral or basilar arteries were characterized by the highest rate and shortest duration of repeated attacks. The most severe clinical course was characteristic of transient ischemic attacks in patients with atrial fibrillation. It was featured by the longest duration of symptoms, highest rate of vision loss, limb numbness and weakness during the attack, high rate of focal neurological signs and high rate of old cerebral infarcts and vascular white matter abnormalities on neuroimages as well as the elevated plasma level of C-reactive protein. Transient ischemic attacks in patients with isolated arterial hypertension were characterized by relatively mild clinical course of the disease.
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PMID:[Clinical peculiarities of pathogenetic subtypes of vertebrobasilar transient ischemic attacks in elderly and aged patients]. 1819 30


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