Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 62-year-old African-American man with a history of hypertension, asthma, and prostate cancer, but no prior history of haemophilia presented with gross haematuria following a motor vehicle accident. Coagulation studies revealed a prolonged partial thromboplastin time. Subsequent mixing study and factor analysis confirmed factor VIII (FVIII) deficiency. The patient subsequently developed a knee haemarthrosis associated with persistent haematuria and a profoundly elevated FVIII inhibitor titre. Fresh frozen plasma was initiated upon presentation. Once FVIII inhibitor was discovered, immunosuppressive agents were started. Concurrent treatment with acute bypass agents including porcine FVIII, and recombinant human factor VIIa (rFVIIa;NovoSeven), was also given. Ultimately, anti-inhibitor coagulant complex (Autoplex T) was administered, stabilizing the haematuria and haemarthrosis. There was no additional bleeding 6 months after the last dose of anti-inhibitor coagulant complex. This case is consistent with others in which anti-inhibitor coagulant complex therapy was used successfully to manage patients with serious acute bleeding problems who are found to have acquired inhibitors to factor VIII.
Haemophilia 2002 Sep
PMID:Anti-inhibitor coagulant complex for the rescue therapy of acquired inhibitors to factor VIII: case report and review of the literature. 1219 81

Haematuria is common among persons with haemophilia (PWH), but its long-term effects on the kidney and renal function are not well defined. In addition, infection with human immunodeficiency virus (HIV) or hepatitis C, or exposure to nephrotoxic agents as therapy for these infections may place PWH at increased risk for renal disease. To examine factors associated with chronic renal disease (CRD) and acute renal disease (ARD) in PWH, we analysed data collected from the medical records of 3422 males with haemophilia living in six US states from 1993 to 1998. Renal disease cases were ascertained from among 2075 persons who were hospitalized at least once over the 6-year period. Of these, 60 (2.9%) were diagnosed during one or more hospitalizations with either ARD (29/60) or CRD (31/60). In multivariate analyses, we examined associations between renal disease and demographic and clinical factors including age, race, haemophilia type and severity, hypertension, diabetes, history of recent renal bleeds, presence of an inhibitor, and infection with hepatitis C or HIV. HIV infection and hypertension were strongly associated with both ARD and CRD. PWH who had ARD were also more likely to have an inhibitor than those without this diagnosis. PWH who had CRD were more likely to be older and non-white and to have had a recent admission for a kidney bleed than those without diagnosed CRD. In summary, we found that HIV infection and haemophilia-related factors including inhibitors and kidney bleeds were associated with renal disease in a cohort of males with haemophilia.
Haemophilia 2003 Nov
PMID:Renal disease among males with haemophilia. 1475 Sep 36

There have been conflicting reports in the literature about the protective effect of hemophilia on the occurrence of ischemic heart disease (IHD). Circulatory disease has been reported as the second most common cause of death in persons with hemophilia in the United States. In addition to diabetes and hypertension, high levels of FVIII, as may occur during factor concentrate infusions, may increase IHD risk in this population. To estimate the prevalence of heart disease and examine factors associated with IHD and other heart diseases among persons with hemophilia, we analyzed data collected from the medical records of 3,422 males with hemophilia living in six U.S. states from 1993 to 1998. Heart disease cases were ascertained from among 2,075 persons who were hospitalized at least once during the 6-year period. Of these, 48 were diagnosed with IHD and 106, with other types of heart disease. The age-specific prevalence of IHD ranged from 0.05% in those under 30 years to 15.2% in those 60 years or older. Hospital discharge rates in males with hemophilia with IHD and other types of heart disease were lower compared to rates in age-matched U.S. males. In our cohort, as in the general population, IHD was independently associated with age, hypertension, diabetes, and hyperlipidemia. Other heart diseases were associated with HIV infection, hypertension, hemophilia B, and diabetes. In summary, persons with hemophilia have unique risk factors such as infusion of factor concentrates and infection with HIV that may predispose them to heart disease as their life expectancy increases.
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PMID:Prevalence and risk factors for heart disease among males with hemophilia. 1584 61

Prophylaxis with von Willebrand factor (VWF)-containing concentrates is considered to be a potential approach for patients with von Willebrand disease (VWD) and severe bleeding tendency. We report the case of a 57-year-old man with type 3 VWD and a history of recurrent melaena. Bleeding frequency and severity had progressively increased and the patient showed chronic anaemia and persistent haemoglobin in the stools. Endoscopic examinations revealed multiple vascular mucosal abnormalities (MVA) of the stomach and large bowel. Photocoagulation of some actively bleeding lesions and octreotide did not significantly affect his clinical conditions: six red cell transfusions and >400 000 IU of intermediate-purity factor VIII (FVIII) concentrate (Haemate P) on-demand were needed during 2002. Prophylaxis with Haemate P 40 IU kg(-1) (102 IU kg(-1) VWF:RCo) thrice weekly was associated with improvement of his mean haemoglobin levels, cessation of clear-cut melaena and red cell transfusions and reduction of total Haemate P requirements (-20% over 2003-04). Prophylaxis with Haemate P is still ongoing without any adverse event over a 30-month period. Clinical course and pharmacokinetic evaluations led to administer Haemate P each 72-96 h. Possible vascular complications were excluded by a careful clinical follow up, as the patient suffered from arterial hypertension and diabetes mellitus; thrombophilic abnormalities were previously excluded and no signs of abnormal coagulation activation or FVIII:C levels >150% were detected thereafter. Long-term prophylaxis with Haemate P has been shown to be safe, effective (also in terms of quality of life) and cost saving in this patient with severe gastrointestinal bleeding due to MVA and VWD.
Haemophilia 2006 Jan
PMID:Long-term prophylaxis with intermediate-purity factor VIII concentrate (Haemate P) in a patient with type 3 von Willebrand disease and recurrent gastrointestinal bleeding. 1640 82

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening, hereditary disease. The prevalence of ADPKD is more common than Huntington disease, haemophilia, sickle cell disease, cystic fibrosis, myotonic dystrophy and Down syndrome combined. In recent years there have not only been advances in the understanding of the genetic and molecular events involved in ADPKD, but some diagnostic and therapeutic advances have also emerged. In the genetics area, the gene for PKD1 was localised to chromosome 16, is associated with polycystin-2 protein, and found to account for approximately 85% of patients with ADPKD. The gene for PKD2, found in chromosome 4, accounts for approximately 15% of ADPKD, and is associated with the polycystin-2 protein. While these genetic and molecular biology findings have stimulated a great deal of exciting basic research in ADPKD, therapies to decrease morbidity and mortality in ADPKD patients have yet to emerge from these findings. In contrast, the early diagnosis and treatment of hypertension with inhibitors of the renin-angiotensin-aldosterone system have the potential to decrease or prevent left ventricular hypertrophy cardiac complications and slow the progression of the renal disease.
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PMID:Optimal care of autosomal dominant polycystic kidney disease patients. 1688 82

A 66-year-old man with hypertension and hyperlipidemia developed a hemorrhagic stomal ulcer and massive hematoma of the face at 4 and 7 months, respectively, after fundusectomy for early gastric cancer. The diagnosis of acquired hemophilia A was made based on the marked prolongation of activated partial thromboplastin time, an extremely low factor VIII activity, and a very high-titer factor VIII inhibitor. After admission, oral prednisolone and cyclophosphamide were started. In addition, activated prothrombin complex concentrates and recombinant activated factor VII were intravenously administered which successfully controlled his hemorrhage. Only 1 week after the episode of bleeding, however, he complained of abdominal pain accompanied by watery stool with fresh blood. The diagnosis of ischemic colitis was made based on the clinical course and the findings on both CT-scan and colon fiberoscopy. The colitis spontaneously and quickly resolved with conservative observation. To the best of our knowledge, this is the first reported case of ischemic colitis that occurred in an acquired hemophilia patient without simultaneous administration of coagulation factors or antifibrinolytic agents. We should thus pay attention to the possible occurrence of thrombotic events even in acquired hemophilia patients in the presence of risk factors for thrombosis.
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PMID:[Ischemic colitis following the treatment of acute hemorrhage in a patient with acquired hemophilia A]. 1671 66

The rapid advances associated with the Human Genome Project combined with the development of proteomics technology set the bases to face the challenge of human gene therapy. Different strategies must be evaluated based on the genetic defect to be corrected. Therefore, the re-expression of the normal counterpart should be sufficient to reverse phenotype in single-gene inherited disorders. A growing number of candidate diseases are being evaluated since the ADA deficiency was selected for the first approved human gene therapy trial (Blaese et al., 1995). To cite some of them: sickle cell anemia, hemophilia, inherited immune deficiencies, hyper-cholesterolemia and cystic fibrosis. The approach does not seem to be so straightforward when a polygenic disorder is going to be treated. Many human traits like diabetes, hypertension, inflammatory diseases and cancer, appear to be due to the combined action of several genes and environment. For instance, several wizard gene therapy strategies have recently been proposed for cancer treatment, including the stimulation of the immune system of the patient (Xue et al., 2005), the targeting of particular signalling pathways to selectively kill cancer cells (Westphal and Melchner, 2002) and the modulation of the interactions with the stroma and the vasculature (Liotta, 2001; Liotta and Kohn, 2001).
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PMID:Skin gene therapy for acquired and inherited disorders. 1687 66

Joint haemorrhage and subsequent haemophilic arthropathy are significant complications of haemophilia. The pathophysiology involves inflammation and angiogenesis. Cyclo-oxygenase 2 (COX-2) inhibitors have anti-inflammatory, anti-angiogenic and analgesic properties yet do not affect platelet function in the manner of traditional non-steroidal anti-inflammatory drugs. We have previously reported the successful use of rofecoxib in the management of haemophilic arthropathy and currently report our use of celecoxib. A retrospective chart review was conducted of all patients with haemophilia A or B seen at the Children's Hospital of Orange County and treated with celecoxib for chronic synovitis, target joint or pain. Efficacy in chronic synovitis and pain reduction was judged subjectively as effective, partially effective or ineffective. Efficacy in resolution of target joints was judged as effective if the target joint resolved or ineffective if it did not resolve. Twelve patients between 9 and 54 years old were treated for a total of 14 courses of celecoxib treatment. All courses were evaluated for safety and efficacy. Celecoxib was used in eight patients with chronic synovitis, three patients with pain, and in one patient with a target joint on three occasions. A response was noted in seven of eight for synovitis, three of three with pain, but no response in the target joint patient. No serious adverse events including hypertension were observed. This is the first study evaluating celecoxib as adjunctive therapy in haemophilia and suggests that celecoxib is safe and effective in treating chronic synovitis and joint pain similar to the previous study of rofecoxib.
Haemophilia 2006 Sep
PMID:Celecoxib in the treatment of haemophilic synovitis, target joints, and pain in adults and children with haemophilia. 1691 82

Polycystic kidney diseases (autosomal dominant and autosomal recessive) are progressive renal tubular cystic diseases, which are characterised by cyst expansion and loss of normal kidney structure and function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common life- threatening, hereditary disease. ADPKD is more prevalent than Huntington's disease, haemophilia, sickle cell disease, cystic fibrosis, myotonic dystrophy and Down's syndrome combined. Early diagnosis and treatment of hypertension with inhibitors of the renin-angiotensin-aldosterone system (RAAS) and its potential protective effect on left ventricular hypertrophy has been one of the major therapeutic goals to decrease cardiac complications and contribute to improved prognosis of the disease. Advances in the understanding of the genetics, molecular biology and pathophysiology of the disease are likely to facilitate the improvement of treatments for these diseases. Developments in describing the role of intracellular calcium ([Ca(2+)](i)) and its correlation with cellular signalling systems, Ras/Raf/mitogen extracellular kinase (MEK)/extracellular signal-regulated protein kinase (ERK), and interaction of these pathways with cyclic adenosine monophosphate (cAMP) levels, provide new insights on treatment strategies. Blocking the vasopressin V(2) receptor, a major adenylyl cyclase agonist, demonstrated significant improvements in inhibiting cytogenesis in animal models. Because of activation of the mammalian target of rapamycin (mTOR) pathway, the use of sirolimus (rapamycin) an mTOR inhibitor, markedly reduced cyst formation and decreased polycystic kidney size in several animal models. Caspase inhibitors have been shown to decrease cytogenesis and renal failure in rats with cystic disease. Cystic fluid secretion results in cyst enlargement and somatostatin analogues have been shown to decrease renal cyst progression in patients with ADPKD. The safety and efficacy of these classes of drugs provide potential interventions for experimental and clinical trials.
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PMID:Potential pharmacological interventions in polycystic kidney disease. 1803 88

In countries with a good standard of health care, intracranial haemorrhage (ICH) during the neonatal period affects 3.5-4.0% of all haemophilia boys, which is considerably (40-80 times) higher than expected in the normal population. ICHs are also frequent after the neonatal period, affecting 3-10% of the haemophilia population who are mainly treated on demand. The risk is higher in inhibitor patients. Spontaneous haemorrhage is reported more frequently than trauma-induced haemorrhage in most studies. The prevalence of ICH in patients treated with a prophylactic regimen is not known. Although more frequent in younger patients, a substantial proportion of ICH occur in adults, suggesting that general risk factors because of age, such as hypertension, are increasingly important as the haemophiliac gets older. Some studies have reported a substantial proportion of ICH affecting patients with milder forms of haemophilia. The risk of ICH has to be considered when discussing treatment strategies for haemophilia patients.
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PMID:Intracranial haemorrhage in haemophilia A and B. 1808 90


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