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Prevention of restenosis after percutaneous coronary intervention: the continuing challenge.

Percutaneous coronary intervention with angioplasty and stenting is well established in the treatment of coronary artery disease. However, the many advances in technique and equipment over the last couple of decades have yet to significantly reduce the incidence of restenosis. This Achilles' heel has necessitated frequent re-interventions and also introduced a new iatrogenic disease of in-stent restenosis. Brachytherapy and coated stents may be the answer to this difficult problem. Many papers have been published in the last few years on these two new modalities of treatment, and we review the evidence available so far. Early results show that brachytherapy significantly reduce the incidence of restenosis when used in restenotic lesions, and coated stents significantly reduce restenosis in de novo lesions. This early promise of brachytherapy and coated stents, if confirmed in longer-term studies, will represent a breakthrough in the battle against restenosis and may dramatically change the practice of interventional cardiology in the near future.

Adult↗

Dermatologic therapy of chronic genital disease.

The adaptation of dermatology for the genital area requires several modifications of standard therapy. This unique area produces issues of both psychological sensitivity and unique environmental factors of constant moisture, warmth, and friction. These issues become far more important when symptoms are chronic. Recognition of normal variants, the multifactorial nature of many genital symptoms, and the avoidance of creating secondary iatrogenic disease are all important.

Chronic Disease↗

The effect of dementia on acute care in a geriatric medical unit.

Treatment of dementia costs billions of dollars in long-term care and community services every year. Dementia also burdens the acute care system and may contribute to financial problems for hospitals serving large numbers of demented elderly. In a specialized geriatric medical unit devoted to acute care of the frail elderly, Alzheimer's disease and vascular and mixed dementias afflicted 63% of inpatients and were associated with excess consumption of nursing resources, complications of treatment, nosocomial infections, lengthy hospitalizations, and financial losses to the hospital. Due in part to the effects of dementia on mobility, continence, and nutrition, demented patients suffered more frequently from life-threatening infections, sepsis, iatrogenic disease, and prolonged hospital stays. Hospital losses were 75% higher for demented patients than for nondemented patients. Dementia affected the majority of acute care patients in this study. However, it was rarely coded as an admitting diagnosis, even though it may have been the proximate cause of the medical morbidity which led to the acute hospitalization. In addition, despite the significant impact of dementia on the hospital course and costs, it was a factor in hospital reimbursement in less than one third of cases. The results indicate that dementia was not considered to be an acute diagnosis, nor was it recognized as a complex medical illness. The impact of dementia on acute hospitalization, including the mechanisms by which dementia prolongs the hospital stay, requires further investigation.

Activities of Daily Living↗

Fetal and neonatal liver disease.

The pathology of fetal and neonatal liver disease is reviewed and particular emphasis is laid on discriminating between diseases of known aetiology or of genetic importance and idiopathic disorders. These are discussed in relation to the particular metabolic differences between the fetal an neonatal liver and the adult liver. Common disorders such as rhesus isoimmunization are only touched on in respect of their effects on the metabolic function of the liver. The importance of iatrogenic disease in this age group is stressed.

Bile Acids and Salts↗

Neuropathologic verification of Creutzfeldt-Jakob disease in the exhumed American recipient of human pituitary growth hormone: epidemiologic and pathogenetic implications.

Beginning at age 12, a boy with idiopathic hypopituitarism was treated with cadaver pituitary-derived human growth hormone during the period from 1963 to 1969. Fifteen years after the last treatment, the then 32-year-old man developed Creutzfeldt-Jakob disease (CJD). The illness was atypical in showing predominantly cerebellar signs, little mental deterioration, and no abnormal movements or periodic EEG activity. Examination of the embalmed brain, 7 months after interment, revealed the characteristic changes of CJD mainly in the cerebellum and basal ganglia. This case establishes the contamination of at least two American lots of human growth hormone and, together with other cases of iatrogenic disease, suggests that virus enters the brain from the blood, rather than along neural pathways.

Animals↗

Feline injection site sarcomas.

Injection site sarcomas in cats have been the topic of more than 40 articles and over 20 scientific abstracts as well as multiple letters to veterinary journals, articles in the popular press, and Internet-based web sites. With the level of discussion that has surrounded this tumor entity, one might expect that great strides have been made in determining the etiology, epidemiology, and preferred treatment options for this disease. Nearly half of the publications on this subject are review articles, however, and that alone indicates both the high level of interest and the lack of information in this situation. This article summarizes the development of our current understanding of this tumor with regard to areas of research into the cause of injection site sarcomas, epidemiology, and the current standard of care for treatment of this iatrogenic disease.

Animals↗

Unusual aspects of urinary calculi in children.

Urinary calculous disease is unusual in children in the United States. During the last 5 years (1972 to 1977) we have examined and treated 35 children with urinary calculi. The predisposing factors to calculus formation have been established in 20 children. Metabolic screening, although mandatory, has proved unrewarding in the evaluation of children with urinary calculi. Obstructive uropathy, immobilization, urinary stasis and infection, previously undiagnosed urologic anomalies, steroid therapy, milk-alkali syndrome, iatrogenic disease and endemic disease have contributed to stone formation. The management of children with urinary calculi generally parallels that of adults but reflects a need for caution when performing transurethral extraction of lower ureteral calculi. Reduction in dairy product intake, fluid diuresis and frequent changes in position may provide adequate prophylaxis against urinary calculi in children who must be immobilized.

Adolescent↗

Review: pathology of variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease that results from exposure to the bovine spongiform encephalopathy (BSE) agent, probably by the oral route. The pathological features of vCJD are unique, with extensive involvement of lymphoid tissues in addition to the central nervous system. This article reviews the histopathology and biochemistry of vCJD, emphasising diagnostic features and indicating several areas of active research. The widespread distribution of infectivity in lymphoid tissues in vCJD has lead to concerns over the possibility of iatrogenic disease transmission by contaminate surgical instruments, or by blood transfusion. vCJD has so far only occurred in individuals within a genetic subset defined by the natural polymorphism at codon 129 in the prion protein gene. It remains uncertain if this disease will occur in other genetic subgroups within the population. Continuing surveillance of vCJD in the UK and other countries in which BSE has been identified will be necessary for future estimations of disease numbers worldwide.

Amyloid↗

Preoperative patient evaluation.

Screening laboratory testing seemed logical: if you could spot abnormalities before overt disease occurred, you could prevent disability. But it has not worked out that way for the majority of preoperative tests. We are now spending over $40 billion a year in the United States on preoperative testing and evaluation; 60 per cent of it is wasted. This is like saying, "If a little epinephrine is good, more is better." That is wrong in the use of epinephrine and it can be wrong with too much testing. Worse than wasteful, I believe this extra testing is causing iatrogenic disease by pursuit and treatment of borderline and false-positive test results. It is increasing our medicolegal risk and decreasing the efficiency of practice. Fortunately, this history of too much testing can now be turned to our advantage. It provides an arena where we can demonstrate to our constituency, the patient, and our watchdog, the bureaucrat, that we can use inexpensive technology to reduce costs substantially and improve the quality of care.

Diagnostic Tests, Routine↗

Variability of methotrexate pharmacokinetics and pharmacodynamics.

It is apparent that MTX is a useful agent in the treatment of rheumatoid arthritis resistant to first and second line therapies. However, despite its long term use in this disease, considerable uncertainty exists about the basic pharmacokinetics of low dose oral MTX and therefore about its pharmacodynamics. It is probable that when MTX is re-examined with the help of modern analytical technology in a rheumatoid setting that pharmacological insights to the variability in dose-response relationships for efficacy and certain toxicities may emerge. There is still considerable uncertainty of the hepatotoxic potential of MTX. Further investigation of the accumulation of active polyglutamated MTX in liver may throw light on the likelihood of promoting iatrogen disease and perhaps the contribution of oral administration to this problem. Finally, examination of dose-response relationship utilising accurate pharmacokinetics may help to establish guidelines for the safe and effective usage of MTX in rheumatoid arthritis.

Administration, Oral↗

Role of surgery in antibiotic-induced pseudomembranous enterocolitis.

With the increased use of prophylactic and broad-spectrum antibiotics, pseudomembranous colitis has emerged as a significant clinical problem. Management with specific anti-Clostridium difficile therapy (vancomycin or metronidazole) has reduced mortality to less than 2%. Nevertheless, the disease may progress to a fulminant toxic colitis or colonic perforation. Additionally, another subset of patients will present with a dramatic clinical picture, suggesting acute peritonitis, eventuating in unnecessary laparotomy. This report reviews both the medical and surgical literature during the past 15 years of patients treated for pseudomembranous colitis. Analysis of this clinical data has provided us with the opportunity to both define the role of surgery in this disorder and illustrate the necessity for a combined medical and surgical cooperative approach in the early management of this iatrogenic disease.

Enterocolitis, Pseudomembranous↗

Principles of hematotoxicology: laboratory assessment and interpretation of data.

The toxicologic evaluation of the hematopoietic system is part of most preclinical and clinical safety studies and has become routine in monitoring a variety of novel and conventional therapies in humans and animals. As with spontaneous disease, iatrogenic blood dyscrasias may be primary but are frequently secondary to other tissue toxicity. The latter tendency makes this easily accessible tissue particularly useful in monitoring for systemic toxicity, while primary hematotoxicity ranks with liver and kidney effects as important and often limiting complications. Although the principles driving the diagnostic approach to spontaneous (clinical) blood disorders generally apply to preclinical and clinical safety studies, there are important differences, particularly regarding control of variables, feasibility of testing, and interpretation of resulting data. The luxury of studying a homogenous population of subjects free of complicating disease under controlled (uniform) laboratory and environmental conditions allows changes to be defined with greater precision and sensitivity. There are generally more options regarding the assays available and frequency of monitoring. Moreover, the hierarchy of tests applied are influenced by regulatory as well as scientific or problem-driven indications. Finally, interpretation of laboratory findings is usually based on the use of subjects as their own controls (pretreatment and sequential monitoring), comparison to a control population and well-defined reference ranges specific for the population under study, and in accordance with the principles of pathology and internal medicine.

Animals↗

Pediatric ribs: a spectrum of abnormalities.

The manifestations of many congenital and acquired conditions can be seen in the ribs of children. Normal variants are usually clinically insignificant; they are occasionally palpated at clinical examination or detected incidentally at chest radiography. Signs of abnormality can appear in the ribs as variations in number, size, mineralization, and shape. These changes can be focal or generalized. Abnormalities detected in the ribs may be the initial indication of previously unsuspected systemic disease. The ribs can yield important diagnostic clues in the work-up of patients with congenital bone dysplasias, acquired metabolic diseases, iatrogenic conditions, trauma (especially child abuse), infection, and neoplasms. Routine evaluation of the ribs on every chest radiograph is important so that valuable diagnostic data will not be overlooked. The diagnostic information obtained from evaluation of the ribs can help tailor the radiologic and laboratory studies that may be necessary to complete a patient's diagnostic work-up.

Adolescent↗

Survival of patients with SLE admitted to an intensive care unit-a retrospective study.

We examined the demography, reasons for admission and cause of death in systemic lupus erythematosus (SLE) patients admitted to a medical intensive care unit (ICU) over a 7-year period. Fourteen patients were admitted during this period-all were female, 13 were of mixed ethnic ancestry and one a black South African. Of the 14 patients, 12 were admitted as a result of lupus activity, 2 had sepsis as the major cause of admission, although 5 other patients developed infection during their admission. Five patients had a generalised flare of their disease or progressive renal failure. Seven patients were admitted with a variety of lupus-related pathologies. In general the precise cause of death was difficult to determine. Of the 14 patients, 9 had impaired renal function on admission including 1 with sepsis and 1 of the survivors. Three patients (21%) survived, one with respiratory failure due to shrinking lung, a second with an acute flare of SLE and a third with pulmonary emboli. This study demonstrates that lupus in our community may produce life-threatening flares. Although cause of death was not always definitely identified, admission to the ICU was primarily due to active SLE and not sepsis or iatrogenic disease.

Adolescent↗

Ischaemic optic neuropathy.

Ischaemic optic neuropathy is of two types: anterior (AION) and posterior (PION), the first involving the optic nerve head (ONH) and the second, the rest of the optic nerve. Pathogenetically AION and PION are very different diseases. AION represents an acute ischaemic disorder of the ONH supplied by the posterior ciliary artery (PCA), while PION has no specific location in the posterior part of the optic nerve and does not represent an ischaemic disorder of any definite artery. The most important step towards a logical understanding of the underlying causes, clinical features, pathogenesis and rational management of AION, is to understand the basic scientific issues involved; these are discussed in some detail. AION clinically is of two types: (1) that due to giant cell arteritis (arteritic AION: A-AION) and (2) non-arteritic AION (NA-AION). NA-AION, the more common of the two, is one of the most prevalent and visually crippling diseases in the middle-aged and elderly, and is potentially bilateral. NA-AION is a multifactorial disease, with many risk factors collectively contributing to its development. Although there is no known treatment for NA-AION, reduction of risk factors is important in decreasing chances of involvement of the second eye and of further episodes. Our studies have suggested that nocturnal arterial hypotension is an important risk factor for the development and progression of NA-AION. The role of nocturnal arterial hypotension in the pathogenesis of NA-AION and management of nocturnal hypotension is discussed. Potent antihypertensive drugs, when used aggressively and/or given at bedtime, are emerging as an important risk factor for nocturnal hypotension, and there is some evidence that NA-AION may be occurring as an iatrogenic disease in some individuals. A-AION, by contrast, is an ocular emergency and requires immediate treatment with systemic corticosteroids to prevent further visual loss. The clinical parameters which help to differentiate the two types of AION, and their respective management are discussed.

Blood Pressure↗

[Misdiagnoses and mismanagement in thyroid diseases (author's transl)].

Measures prior to diagnosis and treatment already installed were assessed retrospectively in 8501 patients with suspect thyroid disease between the years 1976 and 1979. In 10.5% of these patients there were 11.2% misdiagnosis or wrong treatment. The most common misdiagnoses were hyperthyroidism in euthyroid patients (1.9%), hypothyroidism in euthyroidism (0.8%), non-recognition or non-aspiration of cold nodules (0.9%), missing a goitre (0.6%). Among diagnostic methods the radio-iodine test was reason for a wrong diagnosis most commonly (66%). The TRH-test proved to be least erroneous, technical reasons being the cause of the 9.6% of misdiagnoses. The most common mismanagements were due to lack of prophylaxis of recurrence after goitre operation (1.5%), external irradiation of the thyroid gland with radium or Roentgen rays (0.7%), and during thyroid hormone treatment of goitre (1.3%). Iatrogenic disease existed mainly as factitious hyperthyroidism (0.7%), non-treated hypothyroidism after treatment with radio-iodine of hyperthyroidism (0.1%), and as goitre recurrence due to lack of prophylaxis of recurrence (0.8% of all patients). As every 10th patient was subjected to misdiagnosis or mismanagement, shifting to endocrinological advisory centers may prevent future mismanagement of thyroid disorders.

Berlin↗

Should intramuscular vitamin K prophylaxis for haemorrhagic disease of the newborn be continued? A decision analysis.

Haemorrhagic disease of the newborn is now a rare life threatening disease due to the widespread use of effective prophylaxis with vitamin K at birth. In recent years the continued need for routine prophylaxis has been questioned and alternative strategies proposed. We have reviewed the literature and using techniques of decision analysis, we reaffirm the need for continued prophylaxis. The cost for each life saved by an oral programme is $4500 and $11,000 for intramuscular prophylaxis. The cost to the state of no prophylactic programme is $6.40 per child born and $0.81 for an oral prophylactic programme. It is recommended that the oral route of vitamin K prophylaxis be adopted as it is equally efficacious with the intramuscular route, but cheaper, more consumer acceptable, and has a lower risk of iatrogenic disease.

Administration, Oral↗

Is fibrosing colonopathy an immune mediated disease?

Fibrosing colonopathy, a recently described complication of patients with cystic fibrosis, manifests clinically approximately 7-12 months after starting high dose pancreatic enzyme treatment. Although the pathogenesis of fibrosing colonopathy is unknown, it is highly correlated with pancreatic enzyme dose. In this study, immune mediated factors which may be associated with fibrosing colonopathy were explored. Sera from 14 patients with cystic fibrosis and meconium ileus were collected at diagnosis and then longitudinally for four to five years after enzyme treatment. Sera were analysed for total IgG and antiporcine trypsin IgG using an ELISA assay. Before enzyme treatment, serum antiporcine trypsin IgG concentrations were negligible, at 2.9 (SD 0.3) micrograms/ml. Thirteen patients (93%) developed a significant antibody response to porcine trypsin after starting enzyme treatment, reaching a peak concentration of 69.4 (20.1) micrograms/ml 7-12 months after the introduction of enzymes. Since peak IgG concentrations coincided with published reports of time of onset of symptoms of fibrosing colonopathy, local injury by protease or by immune mediated mechanisms may be responsible for the pathological changes in this iatrogenic disease.

Animals↗