Albert A. Driedger

Acute Interstitial Nephritis Due to Drugs: Review of the Literature with a Report of Nine Cases

Acute interstitial nephritis due to drugs commonly presents as acute renal failure and may be commoner than is presently realized. Drugs implicated include not only methicillin and other penicillins but also diuretics and nonsteroidal anti-inflammatory agents. The mechanism of injury likely involves an immunologic disturbance, possibly a delayed hypersensitivity reaction. Differential diagnosis from other causes of acute renal failure may be difficult, but coincident evidence of an acute allergic reaction may help, as may the detection of eosinophils in the urine or avid uptake of 67Ga by the kidneys. Definitive diagnosis may require renal biopsy, which will reveal normal glomeruli and a patchy but usually heavy interstitial infiltrate with lymphocytes, plasma cells, and eosinophils. Diagnosis of acute interstitial nephritis is important, because withdrawal of the offending agent will usually result in rapid improvement in renal function, and steroid therapy may reduce residual chronic renal damage.

Right ventricular function in acute disease states: pathophysiologic considerations.

In critically ill patients, alterations in pulmonary vasomotor tone profoundly influence right ventricular (RV) function. An increase in end-diastolic volume (EDV) follows elevations in the RV afterload, this increase in preload probably subserving the increased RV stroke work (SW) required to ensure unchanged RV pump function. The maintenance of a normal left ventricular (LV) preload is essential in the cardiovascular adaptation to an acute illness. With volume overload of the RV consequent upon pulmonary artery hypertension (PAH), leftward septal shift occurs and reduces LV diastolic compliance. With extremely high levels of RV loading conditions, a depression in RV contractility and reduced RV pump function are eventually seen, both of which then become partially responsible for LV pump failure.Hence, abnormalities in RV function will have a marked clinical influence on the circulatory response seen in critically ill patients. Future investigation should be directed toward the effects of augmenting or improving RV function with pharmacologic agents in this patient population.

Does the pulmonary capillary wedge pressure predict left ventricular preload in critically ill patients

The construction of a Frank-Starling myocardial function curve relating heart work to left ventricular preload is clinically utilized to assess therapeutic protocols in critically ill patients. The pulmonary capillary wedge pressure (PWP) is the index of left ventricular filling pressure most frequently utilized as representative of left ventricular preload.The authors assessed the relationship between left ventricular preload measured as the left ventricular end-diastolic volume (LVEDV), and the PWP, in acutely ill patients with sepsis and cardiac disease. Within each group, no relationship was found between the LVEDV and the PWP; however, when omitting the effect of PEEP, a modest correlation was noted (r = 0.302; p < 0.01). Of the left ventricular ejection fraction. LVEDV and PWP, the PWP accounted for less than 5% of the explained variance in the stroke volume index.The PWP is a poor predictor of left ventricular preload, probably because of abnormalities of left ventricular compliance in critically ill patients.

Biventricular Function in the Adult Respiratory Distress Syndrome: Hemodynamic and Radionuclide Assessment, with Special Emphasis on Right Ventricular Function

We examined biventricular function in patients with the adult respiratory distress syndrome (ARDS) by a combmation of invasively determined pressures and flows and concomitant radionuclide angiography. Right (RVEF) and left (LVEF) ventricular ejection fractions were measured; right and left ventricular end-diastolic (EDVI) and end-systolic (ESVI) volume indices were calculated from the respective ejection fraction and measured ther. modilution stroke volume. With an increase in the outflow pressure load on the right ventricle,measured as the mean pulmonary artery pressure (PAP), the RVEF fell (Y66.25-l.O1X; r2.42; p <.001) and both the RVEDVI (y13.39+3.66X; r�.33; p <.001)and RVESVI (Y = 23.9 + 3.57X; r’ .41; p <.001) increased. Progressive Acute microvascular lung injury, a complication of

Follow-Up of Low-Risk Differentiated Thyroid Cancer Patients Who Underwent Radioiodine Ablation of Postsurgical Thyroid Remnants after Either Recombinant Human Thyrotropin or Thyroid Hormone Withdrawal

BACKGROUND We previously demonstrated comparable thyroid remnant ablation rates in postoperative low-risk thyroid cancer patients prepared for administration of 3.7GBq (131)I (100 mCi) after recombinant human (rh) TSH during T(4) (L-T4) therapy vs. withholding L-T4 (euthyroid vs. hypothyroid groups). We now compared the outcomes of these patients 3.7 yr later. PATIENTS AND METHODS Fifty-one of the 63 original patients (28 euthyroid, 23 hypothyroid) participated. Forty-eight received rhTSH and serum thyroglobulin (Tg) sampling. A (131)I whole-body scan was performed in 43 patients, and successful ablation was defined by criteria from the previous study. Based on the criterion of uptake less than 0.1% in thyroid bed, 100% (43 of 43) remained ablated. When no visible uptake instead was used, five patients (four euthyroid, one hypothyroid) had minimal visible activity. When the TSH-stimulated Tg criterion was used, only two of 45 (one euthyroid, one hypothyroid) had a stimulated Tg level greater than 2 ng/ml. RESULTS No patient in either group died, and no patient declared disease free had sustained tumor recurrence. Nine (four euthyroid, five hypothyroid) had received additional (131)I between the original and current studies due to detectable Tg or imaging evidence of disease; with follow-up, all now had a negative rhTSH-stimulated whole-body scan and seven (three euthyroid, four hypothyroid) had a stimulated serum Tg less than 2 ng/ml. CONCLUSIONS In conclusion, after a median 3.7 yr, low-risk thyroid cancer patients prepared for postoperative remnant ablation either with rhTSH or after L-T4 withdrawal were confirmed to have had their thyroid remnants ablated and to have comparable rates of tumor recurrence and persistence.

Anatomic and cardiopulmonary responses to trauma with associated blunt chest injury.

Myocardial dysfunction may result from severe trauma. Therefore, left (LV) and right ventricular (RV) function were prospectively assessed by ECG-gated blood pool radionuclide (RN) angiography in 25 consecutive patients who had sustained severe trauma including blunt chest injuries. Focal abnormalities of RV and LV wall motion were defined in 17 patients; 12, RV; two, LV; and three, biventricular. In two patients traumatic tricuspid insufficiency was also demonstrated, and subsequently verified by contrast angiography. Other means to detect myocardial contusion (enzymatic, electrocardiographic, and Tc-99m pyrophosphate scintigraphy) proved to be insensitive when compared to RN angiography. Two of the five deaths in the group were attributed to refractory arrhythmias. Surgical or post-mortem evidence of traumatic myocardial injury was obtained in five instances when RN angiography indicated contusion. Of the 13 patients available for followup examinations, 11 showed complete or partial resolution of the abnormality and two were unchanged. Comprehensive cardiopulmonary monitoring revealed an inverse relationship between right ventricular ejection fraction (RVEF) and pulmonary vascular resistance (PVR) (R2 = 0.42; p < 0.01) and between the PVR and left ventricular ejection fraction (LVEF) (R2 = 0.48; p < 0.01) and left ventricular end-diastolic volume (LVEDV) (R2 = 0.69; p < 0.01). Further, as right ventricular end-diastolic volume (RVEDV) was increased in trauma, left ventricular function and compliance were reduced. In blunt chest trauma RV contusion occurs more frequently than previously recognized and positive RN angiography constitutes prima facie evidence of direct myocardial injury. Further, LV function remains preload dependent, but may be depressed by elevated PVR impeding the blood flow from RV to LV and/or decreases in LV compliance.

Frequency of myocardial injury after blunt chest trauma as evaluated by radionuclide angiography

Seventy-seven patients who had sustained multisystem trauma, including severe blunt chest injury, were prospectively evaluated to assess the frequency of associated traumatic myocardial injury. Traumatic injury to either the right or left ventricle was defined by the presence of discrete abnormalities of wall motion on electrocardiographically gated cardiac scintigraphy in patients without a clinical history of heart disease. Forty-two patients (55%) (Group 1) had focal abnormalities of wall motion; 27 involved the right ventricle, 7 the left ventricle, 7 were biventricular, and 1 involved only the septum. Both the right and left ventricular ejection fractions were significantly (p less than 0.01) lower (31 +/- 11% and 47 +/- 14%, respectively) than those in the 35 traumatized patients without wall motion abnormalities on scintigraphy (Group 2) (49 +/- 8% and 58 +/- 11%, respectively). Repeat scintigraphic examination in 32 Group 1 patients at a time remote from initial injury showed improvement or resolution of previously defined focal wall motion abnormalities in 27 of 32 patients (84%). The electrocardiogram and serum enzyme tests were insensitive indexes of traumatic myocardial injury when defined by the scintigraphic abnormalities. Thus, severe blunt chest trauma results in a higher frequency of traumatic myocardial injury than heretofore recognized, and frequently involves the anteriorly situated right ventricle.

Pulmonary accumulation of polymorphonuclear leukocytes in the adult respiratory distress syndrome

The polymorphonuclear leukocyte (PMN) plays an integral role in the development of permeability pulmonary edema associated with the adult respiratory distress syndrome (ARDS). This report describes 3 patients with ARDS secondary to systemic sepsis who demonstrated an abnormal diffuse accumulation of Indium (111In)-labeled PMNs in their lungs, without concomitant clinical or laboratory evidence of a primary chest infection. In one patient, the accumulation of the pulmonary activity during an initial pass suggested that this observation was related to diffuse leukoaggregation within the pulmonary microvasculature. A 4th patient with ARDS was on high-dose corticosteroids at the time of a similar study, and showed no pulmonary accumulation of PMNs, suggesting a possible reason for the reported beneficial effect of corticosteroids in human ARDS.

Relative myocardial depression in normotensive sepsis

To assess biventricular performance in normotensive sepsis, the measurements of cardiovascular function in 69 septic patients were compared with those in 18 similarly hyperdynamic patients who had sustained multisystem trauma. All studies were performed following initial resuscitation, during a period in which the blood pressure was stable and no sympathomimetics were required. Although the two study groups demonstrated a similar increase in the mean cardiac index (CI), and similar levels of systemic oxygen transport and consumption, the machanisms by which these groups maintained the high Cl were dissimilar. Mean ejection fractions were significantly lower in the septic group than in the trauma group for both the left ventricles (0.49 ± 0.13 v 0.62 ± 0.10; P < .001) and right ventricles (0.41 ± 0.10 v 0.50 ± 0.10; P < .005). Concurrently, mean end-diastolic volume indexes were significantly greater in the septic group for both the left ventricles (97 ± 31 v 74 ± 18 mL/m2; P < .005) and right ventricles(117 ± 45v 91 ± 25 mL/m2; P < .05). Thus, indexes of myocardial performance influenced by ventricular contractility were not augmented in septic patients to the same degree as was found in a similarly hyperdynamic reference group. This study suggests that normotensive, hyperdynamic sepsis is associated with a “relative” depression in biventricular contractile performance when compared with a reference group of similarly hypermetabolic, but nonseptic, patients.

Modified-Release Recombinant Human TSH (MRrhTSH) Augments the Effect of 131I Therapy in Benign Multinodular Goiter: Results from a Multicenter International, Randomized, Placebo-Controlled Study

BACKGROUND Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.