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PubMed1988

Peripheral diabetic neuropathy.

Diabetic neuropathy is a common complication of diabetes mellitus with significant morbidity and mortality. Hyperglycemia with its secondary metabolic, vascular, and enzymatic consequences is most likely to be the predominant cause. The clinical manifestations includes a wide range of somatic and autonomic syndromes. Painful diabetic neuropathy may require symptomatic treatment. The precise role of therapies such as continuous subcutaneous insulin therapy and aldose reductase inhibitors remains to be clarified.

Autonomic Nervous System Diseases↗

PubMed1993

Gastroesophageal reflux.

Gastroesophageal reflux is a common disease that accounts for approximately 75% of esophageal pathology. Motility abnormalities of the esophagus and stomach, including an incompetent lower esophageal sphincter, are responsible for pathologic reflux in the majority of patients. Surgical treatment offers the only chance for long-term cure. Obtaining optimal results following surgery of the esophagus is one of the most challenging aspects of modern surgical therapy. Given a precise diagnosis, careful patient selection, critical attention to detail in the perioperative period, and the meticulous performance of the appropriate anti-reflux procedure, long-term success can be assured in more than 90% of patients.

Gastroesophageal Reflux↗

PubMed2000

Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons.

Neurotrophic factors therapy requires their precise delivery to the targeted neuronal population. For this purpose, a wide range of strategies have been developed, and among them the stereotaxic implantation of biodegradable microparticles. To assess the in vivo activity of NGF-releasing PLGA microspheres, unloaded and NGF-loaded microparticles were implanted in the rat brain, near the septal cholinergic neurons, axotomized by an unilateral transection of the fornix-fimbria. Histological analysis at two and six weeks after implantation revealed a non-specific astro- and micro-glial reaction around the microspheres, identical for both unloaded and NGF-loaded microspheres. No neuronal toxicity was noticed, and healthy looking neurons were observed in contact with the microspheres. In the non-treated animals, the percentage of axotomized surviving neurons, when compared to the contralateral intact side, was 31 +/- 2 and 27 +/- 1% at two and six weeks, respectively. Unloaded microspheres caused no protective nor neurotoxic effects (40 +/- 9 and 39 +/- 6% of surviving cholinergic neurons at two and six weeks, respectively). In contrast, NGF-loaded microspheres showed a significant effect on the survival of axotomized cholinergic neurons at two and six weeks after implantation (66 +/- 9 and 61 +/- 5% when compared to the contralateral intact side, respectively). These results show that PLGA microparticles present no neurotoxicity and release sufficient amounts of bioactive NGF to significantly limit the lesion-induced disappearance of cholinergic neurons in the septum during at least six weeks. PLGA microparticles can be used in the future to administer neurotrophic factors in central nervous system disorders.

Animals↗

PubMed2002

Improving the consistency in cervical esophageal target volume definition by special training.

PURPOSE: Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. METHODS AND MATERIALS: A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared. RESULTS: There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training. CONCLUSION: For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.

Education, Medical, Continuing↗

PubMed1996

Radiation therapy of breast carcinoma: confirmation of prescription dose using diodes.

PURPOSE: To quantitate the dose delivered during tangential breast radiation therapy and measure the scatter dose to the contralateral breast for three different breast setup techniques. METHODS AND MATERIALS: A commercial semiconductor diode system is used for dose measurements. The diode characteristics were studied by comparing the diode response against a standard ionization chamber response in a reference configuration. In vivo dose measurements on 11 patients undergoing tangential breast radiation therapy with 6 MV photons were performed. Medial and lateral field entrance and exit doses were measured and compared with the expected values from the treatment planning system. Scatter doses to the contralateral breast for three breast setup techniques were measured and documented as a function of distance from the field edge and various beam modifiers commonly used in breast radiation therapy. RESULTS: The diodes used in this study exhibited excellent linearity, dose reproducibility, and minimal anisotropy. The in-phantom measurements resulted in dose accuracy within +/- 1.5%. Dose measurements on patients resulted in standard deviations of 1.2 and 2.3% for the medial entrance and exit doses and 1.7 and 2.2% for the lateral entrance and exit doses, respectively. In patients, the scatter doses to the opposite breast at a 5 cm perpendicular distance from the medial field edge resulted in cumulative scatter doses of 2.47 to 5.30 Gy from the tangential fields and an additional 0.50 Gy from the supraclavicular or axillary field, if included. CONCLUSION: Quantitative verification of the prescribed daily dose is important in breast radiation therapy to ensure precision in patient setup and accuracy in dose delivery. Diodes provide a convenient way of real-time patient dose verification and are easy to use by the therapists.

Breast Neoplasms↗

PubMed2002

The genetics of congenital heart disease: a point in the revolution.

Extraordinary diagnostic precision and definitive therapies characterize the current management of congenital heart disease, but the state of the art is not perfect; and in spite of tremendous progress in diagnosis and treatment, our understanding of cause is rudimentary. During the past decade, advances in molecular genetics have defined disease gene loci and lead to identification of genes whose mutations cause congenital heart disease. Identification of additional genes and mutations will lead to improved understanding of pathophysiology of cardiovascular disease in the young. Better understanding of pathophysiology and identification of individuals at risk will provide an opportunity to develop preventive strategies. Taken as a whole, the prospect of understanding the genetic basis of congenital heart disease and translating it into improved diagnostic and therapeutic strategies has never been better.

Animals↗

PubMed2003

Diagnosis and management of electrolyte emergencies.

Electrolyte and fluid imbalances are disorders frequently observed in critical care patients. In many instances patients are asymptomatic, but they may also present with neurological alterations, severe muscle weakness, nausea and vomiting or cardiovascular emergencies. Therefore, a pathophysiological understanding of these disorders is necessary for initiating an appropriate therapy. After a precise history-including drug prescriptions-has been obtained from the patient or his/her relatives, determination of the hydration status of the patient and measurement of acid-base status, plasma and urine osmolality and electrolytes are the first steps in the assessment of the disease. Once a diagnosis has been established, great attention has to be paid to the rate at which the disorder is corrected because this-if inappropriate-may cause more severe damage to the patient than the disease itself. This chapter addresses the initial diagnostic and therapeutic steps of the most common electrolyte emergencies.

Calcium↗

PubMed1999

Intracavernous self-injection of prostaglandin E1 in the treatment of erectile dysfunction.

In a three-year follow-up study of 69 patients found that erectile dysfunction (ED) impairs many elderly men's life: up to 25% of the men aged 65 y and 80% of those aged 75 y suffer from erectile dysfunction. The most effective non-surgical treatment of ED is intracavernosal pharmacotherapy, and the most common vasoactive agent currently used is prostaglandin E1 (PGE1). The purpose of this study was to assess the long-term outcome of PGE1 treatment and the patients' overall satisfaction with their sexual life. Sixty-nine patients who had started ICI therapy three years earlier were invited to a control examination. The mean age of the patients was 60.5 y. The patients filled in a questionnaire, which included questions about the use of PGE1 treatment at home. All the patients evaluated their own satisfaction with their erection, ejaculation, orgasm and libido on a visual analytical scale (VAS, 0-100%). A clinical examination was made, and the penile shaft was examined by ultrasonography. Erection with the home dose of PGE1 was estimated by Rigiscan, and the degree of erection was also estimated clinically (grades 0-5) by a doctor. The most common doses of PGE1 used at home were between 10 and 20 m (58%), 46.4% of the patients had discontinued PGE1 therapy, the mean time of using PGE1 was 23.3 months. The mean coital frequency with PGE1 was 2.8 times per month. 34.8% of the patients (24 out of 69) reported that their own spontaneous erections had improved after the beginning of PGE1 therapy. The most common problem was hematomas in 10.1% of the patients (7 out of 69), which, however, were small and did not cause discontinuation of the therapy. There were three instances of priapism (4.3%), and four patients (5.8%) had fibrosis in ultrasonography. The patients' satisfaction with their erection at home was 67.3% with PGE1. The mean coital frequency with PGE1 therapy was quite low, 2.8 times per month, even though the patients' mean age was only 60.5 y, one reason may be the high price of PGE1 injections. The rate of improvement of spontaneous erections while using PGE1 was quite high, accounting for 34.8% of the patients. Most of the patients who discontinued the PGE1 therapy had a psychogenic etiology. There were no systemic side-effects with PGE1. Only 7.2% of the patients had prolonged pain after the injection, leading to drug discontinuation. It can be concluded that treatment with intracavernous injections of PGE1 is well tolerated and involves only minor problems. The patients' satisfaction with their erections at home with PGE1 therapy was good. Precise determination of the home dose of PGE1 and the teaching of the technique of injection are important at the beginning of this treatment modality.

Adult↗

PubMed1989

Direct cholangiography.

The role of direct cholangiographic methods has evolved significantly over the last two decades as other high-resolution imaging modalities have become available. Most of the time, careful clinical evaluation of a patient combined with ultrasonography or CT will enable a physician to arrive at a correct diagnosis with a high level of precision. In this article we have attempted to indicate situations in which direct cholangiographic methods are necessary to diagnose and treat certain hepatobiliary problems. Considerable controversy exists concerning the application of these methods for treatment of biliary problems. However, in circumstances in which the issues are openly discussed, application of these techniques can be agreed on. Direct cholangiography, like coronary angiography, is a technology that provides considerable valuable information that at present cannot be obtained by other techniques, and, in well-defined circumstances, is necessary for precise diagnosis and therapy.

Biliary Tract Diseases↗

PubMed2000

Problems and possibilities in understanding the natural history of asthma.

In early life, asthma symptoms can occur intermittently or may not be severe enough to limit normal activities, which makes it difficult for the clinician to make reliable predictions and administer therapy with some precision. In the case of pediatric asthma, the identification of children who will experience the development of a clinically important illness that will impair their quality of life can be a complex process. The usual methods for describing this information include the prognostic statistics of sensitivity, specificity, likelihood ratio, and positive predictive value. The sensitivity, specificity, and likelihood ratio of various early markers of asthma have been calculated from several cohort studies.

Asthma↗

PubMed1999

Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma.

Conventional chondrosarcoma (CSA) of the skull base is an uncommon neoplasm that can resemble chordoma, and indeed it is misdiagnosed frequently as such. This has important clinical implications, because when treated with similar aggressive treatment strategies, CSA has a much better prognosis than chordoma. In an effort to identify those morphologic and immunohistochemical features that help to identify conventional skull base CSA correctly and to understand its prognosis better, particularly compared with chordoma, when treated with surgery and proton beam irradiation, the authors performed a clinicopathologic analysis of 200 CSAs. The patients ranged in age from 10 to 79 years (mean, 39 years), 87 patients were male and 113 patients were female, and most presented with symptoms related to the central nervous system. Approximately 6% of the tumors arose in the sphenoethmoid complex, 28% originated in the clivus, and 66% developed in the temperooccipital junction. Histologically, 15 tumors (7.5%) were classified as hyaline CSA, 59 (29.5%) as myxoid CSA, and 126 (63%) as mixed hyaline and myxoid CSA. A total of 101 (50.5%) tumors were grade 1, 57 (28.5%) had areas of grades 1 and 2, and 42 (21%) were pure grade 2 neoplasms. The vast majority of patients originated from referring hospitals, and the diagnosis was changed prospectively at our institution to CSA from chordoma in 74 patients (37%). Of the tumors studied immunohistochemically, 96 of 97 (98.9%) stained for S-100 protein, 0 of 97 (0%) stained for keratin, and faint staining for epithelial membrane antigen was seen in 7 of 88 tumors (7.95%). All patients underwent high-dose postoperative fractionated precision conformal radiation therapy with a dose that ranged from 64.2 to 79.6 Cobalt-Gray-equivalents (median, 72.1 Cobalt-Gray-equivalents, given in 38 fractions. The 200 patients had a median follow-up of 63 months (range, 2.1 mos - 18.5 yrs). Tumor control was defined as lack of progression by clinical and radiographic assessment. Based on this definition, there were three local recurrences, and two of these patients died of tumor-related complications. The 5- and 10-year local control rates were 99% and 98% respectively, and the 5- and 10-year disease-specific survival rates were both 99%. In contrast to CSA, the 5- and 10-year survival rates of chordoma have been reported to be approximately 51 % and 35% respectively, and in our institution intensive treatment has resulted in 5- and 10-year progression-free survival rates of 70% and 45% respectively. CSA of the skull base can be distinguished reliably from chordoma, and this distinction is important because skull base CSA has an excellent prognosis when treated with surgery and proton beam irradiation, whereas chordomas have a substantially poorer clinical course despite similar aggressive management.

Adolescent↗

PubMed2000

Immunosuppressive-associated leukoencephalopathy in organ transplant recipients.

Immunosuppressive-associated leukoencephalopathy is a significant complication of cyclosporine (CsA) or tacrolimus therapy. However, the precise time of onset, role of putative risk factors, differences, if any, in presentation in various types of organ transplantation and outcome of this entity, remain poorly defined. Fifty cases of immunosuppressive-associated leukoencephalopathy reported in the literature in organ transplant recipients, were reviewed. Of 50 cases, 31 occurred in liver, 8 in renal, 6 in lung, and 5 in heart transplant recipients. Median time to onset was 28 days (range 3-1512 days); 82% occurred within 90 days of transplantation. Lesions tended to occur earlier in the liver transplant recipients, compared with other organ transplant recipients (median 9 vs. 29 days, P=.19). Seizures 74%, altered mental status 50%, and visual abnormalities 28% were the most frequently presenting features. Ten percent of the patients had fever with no documented source of infection. Systemic hypertension (P=.001), and lesions in the presence of therapeutic drug levels (P=.11) were more likely to occur with CsA than tacrolimus. Neuroimaging and clinical abnormalities were reversible on cessation or reduction of CsA or tacrolimus in all but two cases. Resolution of neurologic signs/symptoms occurred a median of 4 days and neuroimaging abnormalities in a median of 20 days on reduction/cessation of the drug. Immunosuppressive-associated leukoencephalopathy is a unique entity that can usually be diagnosed on the basis of its distinctive time of onset, and clinical and neuroimaging characteristics, and it is potentially reversible if promptly diagnosed. Despite identical clinical presentation of this syndrome in the recipients of CsA and tacrolimus, above noted variations in risk factors suggest that a difference in pathophysiologic mechanism may exist.

Cyclosporine↗

PubMed1998

Emerging strategies in the treatment of testis cancer.

The state of the art in the study and therapy of germ-cell tumors of the testis is reflected in this year's literature. For the majority of patients with germ-cell tumors, the therapeutic dilemma no longer relates to cure. For such patients with low-volume non-seminomatous germ-cell tumors of the testicle and those with a pure seminoma, therapeutic dilemmas relate more to selection of the appropriate therapy to achieve cure, the toxicity of therapy, and the precise prediction of outcome. However, a high cure rate cannot be anticipated with equal frequency in those patients with high-volume non-seminomatous germ-cell tumors of the testicle.

Journal Article↗

PubMed2006

Radiofrequency ablation and percutaneous ethanol injection treatment for recurrent local and distant well-differentiated thyroid carcinoma.

OBJECTIVE: To assess the long-term efficacy of radiofrequency ablation (RFA) and percutaneous ethanol (EtOH) injection treatment of local recurrence or focal distant metastases of well-differentiated thyroid cancer (WTC). BACKGROUND: RFA and EtOH injection techniques are new minimally invasive surgical alternatives for treatment of recurrent WTC. We report our experience and long-term follow-up results using RFA or EtOH ablation in treating local recurrence and distant focal metastases from WTC. METHODS: Twenty patients underwent treatment of biopsy-proven recurrent WTC in the neck. Sixteen of these patients had lesions treated by ultrasound-guided RFA (mean size, 17.0 mm; range, 8-40 mm), while 6 had ultrasound-guided EtOH injection treatment (mean size, 11.4 mm; range, 6-15 mm). Four patients underwent RFA treatment of focal distant metastases from WTC. Three of these patients had CT-guided RFA of bone metastases (mean size, 40.0 mm; range, 30-60 mm), and 1 patient underwent RFA for a solitary lung metastasis (size, 27 mm). Patients were then followed with routine ultrasound, I whole body scan, and/or serum thyroglobulin levels for recurrence at the treatment site. RESULTS: No recurrent disease was detected at the treatment site in 14 of the 16 patients treated with RFA and in all 6 patients treated with EtOH injection at a mean follow-up of 40.7 and 18.7 months, respectively. Two of the 3 patients treated for bone metastases are free of disease at the treatment site at 44 and 53 months of follow-up, respectively. The patient who underwent RFA for a solitary lung metastasis is free of disease at the treatment site at 10 months of follow-up. No complications were experienced in the group treated by EtOH injection, while 1 minor skin burn and 1 permanent vocal cord paralysis occurred in the RFA treatment group. CONCLUSIONS: RFA and EtOH ablation show promise as alternatives to surgical treatment of recurrent WTC in patients with difficult reoperations. Further long-term follow-up studies are necessary to determine the precise role these therapies should play in the treatment of recurrent WTC.

Adult↗

PubMed1998

Isolation, identification and increasing importance of 'free-living' amoebae causing human disease.

Amphizoic small amoebic protozoa are capable of existing both in 'free-living' and in 'parasitic' form depending on the actual conditions. Two genera (Naegleria and Acanthamoeba) have become recognised as opportunist human parasites. Since the first description in 1965 of a lethal case of primary amoebic meningoencephalitis (PAM) caused by Naegleria, many more (mostly lethal) cases have been reported, while granulomatous amoebic encephalitis (GAE), as well as eye (keratinitis, conjunctivitis, etc.), ear, nose, skin and internal organ infections caused by Acanthamoeba have also occurred in rapidly increasing numbers. Both pathogenic and non-pathogenic species of Naegleria and Acanthamoeba are found worldwide in water, soil and dust, where they provide a potential source of infection. Successful differential diagnosis and appropriate (specific) therapy depends on precise laboratory identification of the 'free-living' amoebae. In most cases, isolation from the environment can be achieved, but identification and differentiation of the pathogenic and non-pathogenic strains is not easy. The methods presently available do not fulfil completely the requirements for specificity, sensitivity and reliability. Morphological criteria are inadequate, while thermophilic character, pH dependency and even virulence in infected mice, are not unambiguous features of pathogenicity of the different strains. More promising are molecular methods, such as restriction endonuclease digestion of whole-cell DNA or mitochondrial DNA, as well as iso-enzyme profile analysis after iso-electric focusing and staining for acid phosphatase and propionyl esterase activity. Use of appropriate monoclonal antibodies has also yielded promising results in the differentiation of human pathogenic and non-pathogenic strains. However, quicker, simpler, more specific and reliable methods are still highly desirable. The significance of endosymbiosis (especially with Legionella strains) is not well understood. The results of a systematic survey in Hungary for the isolation and identification of 'free-living' amoebae, including an investigation of the Hungarian amoebic fauna, the isolation of possibly pathogenic Naegleria strains and of some Acanthamoeba strains from eye diseases, as well as the finding of a case of endosymbiosis, are also reported here.

Acanthamoeba↗

PubMed2026

Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that accounts for about 15%-20% of childhood leukemias. Despite therapeutic advances, relapses remain common, and survival for high-risk patients is below 60%. Unlike adult AML, pediatric AML displays distinct genetic mutations, including FLT3-ITD, NPM1, KMT2A rearrangements, and core-binding factors (CBF) fusions, as well as extensive epigenetic dysregulation. Aberrant DNA methylation, histone modifications, and altered non-coding RNA expressions disrupt hematopoietic differentiation and activate oncogenic transcriptional networks. Recent advances in silico transcriptomic analysis have transformed the study of pediatric AML by integrating gene expression and epigenetic data to identify molecular drivers and regulatory networks. Computational RNA-seq pipelines and pathway analyses have highlighted key epigenetic regulators, including DNMT3A, TET2, and HDACs, as potential therapeutic targets. Multi-omics approaches combining transcriptomic, methylomic, and chromatin accessibility data are increasingly used to define biomarkers for diagnosis, prognosis, and therapeutic response. This review provides a comprehensive overview of the molecular and epigenetic landscape of pediatric AML, emphasizing the power of in silico transcriptome analysis to uncover disease mechanisms, refine patient stratification, and guide the development of precision-based epigenetic therapies aimed at improving long-term outcomes in children with AML.

Humans↗

PubMed1996

Augmented two-channel arrhythmia detection: an efficient diagnostic method for implantable devices.

ICDs are highly effective in preventing sudden cardiac death. However, inappropriate device shocks caused by false-positive diagnoses are estimated to happen in 20% of all patients. The need for implantable electrical devices to detect with precision arrhythmias requiring therapy has spawned a variety of proposals for better means of tachycardia identification. To address this problem, the augmented two-channel arrhythmia detection (A2CAD) algorithm, a real-time scheme utilizing timing and morphology from both the atrial and ventricular channels, is introduced. The algorithm uses rate detection as a first stage and augments this with morphological signal analysis in rhythms that confound the rate only diagnoses. The software executes in real-time (online), and has been tested on 60 passages of two-channel intracardiac signals. The following arrhythmias constituted the test set: 10 AF and/or atrial flutter; 15 SVT; 16 VT; 10 ventricular flutter or VF; 5 sinus tachycardia; and 4 cases of AF concurrent with VF. Results from 60 patient cases indicate 57 (95%) of 60 success rate for A2CAD, validating its potential for implementation in future implantable devices.

Algorithms↗

PubMed2000

Failure of short-course ceftriaxone chemotherapy for multidrug-resistant typhoid fever in children: a randomized controlled trial in Pakistan.

The precise duration of therapy of multidrug-resistant (MDR) typhoid with broad-spectrum cephalosporins is uncertain. We prospectively randomized 57 children with culture-proven MDR typhoid to receive treatment with intravenous ceftriaxone (CRO) (65 mg/kg of body weight/day) for 7 days (short course; n = 29) or 14 days (conventional; n = 28). The response to therapy, as evaluated by the serial monitoring of the typhoid morbidity score and bacteriological clearance, was comparable between groups. In contrast to the conventional therapy, 14% of the children receiving CRO for 7 days had a confirmed bacteriological relapse within 4 weeks of stopping therapy.

Ceftriaxone↗