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Biomedical subjects

David Podwall

Publications and source records attributed to David Podwall.

5 recordsLinked to original sources

Medication-induced exacerbation of neuropathy in Charcot Marie Tooth disease.

Toxin or medication-induced worsening of preexisting peripheral neuropathy is a generally accepted but not well-studied phenomenon in humans. Drug-induced exacerbation of Charcot Marie Tooth disease (CMT) neuropathy is a common concern; a list of potential drugs to avoid is maintained by the CMT Association but with limited direct evidence or advice on relative risk. An extensive literature search for reported cases of drug effects in CMT patients found the vast majority concerned excessive vincristine toxicity in patients with undiagnosed demyelinating forms of CMT, many after 1 or 2 doses. The CMT North American database was also queried for all drug-related effects. All but one drug cited as worsening neuropathy was present on a compiled inclusive list. These results and other available evidence were used to develop a revised risk stratified list for CMT patients and clinicians to consult prior to discussing risk to benefit ratios and making treatment decisions.

Antineoplastic Agents, Phytogenic↗

Diabetic neuropathy: clinical features, etiology, and therapy.

Diabetes mellitus is a common cause of peripheral nervous system disorders that manifest in a variety of clinical forms, many of which are often misdiagnosed. Over the past two decades, our understanding of the pathophysiology of diabetic nerve injury has improved remarkably through the elucidation of the important roles of the polyol pathway of glucose metabolism, oxidative injury, advanced glycosylation end-products, vascular insufficiency, and other mechanisms. A large number of clinical treatment trials based upon this abundant scientific data have met with limited success, but ongoing and future trials offer promise for more dramatic success in treating this common cause of morbidity and mortality in the diabetic population.

Antioxidants↗

The diabetic neuropathies.

BACKGROUND: Diabetes remains the most common cause of neuropathy in the United States and is a significant source of morbidity and mortality, accounting for substantial suffering and billions of dollars in health care expenditures each year. REVIEW SUMMARY: Our insight into the pathophysiology of the diabetic neuropathies has increased considerably over the last decade. aided by advances in the basic science of diabetes itself. A wide variety of potential mechanisms for nerve injury in diabetes has been identified, including the polyol pathway of glucose metabolism, oxidative nerve injury, the deposition of advanced glycosylation end products within the nerve and the effects of vascular insufficiency, among others. Diabetic neuropathy may take a variety of clinical forms beyond the well-known distal symmetric neuropathy, many of which are often misdiagnosed or overlooked entirely, sometimes with serious consequences for the patient. Proper therapy after diagnosis is also critical and may include not only primary management, but also treatment of painful diabetic neuropathy through an expanding repertoire of increasingly effective pharmacologic agents. Though primary treatment trials have not yet provided effective therapies, ongoing and future trials offer continuing promise. CONCLUSIONS: The diabetic neuropathies are exceedingly common, but often improperly diagnosed and incompletely treated. A proper understanding of the mechanisms underlying these diseases and the clinical recognition of their various forms is highly important as appropriate primary and symptomatic management can substantially reduce the morbidity and mortality associated with these disorders.

Aldehyde Reductase↗

DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy.

Adriamycin (ADM, or doxorubicin hydrochloride) is an effective antineoplastic agent whose use is restricted by its well-described, dose-dependent cardiotoxicity. This study measures ADM DNA adduct formation by 32P-radiolabeling DNA, enzymatically digesting radiolabeled DNA, separating the formed adducts on two-dimensional thinlayer chromatography (2D-TLC), and quantitating the adducts with autoradiography and densitometry. Thirty-six male Sprague-Dawley rats are randomized to receive ADM at varying intraperitoneal (i.p.) injection concentrations: 0.9% saline i.p. controls, 4 mg/kg ADM i.p., and 6 mg/kg ADM i.p. Myocardial and pulmonary tissues are harvested 48 hours after i.p. injection for autoradiographic and histopathologic analyses. The results indicate differences in the amount and type of adduct formation as a function of ADM concentration. Increased partial depurination of dGMP and dAMP occurs with increasing ADM concentration at equal incubation times. This depurination correlates with the emergence of new adducts HM-dUMP, 8-OH-dGMP, HM-dCMP, and Me-dCMP. The quantification of these adducts can potentially represent an early marker of ADM cardiotoxicity and thereby optimize the efficacy of individual chemotherapy regimens while minimizing adverse effects.

Animals↗

Unilateral auditory neuropathy: case study.

This article reports on an 11-year-old boy who was diagnosed with unilateral auditory neuropathy. After failing his annual medical and school hearing screenings, he was referred for audiologic testing, which identified a profound sensorineural hearing loss in his left ear that has remained stable for the past 3 1/2 years. Subsequently, otoacoustic emissions revealed findings that were consistent with an auditory neuropathy. Neurologic evaluation was remarkable only for a left ear hearing loss. Radiologic studies were unremarkable. Auditory neuropathy is a condition in which patients, on audiologic evaluation, are found to have normal outer hair cell function and abnormal neural function at the level of the eighth nerve. These patients, on clinical testing, are found to have normal otoacoustic emissions, whereas auditory brainstem response audiometry reveals the absence of neural synchrony. Unlike space-occupying lesions, radiologic evaluation reveals normal results. This case is noteworthy because only a handful of the cases of auditory neuropathy reported to date have been unilateral.

Audiometry, Pure-Tone↗