Arturo R. Rolla

Reversible Rapidly Progressive Renal Failure with Nephrotic Syndrome Due to Fenoprofen Calcium

Excerpt Nonsteroidal antiinflammatory drugs have been reported to cause reversible acute renal failure (1-4). Unlike the so-called phenacetin-induced analgesic nephropathy (5), the nephrotoxicity o...

Pharmacokinetic and pharmacodynamic advantages of insulin analogues and premixed insulin analogues over human insulins: impact on efficacy and safety.

Human insulin preparations administered to patients with diabetes mellitus fail to reproduce the normal physiologic pattern of insulin secretion. Modifications have been made in the amino acid sequence of the insulin molecule with the aim of overcoming the pharmacokinetic shortcomings of human insulins. Such modifications have produced long-acting analogues, with relatively flat time-action profiles, for controlling glycemic levels between meals; and rapid-acting analogues with a fast onset and short duration of action, for controlling postprandial hyperglycemia. Premixed formulations of the rapid-acting analogues, containing both rapid-acting soluble and intermediate-acting protaminated forms, are also available. Trials of long-acting insulin analogues have consistently shown efficacy in controlling fasting plasma glucose and glycosylated hemoglobin (HbA1c), as well as a markedly reduced risk of hypoglycemia compared with neutral protamine Hagedorn insulin. The rapid-acting and premixed analogues offer better control of postprandial glucose excursions than do regular human insulin, resulting in similar or lower HbA1c levels. Furthermore, the analogues can offer patients greater flexibility and more convenience in administration compared with human insulins. This review provides an overview of the insulin analogues available today and describes their structure, pharmacokinetics, pharmacodynamics, efficacy, and safety.

Case Report: Spontaneous Hematoma of a Parathyroid Adenoma

A patient with long-standing, asymptomatic, primary hyperparathyroidism developed pain in the anterior neck area, with cough, dysphagia and increasing shortness of breath. This led to respiratory insufficiency, which required endotracheal intubation and respirator assistance. During the ensuing hours the patient developed an area of ecchymosis on the anterior chest. Chest x-ray showed widening of the superior mediastinum, and CT scan showed a large mass with a fluid level. Surgery revealed a large hematoma originating from a mediastinal parathyroid adenoma with a hemorrhagic infarct. Serum calcium, previously elevated, decreased to normal with the onset of neck pain, and the patient remains normocalcemic. Previous reported cases of this rare complication of parathyroid adenomas are reviewed. Hemorrhagic infarct of a parathyroid adenoma may present with a rapidly enlarging mediastinal mass, and/or hypercalcemic crisis. Surgical removal of the infarcted adenoma can return the serum calcium to normal.

The pathophysiological basis for intensive insulin replacement.

Both type I and type II diabetes are characterised by a progressive decrease in beta-cell function and mass. In type I diabetes, autoimmune destruction results in rapid loss of beta-cell function, and insulin therapy is essential to maintain normoglycaemia. In type II diabetes, a diminished or absent first-phase insulin release is the earliest metabolic defect, which is accompanied by lack of prandial suppression of hepatic glucose production, increased postprandial glucose excursions and late insulin hypersecretion. Furthermore, chronic exposure to elevated glucose, even to intermittent postprandial spikes, results in further deterioration of the beta-cell function (‘glucotoxicity’). By the time type II diabetes is diagnosed, beta-cell function and mass have declined by about 50%. With the progression of the disease and glucotoxicity there is continuous decrease in beta-cell mass due to increased apoptosis that results in absolute insulin deficiency. By then, patients require insulin administration to maintain glucose control. An increasing body of evidence demonstrates the importance of preserving endogenous beta-cell function both in type I and type II diabetes. Early and intensive glycaemic control, using regimens which re-create a physiological insulin profile, controlling postprandial as well as fasting glucose levels, offers the most promise for preserving beta-cell function, decreasing disease progression, and reducing the chronic complications of diabetes.

Iatrogenic Cushing's syndrome due to dexamethasone nasal drops

Iatrogenic Cushings syndrome presents all of the metabolic and immunologic abnormalities of the disease plus a suppressed hypothalamic-pituitary-adrenal axis. Most of the time the intake of steroids is quite evident, but occasionally it is not. This report presents such a patient who was using dexamethasone nasal drops for allergic rhinitis and in whom Cushings syndrome developed. Five other similar cases were found in the literature. All except one were reported from outside the United States where these nasal steroid preparations are easily obtained over the counter. Absorption through the nasal mucosa and partly through the intestinal mucosa after a portion of the dose is swallowed is the mechanism of the systemic effect. Treatment consists in the discontinuation of the intranasal steroid preparation and tapering doses of prednisone to cover the secondary adrenal insufficiency until the axis recovers. Patients with Cushings syndrome and suppressed levels of ACTH and cortisol should be asked about steroid intake, including nasal sprays and drops, particularly if they come from outside the United States. All of the cases reported occurred with dexamethasone. The newer intranasal steroids (beclomethasone and flunisolide) are not absorbed as readily through the nasal mucosa and are inactivated in the liver after gastrointestinal absorption. Therefore, it is not expected that they will produce Cushings syndrome or adrenal suppression.

Untreated thyrotoxicosis as a manifestation of anorexia nervosa

A patient with anorexia nervosa refused treatment for her thyrotoxicosis for 18 years in an attempt to keep her weight low. Severe congestive heart failure and impending thyroid storm prompted her family to force her to seek medical attention.

Diabetic gastroparesis: A review

Diabetic gastroparesis (DGP) was first described by Rundles in 1945 as part of a generalized autonomic neuropathy.’ Kassander in 1954 coined the phrase “gastroparesis diabeticorum” to describe the syndrome.* Since these original descriptions much has been learned, but fundamental questions concerning the pathophysiology, diagnosis, treatment, and prognosis of the DGP syndrome remain unanswered.

Case report: granuloma-related hypercalcemia in lipoid pneumonia

ABSTRACT A patient with hypercalcemia, suppressed serum PTH levels, and elevated serum levels of calcitriol was found to have a granulomatous lipoid pneumonia due to chronic aspiration of a “vaporizing ointment.” After the surgical removal of the largest granuloma, the serum calcium and calcitriol levels rapidly returned to normal. This is a new instance of granuloma-induced hypercalcemia, probably mediated by the activation of vitamin D by cells of the granulomatous reaction.

Alkalemia in diabetic ketoacidosis

A patient with a history of diabetes mellitus and congestive heart failure was taking furosemide and metolazone as diuretics. Diabetic ketoacidosis developed, and the patient became lethargic and confused. Initial biochemical determinations showed an alkalemic pH, serum and urine ketones with an anion gap, and hyperventilation. The hyperventilation was appropriate for the degree of ketoacidosis but it was grossly inappropriate for the alkalemia. This could be explained by a direct effect of ketones on the respiratory center or a sudden increase in hydrogen ion concentration superimposed on previously chronic alkalemic pH due to the potent combination of furosemide and metolazone.

Coagulopathy Associated with the use of Cephalosporin or Moxalactam Antibiotics in Acute and Chronic Renal Failure

Nine azotemic patients who developed a coagulopathy associated with the use of either cephalosporin or moxalactam antibiotics are reported. The acute renal failure patients had neoplastic disorders and were considered to be septic at the time that multiple antibiotics were administered. Four of 5 chronic hemo- or peritoneal dialysis patients also received multiple antibiotics. Nevertheless, the coagulopathy seemed to be most closely associated with the administration of the cephalosporin. One patient received moxalactam as part of the combination therapy for diffuse pulmonary infiltration during renal transplant rejection. Bleeding occurred into the gastrointestinal tract in four patients, into the kidney-urinary tract in three patients, into vascular surgical sites in two patients, and one each into the pulmonary-bronchial and cerebral-ventricular systems. Five operations were performed in four patients: a nephrectomy for massive subcapsular hemorrhage with a prothrombin time that exceeded 100 seconds; arteriovenous graft complicated by post-operative bleeding associated with prolongation of the prothrombin time; elective femoral-popliteal bypass complicated by a prolonged prothrombin time, bleeding into the graft site, hypotension, and a subendocardial myocardial infarction; elective cholecystectomy complicated by a two unit bleed associated with a slightly prolonged prothrombin time, followed by elective femoral-popliteal bypass complicated by a fatal intercerebral bleed associated with a more than twice normal prothrombin time. Cephalosporins are most likely associated with Vitamin K deficiency. Moxalactam is more likely to be associated with platelet dysfunction. Monitoring of the prothrombin time for cephalosporins or the bleeding time for moxalactam is the most reliable way to prevent what may be rapid emergence of clinical bleeding in patients with renal failure.