Gene/Protein Disease Symptom Drug Enzyme Compound
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Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.
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PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

It is important to establish the diagnosis of temporal arteritis because the disease is treatable; treatment may prevent blindness and even death. Temporal arteritis usually occurs in people older than 51 years of age, although very rarely, histologically documented disease occurs in younger people. The onset may be occult, so that there are few findings. A multitude of signs and symptoms may occur such as fever, headaches, malaise, weight loss, anemia, stroke, cranial nerve palsies, polymyalgia rheumatica, aortitis and other large vessel involvement. The eye may suffer from ischemic optic neuropathy (anterior or posterior), central or cilio-retinal arterial occlusion, ophthalmic artery ischemia, or extraocular muscle palsies. An arterial biopsy showing giant cell arteritis establishes the diagnosis. However, a negative biopsy does not rule out the disease because of the occasional presence of skip areas. Arteriography has only rarely yielded a positive temporal artery biopsy when the initial biopsy done elsewhere was negative. As a diagnostic parameter, the erythrocyte sedimentation rate is nonspecific, being elevated in diseases other than temporal arteritis and sometimes being falsely lowered by technical factors. Furthermore, the temporal artery biopsy is occasionally positive despite a normal erythrocyte sedimentation rate. Treatment is aimed at relieving the patient's symptoms and normalizing the erythrocyte sedimentation rate. Because of the wide spectrum of clinical and laboratory finding in temporal arteritis, no one specific treatment regimen with systemic corticosteroids works for all patients. Temporal arteritis is a well known disease of the elderly which ir rarely fatal but results in significant visual morbidity (Hinzpeter & Naumann, 1976; Spencer & Hoyt, 1960). Since Hutchinson's (1890) description, more than a thousand articles have been written on the subject (Cohen & Smith, 1974). Despite this, many unanswered questions and controversies remain concerning the diagnosis, prognosis and treatment of temporal arteritis. My goal is to review these questions and areas of controversy.
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PMID:Controversies regarding giant cell (temporal, cranial) arteritis. 39 20

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.
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PMID:Cerebral blood flow variations in CNS lupus. 229 89

Pituitary apoplexy is characterized by a wide spectrum of clinical features. A quite rare case of painless thyroiditis, hypopituitarism and central diabetes insipidus (DI) followed by pituitary apoplexy was presented. A 61-year-old woman was admitted to our hospital in May, 1986 because of marked general malaise, polydipsia and weight loss which became progressively worse. Four months earlier she had experienced episodes of abrupt onset of severe headache associated with nausea and blurring vision. Physical examinations revealed a fine tremor, dry skin and nervousness. The thyroid gland was not palpable. Visual fields were intact. Her blood pressure was 105/64 mmHg with variable tachycardia. The routine laboratory studies were normal or negative except for hypoalbuminemia, hypocholesterolemia and hypernatremia. Erythrocyte sedimentation rate was 12 mm/hr. An impairment in corticotropin secretion was suspected from the low plasma cortisol and the low urinary excretion of 17-OHCS and the sufficient response to ACTH. Basal levels of GH and gonadotropin were also low, and responses to the stimulation tests (Insulin-stress, L-DOPA, and LH-RH) were all blunted. Brain computed tomographic scan and magnetic resonance imaging demonstrated a suprasellar mass that, after infusion, developed peripheral ring-like enhancement and large hyperintense pituitary mass, respectively. A diagnosis of pituitary apoplexy with anterior pituitary failure was made. However, the initial levels of thyroid hormones showed elevated as follows: Free T3 7.6 pg/ml, Free T4 3.3 ng/dl and T3-resin uptake 41.1%. TSH responses to TRH were all suppressed. TSH receptor antibody (TBII) was negative. Both antithyroglobulin and antimicrosomal antibodies were repeatedly positive. A thyroid scan with 99mTc revealed no uptake in the thyroid area. These findings led us to the diagnosis of "painless autoimmune thyroiditis". She had become hypothyroid without any medication. At that time radioactive 99mTc and 123I uptakes increased significantly. When hydrocortisone was substituted, daily urine output abruptly increased to about 10 liters with low osmolality, and the presence of DI was suspected. This diagnosis was confirmed by water deprivation and hypertonic saline infusion tests and subsequent pitressin test. She is currently quite well on L-thyroxine, hydrocortisone and desmopressin (1988). This association with pituitary apoplexy must be a rare occurrence, as a literature search has failed to find a similar case. The pathogenetic trigger of "painless thyroiditis" in this case may be responsible for some immunological change due to secondary adrenal insufficiency after pituitary apoplexy.
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PMID:[An unusual association of transient resolving thyrotoxicosis due to painless thyroiditis, hypopituitarism and central diabetes insipidus associated with spontaneous pituitary apoplexy]. 230 57

The study is a retrospective analysis of the clinical features of 122 patients from Finland, whose serum showed in immunoelectrophoresis (IEP) a cathodic elongation of the albumin line, "tailing albumin" (TA), not associated with an M-component. One hundred and seventeen of these cases were found among about 40,000 consecutive routine serum IEP examinations in two laboratories during 1967-1980. Five further cases were detected during the collection of the control series. Only a few TA cases of corresponding type have been reported from elsewhere. Previous studies of some of the patients of the present series had shown that the TA phenomenon was due to complexes between albumin and IgG class autoantibodies against albumin. Clinical data were collected mainly from the hospital records. The chest radiographic findings were classified by the ILO (International Labour Office) method. The author herself examined 33 of the patients during the current disease or during the follow-up. One hundred and ten patients were followed up for a period of three months to nine years (mean 2.5 years). The patients were mostly elderly, and 93% of them were women. Most of the patients had one or more previously diagnosed chronic illnesses, for which they were receiving one or several drugs as long-term therapy. Eighty percent of the patients were receiving nitrofurantoin (NF) as prophylaxis for recurrent urinary tract infections. However, urinary tract infection was not a current problem in any of the cases. There was evidence of a role of NF in the development of both the immunologic abnormalities and the clinical disease in the TA patients. On the basis of long-term NF treatment the patients were divided into two groups: 1) 97 patients with NF therapy (NF+ group) and 2) 25 patients without NF therapy (NF- group). The patients had mostly undergone the examinations because of cough, dyspnoea, and general symptoms (fatigue, weakness, malaise, loss of weight). The symptoms had usually started insidiously, and in 50% of the patients they had lasted for at least three months. Eight of the patients had been hospitalized because of various acute diseases (e.g. cerebral stroke). Ten of the patients were subjectively symptomless. The most common pathologic laboratory findings were high erythrocyte sedimentation rate (over 100 mm/h in 47%), IgG class antinuclear antibodies (in 88%; the titre was greater than or equal to 1000 in 56%), high serum IgG (mean 30.6 g/l), and elevated levels of serum aminotransferases (in 54% of the patients examined).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunoelectrophoretic tailing albumin phenomenon. Associations with clinical characteristics of the patients and with nitrofurantoin treatment. 320 74

The ambulant recording of the electrocardiogram by the Holter technique has become one of the non invasive examinations widely used in two indications: paroxysmal arrhythmias and coronary disease. However, the technical limitations of the method and the occasionally improper extension of the indications of Holter recording lead to disappointing results. The aim of this work is an estimation of the usefulness of Holter as a function of the desired information by a statistical study. Of 646 consecutive recordings, 200 were taken at random; 169 usable ones were classed in 7 categories according to the clinical requirement; the overall usefulness amounts to 27.5 percent of the cases in which Holter permits a diagnosis. As far as paroxysmal disturbances of rhythm are concerned, Holter is more efficacious than the standard electrocardiogram. However, the efficiency of the method is low: 17.4 percent of cases when it was required to find a cardiac arrhythmia causing a cerebral vascular accident, and even lower, 5.1 percent, when a malaise was concerned. In 20 percent of the cases was a useful tool in diagnosing thoracic pain. In 9.5 percent of the cases the tracings were not interpretable owing to their poor quality. These findings urge more rigor in the choice of indications and a better control of technical problems if the efficacy of the method is to be improved.
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PMID:[Statistical study of the profitability of recording cardiac electric activity by Holter's technic in diagnostic practice. Apropos of 200 cases]. 370 14

We describe 20 adult patients with malignant lymphoma with primary presentation in the spleen. The most common presenting symptoms were fever, malaise, and weight loss. Physical examination revealed prominent splenomegaly without palpable lymphadenopathy. Small lymphocytic lymphoma was the most frequent histologic type (11/20), followed by large cell lymphoma and mixed cell lymphoma (3/20 each). Bone marrow involvement was found in ten of 17 patients. At laparotomy, lymph node involvement, usually retroperitoneal, was found in six of 13 patients. There was liver involvement in seven of 15 patients. Follow-up has been relatively short, with an average of 24 months (range, one to 48 months). Four patients died as a result of progressive disease, one died of sepsis after splenectomy, and one died two years after diagnosis of a stroke. The prognosis in primary splenic lymphoma appears to be similar to that in nodal lymphoma.
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PMID:Malignant lymphoma with primary presentation in the spleen. A study of 20 patients. 384 Sep 80

Pituitary apoplexy is a neuroendocrine emergency produced by hemorrhage or infarction of pituitary tumors, and its accurate diagnosis has relied mainly on clinical manifestations and computed tomography (CT) scan of sella in the past. A case is reported of pituitary apoplexy which was demonstrated on magnetic resonance imaging (MRI). The 72-year-old male patient was admitted to the Nephrology Section of VGH-Taipei with symptoms of general malaise, poor appetite for four months and apparent hyponatremia (Na 102 mEq/L) on laboratory findings. Under the impression of syndrome of inappropriate secretion of antidiuretic hormone (SIADH), fluid restriction and infusion of isotonic saline were prescribed, but in vain. The patient was transferred to the Endocrinology Section because of lowered serum cortisol, T3, T4, and hs-TSH levels. Dynamic pituitary function tests confirmed the diagnosis of panhypopituitarism. Contrast enhanced CT scan of sella revealed displacement of the pituitary stalk to the right side. T1-weighted MRI showed persistent high intensity in left sella and T2-weighted MRI showed persisting isointense to white matter. The hyponatremia and clinical symptoms resolved within a few days after replacement therapy with glucocorticoid and thyroid hormone. It was concluded that MRI is more sensitive than CT scan for detecting subacute or chronic pituitary apoplexy.
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PMID:Pituitary apoplexy diagnosed by magnetic resonance imaging: a case report. 775 60

Aspiration is the leading cause of anaerobic lung infections. Risk factors for these infections include a depressed level of consciousness, a history of seizure, general anesthesia, central nervous system or neuromuscular disease, cerebrovascular accident, impaired swallowing and use of a tracheal or nasogastric tube. Clinical presentation includes fever, weight loss, malaise and cough productive of foul-smelling sputum. Diagnosis is based on radiographic findings, clinical features and a characteristic morphology of mixed flora on Gram stain of uncontaminated pulmonary specimens. The diagnosis is confirmed by isolation of organisms, usually polymicrobial, on culture. Treatment includes proper drainage, debridement of necrotic tissue and an antibiotic regimen (often initially empiric) with an agent active against anaerobic and aerobic organisms.
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PMID:Anaerobic lung infections. 820 19

Endotoxemia occurs when intestinal ischemia allows bacterial lipopolysaccharide to translocate from colonic flora into the bloodstream, which triggers release of cytokines that can cause hypotension, rigors, fever, shock, and even death. Recently, blood endotoxin levels were shown to be higher in athletes needing medical attention (330 pg.ml-1) than in their competitors with similar performances (81 pg.ml-1). Though there were no data showing that these athletes had elevated core temperatures or severe illness, speculation followed that endotoxin may play a causal role in heat stroke. We examined the relationship between endotoxemia and mild post-exertional illness in 39 cyclists after a 100-mile ride. Thirteen cyclists had at least one of the following: orthostatic hypotension, rigors, nausea, vomiting, diarrhea, or syncope. Only 2/26 case-controls had any of these symptoms. Data were collected on vital signs, hemoglobin, sodium, creatine kinase, creatinine, and uric acid. Endotoxin titer was determined by chromogenic assay; tumor necrosis factor alpha (TNF-alpha) titer was determined by ELISA. One ill cyclist had an endotoxin level of 330 pg.ml-1, one control had an endotoxin level of 150 pg.ml-1, but endotoxin level was < or = 64 pg.ml-1 in all others. Comparison of pre- and post-ride data showed that controls increased creatine kinase activity (154 +/- 34 vs 561 +/- 191 IU.dl, P < 0.05), creatinine concentration (1.5 +/- 0.0 vs 1.6 +/- 0.0 mg.dl-1, P < 0.05), and uric acid concentration (5.4 +/- 0.3 vs 6.3 +/- 0.3 mg.dl-1, P < 0.05). Ill cyclists had lower serum sodium than post-ride controls (138 +/- 2 vs 142 +/- 0.6 mEq.l-1, P < 0.05), but there were no differences between groups in CK, creatinine, or uric acid. These findings suggest that endotoxemia may complicate, but does not cause mild post-exertional illness in cyclists.
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PMID:Exercise-associated collapse in cyclists is unrelated to endotoxemia. 853 21


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