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At least 505 records · Page 28Linked to original sources
PubMed1997

Enalapril-induced anemia in a renal transplant patient.

Side-effects of angiotensin converting enzyme (ACE) inhibitors, such as a slight decrease in hematocrit, are increasingly being reported. A 14-year-old renal transplant patient on enalapril therapy developed anemia with reticulocytosis. She was investigated for other causes of anemia and enalapril therapy was ceased. Her hemoglobin level increased and reticulocyte count decreased after cessation of therapy. No other cause of anemia was found. Although anemia in patients receiving ACE inhibitors such as enalapril has previously been reported, this is the first reported patient who developed anemia associated with mild reticulocytosis and macrocytosis.

Adolescent↗
PubMed2026

A brief history of gene therapy for ornithine transcarbamylase deficiency.

Gene therapy encompasses the use of nucleic acids, including DNA and RNA, as therapeutic agents. This broad category includes approaches that permanently modify the genome to correct pathogenic variants, as well as strategies that restore gene expression without altering genomic DNA. In ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder, the goal of somatic gene therapy is to restore hepatic expression of functional OTC enzyme and thereby reestablish urea cycle activity. Both viral and non-viral delivery platforms have been investigated in preclinical models and clinical studies to achieve therapeutic OTC expression. Despite contemporary medical therapy, individuals with OTC deficiency (OTCD) remain at risk for recurrent hyperammonemia which may result in neurocognitive impairment and reduced quality of life. Novel therapy that restores liver OTC expression and lessens chronic disease burden is highly desired. In this manuscript, we summarize the history of gene therapy development for OTC deficiency, spanning early preclinical investigations to contemporary clinical trials. Although a definitive cure through gene therapy has not yet been achieved, substantial progress has been made toward the development of safe and effective liver-directed nucleic acid therapeutics for this disorder.

Adeno-associated virus vector↗
PubMed2003

Lipid profiles associated with antiretroviral drug choices.

PURPOSE OF REVIEW: In this review we will discuss the recent finding that different drug classes/antiretroviral therapy regimens may differ importantly with respect to their effect on the plasma lipid profile. On the basis of this we will illustrate how such differences, together with knowledge of the presence of other classic coronary artery disease risk factors, open the door for individualized treatment based on criteria in addition to the HIV-1 viral load and CD4 cell count. RECENT FINDINGS: A large proportion of patients using protease inhibitor-based therapy develop insulin resistance and elevated plasma concentrations of LDL-cholesterol, total cholesterol and triglycerides, which has raised the concern that HIV-infected patients treated with antiretroviral therapy may be at an increased risk of developing premature coronary artery disease. Recent findings suggest that the use of non-nucleoside reverse transcriptase inhibitor-based therapy, in particular nevirapine, results in an elevation in HDL-cholesterol, which may be associated with a decreased incidence of coronary artery disease. SUMMARY: It is becoming increasingly important to carry out an adequate coronary artery disease risk assessment in each patient both before and approximately annually after the initiation of antiretroviral therapy. In patients with an already considerable risk of coronary artery disease based on traditional risk factors, particularly when it is expected to be difficult to modify these, starting with either a triple nucleoside reverse transcriptase inhibitor or a non-nucleoside reverse transcriptase inhibitor-based regimen may be the preferred option, given the propensity of such regimens to have either no effect or potentially even beneficial effects on the lipoprotein profile.

Anti-HIV Agents↗
PubMed2004

Gene therapy for type 1 diabetes: a novel approach for targeted treatment of autoimmunity.

It has been difficult to develop therapies that target those T cells initiating and mediating the pathogenesis of autoimmune disease. Indeed, most current treatments indiscriminately affect both the autoreactive T cells and the "good" T cells, putting the patient at risk of compromised immune function. A new approach raises the possibility of targeted therapy for autoimmunity. Transplantation of hematopoietic stem cells modified to express a protective form of MHC class II corrects a defect in central tolerance. This method contrasts with other targeted therapies that attempt to modify peripheral tolerance, which is also defective in type 1 diabetes mellitus.

Animals↗
PubMed1978

A possible ACTH secreting tumour of the pituitary developing in a conventionally treated case of Addison's disease.

A patient with Addison's disease, treated with conventional corticosteroid therapy, developed endocrine and radiological features suggestive of an ACTH secreting pituitary tumour. The negative feedback control of ACTH secretion by the inhibitory effect of hydrocortisone was shown to be preserved although attenuated. Retiming and alteration of corticosteroid therapy reinforced this feedback control, without the need for supraphysiological amounts of steroid, and resulted in the regression of the endocrine disorder.

Addison Disease↗
PubMedDate not supplied

Education in clinical pharmacology at the Rijeka School of Medicine, Croatia.

OBJECTIVE: Irrational drug prescribing is a global problem that exists both in developed and developing countries. Education is the key to improved effectiveness and safety in drug therapy. Development of clinical pharmacology (CP) as an independent discipline at the Rijeka School of Medicine has been slow and unsatisfactory. It was taken only as a part of some postgraduate courses. In the 1995/1996 academic year clinical pharmacology was offered for the first time to sixth year medical students as a non-mandatory subject. The purpose of this study was to emphasize the importance of education in clinical pharmacology at the Rijeka School of Medicine. METHODS: This survey was an uncontrolled study based on responses to questionnaires and a test consisting of written patient problems given to sixth year medical students and to general practitioners who were following a course in clinical pharmacology. RESULTS: The results of the questionnaire showed that both undergraduate and postgraduate students consider that they are not being adequately trained to prescribe drugs rationally and that they believe that clinical pharmacology should become a mandatory subject in the undergraduate medical curriculum. The results of the written patient problem test support this. Both groups of students demonstrated greater skills in solving the diagnostic part than the therapeutic part of the test. A great improvement in the students' ability to solve the therapeutic part was observed after they had completed the CP course. CONCLUSION: The results of this survey underline the necessity of education in clinical pharmacology.

Croatia↗
PubMed1975

Combination chemotherapy and radiation therapy in the treatment of metastatic osteogenic sarcoma.

Fourteen patients with 16 metastatic ostogenic sarcoma lesions were treated with high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR), adriamycin, and pulse high-dose cyclophosphamide combined with radiation therapy. Thirteen of 16 lesions responded. Responses consisted of relief of pain (6/6 patients) in bone lesions, roentgenographic and clinical evidence of decrease in the size of the bone lesions (6/7 patients), and a decrease in the size of pulmonary metastases (2/4 patients). The 2 patients whose pulmonary metastases responded to combined therapy developed pulmonary fibrosis and pneumonitis in the treated areas 3 months after radiation therapy (RT) (1400 and 1600 rads respectively). Of two bulky primary tumors that appeared to respond, both were ultimately found to contain viable tumor; a third less bulky primary tumor appeared to respond more completely. Three smaller metastatic bone lesions that were ultimately biopsied showed no evidence of active tumor. It is concluded that: 1) combination therapy (particularly HDMTX and RT) has an additive effect in controlling osteogenic sarcoma bone lesions, but bulky primary tumors cannot be completely eradicated; 2) although synergistic in treating osteogenic sarcoma, combination therapy can produce enhanced toxicity in surrounding normal lung tissue; and 3) combination therapy is of value in the palliative treatment of metastatic lesions other than that of lung, and in the treatment of small primary bone lesions. However, experience to date does not justify the delay in surgical ablation of a primary lesion in a child who presents without metastatic disease.

Adolescent↗
PubMed2004

Adequate timing of ribavirin reduction in patients with hemolysis during combination therapy of interferon and ribavirin for chronic hepatitis C.

BACKGROUND: Hemolytic anemia is one of the major adverse events of the combination therapy of interferon and ribavirin. Because of ribavirin-related hemolytic anemia, dose reduction is a common event in this therapy. In this clinical retrospective cohort study we have examined the suitable timing of ribavirin reduction in patients with hemolysis during combination therapy. METHODS: Thirty-seven of 160 patients who had HCV-genotype 1b, had high virus load, and received 24-week combination therapy developed anemia with hemoglobin level <10 g/dl or anemia-related signs during therapy. After that, these 37 patients were reduced one tablet of ribavirin (200 mg) per day. After reduction of ribavirin, 27 of 37 patients could continue combination therapy for a total of 24 weeks (group A). However, 10 of 37 patients with reduction of ribavirin could not continue combination therapy because their <8.5 g/dl hemoglobin values decreased to or anemia-related severe side effects occurred (group B). We assessed the final efficacy and safety after reduction of ribavirin in groups A and B. RESULTS: A sustained virological response (SVR) was 29.6% (8/27) in group A and 10% (1/10) in group B, respectively. A 34.4% (12/27) of SVR + biological response in group A was higher than 10% (1/10) in group B ( P = 0.051), with slight significance. With respect to hemoglobin level at the time of ribavirin reduction, a rate of continuation of therapy in patients with > or =10 g/dl hemoglobin was higher than that in patients with <10 g/dl ( P = 0.036). CONCLUSIONS: Reduction of ribavirin at hemoglobin level > or =10 g/dl is suitable in terms of efficacy and side effects.

Anemia, Hemolytic↗
PubMed2001

Depot-leuprolide acetate for treatment of paraphilias: a report of twelve cases.

A new class of antiandrogen medications, gonadotropin-releasing hormone agonists, offers promise in the treatment of the paraphilias, with substantially less side effects than medroxyprogesterone acetate or cyproterone acetate. This paper reports the results of treatment using a depot suspension of leuprolide acetate on 12 patients with paraphilic disorders or with sexual disorders not otherwise specified to suppress or help these individuals control their deviant sexual behavior or impulses. The method involved uncontrolled observations of individuals treated with depot-leuprolide acetate for various lengths of time, from 6 months to 5 years, with the follow-up intervals ranging from 6 months to 6 years. Leuprolide acetate resulted in a significant suppression of deviant sexual interests and behavior as measured by self-report and was well tolerated. However, the three patients who were on long-term therapy developed bone demineralization, suggesting that this is a significant side effect of prolonged therapy. Leuprolide acetate shows promise as a treatment for the paraphilias.

Adult↗
PubMed2002

Management of viral hepatitis C.

The hepatitis C virus was first identified in 1989. It causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Global anti-HCV prevalence is 1-3%. Contaminated blood product, dirty needles and instruments, and injection drug use are the main parenteral routes of transmission. Cultural practices, such as acupuncture, tattoo, body piercing and scarring, also play a role. Universal precaution is the mainstay for prevention before vaccine is developed. Therapy for chronic hepatitis C (CHC) with interferon (IFN) is not satisfactory. Non-response and early relapse reduce sustained response (SR). In 1997, National Institute of Health consensus recommended IFN therapy only for selected patients with compensated CHC, raised ALT and moderate to severe histologic disease activity; 15-20% SR is expected. Major advances in CHC therapy is combination therapy. Ribavirin in combination with IFN significantly increases SR to 30-40%. Even patients with high viral load, genotype 1, significant fibrosis or cirrhosis respond better. EASL and APASL Consensus in 1999 recommended IFN-ribavirin combination as the first line therapy. Recent data on pegylated IFN showed very encouraging results. Combined with ribavirin, 60% SR was achieved. It benefits patients with severe bridging necrosis and also cirrhosis. However, 23-27% of patients receiving combination therapy with either IFN type, experienced adverse events and required therapy discontinuation. Many important issues remained unsolved. Therapy for children, the elderly, patients with comorbidity and extra-hepatic syndromes need to be addressed. Therapy is too expensive and not affordable to the majority of patients in developing countries.

Consensus Development Conferences, NIH as Topic↗
PubMed2005

Gabapentin-induced myopathy in 2 patients on short daily hemodialysis.

Gabapentin is an antiepileptic medication that also has been used for restless legs syndrome. The mechanism of action is unknown. The most commonly reported adverse effects of this medication include somnolence, dizziness, ataxia, fatigue, nystagmus, and tremor. Myalgia has been reported in 2% of gabapentin users compared with 1.9% of patients in placebo-controlled add-on trials. Two patients on short daily hemodialysis therapy developed neuromuscular symptoms and an elevation in creatine kinase levels after starting gabapentin therapy. To our knowledge, this is the first case report of an increase in creatine kinase level after the administration of gabapentin.

Adult↗
PubMed1990

The small intestine: prospects for therapeutic approaches in secretory diarrhoeal diseases.

In many diarrhoeal diseases the intestinal mucosa is stimulated to secrete salt and water. This occurs in diarrhoea as a result of several bacterial toxins, is associated with inflammation and release of inflammatory mediators, and, in many instances, occurs when a neural element is evident. An understanding of the basic underlying mechanisms of secretion could lead to improvements in therapy. Development of vaccines against cholera is showing promise, and a knowledge of the complex field of inflammatory mediators, many of which provoke secretion, provides a foundation for development of more specific and selective anti-inflammatory agents. A detailed understanding of the complicated intracellular second-messenger systems, which are switched on by externally perceived signals, and of the ion transport responses, which are responsible for secretion, may lead to the development of specific anti-diarrhoeal drugs. Meanwhile, the message that oral rehydration therapy for severe diarrhoea, including cholera, is successful, should continue to be widely promulgated and taken up.

Acute-Phase Proteins↗
PubMed1975

[The effectiveness ot thyroid-hormone therapy following goiter-resection].

The effectiveness of a postoperative thyroid-hormone therapy in preventing a goiter-recidiv was investigated two years after goiter-resection. Of 3381 patients with goiter, who were operated on in the years 1964 to 1973 in the Surgical Department of the Krankenhaus Nordwest in Frankfurt/Main, Germany, 129 patients who were operated on in the first six months of 1969, were questioned and examined in a follow-up study. A rezidiv-goiter was found in 4, 6 p.c. of patients. If only palpable recidiv-goiters are taken into consideration 2, 3 p.c.), patients without postoperative thyroid-hormone therapy developed a recidiv goiter twice as often as patients with thyroid-hormone therapy.

Adolescent↗
PubMedDate not supplied

Wegener's granulomatosis and relapsing polychondritis: a case report.

Relapsing polychondritis, a rare disorder characterized by inflammation of cartilaginous tissue, is often associated with vasculitic features. Wegener's granulomatosis is an uncommon form of vasculitis, usually responsive to treatment with cyclophosphamide. A 59-yr-old man with relapsing polychondritis, initially well controlled by corticosteroid therapy, developed pulmonary infiltrates and glomerulonephritis. After pathological confirmation of Wegener's granulomatosis, cyclophosphamide therapy was instituted and remission achieved.

Cyclophosphamide↗
PubMed1995

[Urogenital sinus and cloacal malformations in infancy and childhood: surgical considerations].

The relative rarity of urogenital sinus and cloacal anomalies, the wide range of their anatomical variants furthermore the number of different surgical options makes the successful management of a child with such urogenital abnormality one of the greatest challenges to the paediatric surgeon. Based on their own experience and the literature the authors give a review of embryology, pathology, and diagnosis of urogenital sinus and cloacal abnormality. They detail the new surgical therapy developed by Hendren and Pena which has been adopted in their routine. This therapy has significantly improved the functional outcome and prognosis of these anomalies. Over the past 20 years 25 patients with urogenital sinus and cloacal abnormalities were surgically treated in the author's institute.

Adolescent↗
PubMed1994

Eosinophils activation in post-autologous bone marrow transplanted patients treated with subcutaneous interleukin-2 and interferon-alpha 2A immunotherapy.

We evaluated eosinophils morphology, physical properties and antileukemic activity in autologous bone marrow transplanted (ABMT) patients treated with subcutaneous recombinant interleukin 2 (rIL-2) and recombinant human interferon alpha 2a (IFN alpha) given as outpatient immunotherapy. All patients receiving rIL-2/IFN alpha therapy developed peripheral blood eosinophilia of 20-40% peaking at 2-4 weeks of therapy. While on rIL-2/IFN alpha therapy the eosinophils became hypodense and hypersegmented. The antibody dependent cell-mediated cytotoxic activity (ADCC) of the eosinophils against the human B-cell lymphoma cell line (Raji) was depressed post-ABMT. Prolonged (28 days) in vivo rIL-2/IFN alpha immunotherapy enhanced ADCC activity of the eosinophils and brought them to normal levels. Similarly, rIL-2/IFN alpha immunotherapy enhanced the depressed cytotoxic activity of neutrophils post-ABMT to normal levels. Thus, eosinophils and neutrophils from rIL-2/IFN alpha-treated ABMT recipients may be targeted toward tumor cells by antibody, and express tumoricidal activity. No effect of rIL-2/IFN alpha was observed on monocyte-dependent ADCC activity which remained normal post-ABMT. We conclude that in addition to their effect on lymphocytes, cytokine-mediated immunotherapy consisting of subcutaneous low doses of riL-2 and IFN alpha may mediate their therapeutic effects in cancer therapy by increasing the number of eosinophils and enhancing the antitumor activity of eosinophils and neutrophils, provided that tumor-specific or tumor-associated antibodies are present.

Adolescent↗
PubMed1992

Development of the principle of guided tissue regeneration.

Guided tissue regeneration (GTR) is a new treatment principle in surgical therapy, developed from the result of studies in experimental animals. It implies that only those types of cells with the capacity of producing regeneration are allowed to invade the surgically treated lesion during healing. This is accomplished by the placement of a physical barrier with excludes undesirable types of tissue. Healing of periodontal bony lesions can be obtained predictably by treatment according to the principle of guided tissue regeneration but several studies have suggested that the same principle can also be applied successfully in other fields of dentistry. In implantology, the method has been used for immediate placement of implants into extraction sockets, for healing of peri-implant bony defects and for augmentation of atrophic alveolar ridges.

Alveolar Bone Loss↗
PubMed2002

Evolution of primary protease inhibitor resistance mutations during protease inhibitor salvage therapy.

In order to track the evolution of primary protease inhibitor (PI) resistance mutations in human immunodeficiency virus type 1 (HIV-1) isolates, baseline and follow-up protease sequences were obtained from patients undergoing salvage PI therapy who presented initially with isolates containing a single primary PI resistance mutation. Among 78 patients meeting study selection criteria, baseline primary PI resistance mutations included L90M (42% of patients), V82A/F/T (27%), D30N (21%), G48V (6%), and I84V (4%). Despite the switching of treatment to a new PI, primary PI resistance mutations present at the baseline persisted in 66 of 78 (85%) patients. D30N persisted less frequently than L90M (50% versus 100%, respectively; P < 0.001) and V82A/F/T (50% versus 81%, respectively; P = 0.05). HIV-1 isolates from 38 (49%) patients failing PI salvage therapy developed new primary PI resistance mutations including L90M, I84V, V82A, and G48V. Common combinations of primary and secondary PI resistance mutations after salvage therapy included mutations at amino acid positions 10, 82, and 46 and/or 54 in 16 patients; 10, 90, and 71 and/or 73 in 14 patients; 10, 73, 84, 90, and 46 and/or 54 in 5 patients; 10, 48, and 82 in 5 patients; and 30, 88 and 90 in 5 patients. In summary, during salvage PI therapy, most HIV-1 isolates with a single primary PI resistance mutation maintained their original mutations, and 49% developed additional primary PI resistance mutations. The persistence of L90M, V82A/F/T, G48V, and I84V during salvage therapy suggests that these mutations play a role in clinical resistance to multiple PIs.

Drug Resistance, Microbial↗