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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the prognosis of acute porphyria among 206 adult Finnish patients with acute intermittent porphyria (AIP) or variegate porphyria (VP). The series represents all known patients with these porphyrias in Finland. Of the 47 patients who had a total of 117 acute attacks during the period 1967-1989, 6 died during an attack and 21 attacks were associated with paresis; the frequency of severe attacks was significantly smaller than before 1967 (p = 0.00002). Most pareses and deaths occurred because of a delay in diagnosis and inappropriate treatment of porphyria. For those patients who were symptom-free at the time of diagnosis (1365 follow-up years), the risk of the first subsequent attack was significantly smaller than for those who had had an acute attack before the diagnosis of porphyria (1047 follow-up years, p = 0.005). In addition, milder symptoms of porphyria were more common among those who had had previous attacks than among those who had not (p less than 0.00001). In AIP the risk of attacks correlated with the excretion of porphobilinogen in the urine during remission among adults (p = 0.03); a low rate of excretion predicted freedom from acute attacks. A regular use of many precipitating drugs was never associated with symptoms of porphyria. Two percent of the surgical operations and 4% of the pregnancies were associated with acute attacks. Nearly one-third of the women had symptoms of porphyria associated with the menstrual cycle, but these seldom proceeded to an acute attack. Forty-six percent of the women had used sex-hormone preparations regularly; 2 of them (4.5%) experienced associated acute attacks. Patients with AIP or VP showed increased incidences of hepatocellular carcinoma, and probably also chronic renal failure and hypertension.
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PMID:Prognosis of acute porphyria: occurrence of acute attacks, precipitating factors, and associated diseases. 154 56

Among many metabolic disorders, porphyrias and Fabry disease are known to affect autonomic nervous system. In patients with acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, autonomic symptoms such as abdominal pain, vomiting, hypertension and tachycardia are among the most prominent clinical manifestations. Fabry disease is clinically characterized by severe limb pain, hypohidrosis, angiokeratomas and various autonomic symptoms. In both porphyrias and Fabry disease, pathological changes in the central and peripheral autonomic nervous system have been documented. In porphyrias, a loss of myelinated fibers, axonal degeneration, and segmental demyelination in peripheral autonomic nerves as well as chromatolysis of several brain stem nuclei have been found. In Fabry disease, abnormal amount of the substrates of alpha-galactosidase, i.e. ceramide di- and trihexoside, are found to be accumulated in the central and peripheral autonomic nerves.
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PMID:[Autonomic dysfunction in metabolic diseases]. 161 65

Acute porphyria afflicts a large kindred in Chester that stems from a marriage in 1896 that has produced 200 descendants; this is the largest porphyric kindred to be identified in the United Kingdom. Six members aged 51 or under died from the condition over the past eight years. The diagnosis of porphyria was overlooked in some as the symptoms may mimic those of other acute illnesses, so that incomplete or incorrect death certificates have been issued. Psychosis, hypertension, and renal complications are particularly common. The porphyric members of the kindred show a previously undescribed hereditary disorder in which the characteristic enzymatic defects of acute intermittent porphyria and variegate porphyria coexist in the same subject. Acute porphyria is poorly understood by hospital and general practitioners, and this has caused anxiety in the kindred. A register of the kindred has been established, and families at risk should be offered biochemical screening, education, and genetic counselling.
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PMID:Chester porphyria: a clinical study of a new form of acute porphyria. 308 Nov 25

Hereditary coproporphyria (Hepatic coproporphyria: HCP); HCP is the rarest and least recognized among hepatic porphyrias and is characterised by an excess of faecal and urinary excretion of coproporphyrin (mainly isomer III). The deficiency is in coproporphyrinogen oxidase. HCP was first described by Berger and Goldberg in 1955 and was considered an asymptomatic biochemical abnormality. It later became evident that HCP could provoke acute attacks similar to those of acute intermittent porphyria (AIP) and variegate porphyria (VP). Such episodes are often provoked by barbiturates, sulphonamides and other drugs, and include automatic symptoms (hypertension, tachycardia, abdominal pain, constipation), central (epileptic seizures, mental disturbances) and peripheral nervous system dysfunction. During acute attacks, urinary ALA (delta-aminole-vulinic acid) and PBG (porphobilinogen) are elevated just as in AIP and VP, however, a marked elevation of faecal COPRO (coproporphyrin) is diagnostic of HCP. Laparoscopic finding of our case showed a map-like appearance of the liver surface with slightly depressed dark-bluish areas and reddish-brown areas. The liver biopsy specimen showed red fluorescence under ultraviolet light. On HE staining, hydropic degeneration of the hepatocytes and many brown granules in the hepatocytes were seen. A part of the granules stained positive for iron. Schmorl's stain showed many needle-shaped crystallines. Erythropoietic coproporphyria (ECP); Heilmeyer and Clotten have described that elevated PROTO (protoporphyrin) and COPRO were found in the RBC of the patient. Topi et al. described two brothers with cutaneous photosensitivity similar to that of erythropoietic protoporphyria, but with elevated RBC PROTO and COPRO III in both. Very little is known about this disease.
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PMID:[Hereditary coproporphyria (Hepatic coproporphyria), Erythropoietic coproporphyria]. 761 59

A 23-year-old man with epilepsy and a past history of abdominal pain and ileus, developed hypertension and arm and bulbar weakness when valproic acid and carbamazepine were reinitiated. Electrophysiologic studies demonstrated a peripheral neuropathy with features of axonal degeneration and demyelination. Axonal degeneration was documented by sural nerve biopsy. Markedly elevated urinary delta-aminolevulinic acid and porphobilinogen indicated a diagnosis of acute porphyria. Other laboratory studies were most consistent with hereditary coproporphyria. Motor function improved considerably but incompletely over 1 year. An acute, primarily motor neuropathy can occur in several forms of porphyria, including acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria, sometimes even in the absence of concomitant gastrointestinal symptoms.
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PMID:Acute peripheral neuropathy due to hereditary coproporphyria. 800 8

Four types of hepatic porphyria (acute intermittent porphyria; hereditary coprophorphyria; variegate porphyria; delta-aminolevulinate dehydratase deficiency porphyria) present clinically with an identical neurological syndrome. Symptoms include severe abdominal pain, vomiting, constipation, hypertension, tachycardia, and bladder dysfunction. These symptoms have been ascribed to autonomic neuropathy. Other symptoms are motor weakness and sensory involvement, which correlate with peripheral axonal neuropathy, and mental symptoms occurring without clear morphological findings in the cerebrum. The pathogenetic mechanisms which lead to the neurological dysfunction have remained poorly understood, partly due to the lack of a suitable animal model of these rare disorders. Two hypotheses, the possible neurotoxicity of delta-aminolevulinate (ALA) and heme deficiency in nervous tissue are discussed and corresponding data from porphobilinogen-deaminase deficient mice are presented. The present evidence suggests that multiple mechanisms interact in causing the varied symptoms, including ALA interaction with GABA receptors, altered tryptophan metabolism, and possibly heme depletion in nerve cells.
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PMID:Acute porphyrias: pathogenesis of neurological manifestations. 951 77

Three hepatic porphyrias--acute intermittent porphyria, hereditary coproporphyria and variegate porphyria--are characterized by episodic acute attacks that consist of various neuro-psychiatric symptoms and signs, such as abdominal pain, vomiting, constipation, hypertension and tachycardia associated with increased excretion of porphyrins and porphyrin precursors. Peripheral neuropathy is manifested as pain in the extremities, and it may progress to a severe motor neuropathy. Measurement of porphobilinogen in the urine gives a prompt diagnosis during acute attacks. Attacks are often induced by precipitating factors such as drugs, alcohol, infection, fasting or changes in sex-hormone balance, and they should be eliminated when a patient is treated during an attack. Heme, the end biosynthetic product, is the most effective therapy for restoration of porphyrin biosynthesis to normal, and it is usually infused at 3 mg/kg daily for 4 days. Adequate calories are necessary and parenteral nutrition with carbohydrates may be necessary. Attacks may also require therapy for hypertension, pain and epileptic seizures. Strict avoidance of all precipitating factors may not be necessary in the asymptomatic phase.
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PMID:Management of the acute porphyrias. 963 23

Resistance to thyroid hormone (RTH) is usually inherited in a dominant fashion, and is characterized by elevated serum thyroid hormone levels and failure to suppress pituitary secretion of thyroid-stimulating hormone, with variable refractoriness to hormone action in peripheral tissues. Two major forms of the disorder are recognized: asymptomatic individuals with generalized resistance (GRTH) and patients with thyrotoxic features suggesting predominant pituitary resistance (PRTH). In over 100 families with GRTH or PRTH, we have identified heterozygous mutations in the thyroid hormone receptor beta isoform (TRbeta), which localize to three regions (amino acids 234-282, 310-353 and 429-461) of the hormone-binding domain of the receptor. The mutant receptors are transcriptionally impaired, due either to reduced ligand binding or to attenuated interaction with co-activators, and inhibit wild-type TR action in a dominant-negative manner. In the TRbeta crystal structure, most RTH mutations cluster around the hormone-binding pocket, with receptor regions that mediate functions (DNA binding, dimerization, co-repressor recruitment) required for dominant-negative activity being devoid of natural mutations. The pathogenesis of variable tissue resistance is not fully understood, but may be related to the differing tissue distributions of TRalpha and TRbeta, and to variable dominant-negative activity of mutant receptors on different target genes. The nuclear receptor peroxisome-proliferator-activated receptor gamma (PPARgamma) regulates adipogenesis and mediates the action of thiazolidinediones - novel anti-diabetic agents which enhance tissue insulin sensitivity. The PPARgamma gene was screened in 85 subjects with severe insulin resistance, and two different heterozygous receptor mutations (P467L and V290M) were identified in three affected individuals. The PPARgamma mutants are markedly transcriptionally impaired due to altered ligand binding and co-activator recruitment. Analogous to RTH, they inhibit the function of wild-type PPARgamma when co-expressed, and such dominant-negative inhibition is linked to their ability to silence basal gene transcription via aberrant interaction with co-repressors. In addition to insulin resistance, all three affected subjects developed Type II diabetes mellitus and hypertension at an unusually early age. Our findings provide compelling evidence that PPARgamma is important in the control of insulin sensitivity, glucose homoeostasis and blood pressure in humans. Future studies aim to elucidate the mechanism by which this receptor regulates insulin action and vascular tone.
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PMID:Resistance to thyroid hormone, and peroxisome-proliferator-activated receptor gamma resistance. 1135 59

In this paper a case of 46-year-old woman suffering from the acute intermittent porphyria (AIP) was presented. She developed the chronic renal failure due to the hypertension, reccurent urinary tract infections and neurogenic urinary bladder following the autonomic neuropathy. The patient eventually died in spite of haemodialysis. Skin lesions observed in the last stage of the disease could be an evidence of the possible conversion of AIP in variegate porphyria (VP). However, this suspicion is only the hypothesis due to the lack of the adequate enzymatic lab tests.
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PMID:[Acute intermittent porphyria coexisting with chronic postinfectious renal failure]. 1567 71

The acute or inducible hepatic porphyrias comprise four inherited disorders of heme biosynthesis. They usually remain asymptomatic for most of the lifespan of individuals who inherit the specific enzyme deficiencies but may cause life-threatening attacks of neurovisceral symptoms. Failure to consider the diagnosis frequently delays effective treatment, and inappropriate diagnostic tests and/or mistaken interpretation of results may lead to misdiagnosis and inappropriate treatment. The four disorders are ALA dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Other conditions that clinically and biochemically may mimic acute porphyria include lead poisoning and hereditary tyrosinemia type I. The diagnosis of one of these acute porphyric syndromes should be considered in many patients with otherwise unexplained abdominal pain, severe constipation, systemic arterial hypertension, or other characteristic symptoms. Critical to the rapid diagnosis of the three most common of these disorders is demonstration of markedly increased urinary porphobilinogen (PBG) in a single-void urine specimen. The treatment of choice for all but mild attacks of the acute porphyrias is intravenous hemin therapy, which should be started as soon as possible. Intravenous glucose alone is recommended only for mild attacks (no weakness or hyponatremia) or until hemin is available.
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PMID:Neurovisceral porphyrias: what a hematologist needs to know. 1630 55


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