Clinical pitfalls related to short and long echo times in cerebral MR spectroscopy.

MR-spectroscopy (MRS) is a multiparameter diagnostic tool and modification of each parameter results in spectrum morphology changes. In particular, changing the echo time (TE) represents a useful tool to highlight different diagnostic elements, but also has significant impact on the spectrum morphology. Diagnostic errors can result if the role of TE is not properly considered. This article reviews the four most common TE-related pitfalls of MRS interpretation. Clinical practical methods to avoid such pitfalls are also suggested.

The effect of statin pretreatment on infarct volume in ischemic stroke.

BACKGROUND: Treatment with statins reduces infarct volume in animal models of ischemic stroke, independently of the effect on cholesterol. This study examined this effect in humans by testing whether patients taking statins at onset of ischemic stroke had smaller infarct volumes than those not taking statins. METHODS: The study design was a retrospective cohort analysis of all verified ischemic stroke patients admitted to the Medical University of South Carolina Hospital, in 2002-2006, with magnetic resonance diffusion-weighted imaging (DWI). Patients were grouped according to statin status at admission and compared relative to infarct volume, calculated (blinded to statin status) from DWI. RESULTS: A smaller than median infarct volume following ischemic stroke was associated with the interaction of statin pretreatment and positive diabetes status. This association remained significant (p = 0.01) in multivariable analysis even after controlling for factors related to demographics, comorbidities and risk factors, clinical features on admission, use of other medications and stroke features. CONCLUSIONS: Among ischemic stroke patients in this study, infarct volume below the median was significantly associated with statin pretreatment among those with diabetes.

Idiopathic hypertrophic spinal pachymeningitis: report of two cases with typical MR imaging findings.

SUMMARY: Two patients with a chronic progressive myelopathy were successfully surgically treated and idiopathic hypertrophic spinal pachymeningitis (IHSP) was found on histology. In both patients, an extensive extramedullary mass of low T2 signal with peripheral contrast enhancement was compressing the spinal cord on MR imaging. This imaging appearance in patients with chronic progressive myelopathy should suggest the diagnosis of IHSP.

Apparent diffusion coefficients for differentiation of cerebellar tumors in children.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps provide information at MR imaging that may reflect cell attenuation and integrity. We hypothesized that cerebellar tumors in children can be differentiated by their ADC values. METHODS: Brain MR imaging studies that included ADC maps were retrospectively reviewed in 32 patients with histologically proved cerebellar neoplasm. There were 17 juvenile pilocytic astrocytomas (JPA), 8 medulloblastomas, 5 ependymomas, and 2 rhabdoid (atypical teratoid/rhabdoid tumor [AT/RT]) tumors. Absolute ADC values of contrast-enhancing solid tumor regions and ADC ratios (ADC of solid tumor to ADC of normal-appearing white matter) were compared with the histologic diagnosis. ADC values and ratios of JPAs, medulloblastomas, and ependymomas were compared by using a 2-tailed t test and one-way analysis of variance (ANOVA). RESULTS: ADC values were significantly higher in pilocytic astrocytomas (1.65 +/- 0.27) (mean +/- SD) than in ependymomas (1.10 +/- 0.11) (P = .0003) and medulloblastomas (0.66 +/- 0.15) (P < .0001). Ependymomas demonstrated significantly higher ADC values than medulloblastomas (P = .0005). The observed differences were statistically significant on ANOVA (P < .001). ADC ratios were also significantly different among these 3 tumor types. AT/RT ADC values were similar to medulloblastoma. The range of ADC values and ratios within JPAs and ependymomas did not overlap with that of medulloblastomas. CONCLUSION: Assessment of ADC values of enhancing solid tumor is a simple and reliable technique for preoperative differentiation of cerebellar tumors in pediatric patients. Our cutoff values of >1.4 x 10(3) mm(2)/s for JPA and <0.9 x 10(3) mm(2)/s for medulloblastoma were 100% specific.

Imaging of oral cavity cancer.

Despite many advances in surgical techniques, technology, radiation therapy, and chemotherapy, survival rates for head and neck cancer (HNCa) have not improved significantly in decades, with many patients being diagnosed at advanced disease stages. Adequate assessment of oral cavity malignancies is critical for appropriate planning of surgical, radiation, and chemotherapy treatment. Imaging modalities used to evaluate the oral cavity include plain radiography (panoramic radiography and intraoral radiography), nuclear medicine scintigraphy, ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). This review describes these imaging techniques and their utility, primarily CT and MRI.

Osteoblastic response to the defective matrix in the osteogenesis imperfecta murine (oim) mouse.

This work examines the cellular pathophysiology associated with the weakened bone matrix found in a murine model of osteogenesis imperfecta murine (oim). Histomorphometric analysis of oim/oim bone showed significantly diminished bone mass, and the osteoblast and osteoclast histomorphometric parameters were increased in the oim/oim mice, compared with wild-type (+/+) mice. To assess osteoblast activity, a rat Col1a1 promoter linked to the chloramphenicol acetyltransferase reporter transgene was bred into the oim model. At 8 d and 1 month of age, no difference in transgene activity between oim and control mice was observed. However, at 3 months of age, chloramphenicol acetyl transferase activity was elevated in oim/oim;Tg/Tg, compared with +/+;Tg/Tg and oim/+;Tg/Tg. High levels of urinary pyridinoline crosslinks in the oim/oim;Tg/Tg mice were present at all ages, reflecting continuing high bone resorption. Our data portray a state of ineffective osteogenesis in which the mutant mouse never accumulates a normal quantity of bone matrix. However, it is only after the completion of the rapid growth phase that the high activity of the oim/oim osteoblast can compensate for the high rate of bone resorption. This relationship between bone formation and resorption may explain why the severity of osteogenesis imperfecta decreases after puberty is completed. The ability to quantify high bone turnover and advantages of using a transgene that reflects osteoblast lineage activity make this a useful model for studying interventions designed to improve the bone strength in osteogenesis imperfecta.

Gender differences in triggering of acute myocardial infarction.

The frequencies of potential triggers of acute myocardial infarction differ between men and women. There is a possibility that anti-ischemic drugs protect against trigger-related infarctions.

Ramipril decreases chlorthalidone-induced loss of magnesium and potassium in hypertensive patients.

A double-blind clinical trial was conducted to compare the efficacy of and electrolyte changes caused by ramipril-chlorthalidone combination treatment (5 mg + 25 mg) and chlorthalidone monotherapy (25 mg daily) in patients with hypertension. After a 4-week placebo period, 32 patients (mean age, 51 +/- 9 years) with essential hypertension (average blood pressure of 181.4/104.5 +/- 13.0/6.9 mmHg) were randomly assigned to receive combination therapy (group A, n = 17) or monotherapy (group B, n = 15). After 12 weeks of active treatment, systolic and diastolic blood pressure decreased by 16.1% and 13%, respectively, for patients taking combined therapy, and by 12.7% and 9.8%, respectively, for patients taking monotherapy. The difference was significant for between-group comparisons. There were no changes in serum sodium concentration, but a significant similar increase in 24-hour urinary sodium excretion was seen in both groups. Serum calcium levels increased slightly and 24-hour urinary calcium excretion decreased significantly in both groups, probably due to chlorthalidone administration. Serum potassium levels increased slightly in group A (from 4.16 +/- 0.39 mmol/L to 4.30 +/- 0.42 mmol/L) and decreased slightly in group B (from 4.18 +/- 0.32 mmol/L to 3.99 +/- 0.49 mmol/L). Urinary potassium excretion did not change significantly in group A, but increased by approximately 15% in group B. There was a decrease in 24-hour urinary magnesium excretion (from 4.01 +/- 1.24 mmol/24 hours to 3.50 +/- 0.93 mmol/24 hours) in group A and an increase (from 3.49 +/- 0.98 mmol/24 hours to 4.35 +/- 1.12 mmol/24 hours) in group B. At the end of the trial these changes were significant in between-group comparisons. Consistent with the previously shown amelioration by ramipril of thiazide-induced metabolic side-effects, ramipril appears to improve magnesium balance during cotreatment with chlorthalidone.

Indapamide versus beta-blocker therapy: a double-blind, crossover study in essential hypertension.

A controlled, double-blind, double-placebo, crossover clinical trial was carried out in 24 mild to moderate hypertensives of either sex to compare the anti-hypertensive and other effects of indapamide (2.5 mg) and pindolol (15 mg). After a 2-week run-in placebo period the patients were randomly assigned to one of the drugs in the study for 6 weeks. After a second 2-week placebo period, the subjects received the alternative drug for an additional 6 weeks. Both drugs produced a significant and similar decrease in arterial blood pressure (averaging 19 mmHg for systolic and 15 mmHg for diastolic blood pressure; p less than 0.05), with minimal differences between the drugs in this respect (p greater than 0.10). Pulse, rate, however, was significantly reduced (from 76 to 67 beats/min; p less than 0.05) only with pindolol. The laboratory data did not change appreciably, and few side-effects were reported. It is concluded that indapamide and pindolol at the dosage levels used are drugs of comparable antihypertensive activity.

Q-T interval as predictor of serum calcium level.

To assess whether measurement of the electrocardiograhic (ECG) Q-T interval is a useful predictor of total serum calcium concentration, 15 uraemic patients were studied (10 female, five male; age range, 25-60 years). Resting ECGs were interpreted by three independent observers without knowledge of the patients' identity or serum calcium. Three variants of measurement of the Q-T interval were analysed, of which Q-aTc, the interval from the beginning of the Q-wave to the apex of the T-wave, was the most consistent (coefficient of variation, 2.7%). This also provided the best correlation with measured serum calcium concentration (P < 0.001). When compared to biochemical measurements, the predicted serum calcium concentration was within 95% confidence limits in 14 of the 15 patients studied. However, the wide confidence limits of this technique mean that it cannot be recommended in routine clinical practice.

The influence of the atrial natriuretic factor on venous tone in man.

To assess the effect of the human atrial natriuretic factor (ANF) in vivo on human veins, a series of investigations was done on the dorsal hand vein of 11 healthy volunteers (ten men, one woman), aged from 25 to 49 years. In the case of intact veins the human ANF effect was evaluated by the "venoconstriction" test; on veins constricted by a reflex sympathetic discharge, the ANF effect was evaluated by the test of "venous reflexes", and on veins constricted with serotonin and angiotensin II by the "preconstriction" test. The results were expressed in venoconstrictive units (VCU). ANF was injected into the vein under study in increasing bolus doses (from 50 pg to 500 ng). The results indicate that this peptide did not affect either intact veins or these constricted by sympathetic discharge. On veins preconstricted with serotonin, ANF had a slight, statistically insignificant effect (848.57 +/- 378.67 VCU 30 sec before, compared to 670.00 +/- 460.25 VCU 30 sec after the injection of 50 pg; n = 7; p greater than 0.05), up to a maximal local dose of 500 ng. The same was true for the vein preconstricted with angiotensin II. It is concluded that the human atrial natriuretic factor has no significant influence on peripheral venous tone in man.

Enalapril versus captopril: a double-blind multicentre comparison in essential hypertension.

A collective, multicentre (Ljubljana, Split, Zagreb) comparison of the antihypertensive effects between two angiotensin converting enzyme inhibitors (ACEI) captopril and enalapril was made in 69 hypertensives of both sexes, having a diastolic blood pressure (DBP), following two weeks on a placebo, of between 110 and 130 mm Hg (14.7 and 17.3 kPa). There were 35 patients on enalapril (20-40 mg), and 34 on captopril (50-100 mg). Both drugs under study decreased significantly the mean DBP already after the first week of ACEI treatment (p less than 0.001). By the end of the trial (9th week) captopril had decreased the DBP in the supine position from the initial 180.3 +/- 15.3/117.7 +/- 6.4 mm Hg to 151.6 +/- 11.1/96.8 +/- 7.2 mm Hg. Enalapril had lowered the DBP more efficiently: from 182.7 +/- 16.7/118.7 +/- 7.7 to 145.6 +/- 12.8/92.2 +/- 6.4 mm Hg (p less than 0.05). The average reduction in mean DBP was 16.9% on captopril, and 20.9% on enalapril. Low dose ACEI monotherapy (i.e. 50 mg and 20 mg) achieved DBP normalization in 11.8% on captopril and in 26.4% on enalapril (p less than 0.01). There were no significant heart rate changes. The laboratory results did not change appreciably and there were no relevant side-effects, although particular attention was paid to the expected adverse reactions, such as cough, ageusia or proteinuria. It is concluded that the ACEIs under study showed comparable effectiveness within the used dose range, enalapril being more potent, longer acting, and possibly safer.

Diazoxide vs labetalol: a cross-over comparison of short-term effects in hypertension.

In a randomized cross-over study the acute effects of intravenous labetalol (1-2 mg/kg; mean dose 86.5 mg) were compared with those of diazoxide (3-5 mg/kg; mean dose 253.8 mg) in 13 severely hypertensive patients with diastolic blood pressure above 110 mm Hg (36.3 kPa) and a mean arterial pressure (MAP) of 165.4 mm Hg (22.0 kPa). Within five minutes following injection of both drugs an immediate fall in arterial pressure was observed (P less than 0.05), which was even more pronounced during subsequent minutes (P less than 0.01). The reduction in MAP after 30 minutes averaged 20% (P less than 0.01), with no significant differences between the drugs under trial or administration schedules. Diazoxide did not increase the heart rate as much as expected (P greater than 0.10), while labetalol slowed it down moderately but significantly (P less than 0.05). There were no notable changes in the blood levels of glucose and potassium and no particular side-effects were observed. It is concluded that the acute effects of intravenous labetalol are comparable to those of diazoxide and that labetalol can be used with advantage as a complemental alternative to diazoxide in the emergency treatment of some hypertensive crises.

The impact of the menstrual cycle and ondansetron on postoperative nausea and vomiting.

The incidence of postoperative nausea and vomiting was studied in a prospective group of 94 women of child-bearing age (18-42 years), undergoing unilateral elective thyroid surgery. In a subgroup of 47 examinees the postoperative nausea and vomiting episodes were analyzed according to the time of surgery within their menstrual cycle: the highest occurrence was observed in the periovulatory and premenstrual periods (65.5% vs. 27.8%, p < 0.02). In the formal part of this study, 25 patients randomly received ondansetron (8 mg intravenous [i.v.]): they had significantly less postoperative nausea and vomiting than their 22 placebo controls (4 ml saline i.v.): 16.0% vs. 45.5% (p < 0.04). It is concluded that elective surgery in young and middle-aged female patients is best avoided premenstrually and in the middle of their cycle. In these very periods, however, ondansetron effectively reduces the incidence and intensity of postoperative nausea and vomiting by about 70%.

Vascular effects of chlorthalidone in mild hypertensives.

In a randomized trial with chlorthalidone, 30 hypertensive outpatients of both genders, aged 50.4 +/- 8.6 years, having diastolic blood pressure between 95 and 110 mm HG were divided into 2 groups of 15, after a two-week placebo period. The A group received chlorthalidone in a single dose of 23 mg for one month, and the next month was given a 12.5 mg alternative dose, whereas the B group was given 12.5 mg in the first month and 25 mg in the second. Changes in vascular reactivity were measured by occlusive plethysmography (mercury strain-gauge) at the ends of the placebo period, the first and the second month of therapy. All the observed parameters, i.e. rest flow, peak flow, venous capacity, and maximal venous outflow, were found to have increased with 25 mg chlorthalidone, and similar findings were registered when 12.5 mg of the drug were given. Venous capacity increased significantly in both groups (from 2.6 to 3.2 and from 3.0 to 3.4 ml/100 ml). The peak-flow values augmented significantly only in the group where 25 mg of chlorthalidone were given first (from 18.6 to 23.9 ml/100 ml/min). Both doses had a similar antihypertensive effect, decreasing the mean arterial pressure by some 8% in the upright, sitting, and supine position. It is concluded that the antihypertensive effect of chlorthalidone is, at least partly, due to changes in vascular reactivity; vasodilation is more prominent on the venous side of the circulation. Low-dose chlorthalidone is equipotent as antihypertensive, its side-effects are rare, and the cost of such a therapy is by far the lowest.

Role of digoxin in right ventricular failure due to chronic cor pulmonale.

The effect of digoxin in the treatment of decompensated chronic cor pulmonale was investigated in a randomized double-blind, cross-over, placebo-controlled trial. A total of 34 successive patients with evident right heart failure were included in the study. The mean maintenance daily dose of digoxin was 0.30 +/- 0.03 mg with the mean serum level of 1.7 +/- 0.7 nmol/L. The severity of heart failure was assessed according to a clinicoradiographic scoring system (Heart Failure Score). The heart failure worsened during the placebo-period in eight (23.5%) patients (four with atrial fibrillation, two with a third heart sound (S3), one with a cardiothoracic ratio of more than 0.5 and one with sinus rhythm). By regression analysis, the heart failure significantly worsened only in the subgroup of patients with atrial fibrillation. Digoxin was successfully (without worsening of the heart failure) discontinued in 26 (76.5%) patients. No significant improvement was observed in the patients with S3 gallop. It was concluded that digoxin had no beneficial effect in chronic cor pulmonale patients with heart failure, except in those with atrial fibrillation.

Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure.

In a randomized, single-blind, crossover clinical trial, the diuretic efficacy of the same total dose of furosemide (2 x 40 mg) administered in either conventional intravenous bolus injection or continuous infusion was studied in 20 patients (nine males and 11 females), aged 37-75 years, with congestive heart failure. Furosemide infusion, administered first, produced a significantly greater diuresis than the bolus when compared with baseline (86%: 29.6%; p = 0.029). This was followed by a similar increase in 24-h urinary sodium, potassium and chloride excretion, with no significant difference from the bolus effect. The following day, diuretic and saluretic effects of furosemide did not differ significantly between the study groups. Nevertheless, when continuous furosemide infusion was administered first, it produced a greater increase in urinary volume, 24-h urinary sodium, potassium and chloride than when bolus injection was applied the next day. Conversely, when furosemide bolus was administered first, followed by the infusions the next day, the effects were almost equal, regardless of the mode of administration. It is concluded that in the treatment of refractory edema in patients with congestive heart failure, continuous intravenous infusion of furosemide is superior to the conventional intermittent bolus injection, especially if it is administered at the very beginning of the hospital treatment, and presumably is even better with higher dosage and longer infusion time span.

Controlled multicentre comparison of captopril versus lisinopril in the treatment of mild-to-moderate arterial hypertension.

The antihypertensive efficacy and safety of lisinopril (L), a novel ACE inhibitor, were compared to those of captopril (C), the familiar drug of the same class, in a multicentre controlled trial. The study included 91 mild-to-moderate, middle-aged hypertensives of both genders, 46 of which were randomized to C and 45 to L. After a two-week placebo period the examinees were receiving either L o.d. in increasing dosage of 10, 20, or 40 mg per day (amount necessary to achieve normotension), or C b.i.d. in a corresponding daily dose of 25, 50, or 100 mg. During the eight-week formal part of the trial, L decreased the systolic blood pressure from the initial values by an average of 14.9%, and the diastolic pressure by some 15.2%. The same parameters were lowered on C by 11.2%, and 11.7%, respectively. The mean arterial pressure from an initial average of 125.5 mmHg was lowered to 110.9 mmHg on C (11.6% reduction, p < 0.01), and from 125.3 mmHg to 108.2 mmHg on L (13.6% reduction, p < 0.01). Although the L effects were more pronounced, the observed between-group differences did not reach the level of statistical significance, except for the achievement of normotension, which disclosed the superiority of L (p < 0.05). The tolerability of both drugs was good and only one examinee had to be excluded because of side-effects (proteinuria). It is concluded that both ACEIs under study showed comparable efficacy and safety, L being marginally more potent and longer acting.

Comparison of chlorthalidone, propranolol and bopindolol in six-month treatment of arterial hypertension.

The aim of this study was to test the hypothesis that prolonged treatment of mild to moderate hypertension with low-dose thiazide diuretics or beta blockers does not induce any of the major untoward biochemical changes, such as hypertriglyceridemia, hypercholesterolemia, hyperuricemia and electrolyte imbalances. The effect of these drugs was analyzed in 100 outpatients (52 males and 48 females) aged 52.0 +/- 7.9 years with mild to moderate hypertension, in a prospective 6-month study. After an appropriate workup, the patients were randomized to either 25 mg chlorthalidone (40 patients), 120 mg propranolol (30 patients), or 2 mg per day bopindolol (30 patients). A significant reduction of approximately 10% in systolic and diastolic blood pressure was recorded in all the groups. At the end of the 6th month, in the chlorthalidone group triglycerides increased to 3.0 +/- 2.1 mmol/l from 2.8 +/- 1.6 mmol/l, while cholesterol after an initial increase to 6.6 +/- 1.6 from 6.4 +/- 1.6 mmol/l returned to the baseline level. Uricemia and serum potassium concentration decreased by 4%. The body weight was reduced to 83.8 +/- 13.4 kg from 86.1 +/- 13.4 kg. There was no change in serum glucose level. In the propranolol group, as expected, heart rate decreased by 20%, but there were no significant changes in glucose and potassium plasma concentration. Triglycerides did not change significantly, while cholesterol, after a small increase, returned to the initial levels. Similar results were obtained in the bopindolol group, apart from the triglycerides, which increased significantly (to 2.5 +/- 1.1 from 2.2 +/- 0.4 mmol/l), probably because of the lower baseline concentration. We conclude that in prolonged treatment, chlorthalidone, propranolol and bopindolol do not induce significant untoward biochemical changes that alone might increase cardiovascular risk.

Nicardipine versus nifedipine: multicentre controlled trial in essential hypertension.

Ninety-five hypertensive outpatients of both sexes, aged 23 to 65 years with diastolic blood pressures above 105 but below 120 mmHg (greater than 14.0 but less than 16.0 kPa), after one week on a placebo were randomly assigned either to nicardipine plus a placebo (40 mg/day - 48 patients) or nifedipine sustained-release plus a placebo (20 mg/day - 47 patients) for an additional six weeks. The study groups were homogeneous and comparable. After the run-in period the average blood pressure was 181 +/- 17/116 +/- 9 mmHg (24.1 +/- 2.3/15.5 +/- 1.2 kPa) in the nicardipine and 177 +/- 22/116 +/- 9 mmHg (23.6 +/- 2.9/15.5 +/- 1.2 kPa) in the nifedipine group (p greater than 0.10). In the acute oral test (nicardipine 40 mg to all the subjects; blood pressure measured at 30 min intervals during two hours) almost identical hypotensive effects within and between groups were observed (mean arterial pressure decrease of 11%, after 120 min; p less than 0.05). At the end of this trial blood pressure decreased further to 152 +/- 12/94 +/- 11 mgHg (20.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nicardipine and to 145 +/- 12/94 +/- 11 mmHg (19.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nifedipine. There were no significant changes in pulse rate. The observed between-group differences were trivial (p greater than 0.10). The laboratory data did not alter appreciably during this study. Three patients on nicardipine and four on nifedipine reported headache, palpitations and flushing: one patient on nicardipine and two on nifedipine were as a result excluded from the trial. It was concluded that nicardipine and nifedipine sustained-release were comparably effective and well-tolerated drugs suitable as the first-line agents for the management of mild to moderate hypertension.