Elements of margin of safety, toxicity and action of sodium selenite in a lipopolysaccharide rat model.

PROJECT: Both septic shock and sodium selenite (Na2SeO3) lead to multiple organ failure through oxidation. Na2SeO3 has direct oxidant effects above the nutritional level and indirect anti-oxidant properties. In a lipopolysaccharide (LPS) rat model we assessed margin of safety, toxicity and beneficial effect of pentahydrate Na2SeO3 (5H2O·Na2SeO3) at oxidant doses. PROCEDURE: In a three-step study on 204 rats we: (i) observed toxic effects of Na2SeO3 injected intraperitoneously (IP) and determined its Minimum Dose Without Toxic effect (MDWT) 0.25-0.35 mg/kg selenium (Se) content; (ii) injected IP LPS at 70% lethal dose (LD) followed, or not, one hour later by IP Na2SeO3 at MDWT and (iii) by doses>MDWT. At 48 h, in survivors, we measured plasma creatinine, lactate, aspartate and alanine aminotransferase (AST, ALT), nitric oxide (NO) and Se concentrations. RESULTS: (i) Na2SeO3 alone did not increase NO and lactate. Encephalopathy appeared at 1mg Se/kg. Creatinine increased at 1-1.75 mg Se/kg, AST, ALT at 3-4.5 mg Se/kg, and the minimum LD was 3 mg Se/kg. (ii) Mortality after LPS was 37/50 (74%, [62-86%]) vs. 20/30 (67%, [50-84%]) when followed by Na2SeO3 at MDWT (p=0.483) with a decreased in NO (-31%, p=0.038) a trend for lactate decrease (-19%, p=0.068) and an increased Se in plasma of survivals. (iii) All rats died at doses ≥0.6 mg/kg (p<0.001). CONCLUSION: Mechanisms of LPS and Na2SeO3 toxicity differ (i.e. NO, lactate). In septic shock 5H2O·Na2SeO3 toxicity increased, margin of safety decrease, but IP administration of dose considered as oxidant of 5H2O·Na2SeO3 showed beneficial effects.

Dr House, TV, and reality...

BACKGROUND: Medical practice in the media is usually far from reality. Thus, the viewer may be led astray. The world-famous fictional Dr House has to face a difficult diagnosis every week. His practice does not seem to reflect reality. The aim of this study was to assess the diagnosis strategy involved in this television program. METHODS: An observer has previewed the 2011 season. The episode running time, the patient's age and sex, the list of all investigations and interventions, the final diagnosis, and the patient's outcome were collected. Number and proportion of French viewers for each episode were recorded. RESULTS: We analyzed 18 episodes. The median running time was 42.5 (42.1-43.2) minutes. Main patient characters were 12 men (66%) and 6 women (33%); the average age was 31 (22-38) years. There were 225 investigations or interventions reported, averaging 14 (9-15) per episode, representing one examination every 3.1 (2.9-4.8) minutes. The most frequently prescribed investigations were magnetic resonance imaging (MRI; 13; 72%), blood sample (11; 61%), and biopsy (10; 56%). The most frequent interventions were surgery, anti-infectious treatments, and steroid treatments (9 each; 50%). Two patients (11%) died. The median number of spectators was 8.4 (8.1-8.7) million, corresponding to 33% (33%-34%) of the French national audience. CONCLUSION: The population and the examination strategies used by Dr House were unrealistic. Because of this distortion, patients may not understand, nor accept the delay, the investigation choices, the intervention costs, risks, nor failures of a daily medical practice. Physicians should be aware of this "information bias."

Urgent endoscopy in severe non-variceal upper gastrointestinal hemorrhage: does the Glasgow-Blatchford score help endoscopists?

OBJECTIVE: The Glasgow-Blatchford score (GBS) has been validated to select severe patients with non-variceal upper gastrointestinal hemorrhage (UGIH). The aim was to compare the yield of the triage based on the GBS with an endoscopist' decision to perform an urgent upper gastrointestinal endoscopy (UGIE) in newly admitted patients and inpatients with UGIH in the setting of an endoscopy on-duty service in 13 tertiary care centers. MATERIAL AND METHODS: During a 6-month period, GBS and patient data were collected for all patients with non-variceal UGIH for whom an UGIE was requested in emergency. If patients experienced severe endoscopic lesion, surgery or death, they were categorized as patients who had been at need for urgent UGIE. RESULTS: The 102 UGIH patients included (mean age 62, men 73%) had a median GBS of 12 (range 0-21), significantly lower for new patients compared with inpatients (11, range 0-21 vs. 14, range 2-21, respectively, p = 0.001). If triage for urgent UGIE had followed the GBS, no more patients would have had an urgent UGIE compared with what endoscopists performed (99/102 (97%) vs. 92/102 (90%), respectively, p = 0.09). Sensitivity for the detection of patients who needed an UGIE was no different with the GBS than endoscopists (98% vs. 98%, respectively, p = 0.10) and both showed insufficient specificity (4% and 19%, respectively). CONCLUSIONS: The GBS does not detect more patients at need for urgent UGIE than on-duty endoscopists. Both methods lead to numerous unjustified UGIEs. A score that would equally help endoscopists in their decision to intervene urgently is still warranted.

Gender as a risk factor for pulmonary embolism after air travel.

It was the objective of this study to confirm the hypothesis that women experience an increased risk of pulmonary embolism (PE) and/or thromboembolic events after long-distance air travel. We systematically reviewed the records of all patients with confirmed pulmonary embolism after arrival at Roissy-Charles-de-Gaulle (CDG) Airport (Paris, France) during a 13-year period. The incidence of PE was calculated as a function of distance travelled and gender using Bayesian conditional probabilities obtained in part from a control population of long-distance travellers arriving in French Polynesia (Tahiti). A total of 287.6 million passengers landed at CDG airport during the study period. The proportion of male to female long-distance travellers was estimated to be 50.5% to 49.5%. Overall, 116 patients experienced PE after landing [90 females (78%), 26 males (22%)]. The estimated incidence of PE was 0.61 (0.61-0.61) cases per million passengers in females and 0.2 (0.20-0.20) in males, and reached 7.24 (7.17-7.31) and 2.35 (2.33-2.38) cases, respectively, in passengers travelling over 10,000 km. Our study strongly suggests that there is a relationship between risk of PE after air travel and gender. This relationship needs to be confirmed in order to develop the best strategy for prophylaxis.

Using data mining techniques to explore physicians' therapeutic decisions when clinical guidelines do not provide recommendations: methods and example for type 2 diabetes.

BACKGROUND: Clinical guidelines carry medical evidence to the point of practice. As evidence is not always available, many guidelines do not provide recommendations for all clinical situations encountered in practice. We propose an approach for identifying knowledge gaps in guidelines and for exploring physicians' therapeutic decisions with data mining techniques to fill these knowledge gaps. We demonstrate our method by an example in the domain of type 2 diabetes. METHODS: We analyzed the French national guidelines for the management of type 2 diabetes to identify clinical conditions that are not covered or those for which the guidelines do not provide recommendations. We extracted patient records corresponding to each clinical condition from a database of type 2 diabetic patients treated at Avicenne University Hospital of Bobigny, France. We explored physicians' prescriptions for each of these profiles using C5.0 decision-tree learning algorithm. We developed decision-trees for different levels of detail of the therapeutic decision, namely the type of treatment, the pharmaco-therapeutic class, the international non proprietary name, and the dose of each medication. We compared the rules generated with those added to the guidelines in a newer version, to examine their similarity. RESULTS: We extracted 27 rules from the analysis of a database of 463 patient records. Eleven rules were about the choice of the type of treatment and thirteen rules about the choice of the pharmaco-therapeutic class of each drug. For the choice of the international non proprietary name and the dose, we could extract only a few rules because the number of patient records was too low for these factors. The extracted rules showed similarities with those added to the newer version of the guidelines. CONCLUSION: Our method showed its usefulness for completing guidelines recommendations with rules learnt automatically from physicians' prescriptions. It could be used during the development of guidelines as a complementary source from practice-based knowledge. It can also be used as an evaluation tool for comparing a physician's therapeutic decisions with those recommended by a given set of clinical guidelines. The example we described showed that physician practice was in some ways ahead of the guideline.

An automated method for analyzing adherence to therapeutic guidelines: application in diabetes.

BACKGROUND: Physicians' adherence to guidelines can be used for measuring prescribing appropriateness. We present a simple approach allowing the automation of this process. DESIGN: The drug therapy is described in terms of treatment type, pharmacotherapeutic classes, international non proprietary names (INN) and doses. A rule-based engine implementing the guideline generates recommendations for each patient record. These are automatically compared with prescriptions of the same patient in three levels of detail. PARTICIPANTS: Ambulatory patients admitted for the follow-up of their type 2 diabetes between June 2003 and September 2004 in a university hospital in France. RESULTS: For 574 patient records included in the study, physicians agreed with the guideline recommendations over the choice of type of treatment in 473 cases (82%). When agreement over pharmacotherapeutic class of drugs was also taken into account, the adherence ratio decreased to 448 cases (78%). Finally, when the dosage of each drug was taken into account, the adherence ratio dropped to 396 cases (69%). Adherence ratios were also dependent on the type of treatment at admission: low for patients on oral tritherapy, and on diet and exercise. The results also highlighted inertia of physicians for beginning drug therapy and the underuse of biguanides. CONCLUSIONS: The proposed method provides an automatable way of measuring the appropriateness of treatment choice, which can be used for chronic diseases.

Association of androgenetic alopecia and hypertension.

Androgenetic alopecia is considered to be associated with coronary heart disease but the explanation of this association remains unknown. Hypertension is highly prevalent in patients with coronary heart disease. Essential hypertension is linked to hyperaldosteronism and spironolactone, an antihypertensive drug which is a mineralocorticoid receptor antagonist, has been used for a long time in the treatment of androgenic alopecia. We recently observed in a double transgenic mouse model that overexpression of a mineralocorticoid receptor targeted to the skin induced the development of alopecia. We prospectively studied the association of hypertension and androgenetic alopecia in Caucasian men. Two hundred and fifty Caucasian men aged 35-65 years were consecutively recruited by 5 general practitioners (50 per practitioner). Data collected included age, androgenetic alopecia score with a simplified Norwood's score (0-4), blood pressure or history of hypertension, smoking, history of diabetes mellitus or hyperlipidemia, familial history of androgenetic alopecia, and treatment. Chi-square, Fisher exact tests and linear regression model were used for statistical analysis. Hypertension was strongly associated to androgenetic alopecia (p < 0.001). Linear regression tests confirmed that this association was independent of age : odds ratio was 2.195 (95% CI : 1.1-4.3). Familial history of androgenetic alopecia was also strongly associated with androgenetic alopecia : odds ratio was 10.870 (95% CI : 4.3-27.1). Other variables (diabetes mellitus, hyperlipidemia, smoking, treatment) were not associated with androgenetic alopecia. We were limited by a relatively small study sample but in this study androgenetic alopecia was strongly associated with hypertension. Association of androgenetic alopecia and hyperaldosteronism warrants additional studies. The use of specific mineralocorticoid receptor antagonists could be of interest in the treatment of androgenetic alopecia.

Intravenous fluid temperature management by infrared thermometer.

BACKGROUND: The management of intravenous (IV) fluid temperature is a daily challenge in critical care, anesthesiology, and emergency medicine. Infusion of IV fluids at the right temperature partly influences clinical outcomes of critically ill patients. Nowadays, intravenous fluid temperature is poorly managed, as no suitable device is routinely available. Infrared (IR) thermometers have been recently developed for industrial, personal, or medical purposes. The aim of this study was to evaluate the accuracy of an IR thermometer in measuring temperature of warmed and cooled infusion fluids in fluid bags. METHODS: This study compared temperatures simultaneously recorded by an infrared thermometer and a temperature sensor. Temperatures of warmed (41 degrees C) and cooled (4 degrees C) infusion fluids in fluid bags were recorded by 2 independent operators every minute until IV bags' temperature reached ambient temperature. RESULTS: The relation curve was established with 576 measures. Temperature measures performed with an IR thermometer were perfectly linear and perfectly correlated with the reference method (R(2) = 0.995, P < 10(-5)). CONCLUSION: Infrared thermometers are efficient to measure IV fluid bag temperature in the range of temperatures used in clinical practice. As these devices are easy to use and inexpensive, they could be largely used in critical care, anesthesiology, or emergency medicine.

Colonic response to food in constipation.

OBJECTIVES: Colonic response to food is possibly abnormal in constipation. METHODS: The colonic response to food was evaluated in 323 patients and 60 healthy subjects by following the movements of radiopaque markers after ingestion of a standard 1,000-cal test meal. Constipated patients were divided into four groups: one with a normal, and three with a delayed colorectal transit time. When the delay was found mainly in the ascending colon, the group was labeled as suffering from "colonic inertia". In "hindgut dysfunction", the delay was predominantly found in the descending colon, whereas the term "outlet obstruction" was reserved for constipated patients whose major site of delay was the rectosigmoid area. Colonic response to food was quantified by evaluating the variation of markers in a given abdominal region and the evolution of the geometric center on the entire plain film of the abdomen. RESULTS: Emptying of the caecum-ascending colon and filling of the rectosigmoid area characterize the colonic response to food in healthy subjects. Constipated patients also filled the rectosigmoid, but different patterns were found in the colon. In constipated patients with transit in the normal range, there was a frequent (41%) absence of colonic response to food as compared to controls (13%) and constipated patients with delayed transit (p<0.0001). The response to food of patients with colonic inertia was similar to that of healthy subjects in terms of distal progression, but less marked. The hindgut dysfunction group emptied the entire left colon but failed to empty the caecum and ascending colon. In the outlet obstruction group, there was no distal progress of the geometric center after meal. CONCLUSIONS: Abnormal colonic response to food is frequently found in constipated patients, with different patterns according to the type of constipation.

Association among individual deprivation, glycemic control, and diabetes complications: the EPICES score.

OBJECTIVE: Previous studies have related poor glycemic control and/or some diabetes complications to low socioeconomic status. Some aspects of socioeconomic status have not been assessed in these studies. In the present study, we used an individual index of deprivation, the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé (Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES]) score, to determine the relationship among glycemic control, diabetes complications, and individual conditions of deprivation. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional prevalence study in 135 consecutive diabetic patients (age 59.41 +/- 13.2 years [mean +/- SD]) admitted in the hospitalization unit of a French endocrine department. Individual deprivation was assessed by the EPICES score, calculated from 11 socioeconomic questions. Glycemic control, lipid levels, blood pressure, retinopathy, neuropathy, and nephropathy were assessed. RESULTS: HbA(1c) level was significantly correlated with the EPICES score (r = 0.366, P < 0.001). The more deprived patients were more likely than the less deprived patients to have poor glycemic control (beta = 1.984 [SE 0.477], P < 0.001), neuropathy (odds ratio 2.39 [95% CI 1.05-5.43], P = 0.037), retinopathy (3.66 [1.39-9.64], P = 0.009), and being less often admitted for 1-day hospitalization (0.32 [0.14-0.74], P = 0.008). No significant relationship was observed with either nephropathy or cardiovascular risk factors. CONCLUSIONS: Deprivation status is associated with poor metabolic control and more frequent microvascular complications, i.e., retinopathy and neuropathy. The medical and economic burden of deprived patients is high.

Basic cardiac life support providers checking the carotid pulse: performance, degree of conviction, and influencing factors.

UNLABELLED: The American Heart Association recently abolished the carotid pulse check during cardiopulmonary resuscitation for lay rescuers, but not for health care providers. OBJECTIVES: The aim of the study was to evaluate health care providers' performance, degree of conviction, and influencing factors in checking the carotid pulse. METHODS: Sixty-four health care providers were asked to check the carotid pulse for 10 or 30 seconds on a computerized mannequin simulating three levels of pulse strength (normal, weak, and absent). Health care providers were asked whether they felt a pulse and how certain were they that they felt a pulse. Performance was evaluated, as well as degree of conviction about the answer, using a visual analog scale. Data were compared by using a general linear model procedure. RESULTS: In the pulseless situations, the answers were correct in 58% and 50% when checking the pulse for 10 and 30 seconds, respectively. In the situation with a weak pulse, the answer was correct in 83% when checking the pulse for 10 seconds. In situations with a normal pulse, the answers were correct in 92%, 84%, and 84%, respectively, when checking the pulse for 10 (twice) and 30 seconds. The exactitude of the answer was correlated with the pulse strength (p < 0.05). The degree of conviction about the answer was correlated with the exactitude of the answer (p < 0.01) and the pulse strength (p < 0.0001). CONCLUSIONS: These results question the routine use of the carotid pulse check during cardiopulmonary resuscitation, including for health care providers.

Membrane and capillary blood components of diffusion capacity of the lung for carbon monoxide in pulmonary sarcoidosis: relation to exercise gas exchange.

BACKGROUND: Resting pulmonary diffusing capacity of the lung for carbon monoxide (DLCO) is known to be the best predictor of arterial desaturation during exercise in patients with sarcoidosis. However, the relative contribution of each of the two components of DLCO-alveolar membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc)-remains unclear. STUDY OBJECTIVES: To evaluate which component is responsible for the decrease of resting DLCO in patients with sarcoidosis, and to determine which resting pulmonary function test, including Dm and Vc, is the best predictor of gas exchange abnormalities during submaximal exercise. DESIGN: Prospective analysis of patients referred to our department of respiratory medicine. PATIENTS: Twenty four patients with pulmonary sarcoidosis were separated into two groups according to chest radiographic findings: group 1, stages 2 and 3 (n = 15); group 2, stage 4 (n = 9). All the patients completed pulmonary function tests (flows, volumes, single-breath DLCO, transfer coefficient [Ka], Dm, Vc) and submaximal exercise (two steady-state levels of mild and moderate exercise corresponding respectively to a target oxygen consumption of approximately 10 to 15 mL/min/kg). RESULTS: DLCO was reduced in the two groups (group 1, 63 +/- 16% of predicted; group 2, 64 +/- 16% of predicted). Dm was severely decreased (group 1, 58 +/- 24% of predicted; group 2, 51 +/- 15% of predicted), whereas Vc was unchanged or only mildly decreased (group 1, 81 +/- 18% of predicted; group 2, 85 +/- 28% of predicted). Whatever the group of patients and the exercise level, Dm and DLCO were the strongest predictors (p < 0.001) of gas exchange abnormalities. Ka or volumes were weak predictors, and Vc or flows were not related with exercise gas exchange. CONCLUSIONS: This study demonstrates that a decrease in Dm mostly accounts for resting DLCO reduction, and that Dm as well as DLCO are highly predictive of gas exchange abnormalities at exercise in patients with sarcoidosis.

Assessing residual neuromuscular blockade using acceleromyography can be deceptive in postoperative awake patients.

UNLABELLED: Postoperative awake patients may have significant residual neuromuscular block. In awake patients, the results of accelerometry are affected by extra movements to which the thumb may be subject. In this study, we evaluated the repeatability of train-of-four (TOF) ratio using acceleromyography in 253 patients recovering from anesthesia. Immediately after arrival in the postanesthesia care unit, the ulnar nerve was stimulated with TOF stimulation. The evoked response at the thumb was measured by the TOF-Watch apparatus. The current intensity was 30 mA. Two TOF stimulations were applied and recorded at 30-s intervals. A Bland-Altman test was used. The Kappa (kappa) test for clinical agreement between the two measurements was also calculated according to the presence or absence of a residual neuromuscular blockade, defined as a TOF ratio <0.9. According to the presence of a residual neuromuscular blockade, the paired TOF ratios were discordant in 61 patients (24%; 95% confidence interval, 21%-27%). The kappa test indicated a moderate agreement (k = 0.47). We demonstrated that accelerometry as used in this study is not always accurate. Two isolated acceleromyograph TOF ratios are not an accurate representation of the neuromuscular status of the patient recovering from anesthesia. IMPLICATIONS: Clinicians should be aware that acceleromyography as used in this study does not always provide precise train-of-four ratio measurements. Two isolated acceleromyograph train-of-four ratios are not an accurate representation of the neuromuscular status of the patient recovering from anesthesia.

Cardiac troponin I in patients with severe exacerbation of chronic obstructive pulmonary disease.

OBJECTIVES: Co-morbid conditions including risk factors for cardiovascular diseases and left ventricular dysfunction are common in patients with chronic obstructive pulmonary disease (COPD). This study assessed the incidence of cardiac troponin I (cTnI) elevation, a specific marker for cardiac injury, and its prognostic significance during severe exacerbation of COPD. DESIGN: Prospective cohort study. SETTING: Two intensive care units. PARTICIPANTS: Seventy-one consecutive patients admitted for severe exacerbation of COPD. INTERVENTION: None. MEASUREMENTS AND RESULTS: Cardiac troponin I was assayed in blood samples obtained on admission and 24 h later (Stratus II immunoassay analyser, Dade International). Levels above 0.5 ng/ml were considered positive. The following data were recorded prospectively: clinical symptoms, co-morbidities, cause of the exacerbation, diagnostic procedures and treatment, general severity score (SAPS II) and in-hospital outcome. CTnI was positive in 18% of patients (95% confidence interval (CI(95)), 11-29%), with a median value at 1.00 ng/ml; CI(95 )(0.60-1.70). Eighteen patients died in the hospital (25%; CI(95), 17-37%). Only cTnI (adjusted odds ratio (ORa), 6.52; CI(95),1.23-34.47) and SAPS II 24 h after admission (ORa, 1.07; CI(95), 1.01-1.13) were independent predictors of in-hospital mortality. CONCLUSION: Elevated cTnI is a strong and independent predictor of in-hospital death in patients admitted for acutely exacerbated COPD.

Surgical resection of lung cancer in patients with underlying interstitial lung disease.

BACKGROUND: The association between interstitial lung disease (ILD) and an increased risk of developing lung cancer has been reported. The goal of this retrospective study was to determine the outcome of lung cancer resection among patients with ILD. METHODS: Between January 1979 and March 1999, 27 patients with both lung cancer and ILD were identified. Seven patients with poor pulmonary function tests or distant metastases underwent medical treatment and were excluded from this study. Twenty patients treated by surgical resection were analyzed. RESULTS: Various types of ILD such as sarcoidosis (n = 7), idiopathic interstitial pneumonia (n = 4), histiocytosis X (n = 4), pneumoconiosis (n = 4), and amiodarone-induced ILD (n = 1) were observed. Tumors were located in the peripheral part of the lung in 16 cases. The most frequent tumor cell types were squamous and adenocarcinoma. The resections consisted of lobectomy (n = 16), bilobectomy (n = 1), and pneumonectomy (n = 3). Most cancers were stage I (n = 10) or II (n = 6). There was no postoperative death. The postoperative course was uneventful in 16 cases. The majority of patients (70%) did not experience respiratory insufficiency during the follow-up period. The actuarial 2-year and 5-year survival rates were, respectively, 83.5% and 66.4%. CONCLUSIONS: In this series, the long-term survival of patients who had lung cancer resection appeared to be not affected by the association with ILD. This could be explained by an adequate preoperative selection based on pulmonary function tests and a preferential choice for lobectomies. Thus, surgical resection should be offered to properly selected patients with lung cancer and underlying ILD.

Aminoglycoside and glycopeptide renal toxicity in intensive care patients studied by proton magnetic resonance spectroscopy of urine.

OBJECTIVE: Aminoglycoside and glycopeptide antibiotics are responsible for renal toxicity. In most cases, the nephrotoxicity is limited to a reversible tubular injury, but an acute and sustained renal failure may occur. The aim of our study was to explore the renal function of patients given these antimicrobial agents with proton magnetic resonance spectroscopy of urine. This technique is able to detect, in urine samples, a wide range of metabolites reflecting renal tubular function. The variables assessed by magnetic resonance spectroscopy were compared with the routine markers of renal function: creatinine, urea, and 24-hr urine volume. DESIGN: Prospective clinical study. SETTING: Intensive care unit. PATIENTS: All patients in an intensive care unit receiving an aminoglycoside and/or a glycopeptide were included in the study if they presented with signs of renal dysfunction. All experiments were performed on urine samples collected for the routine follow-up of these patients. INTERVENTION: Proton spectra were acquired with water suppression, and the peak intensity of each metabolite was reported in relationship to the intensity of the creatinine peak. MEASUREMENTS AND MAIN RESULTS: The ratio values obtained by magnetic resonance spectroscopy were compared with the values of creatininemia and blood urea obtained routinely by biochemistry and with the value of the 24-hr urine volume by logistic regression and general linear models. This statistical analysis showed that the ratio of dimethylamine to creatinine was highly correlated with creatininemia. CONCLUSIONS: Dimethylamine is an osmolyte released from the medullar region of the kidney. Thus, our study demonstrated that nephrotoxicity from aminoglycosides and glycopeptides is not limited to proximal tubular toxicity but also may involve the medullar region (Henle loop and collecting duct) of the nephron.