Sensorineural hearing loss after treatment of nasopharyngeal carcinoma: a longitudinal analysis.

PURPOSE: To analyze the effects of radiotherapy (RT) and chemotherapy in relation to sensorineural hearing loss (SNHL) after contemporary treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS: A total of 87 nasopharyngeal carcinoma patients were treated with RT or chemoradiotherapy using either three-dimensional conformal RT or intensity-modulated RT between 2004 and 2005. Tympanometry and pure-tone audiogram assessments were performed before treatment and then serially at 6-month intervals. The dose-volume data of the cochlea were analyzed. The effects of cisplatin administered in concurrent and nonconcurrent phases was explored. RESULTS: Of the 170 eligible ears, RT (n = 30) and chemoradiotherapy (n = 140) resulted in 40% (n = 12) and 56.4% (n = 79) persistent SNHL (> or = 15 dB loss), respectively, after a median follow-up of 2 years. SNHL at a high frequency was more frequent statistically in the chemoradiotherapy group than in the RT-alone group (55% vs. 33.3%, p < 0.01), but not at a low frequency (7.9% vs. 16.7%, p = 0.14). Within the chemoradiotherapy group, the mean cochlea dose and concurrent cisplatin dose were important determinants of high-frequency SNHL, with an odds ratio of 1.07/Gy increase (p = 0.01) and an odds ratio of 1.008/mg/m(2) increase (p < 0.01), respectively. Age, gender, and nonconcurrent cisplatin dose were not statistically significant factors. A mean radiation dose to the cochlea of <47 Gy would result in <15% of patients developing severe (> or = 30 dB) high-frequency SNHL. CONCLUSION: The results of our study have shown that high-frequency SNHL is significantly related to the mean cochlea dose and the concurrent cisplatin dose. A mean dose constraint of 47 Gy to the cochlea is recommended to minimize SNHL after chemoradiotherapy.

Preferential renal and mesenteric vasodilation induced by barnidipine and amlodipine in spontaneously hypertensive rats.

Barnidipine is a stereoselective single isomer formulation of a long-term acting dihydropyridine calcium antagonist (CaA). In anaesthetised animals, the antihypertensive response to barnidipine is accompanied by a diuretic effect. The aim of the present study was to examine whether barnidipine increased renal blood flow in a conscious animal model for essential hypertension. We compared the regional specific hemodynamic effects of barnidipine with those obtained with its racemic mixture and amlodipine. Male adult spontaneously hypertensive rats (SHR) were instrumented with Doppler flow probes and catheters to measure renal (RVR), mesenteric (MVR) and hindquarter (HQVR) vascular resistance changes. One week after surgery, barnidipine, its racemic mixture, and amlodipine were intravenously administered at three doses (n> or =10 per dose) causing comparable reductions in mean arterial pressure (MAP). At doses of 3, 10 and 30 microg/kg barnidipine reduced MAP (+/- SEM) by 8+/-2, 26+/-3 and 45+/-4 mmHg. Equipotent effects on MAP were achieved by the racemic mixture of barnidipine at 10, 30 and 100 microg/kg, and by amlodipine at doses of 100, 300 and 1000 microg/kg. Following the 3 microg/kg and 10 microg/kg dose, barnidipine reduced MVR (% +/- SEM) by 4+/-4 and 19+/-4, and RVR by 8+/-2 and 15+/-4, respectively. In contrast, HQVR remained unaltered. Similar data were obtained for the racemic mixture of barnidipine and for amlodipine, although for the latter the changes in RVR were half of those found after barnidipine. After the highest doses of barnidipine, its racemic mixture as well as amlodipine, HQVR fell more than 25% whereas RVR and MVR remained unaltered. Analysis of the dynamic response to the CaAs revealed that the reductions in vascular resistance were associated with decreased myogenic-like oscillations in blood flow. We conclude that, in conscious SHR, the single isomer barnidipine reduces MAP at doses which are three times lower than its racemic mixture and 30 times lower than amlodipine. In contrast to short-acting CaAs such as nifedipine and isradipine, which reduce mainly HQVR and do not reduce RVR (Nievelstein et al.; Eur J Pharmacol 113:187-198, 1985), the three long-term acting CaAs preferentially dilated the mesenteric and renal vascular bed. In view of the elevation of RVR in essential hypertension, the reduction of RVR may contribute to the long-term antihypertensive effects of barnidipine and amlodipine.

[Pleuropulmonary staphylococcal infection in infants, in a hospital environment in Ouagadougou (Burkina Faso)]. / La staphylococcie pleuro-pulmonaire du nourisson en milieu hospitalier à Ouagadougou (Burkina Faso).

We observed 36 cases of pleuropulmonary staphylococcal infection (PPS) in infants aged 0 to 30 months, during a prospective study carried out between April 1st 1995 and March 31 1996 at the Pediatrics Department of Ouagadougou University Hospital. PPS accounted for 0.5% of all hospital admissions and 11.6% of all acute basal respiratory infections in children aged less than 30 months. Slightly more boys than girls were affected, with a sex ratio of 1.2. We identified the classic triad of symptoms: cough-fever-polypnea, associated with abdominal ballooning and a change in general condition. On X rays, the typical images showing parenchymatous bubbles were the second most frequent observation (27.8%) after parenchymatous opacities (69.5%). The most frequently used antibiotics were oxacillin (Bristopen), gentamycin (Gentallin) and cefuroxime-axetil (Zinnat). The prognosis of PPS is poor, with a high mortality rate (27.8%) and a risk of pleural recurrence. Being very young, late hospitalization, malnutrition and leukopenia were identified as factors indicating a poor prognosis. Recygling of health care personnel for the management of acute respiratory infections, a decrease in malnutrition and an improvement in vaccination cover are essential if the mortality and morbidity of acute respiratory infections, and PPS in particular, are to be reduced.

Differential time course of the vasodilator action of various calcium antagonists.

It is rather the rate of the vasodilator effect than its magnitude which determines the triggering of reflex tachycardia associated with dihydropyridine calcium antagonists (DHP-CA). We therefore compared the rate of the vasodilator effects of a series of CA (both DHP and non-DHP) in rat isolated mesenteric artery preparations (size 256 +/- 3 microns, length 2 mm) from male Wistar rats (weighing 300-350 g) in an isolated wire myograph according to Mulvany and Halpern [12]. The mean force of the KCl-induced contraction amounted to 2.3 +/- 0.1 mN/mm. Potency (given as IC50-values), differential time course of action and recovery of the contractile response of the vessels after wash-out were established. These three parameters adhere to the following sequences: (1. potency) barnidipine [corrected] > (S)-lercanidipine > barnidipine racemate [corrected]> amlodipine > nifedipine, lacidipine > (R)-lercanidipine > verapamil, mibefradil; (2. differential time course) lacidipine, amlodipine > (S)- and (R)-lercanidipine, barnidipine [corrected], barnidipine racemate [corrected] > mibefradil, verapamil, nifedipine; (3. recovery) nifedipine > verapamil, barnidipine [corrected], amlodipine > barnidipine, lacidipine > mibefradil, (R)-lercanidipine > (S)-lercanidipine. In conclusion, barnidipine [corrected] proved to be the most potent vasodilator agent; interestingly, barnidipine was 20 times less potent when applied as a racemic mixture. A slow onset of action in DHP is a very important mechanism in preventing reflex tachycardia. For non-DHP (verapamil, mibefradil) reflex tachycardia probably is prevented by a direct effect on the conductive tissue in the myocardium.

[Clinical signs of severe malaria in a pediatric hospital in Ouagadougou]. / Formes cliniques du paludisme grave en milieu hospitalier pédiatrique à Ouagadougou.

During the period of transmission of malaria, from August to November of 1993 and 1994, we conducted a study to determine the frequency of the clinical forms of severe and complicated malaria. The study involved children, from 6 months through 15 years old, admitted to the pediatric ward of the hospital in Ouagadougou, Burkina Faso. The criteria for inclusion followed the definition of severe malaria stated by the World Health Organization. We carefully noted the symptoms and signs on admission. Of the total of 719 children enrolled in the study, there was a prevalence of children under 5 years old. The most frequent clinical forms were those of coma (377 cases, 52.4%), prostration (268 cases, 37.3%), convulsion (152 cases, 21.4%), anemia (115 cases, 15.9%), and hypoglycemia (55 cases, 10.3%). No renal failure form was observed. We also observed the respiratory distress form (35 cases, 4.9%) and the hemorrhagic form (11 cases, 1.5%). Malaria remains a major cause of childhood morbidity and mortality in the developing world. Early therapeutic management of febrile attacks with chloroquine would reduce the incidence of severe and complicated malaria.

Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension.

The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([123I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 microCi [123I]MIBG. Initial myocardial uptake and wash-out rates of [123I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular beta-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of beta-adrenoceptors, indicative of increased sympathetic activity. Cardiac [123I]MIBG then showed increased wash-outs, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [123I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity non-invasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in beta-adrenoceptor density were found, whereas [123I]MIBG wash-out rate was increased. Thus, either [123I]MIBG washout or beta-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. Changes in the initial uptake of [123I]MIBG were observed as well. This may be a good marker for the disappearance of cardiac innervation, but it seems not to be a good parameter for distinguishing between loss of sympathetic innervation and enhanced uptake of noradrenaline in pathological conditions.

Hypertensive diabetic rats in pharmacological studies.

Since hypertensive disease and diabetes frequently occur simultaneously there exists a requirement for animal models where both pathological entities are combined. The streptozotocin (STZ)-spontaneously hypertensive rat (STZ-SHR) and the obese Zucker rat are examples of animal models where hypertension and diabetes occur simultaneously. STZ-SHRs develop a hyperglycaemic syndrome, associated with other biochemical and morphological changes that to some extent approach insulin-dependent diabetes mellitus (type 1 diabetes) combined with hypertension. The obese (Fa/?) Zucker rat is characterized by the simultaneous occurrence of obesity, hyperglycaemia, hyperinsulinaemia, hyperlipidaemia and moderate hypertension. As such it approaches the patient with non-insulin-dependent diabetes mellitus (type 2 diabetes) who is simultaneously hypertensive. Lean (fa/fa) Zucker rats are suitable controls with respect to the obese animals. Both animal models (STZ-SHRs and obese Zucker rats) were characterized with respect to their biochemical, morphometric and haemodynamic properties. Both models were examined in particular with respect to the pharmacological characteristics of their cardiovascular system, as discussed in the present survey.

Pharmacodynamic behaviour of isolated resistance vessels obtained from hypertensive-diabetic rats.

The influence of various vasodilator and constrictor drugs was studied in isolated mesenteric arteries obtained from obese and lean Zucker rats. The obese Zucker rats were moderately hypertensive and their isolated small arteries were not hypertrophied. All vasoconstrictor agents studied (noradrenaline, methoxamine, serotonin, calcium chloride, potassium chloride) caused the same effects in isolated arteries taken from obese and lean (control) Zucker rats; respectively. In vessels from obese Zucker rats, the vasodilator responses to sodium nitroprusside, methacholine, the K(+)-channel opener cromakalim and nifedipine were the same as in control preparations. In conclusion, isolated mesenteric arteries from obese Zucker rats do not show relevant structural changes, and the pharmacodynamic behaviour of such vessels appears to be the same as that of control preparations. Neither the diabetic hyperinsulinaemic state not the hyperlipoproteinaemia in the obese Zucker rats appear to cause serious vascular damage.

Contractile responses to various stimuli in isolated resistance vessels from simultaneously hypertensive and streptozotocin-diabetic rats.

Diabetes mellitus and hypertension are common chronic diseases that frequently occur simultaneously. The induction of streptozotocin (STZ) diabetes mellitus in spontaneously hypertensive rats (SHR) offers the opportunity to investigate the influence of both entities in a reproducible manner. We investigated the effects of various vasoconstrictors on isolated small arteries from the mesenteric vascular bed of normotensive rats (Wistar-Kyoto rats, WKY) and SHR with chronic (8 weeks), STZ-induced diabetes mellitus. No consistent changes in hemodynamic parameters of the (STZ-) normotensive and (STZ-) hypertensive rats were noted. The K(+)-normalization procedure yields the individual optimal lumen diameter, which was the same for the arteries of the four groups of rats. The passive wall tension resulting from this normalization procedure was higher only in preparations from the control hypertensive group as compared with those from the control normotensive rats. Morphological investigations showed that small arteries from control SHR had an increased tunica media thickness as compared with those of control WKY; the STZ-WKY had an increased tunica media thickness as compared with preparations from control WKY. The vasoconstriction caused by alpha 1-adrenoceptor stimulation [norepinephrine (NE), methoxamine] and serotonin is unchanged in chronic experimental diabetes. The diabetic state reduced the sensitivity [-log EC50(M)] for the concentration-response curves (CRC) of calcium chloride. The CRC of potassium chloride indicated the same sensitivities, but maximal active wall tensions of vessels from STZ-SHR were reduced as compared with those from STZ-WKY. The well-known enhancement of the effects of various contractile stimuli caused by hypertension could not be demonstrated for the isolated small arteries used in the present study, although a nonsignificant tendency was observed. However, the STZ-diabetic state did not cause important additional pharmacodynamic changes, despite the morphological alterations in those vessels.

Streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats: a pathophysiological model for the combined effects of hypertension and diabetes.

The present study was undertaken to investigate the combined effects of hypertension and streptozotocin-induced diabetes mellitus in the rat. Accordingly, four groups of rats were studied: Wistar Kyoto rats (WKY), diabetic WKY, spontaneously hypertensive rats (SHR) and diabetic SHR, respectively. The mean arterial blood pressure was increased in hypertensive animals compared to normotensive animals. The base excess in the diabetic rats was higher than that of normoglycemic animals. An elevated glucose concentration was found in the blood and urine of streptozotocin-treated rats. Ketone bodies were detected in the urine and blood of the diabetic rats. Mortality rates after treatment were not different among the four groups. In separate experiments, isolated working hearts of the various groups were set up and analyzed. For the maximal left ventricular pressure (mm Hg) the following values were formed: 110.0 +/- 2.6, 93.6 +/- 2.7, 93.4 +/- 3.0, and 87.5 +/- 2.4, respectively. The wet heart weights, dry heart weights, and body weights of the diabetic rats were lower than those of normoglycemic animals. The wet heart weight/body weight ratio, however, was increased by diabetes and hypertension (0.43 +/- 0.01, 0.47 +/- 0.01, 0.47 +/- 0.01, and 0.54 +/- 0.02, respectively). There were no significant differences between the water content of the hearts from the four different groups. Pathologic examination of the hearts showed myocardial hypertrophy and medial hypertrophy of coronary arteries in diabetic and hypertensive animals. There was no difference in relative collagen content in the hearts of the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug-induced endothelium-dependent and -independent relaxations in isolated resistance vessels taken from simultaneously hypertensive and streptozotocin-diabetic rats.

Hypertension and diabetes mellitus often co-exist and both conditions may be expected to cause synergistic vascular damage. Our group has introduced an animal model for simultaneously occurring hypertension and diabetes mellitus by treating spontaneously hypertensive rats with streptozotocin (STZ). We investigated the drug-induced endothelium-independent and -dependent relaxation in isolated mesenteric small arteries (resistance vessels). Concerning the influence of hypertension, the responses to sodium nitroprusside, methacholine, histamine and nifedipine proved unchanged, the vasodilator response to bradykinin was diminished, whereas that to the K(+)-channel opener cromakalim was enhanced. With respect to the influence of STZ-induced diabetes we found that the responses to sodium nitroprusside, methacholine and nifedipine were unchanged, and that to cromakalim was enhanced, also when the preparations were pretreated with glibenclamide. The responses to histamine (STZ WKY versus control WKY) and bradykinin (STZ SHR versus control SHR) proved enhanced in the isolated vessels taken from diabetic animals. These findings suggest that the influence of the diabetic state is more pronounced than that of hypertension. However, our findings do not indicate that either hypertension or diabetes is associated with generalised endothelial damage in the resistance arteries.

Comparison of three in vitro assays for serum IgE with skin testing in asthmatic children.

The diagnostic performance of three commercial assay kits [Phadezym RAST (PhRAST), Pharmacia CAP system (CAP), and multiple chemiluminescent assay (CLA-MAST)] for measuring serum-specific IgE was evaluated and compared using intradermal skin testing or skin prick testing as reference standards. Serum samples were obtained from allergic patients who were tested with either intradermal skin tests or skin prick tests (96 and 49 subjects, respectively). Six different allergen extracts were tested: Dermatophagoides pteronyssinus, Candida albicans, Aspergillus, short ragweed, Bermuda grass, and cockroach mix. Results showed that when using intradermal skin testing as a reference standard, the CLA-MAST had the lowest sensitivity (75%), specificity (80%), and efficiency (85%) but the Pharmacia CAP system achieved the highest sensitivity, specificity, and efficiency (86%, 94%, and 91%, respectively). When compared with these two relatively new assays, the Phadezym RAST had medium sensitivity (80%), specificity (92%), and efficiency (88%). In contrast, when using skin prick testing as a reference standard, the highest specificity was achieved by Phadezym RAST (95%), followed by Pharmacia CAP system (90%), and MAST (81%). As for the sensitivity of each test, the Phadezym RAST was the lowest (60%) and Pharmacia CAP system reached the highest sensitivity (79%); and for the efficiency test, the score was 87% for CAP, 83% for Phadezym RAST, and 75% for MAST. These results suggest, therefore, that the CAP system is the preferred test and provides a useful guide for prescription of environmental control and immunotherapy in unselected patients.

Effects of R 56865 on postischemic ventricular function in isolated rat working heart preparations obtained from healthy, diabetic and hypertensive animals.

The present study was undertaken to evaluate the effects of R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl)- N-methyl-2-benzothiazolamine) (Fig. 1) on postischemic ventricular function, an inhibitor of the Na+/Ca2+ overload, in the working heart preparation of the rat. The hearts were paced at 5 Hz and perfused with Tyrode solution of 37 degrees C at a physiological pH. After 15 min of pretreatment with R 56865, low-flow ischemia (30 min) was induced by reducing the perfusion pressure from 51.5 mmHg to 11.0 mmHg and R 56865 was infused simultaneously. The hemodynamic effects of R 56865 were evaluated in the concentration range [10(-8)-3.10(-6) M]. The five parameters measured were: LVP (Left Ventricular Pressure), +dP/dtmax (maximal rate of pressure increase), AO (Aortic Output), CF (Coronary Flow) and CO (Cardiac Output). They were determined in the working heart mode after 15 min of equilibration and at the end of the experiment. From these data the recovery percentages were calculated. The recovery percentages for the LVP, +dP/dtmax, AO, CF and CO for the control hearts (3.3%, 0.0%, 7.9%, 10.4% and 8.5%, respectively) differed significantly from those at 10(-7) M (39.6%, 40.8%, 25.0%, 41.8% and 29.9% respectively). The recovery percentage were the highest at 10(-6) M (79.6%, 82.1%, 54.7%, 92.7% and 67.2%, respectively). The concentration of 10(-7) M was associated with a smaller reduction in LVP (12.9%) than at 10(-6) M (25.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antiischemic effects of nifedipine in isolated working heart preparations of healthy, diabetic, and hypertensive rats.

We evaluated the antiischemic effects of nifedipine in isolated working rat hearts from age-matched normotensive Wistar-Kyoto rats (WKY), diabetic WKY, spontaneously hypertensive rats (SHR), and diabetic SHR. Diabetes was induced by streptozotocin. First, we constructed concentration-response curves for the negative inotropic effect of nifedipine in every group. After 15 min of pretreatment with nifedipine (EC60), low-flow ischemia (30 min) was induced by reducing the afterload from 51.5 to 11.0 mm Hg and nifedipine was infused simultaneously. The six measured parameters were left ventricular pressure (LVP), maximum rate of pressure increase (+dP/dtmax), maximum rate of pressure decrease (-dP/dtmax), aortic output (AO), coronary flow (CF), and cardiac output (CO), determined after 15-min equilibration in the working heart mode and at the end of the experiment. From these data, the recovery percentages were calculated. There were no significant differences in sensitivity to nifedipine (as measured by the EC50 concentration) between the four groups with respect to LVP, +dP/dtmax, -dP/dtmax, CF, and CO. However, hearts from SHR were less sensitive to nifedipine than those from diabetic SHR and nondiabetic WKY with regard to AO. In isolated hearts from nondiabetic WKY and SHR, there were no significant differences between vehicle-treated organs and nifedipine-treated preparations. In hearts from diabetic WKY and diabetic SHR, however, the nifedipine-treated group (LVP 87.1 +/- 3.3 and 60.5 +/- 12.1%, respectively) recovered significantly (p < 0.05) better from ischemia as compared with the control group (LVP 35.7 +/- 14.7 and 10.7 +/- 9.8%, respectively) (n = 6 for each group).(ABSTRACT TRUNCATED AT 250 WORDS)