An analysis of adverse events and human error associated with the imaging of patients at a major trauma centre in South Africa.

BACKGROUND: There is growing realisation that human error contributes significantly to morbidity and mortality in modern healthcare. A number of taxonomies and classification systems have been developed in an attempt to categorise errors and quantify their impact. OBJECTIVES: To record and identify adverse events and errors as they impacted on acute trauma patients undergoing a computed tomography (CT) scan, and then quantify the effect this had on the individual patients. It is hoped that these data will provide evidence to develop error prevention programmes designed to reduce the incidence of human error. METHODS: The trauma database was interrogated for the period December 2012 - April 2017. All patients aged >18 years who underwent a CT scan for blunt trauma were included. All recorded morbidity for these patients was reviewed. RESULTS: During the period under review, a total of 1 566 patients required a CT scan at our institution following blunt trauma. Of these, 192 (12.3%, 134 male and 58 female) experienced an error related to the process of undergoing a CT scan. Of 755 patients who underwent a CT scan with intravenous contrast, detailed results were available for 312, and of these 46 (14.7%) had an acute deterioration in renal function. According to Chang's taxonomy, physical harm occurred as follows: grade I n=6, grade II n=62, grade III n=45, grade IV n=11, grade V n=27, grade VI n=21, grade VII n=15, grade VIII n=3 and grade IX n=2. Adverse events were performing an unnecessary scan (n=24), omitting an indicated scan (n=23), performing the scan incorrectly (n=8), scanning the wrong body part (n=7), equipment failure (n=18), omitting treatment following the scan (n=6), incorrect interpretation of the scan (n=65), deterioration during the scan (n=6) and others (n=35). The setting for the error was the ward (n=19), the radiology suite (n=126), the emergency department (n=45) and the operating theatre (n=2). The staff responsible for the adverse events were medical (n=155), nursing (n=4) and radiology staff (n=15). There were 67 errors of commission and 125 errors of omission. The primary cause was a planning problem in 78 cases and an execution problem in 114. CONCLUSIONS: Errors and adverse events related to obtaining a CT scan following blunt polytrauma are not uncommon and may impact significantly on the patient. Communication is essential to eliminate errors related to performing the wrong type of scan. The commonest errors relate to misinterpretation of the scan.

Quantifying the burden of trauma imaging on the CT scan service at a major trauma centre in South Africa.

BACKGROUND: Imaging is an integral part of trauma management and the huge burden of trauma in South Africa places substantial pressures on radiology resources. This study aims to provide a holistic overview of the burden of trauma imaging and the cost of trauma to a busy CT scanning facility at a tertiary hospital in South Africa. METHOD: We set out to describe and quantify the impact of blunt poly-trauma on CT scanning services at Grey's Hospital in Pietermaritzburg. We aimed to provide a holistic assessment in terms of use of equipment and staff, cost to the hospital and overall usage of CT scanning. RESULTS: Over the four-year study period, 1572 patients required a CT scan following blunt torso trauma (mean age: 30 years, 81% males). Of the 1572 patients, 625 had a chest radiograph (40%), 383 a cervical spine X-ray (24%), 347 a pelvic X-ray (22%), 292 a skull X-ray (18%), 193 a limb X-ray (12%), 133 an abdominal radiograph (8%), and 86 a FAST scan (5%). The 1572 CT included: 967 head, 568 neck, 65 chest, 241 abdominal, 228 pelvic, 12 upper limb, 38 lower limb and 394 had full body (Pan) CT scan. The mean total cost of the CT scanning for blunt poly-trauma is ZAR 12 000. The total cost of CT scanning for blunt poly-trauma is 0.92% of the total hospital expenditure. Roughly 7.8% of the total hours worked by the CT scanner over the time period under review was dedicated to blunt poly-trauma. CONCLUSION: Blunt poly-trauma is a preventable disease, which has a major financial impact on the healthcare system in general. This study has documented the tremendous burden it places on an already stretched CT scanning service.

An analysis of adverse events and human error associated with the imaging of patients at a major trauma centre in South Africa

Background. There is growing realisation that human error contributes significantly to morbidity and mortality in modern healthcare. A number of taxonomies and classification systems have been developed in an attempt to categorise errors and quantify their impact.Objectives. To record and identify adverse events and errors as they impacted on acute trauma patients undergoing a computed tomography (CT) scan, and then quantify the effect this had on the individual patients. It is hoped that these data will provide evidence to develop error prevention programmes designed to reduce the incidence of human error.Methods. The trauma database was interrogated for the period December 2012 - April 2017. All patients aged >18 years who underwent a CT scan for blunt trauma were included. All recorded morbidity for these patients was reviewed.Results. During the period under review, a total of 1 566 patients required a CT scan at our institution following blunt trauma. Of these, 192 (12.3%, 134 male and 58 female) experienced an error related to the process of undergoing a CT scan. Of 755 patients who underwent a CT scan with intravenous contrast, detailed results were available for 312, and of these 46 (14.7%) had an acute deterioration in renal function. According to Chang's taxonomy, physical harm occurred as follows: grade I n=6, grade II n=62, grade III n=45, grade IV n=11, grade V n=27, grade VI n=21, grade VII n=15, grade VIII n=3 and grade IX n=2. Adverse events were performing an unnecessary scan (n=24), omitting an indicated scan (n=23), performing the scan incorrectly (n=8), scanning the wrong body part (n=7), equipment failure (n=18), omitting treatment following the scan (n=6), incorrect interpretation of the scan (n=65), deterioration during the scan (n=6) and others (n=35). The setting for the error was the ward (n=19), the radiology suite (n=126), the emergency department (n=45) and the operating theatre (n=2). The staff responsible for the adverse events were medical (n=155), nursing (n=4) and radiology staff (n=15). There were 67 errors of commission and 125 errors of omission. The primary cause was a planning problem in 78 cases and an execution problem in 114.Conclusions. Errors and adverse events related to obtaining a CT scan following blunt polytrauma are not uncommon and may impact significantly on the patient. Communication is essential to eliminate errors related to performing the wrong type of scan. The commonest errors relate to misinterpretation of the scan

Reference spirometric values in a Sudanese cohort.

To determine normal values of respiratory function for Sudanese, a randomized stratified cross-sectional study was performed on 2250 healthy Sudanese aged 7-86 years in 2002-05. Data were obtained through a questionnaire, pulmonary function testing and taking anthropometric measurements. Lung function and anthropometric measurements were correlated and regression equations were derived. Sudanese of Arab ethnic background had significantly higher forced vital capacity (FVC), forced expiratory volume in 1 (first) second (FEVI) and peak expiratory flow rate (PEFR) than those of African ethnicity. In adults a positive correlation was found between lung function and height and a negative correlation with age. Gender and ethnic variations in Sudanese lung function were confirmed. Comparisons were made with data from other international studies. These values can be used as reference values in respiratory clinics in Sudan.

Reference spirometric values in a Sudanese cohort

To determine normal values of respiratory function for Sudanese, a randomized stratified crosssectional study was performed on 2250 healthy Sudanese aged 7-86 years in 2002-05. Data were obtained through a questionnaire, pulmonary function testing and taking anthropometric measurements. Lung function and anthropometric measurements were correlated and regression equations were derived. Sudanese of Arab ethnic background had significantly higher forced vital capacity [FVC], forced expiratory volume in 1 [first] second [FEV1] and peak expiratory flow rate [PEFR] than those of African ethnicity. In adults a positive correlation was found between lung function and height and a negative correlation with age. Gender and ethnic variations in Sudanese lung function were confirmed. Comparisons were made with data from other international studies. These values can be used as reference values in respiratory clinics in Sudan

Prostate cancer risk: the significance of differences in age related changes in serum conjugated and unconjugated steroid hormone concentrations between Arab and Caucasian men.

INTRODUCTION: Factors responsible for the low incidence of clinical prostate cancer (3-8/100,000 men/year) in the Arab population remain unclear, but may be related to changes in steroid hormone metabolism. We compared the levels of serum conjugated and unconjugated steroids between Arab and Caucasian populations, to determine if these can provide a rational explanation for differences in incidence of prostate cancer between the two populations. PATIENTS/METHOD: Venous blood samples were obtained from 329 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-80 years. Samples were also obtained from similar Arab men with newly diagnosed prostate cancer or benign prostatic hyperplasia (BPH). The samples were taken between 8:00 am and 12:00 noon. Serum levels of total testosterone, (TT), sex hormone binding globulin (SHBG), free androgen index (FAI); adrenal C19-steroids, dehydroepiandrosterone sulphate (DHEAS) and androstenedione (ADT) were determined using Immulite kits (Diagnostic Systems Laboratories Inc, Webster Texas, USA). The results obtained in Arab men were compared with those reported for similarly aged Chinese, German and White USA men. RESULTS: In all four ethnic groups, median TT and FAI declined with age, while SHBG increased with age. However, the mean TT and SHBG was significantly lower (p < 0.01) and the FAI significantly higher in Arab men (p < 0.01) compared to German men only in 21-30 years age group. In the other age groups the levels of TT and SHBG were higher in the Germans but the differences were not statistically significant. In all the racial groups serum levels of DHEAS and ADT reached a peak by about 20 years of life, and then declined progressively. The mean DHEAS in American Caucasians aged 20-29 years was 11.4 micromol/l compared to 6.22 micromol/l in the Arabs (p < 0.001). The mean DHEAS in USA Caucasians aged 70-79 years was 2.5 micromol/l compared to 1.8 micromol/l (p < 0.03) in the Arabs. There was no significant difference in mean serum levels of DHEAS between German and USA men. Similarly, there was no significant difference in the level of the hormones between Arab and Chinese men. Arab men with newly diagnosed prostate cancer had high serum TT, SHBG and DHEAS compared to those without the disease. CONCLUSIONS: The mean TT and SHBG was significantly lower in Arab men compared to Caucasian men especially in early adulthood. Caucasians have significantly higher serum levels of the precursor androgens DHEAS and ADT especially in early adulthood compared to Arab men. These observations of low circulating androgens and their adrenal precursors in Arab men may partially account for the decreased risk for prostate cancer among Arab men.

Putative role of serum insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) levels in the development of prostate cancer in Arab men.

INTRODUCTION: The incidence of clinical prostate cancer in the Arab population is among the lowest in the world. High serum IGF-1 level has been implicated as a possible risk factor for the development of prostate cancer in Caucasians. The purpose of this study was to determine serum IGF-1 and IGFBP-3 levels in healthy Arab men and in Arab men with newly diagnosed benign prostatic hyperplasia (BPH) and prostate cancer, and to compare these values with values reported in Caucasians. PATIENTS AND METHODS: Subjects were recruited in two groups: (a) indigenous, healthy Arab men aged 15-90 y (n = 383); (b) Arab men with newly diagnosed prostate cancer (n = 30) or BPH (n = 40). Blood was obtained from fasting patients and volunteers, between 8:00 a.m. and 12:00 noon. The serum concentrations of IGF-1 and IGFBP-3 were determined using Immunoradiometric assay (IRMA) kits. RESULTS: As in Caucasians, serum IGF-1 and IGFBP-3 levels declined with age in Arab men. The mean +/- s.d. of serum IGF-1 levels in healthy Arab men in the age group 15-20, 51-60, 61-70 y were lower (376.2 +/- 153.2, 134.9 +/- 105.7 and 89.6 +/- 48.4 ng/ml, respectively), compared to values reported for similarly aged Caucasians. Arab men with newly diagnosed prostate cancer had significantly higher serum IGF-1 level (P < 0.01) and lower IGFBP-3 levels (P < 0.01) compared to age-matched Arabs without the disease. CONCLUSIONS: Arab men have lower serum IGF-1 levels compared to Caucasians and this may be an important factor in the explanation of the low incidence of prostate cancer in the Arab population.

Functional responses of the rat isolated seminal vesicle to electrical field stimulation: a pharmacological analysis.

1. Electrical field stimulation (EFS) of the rat isolated seminal vesicle elicited frequency-dependent and tetrodotoxin sensitive contractions which were unaltered by hexamethonium or mecamylamine. 2. Prazosin alone was not sufficient to abolish these responses, but a combination of atropine and prazosin was fully effective, indicating involvement of both noradrenergic and cholinergic mechanisms. 3. Responses were predominantly cholinergic (blocked by atropine, potentiated by ecothiopate but not significantly altered by prazosin or guanethidine) at 1-8 Hz but became increasingly noradrenergic (blocked by prazosin or guanethidine but relatively unaltered by atropine or ecothiopate) with increasing frequencies of stimulation. 4. Electrical field stimulation of seminal vesicles removed from reserpine or 6-hydroxydopamine (6-OHDA)-pretreated rats produced contractions that were clearly cholinergic in nature. 5. After exposing the seminal vesicles to guanethidine, or after pretreatment of rats with 6-OHDA, responses to EFS remained, indicating that activation of discrete cholinergic and noradrenergic innervations seem to underlie the contractile responses observed. 6. Yohimbine and prazosin potentiated the predominantly cholinergic responses at 1, 2 and 4 Hz in tissues from untreated rats, but not in those from animals pretreated with reserpine or 6-OHDA, indicating the possibility of an interaction between the two innervations. 7. No inhibitory responses to EFS could be demonstrated in tissues precontracted with KCl in the presence of a combination of atropine and prazosin suggesting the absence of a nonadrenergic, noncholinergic inhibitory innervation.

Effects of fish oil and sunflower oil supplementations on gentamicin-induced nephrotoxicity in rat.

1. Nephrotoxicity was induced in rats by intramuscular administration of gentamicin (80 mg k-1 d-1) for 6 days. 2. Oral supplementation with fish oil (5 ml kg-1 d-1), for 2 weeks prior to and during gentamicin exposure, markedly ameliorated the drug-induced nephrotoxicity. The beneficial effects of oil were evidenced by significantly reduced serum creatinine and urea concentrations, increased renal cortical alkaline phosphatase activity and improved renal tubular histology, compared with the non oil-treated animals, receiving gentamicin. 3. Similar supplementation with sunflower oil, rich in omega-6 fatty acids, failed to reverse any of the parameters of nephrotoxicity induced by gentamicin. 4. Hypercholesterolaemia and reduced cortical GSH associated with gentamicin nephrotoxicity were both normalised by supplementation with fish oil, but not by sunflower oil. 5. The beneficial effects of fish oil on gentamicin-induced nephrotoxicity were not related to the extent of uptake and accumulation of the drug by the kidney.

The effect of thyroxine or carbimazole treatment on gentamicin nephrotoxicity in rats.

1. This study examines the effect of treating rats with gentamicin (80 mg kg-1 day-1 intramuscularly (i.m.), for 6 days) alone or with either L-thyroxine or the anti-thyroid drug carbimazole. 2. Gentamicin produced significant increases in serum creatinine and urea concentrations, and significantly reduced the activity of Na+,K+ATPase in renal cortex. The concentration of serum triiodothyronine (T3) was unaffected by graded doses (20, 40 and 80 mg kg-1) of the antibiotic. Histopathologically, gentamicin produced necrosis of proximal tubules in the renal cortical tissues of treated rats. 3. Treatment of rats with either L-thyroxine or carbimazole alone did not significantly affect any of the biochemical variables investigated. Carbimazole alone produced only mild tubular necrosis. 4. Treatment of rats with either L-thyroxine (100 micrograms kg-1 day-1, subcutaneously) for 10 days, and gentamicin (80 mg kg-1, i.m. daily during the last 6 days of treatment significantly reduced the gentamicin-induced increases in serum creatinine and urea concentrations, and increased the activity of cortical N+,K+ATPase to control levels. Histopathologically, the severity of gentamicin-induced tubular necrosis was reduced by L-thyroxine treatment. 5. Carbimazole (12 mg ml-1 in drinking water for 21 days) and gentamicin (80 mg kg-1 i.m.) daily during the last 6 days of treatment, stimulated the increase in serum urea concentration produced by gentamicin, but did not significantly affect the gentamicin-induced changes in serum creatinine or cortical N+,K+ATPase.

Influence of iron, deferoxamine and ascorbic acid on gentamicin-induced nephrotoxicity in rats.

1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg for 6 days. Treated animals demonstrated a typical pattern of nephrotoxicity characterized by increased serum creatinine and urea concentrations, and by necrosis of proximal tubular epithelium. 2. Pretreatment of rats with iron (Fe3+) at daily i.m. doses of 2, 4 and 8 mg/kg for 14 days, with gentamicin given during the last 6 days of treatment, significantly potentiated the gentamicin-induced increases in creatinine and urea concentrations and exacerbated renal histological damage. 3. Gentamicin significantly increased serum Fe3+ concentration in rats treated with Fe3+ and gentamicin, compared to Fe(3+)-treated rats. 4. The Fe3+ antidote deferoxamine (100 mg/kg, i.m.) given with gentamicin was ineffective in antagonizing the potentiating effect of Fe3+ on gentamicin-induced nephrotoxicity. 5. Ascorbic acid (50 mg/kg, i.m. for 14 days) was ineffective in altering the nephrotoxicity of gentamicin (80 mg/kg) given during the last 6 days of treatment. At a dose of 100 mg/kg for 14 days, ascorbic acid significantly reduced gentamicin-induced increases in creatinine and urea levels, and ameliorated proximal tubular damage. However, at a dose of 200 mg/kg, ascorbic acid exacerbated gentamicin-induced increases in creatinine and urea levels and increased the severity of the histological damage.

Effect of fish oil treatment on gentamicin nephrotoxicity in rats.

The effect of fish oil on gentamicin-induced nephrotoxicity was investigated in rats. Gentamicin (80 mg/kg/day intramuscularly for 6 days) produced the typical pattern of nephrotoxicity as shown by increases in serum creatinine and urea concentrations, and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and proximal renal tubular necrosis. Fish oil (5.0 ml/kg/kday per os for 10 days) partially protected against the nephrotoxicity induced by gentamicin administered during the last 6 days of treatment with fish oil by returning the creatinine and urea concentrations and NAG activity to normal and by ameliorating the histopathological damage. Olive oil (5 mg/kg/day per os for 10 days) was ineffective in protecting rats against gentamicin nephrotoxicity.

Effect of gentamicin-induced nephrotoxicity on some carbohydrate metabolic pathways in the rat renal cortex.

Rats were injected with gentamicin at doses of 20, 40 and 80 mg/kg per day for 6 consecutive days. The treatment caused nephrotoxicity as evidenced by dose-related increases in serum creatinine concentration and renal tubular necrosis. The nephrotoxicity was accompanied by reduced renal cortical and fasting blood glucose levels, and by increases in serum lactate concentrations. The activities of cortical malate dehydrogenase and alanine transaminase were significantly reduced by the three doses of gentamicin. On the other hand, aspartate transaminase activity was lowered only by the highest dose of antibiotic used. However, the activity of cortical glucose-6-phosphate dehydrogenase was altered by the 20 and 40 mg/kg doses of gentamicin, but not by the 80 mg/kg dose. The two lower doses reduced the lactate content of the cortex but activated lactate dehydrogenase. The activity of isocitrate dehydrogenase was not altered by any of the gentamicin doses used.

Comparative modulating effects of captopril, diltiazem, dietary calcium and pyridoxal-5'-phosphate on gentamicin-induced nephrotoxicity in the rat.

1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg/day for 6 days. Treated animals demonstrated a typical pattern of aminoglycoside nephrotoxicity characterized histopathologically by necrosis of proximal tubular epithelium, and biochemically by increased serum creatinine and urea concentrations. Reduced glutathione (GSH) concentration in renal cortex was significantly decreased by gentamicin. 2. Simultaneous treatment of rats with gentamicin and either captopril or diltiazem significantly potentiated the gentamicin-induced increases in serum creatinine and urea and did not significantly affect the gentamicin-induced decrease in cortical GSH concentration. 3. Concomitant treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate decreased serum urea level, did not significantly affect serum creatinine concentration, and significantly increased cortical GSH concentration in comparison to the values of these parameters following gentamicin treatment. 4. Histopathologically, the severity of gentamicin-induced renal damage was exacerbated by captopril, and even more so by diltiazem. Simultaneous treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate produced only mild focal atrophy of renal tubular epithelium. Control rats had apparently normal histology. 5. In conclusion, captopril and diltiazem, at the doses used, significantly potentiated gentamicin-induced nephrotoxicity to a broadly similar extent. Although Ca2+ and pyridoxal-5'-phosphate, at the doses used, reduced significantly the severity of some of the manifestations of nephrotoxicity, they were equally ineffective in completely preventing the development of nephrotoxicity.

Plasma lipid profile in rats with gentamicin-induced nephrotoxicity.

1. Administration of gentamicin to rats at doses of 20, 40 or 80 mg kg-1 d-1 for 6 days induced nephrotoxicity exhibited by elevated plasma creatinine concentration and a decrease in alkaline phosphatase activity in rat kidney cortex. 2. Gentamicin treatment produced significant elevation in plasma total cholesterol amounting to 70% at the 80 mg kg-1 dose. At this dose, the combined cholesterol fractions of low density and very low density lipoproteins increased by more than two-fold. 3. Gentamicin treatment also caused significant increase in plasma triglyceride concentration, while plasma phospholipid levels showed dose-dependent reductions. 4. In another experiment recovery of the aforementioned parameters was assessed 7 and 14 days after the withdrawal of gentamicin, administered at a dose of 40 mg kg-1 d-1 for 6 days. After 7 days from drug discontinuation, both plasma creatinine and total cholesterol concentrations returned to the control levels, while triglyceride concentration was still significantly higher than control 14 days after stoppage of treatment. 5. Plasma phospholipid concentration and the activity of cortical alkaline phosphatase were still significantly lower than control 14 days after cessation of the treatment.

The effect of some alpha 2-adrenoceptor agonists and antagonists on gastrointestinal transit in mice: influence of morphine, castor oil and glucose.

1. The effects of graded doses of the alpha 2-adrenoceptor agonists clonidine, tizanidine and BHT-920, and the alpha 2-adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test. 2. The agonists produced significant and dose-dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT-920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg). 3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co-administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg). 4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT-920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg). 5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline-treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT-920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.

Use of rat jejunum for assay of acetylcholine.

Experiments were carried out to determine the advantage in using isolated rat jejunum in the assay of acetylcholine (ACh) in preference to other tissues. Rat jejunum was found to be sensitive to ACh 0.01 micrograms, 5-hydroxytryptamine (5HT) 0.2 to 0.5 microgram and least sensitive to histamine. (Ach greater than 5HT greater than histamine).

Gentamicin nephrotoxicity in rat: some biochemical correlates.

The present work examines the effect of treatment of rats with graded doses of the aminoglycoside antibiotic gentamicin on the concentration of reduced glutathione (GSH) and diamine oxidase (DAO) activity in the kidney, and DAO activity, creatinine and magnesium (Mg) in the plasma. The animals were given the antibiotic intramuscularly in doses of 20, 40, and 80 mg/kg/day for 6 days, and were killed 24 hr after the last injection. In another experiment rats were injected intramuscularly with gentamicin at a dose of 80 mg/kg/day for 6 days and were killed 1, 7 or 14 days after the last injection, and the above parameters were measured. Gentamicin reduced the body weights of rats in a dose-dependent manner. The weight reductions were most marked on days 4, 5 and 6 of the treatment. The body weights gradually recovered on withdrawing of the drug, and by day 14, they were not significantly different from those of the controls. Gentamicin produced significant and dose-dependent decreases in the renal concentration of GSH. Seven and 14 days after withdrawing the drug, the GSH concentrations were still significantly below that of the controls. Plasma Mg concentrations were significantly decreased, and plasma creatinine concentrations significantly increased by gentamicin. These effects persisted 7 and 14 days after cessation of treatment. Plasma DAO activity was not detectable in the control or gentamicin-treated rats. In the renal cortex, the activity of the enzyme, measured 1, 7 and 14 days after the treatment, was not significantly different from that of the control. Histopathologically, the drug produced dose-dependent proximal renal tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Diamine oxidase activity in the duodenal mucosa of rats with cysteamine-induced ulceration.

Cysteamine administration to rats is followed by a high incidence of duodenal ulceration. The effect of cysteamine on the activity of diamine oxidase (DAO, histaminase) in the duodenal mucosa of the rat was investigated. Rats were injected subcutaneously with cysteamine on 2 successive days at doses of 10, 20 and 40 mg/100 g body weight and killed 24 h after the second dose. The results indicated that cysteamine at a dose of 40 mg/100 g body weight inhibited enzyme activity by about 27% (p less than 0.05). Lower doses of cysteamine did not significantly affect enzyme activity. In another experiment, rats were injected subcutaneously with either saline (control) or cysteamine at a single dose of 40 mg/100 g body weight and killed 4, 8, 12, 24, 48 and 60 h thereafter. The ulcerogen produced progressive reductions in enzyme activity, which were significant at 12 h (22% reduction) and 24 h (25% reduction). At 60 h, enzyme activity was not significantly different from that of control.