Mohamed A. Virji

Concise parathyroidectomy: The impact of preoperative SPECT 99mTc sestamibi scanning and intraoperative quick parathormone assay

BACKGROUND Results of initial operation for sporadic primary hyperparathyroidism are generally excellent, yet today there is pressure to improve outcome and resource utilization. METHODS We designed a prospective longitudinal cohort study comparing two approaches to concise parathyroidectomy. Strategy A was defined as the palpation method for selective unilateral exploration. Strategy B was defined as the routine use of both preoperative 99mTc sestamibi single photon emission computed tomography (SPECT) imaging and intraoperative quick parathormone assay. With either strategy the study period was 19 months and patients explored unilaterally were candidates for same-day discharge. We compared surgical outcome for 128 consecutive consenting patients each with 6 months or more of follow-up (mean 12 +/- 7.6 months). RESULTS Demographic, biochemical and pathologic findings did not differ between groups. SPECT imaging precisely localized hyperfunctioning parathyroid tissue. Compared with Strategy A (n = 61), the 67 patients treated by use of Strategy B experienced a higher rate of unilateral exploration (41.0% versus 62.7%, p < 0.00001) and a shorter length of stay (1.07 versus 1.90 days, p < 0.00001) and tended to have shorter operative times, fewer operative failures, and less morbidity. Total perioperative costs did not differ between groups. CONCLUSIONS Routine use of intraoperative quick parathormone measurement and preoperative 99mTc sestamibi SPECT is as safe, effective, and cost-effective as conventional approaches to parathyroidectomy. Use of this strategy is associated with significant reductions in extent of surgery and length of hospital stay.

Cardiovascular Depression Secondary to Ionic Hypocalcemia during Hepatic Transplantation in Humans

Cardiovascular function, serum ionized calcium (Ca+2), and serum citrate were measured intraoperatively in patients (n = 9) undergoing orthotopic hepatic homotransplantation. Serum citrate increased 20-fold (P < 0.0006) following transfusion of citrated blood products in the absence of a functional liver. Serum ionized calcium decreased (P < 0.003) with concomitant decreases in cardiac index (P < 0.005), stroke index (P < 0.004), and left ventricular stroke work index (P < 0.001). Hemodynamic depression and ionic hypocalcemia were reversed following the administration of CaCl2. In contrast to patients with normal hepatic function, who may tolerate large amounts of citrated blood, patients with end-stage liver disease demonstrate acute ionic hypocalcemia with concomitant hemodynamic depression when receiving citrated blood products during the course of hepatic transplantation.

Ionization and Hemodynamic Effects of Calcium Chloride and Calcium Gluconate in the Absence of Hepatic Function

Serial serum ionized calcium concentrations were measured before and after administration of either calcium chloride or calcium gluconate during the anhepatic stage of liver transplantation in 15 patients to determine the release of ionized calcium in the absence of hepatic function. When hypocalcemia (Ca++ less than 0.8 mM) occurred during the anhepatic stage, patients were randomly assigned to treatment with chemically equivalent doses of either calcium chloride (10 mg/kg, n = 8) or calcium gluconate (30 mg/kg, n = 7). Serum concentrations of ionized calcium and citrate, hematocrit, arterial blood gas tensions, acid-base state, and hemodynamic profiles were determined before and up to 10 min after calcium therapy. In both groups of patients initial similar and rapid increases in Ca++ (0.98 +/- 0.14 mM in the calcium chloride group and 1.05 +/- 0.10 mM in the calcium gluconate group) were followed by gradual decreases over the next 10 min. Measured hemodynamic values were similar in the two groups, and neither group showed improvement in cardiovascular function after calcium therapy, possibly because of the decrease in preload that occurred during the anhepatic stage. Equally rapid increases in Ca++ after administration of calcium chloride and gluconate in the anhepatic state suggest that calcium gluconate does not require hepatic metabolism for the release of Ca++ and is as effective as calcium chloride in treating ionic hypocalcemia in the absence of hepatic function.

Free Radical Injury and Liver Tumor Promotion

One of the underlying mechanisms of tumor promotion both in the skin and liver involves free radical mediated injury to informational macromolecules of target cells. A choline-deficient (CD) diet, which is an efficient liver tumor promoter, induces peroxidative damage of liver cell membrane lipids. By modifying components of a CD diet, we have shown that the efficacy of the promotion is correlated with the extent of lipid peroxidation. The substitution of fats in a CD diet with predominantly polyunsaturated fat and the addition of methapyrilene to a CD diet enhances membrane lipid peroxidation and the promoting effects. An antioxidant (BHT) and hypolipidemic peroxisome proliferators (BR.931 and DEHP) suppress both of these effects. Contrary to these findings, phenobarbital did not induce membrane lipid peroxidation, and its addition to a CD diet inhibited the diet-induced lipid peroxidation, though such a combination exerted a stronger promoting action. Thus, a CD diet and phenobarbital exert their promoting actions through different mechanisms. The consequence of membrane lipid peroxidation in the liver cells induced by a CD diet may be multiple. Our recent study of surface membrane insulin receptors of liver cells of rats fed a CD diet showed a decrease in number and an enhanced binding affinity leading to altered responsiveness of liver cells to insulin mediated glycogen synthesis. It is suggested that CD diet-induced lipid peroxidation leads to functional alterations of membrane receptors involved in cell growth control and may thereby exert its promoting action.

Effect of an educational Inpatient Diabetes Management Program on medical resident knowledge and measures of glycemic control: a randomized controlled trial.

OBJECTIVE To investigate the effectiveness of an Inpatient Diabetes Management Program (IDMP) on physician knowledge and inpatient glycemic control. METHODS Residents assigned to General Internal Medicine inpatient services were randomized to receive the IDMP (IDMP group) or usual education only (non-IDMP group). Both groups received an overview of inpatient diabetes management in conjunction with reminders of existing order sets on the hospital Web site. The IDMP group received print copies of the program and access to an electronic version for a personal digital assistant (PDA). A Diabetes Knowledge Test (DKT) was administered at baseline and at the end of the 1-month rotation. The frequency of hyperglycemia among patients under surveillance by each group was compared by using capillary blood glucose values and a dispersion index of glycemic variability. IDMP users completed a questionnaire related to the program. RESULTS Twenty-two residents participated (11 in the IDMP group and 11 in the non-IDMP group). Overall Diabetes Knowledge Test scores improved in both groups (IDMP: 69% ± 1.7% versus 83% ± 2.1%, P = .003; non-IDMP: 76% ± 1.2% versus 84% ± 1.4%, P = .02). The percentage of correct responses for management of corticosteroid-associated hyperglycemia (P = .004) and preoperative glycemic management (P = .006) improved in only the IDMP group. The frequency of hyperglycemia (blood glucose level >180 mg/dL) and the dispersion index (5.3 ± 7.6 versus 3.7 ± 5.6; P = .2) were similar between the 2 groups. CONCLUSION An IDMP was effective at improving physician knowledge for managing hyperglycemia in hospitalized patients treated with corticosteroids or in preparation for surgical procedures. Educational programs directed at improving overall health care provider knowledge for inpatient glycemic management may be beneficial; however, improvements in knowledge do not necessarily result in improved glycemic outcomes.

Toxicology laboratory analysis and human exposure to p-chloroaniline

Introduction. p-Chloroaniline is more potent at producing methemoglobin than aniline in animal models. This case highlights the clinical presentation of an inhalation exposure to p-chloroaniline and associated laboratory analysis. An in-vitro study evaluating the metabolism of p-chloroaniline in human hepatocytes was undertaken to evaluate the metabolic fate more closely. Case presentation. A 20 year-old man was working at a chemical waste plant when he developed dizziness, abdominal pain, and nausea. The exam was remarkable for coma, tachycardia, cyanosis, and pulse oximetry of 75%. Arterial blood gases showed a pH 7.38, pCO2 41 mmHg, pO2 497 mmHg, bicarbonate 24 mEq/L and methemoglobin 69%. Methylene blue administration led to complete recovery without sequelae. p-Chloroaniline was later identified as the chemical involved. He denied direct contact with the chemical, but was not wearing a dust mask or respirator. GC/MS confirmed p-chloroaniline and metabolites in the patients urine. Methods. Human hepatocytes were incubated with 100 μM p-chloroaniline for 24 hours, in both rifampicin- and vehicle only-treated cells. The cell culture medium was collected for GC/MS analysis for p-chloroaniline metabolites. Results. Similar to the patient sample, both p-chloroaniline and p-chloroacetanilide were identified by GC/MS in hepatocytes incubated with p-chloroaniline. Neither p-chloroaniline incubated in empty cell culture nor direct GC/MS injection of p-chloroaniline generated any p-chloroacetanilide via non-enzymatic degradation. Discussion/Conclusion. The seemingly innocuous dermal and inhalation exposure to p-chloroaniline dust can lead to life-threatening methemoglobinemia. The diagnosis can be confirmed with GC/MS analysis of the patients urine, searching for p-chloroaniline and its primary metabolite p-chloroacetanilide.

Lash’s: A bitter medicine: Biochemical analysis of an historical proprietary medicine

Patent medicines were widely used during the late 1800s and early 1900s. Bitters were one important subtype of patent medicines that were typically made from extracts of bitter tasting herbs. Lash’s Bitters was a popular patent medicine that was advertised as an extract of the bark of the buckthorn tree, Rhamnus purshiana, and was sold as a laxative. Analysis of the contents of an undisturbed bottle of Lashs Bitters, ca. 1918, revealed an ethanol content of 19.2% by volume as well as trace amounts of methanol. Potentially toxic concentrations of lead, 295 mg/dl, were also found. Interestingly, the medicine contained none of the active ingredient found in Rhamnus purshiana.

CSF α2-macroglobulin and C-reactive protein as aids to rapid diagnosis of acute bacterial meningitis

alpha 2-Macroglobulin (AMG) and C-reactive protein (CRP) levels in cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis have been analyzed by a rate nephelometric method to determine if these acute phase proteins can aid in differentiation of bacterial from aseptic meningitis. The mean CSF concentrations of AMG and CRP were 15 and 3.5 times greater, respectively, in the bacterial compared to the aseptic meningitis group. Also, the range of AMG levels showed minimal overlap between the two groups. The elevated levels of the proteins persisted after CSF cultures became negative. Quantitation of specific acute phase proteins in CSF may assist the differentiation of bacterial from aseptic meningitis.

Acute Ethanol Intoxication in a 7-Month-old Infant

7-Month-old Infant KUDAKWASHE CHIKWAVA, DARLA R. LOWER, SUSAN H. FRANGISKAKIS, JORGE L. SEPULVEDA, MOHAMED A. VIRJI, AND KALIPATNAPU N. RAO* Department of Pathology, Division of Clinical Chemistry, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA

Circulating prostatic acid phosphatase-immunoglobulin complexes in Sjogren's syndrome

Elevated level of serum prostatic acid phosphatase (PAP) activity in a patient with Sjogrens syndrome was found to be due to the presence of PAP-immunoglobulin complexes in circulation. The patient did not have a prostatic malignancy. The complexes were demonstrated by counter-immunoelectrophoresis, protein A-Sepharose immunoprecipitation and agarose-gel electrophoresis. Free enzyme was not detected in serum, and the activity of the complexed enzyme was probably unaltered on binding with the immunoglobulins.