Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic work-up is useful for the identification of a primary myopathy. However, even sophisticated genetic methods may fail to detect the underlying cause of myopathy as in the following case. The patient is a 52-year-old female with a history of epilepsy, arterial hypertension, atrial flutter requiring cardioversion, ablation, and anticoagulation, coronary heart disease, hyperlipidemia, and hyper-CKemia. At age 52 years, she was referred for heart failure due to ischemic cardiomyopathy requiring appropriate medication and implantation of an ICD. During hospitalization she developed acute muscular respiratory failure requiring mechanical ventilation. Genetic panels for myopathy, neuropathy, and cardiomyopathy revealed variants of unknown significance in the HNRNPDL and SETX genes respectively. Clinical presentation and muscle biopsy, however, suggested metabolic myopathy. Acute muscular respiratory failure may require traditional diagnostic work-up for primary myopathy and long-term invasive and non-invasive ventilation. Panel investigations not necessarily lead to a conclusive diagnosis. The multisystem nature of the condition rather suggests a metabolic defect than LGMD-1G or fALS as genetic findings suggested.
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PMID:Variants in HNRNPDL and SETX Not Necessarily Indicate Familial Amyotrophic Lateral Sclerosis or Limb Girdle Muscular Dystrophy 1G in Acute Muscular Respiratory Failure. 3236 94

We report a case of severe sensory-motor axonal neuropathy on the lower extremities associated with diabetic ketoacidosis (DKA). A sixteen-year-old boy developed coma and admitted to our hospital. We diagnosed him with DKA based on remarkable hyperglycemia, severe acidosis with hyperketonemia. Intensive glycemic control with insulin was immediately started. He had complications of heart failure, rhabdomyolysis, and renal failure, which required intensive care including mechanical ventilation and hemodialysis. When recovered from the critical condition, he noticed severe weakness, numbness, and pain on the lower limbs, and urinary retention. On nerve conduction studies, both motor and sensory action potentials were absent. Serum anti-ganglioside antibodies were negative. Albuminocytologic dissociation was evident in the cerebrospinal fluid. MRI study revealed marked gadolinium enhancement of the cauda equina. After high-dose intravenous immunoglobulin treatment, he was relieved from leg pain, but the leg weakness and bladder bowel dysfunction did not show immediate improvement. It took approximately six months until he became able to stand and walk using ankle orthosis. Acute neuropathy is a rare complication of diabetes mellitus. Painful neuropathy is known to emerge in association with diabetic treatment, but it seldom causes severe motor disturbance. On the other hand, motor-dominant polyneuropathy has been reported to occur acutely along the treatment of DKA and hyperosmolar hyperglycemia syndrome (HHS). Present case and previous cases with DKA and HHS suggest that rapid correction of glucose level is one of the underlying factors of acute neuropathy related with diabetic treatment.
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PMID:[Severe sensory-motor axonal neuropathy following diabetic ketoacidosis]. 3277 97

ATTR amyloidosis is caused by systemic deposition of transthyretin (TTR) and comprises ATTRwt (wt for wild-type) amyloidosis, ATTRv (v for variant) amyloidosis, and acquired ATTR amyloidosis after domino liver transplantation. ATTRwt amyloidosis has classically been regarded as cardiomyopathy found in the elderly, whereas carpal tunnel syndrome has also become a major initial manifestation. The phenotypes of ATTRv amyloidosis are diverse and include neuropathy, cardiomyopathy, and oculoleptomeningeal involvement as the predominant features, depending on the mutation and age of onset. In addition to variant TTR, the deposition of wild-type TTR plays a significant role, even in patients with ATTRv amyloidosis. The formation of amyloid fibrils tends to occur in association with the basement membrane. The thickening or reduplication of the basement membrane surrounding endoneurial microvessels, which is similar to diabetic neuropathy, is observed in ATTRv amyloidosis, suggesting that common mechanisms, such as an accumulation of advanced glycation end products, may participate in the disease process. In addition to direct damage caused by amyloid fibrils, recent studies have suggested that the toxicity of nonfibrillar TTRs, such as TTR oligomers, participates in the process of tissue damage. Although liver transplantation has been performed for patients with ATTRv amyloidosis since 1990, late-onset patients were not eligible for this treatment. However, as the efficacy of orally administered tafamidis and diflunisal, which stabilize TTR tetramers, was suggested in the early 2010s, such late-onset patients have also become targets for disease-modifying therapies. Additionally, recent studies of small interfering RNA (patisiran) and antisense oligonucleotide (inotersen) therapies have demonstrated the efficacy of these gene-silencing agents. A strategy for monitoring patients that enables the choice of an appropriate treatment from comprehensive and long-term viewpoints should be established. As many patients with ATTR amyloidosis are aged and have heart failure, they are at increased risk of aggravation if they are infected by SARS-CoV2. The optimal interval of evaluation should also be considered, particularly in this COVID-19 era.
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PMID:Transthyretin Amyloidosis: Update on the Clinical Spectrum, Pathogenesis, and Disease-Modifying Therapies. 3294 78

ATTR amyloidosis is caused by systemic deposition of transthyretin (TTR) and comprises ATTRwt (wt for wild-type) amyloidosis, ATTRv (v for variant) amyloidosis, and acquired ATTR amyloidosis after domino liver transplantation. ATTRwt amyloidosis has classically been regarded as cardiomyopathy found in the elderly, whereas carpal tunnel syndrome has also become a major initial manifestation. The phenotypes of ATTRv amyloidosis are diverse and include neuropathy, cardiomyopathy, and oculoleptomeningeal involvement as the predominant features, depending on the mutation and age of onset. In addition to variant TTR, the deposition of wild-type TTR plays a significant role, even in patients with ATTRv amyloidosis. The formation of amyloid fibrils tends to occur in association with the basement membrane. The thickening or reduplication of the basement membrane surrounding endoneurial microvessels, which is similar to diabetic neuropathy, is observed in ATTRv amyloidosis, suggesting that common mechanisms, such as an accumulation of advanced glycation end products, may participate in the disease process. In addition to direct damage caused by amyloid fibrils, recent studies have suggested that the toxicity of nonfibrillar TTRs, such as TTR oligomers, participates in the process of tissue damage. Although liver transplantation has been performed for patients with ATTRv amyloidosis since 1990, late-onset patients were not eligible for this treatment. However, as the efficacy of orally administered tafamidis and diflunisal, which stabilize TTR tetramers, was suggested in the early 2010s, such late-onset patients have also become targets for disease-modifying therapies. Additionally, recent studies of small interfering RNA (patisiran) and antisense oligonucleotide (inotersen) therapies have demonstrated the efficacy of these gene-silencing agents. A strategy for monitoring patients that enables the choice of an appropriate treatment from comprehensive and long-term viewpoints should be established. As many patients with ATTR amyloidosis are aged and have heart failure, they are at increased risk of aggravation if they are infected by SARS-CoV2. The optimal interval of evaluation should also be considered, particularly in this COVID-19 era.
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PMID:Transthyretin Amyloidosis: Update on the Clinical Spectrum, Pathogenesis, and Disease-Modifying Therapies. 3298 32

This review takes an inclusive approach to microvascular dysfunction in diabetes mellitus and cardiometabolic disease. In virtually every organ, dynamic interactions between the microvasculature and resident tissue elements normally modulate vascular and tissue function in a homeostatic fashion. This regulation is disordered by diabetes mellitus, by hypertension, by obesity, and by dyslipidemia individually (or combined in cardiometabolic disease), with dysfunction serving as an early marker of change. In particular, we suggest that the familiar retinal, renal, and neural complications of diabetes mellitus are late-stage manifestations of microvascular injury that begins years earlier and is often abetted by other cardiometabolic disease elements (e.g. hypertension, obesity, dyslipidemia). We focus on evidence that microvascular dysfunction precedes anatomic microvascular disease in these organs as well as in heart, muscle and brain. We suggest that early on, diabetes mellitus and/or cardiometabolic disease can each cause reversible microvascular injury with accompanying dysfunction, which in time may or may not become irreversible and anatomically-identifiable disease (e.g., vascular basement membrane thickening, capillary rarefaction, pericyte loss, etc.). Consequences can include the familiar vision loss, renal insufficiency, and neuropathy, but also heart failure, sarcopenia, cognitive impairment, and escalating metabolic dysfunction. Our understanding of normal microvascular function and early dysfunction is rapidly evolving, aided by innovative genetic and imaging tools. This is leading, in tissues like the retina, to testing novel preventive interventions at early, reversible stages of microvascular injury. Great hope lies in the possibility that some of these interventions may develop into effective therapies.
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PMID:Microvascular Dysfunction in Diabetes Mellitus and Cardiometabolic Disease. 3312 68

Ogilvie syndrome or intestinal pseudo-obstruction is a clinical syndrome characterized by autonomic imbalance affecting peristalsis of colon leading to obstructive signs and symptoms. The etiologies commonly implicated are drugs affecting the cholinergic system, narcotics, electrolyte imbalance, severe sepsis, cancer, major surgery, and renal and cardiac failure. Ogilvie syndrome secondary to chemotherapy is a very rare phenomenon with very few reports in the literature. Cisplatin-induced neuropathy has been reported to occur when the cumulative dose exceeds 360 mg/m<sup>2</sup>. It manifests predominantly as peripheral sensory neuropathy with autonomic neuropathy occurring very rarely in a subset of patients. All the reported cases to date who presented with autonomic dysfunction secondary to cisplatin also had peripheral sensory neuropathy. Herein, we report a case of metastatic nonseminomatous germ cell tumor treated with cisplatin based regimen, who presented with severe intestinal pseudo-obstruction when the cumulative dose exceeded 400 mg/m<sup>2</sup> without any other manifestation of neuropathy. To our knowledge this is the first such case reported in the literature.
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PMID:Ogilvie Syndrome in a Refractory Germ Cell Tumor Treated with Vinblastine, Ifosfamide and Cisplatin Regimen. 3317 81


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