SEM and molecular approaches to identify Calicophoron clavula in Saudi Arabia.

In the present study, Calicophoron clavula (Paramphistomidae), a parasite of rumina of sheep and cows, was collected from Taif region, KSA, to investigate its identity and the prevalence of infection in livestock. Specific identification was mainly achieved by ITS molecular technique and surface ultrastructure was studied by SEM. Adult C. clavula is described for the first time from Saudi Arabia. The infection rate is 1% in sheep and 10% in cows. Results indicated that this species isolate was genetically identical with other C. clavula isolates where matching reach 100%. The primary sequence of the rDNA ITS2+ region of the fluke produces amplicon of 647 bp. SEM results show that no observed papillae around its genital opening. Besides, it has very few scattered small papillae around its oral region with few randomly distributed acetabular papillae. These findings were compared with the same corresponding species in other previous works of literatures.

Assessment of left ventricular ejection fraction with late-systolic and mid-diastolic cardiac phases using multi-slice computed tomography.

INTRODUCTION: Multi-slice computed tomography (MSCT) is an accurate tool for the assessment of left ventricular ejection fraction (LVEF). However, in order to reduce radiation dose, prospective acquisition protocols are currently used, in which the end-systole and end-diastole are not scanned. Our aim was to study the accuracy of the assessment of LVEF using fixed late-systolic and mid-diastolic cardiac phases compared with echocardiography. METHODS: MSCT-derived LVEF was measured with off-line commercially available software packages, and compared with echocardiography-derived LVEF using the Simpson's method. LVEF was categorized as normal vs. abnormal (50% cut-off) and was also analyzed as a quantitative parameter. Bland-Altman plots and Pearson correlations were used for inter-technique comparisons. RESULTS: 58 patients were included. The sensitivity and specificity of fixed-phase MSCT when compared with echocardiography for detection of LVEF ≤50% was 79% (95% CI = 65-89%) and 43% (10-82%). Misclassification was associated with older age (68 ± 12 vs. 54 ± 13 years, p < 0.01), faster heart rate (79 ± 14 vs. 68 ± 10 bpm, p = 0.01), and LV hypertrophy (86% vs. 52%, p = 0.03). The quantitative comparison revealed no correlation (r = 0.095, p = 0.478) and a significantly different LVEF (median[IQR], 57.0[50.5-63.1]% vs. 61.0[57.3-64.3]%, p = 0.03). The observed bias between the two methods was -3.7% with broad limits of agreement (±25.5%). CONCLUSIONS: Fixed-phase MSCT assessment using late-systole and mid-diastole agreed in defining normal and abnormal LVEF in 76% of patients when compared with echocardiography. Quantitation of LVEF by this method yielded significantly lower values of LVEF and showed no correlation. Thus, accurate quantitation of LVEF by MSCT requires the acquisition of end-systolic and end-diastolic phases.

Haemolysis as a first sign of thromboembolic event and acute pump thrombosis in patients with the continuous-flow left ventricular assist device HeartMate II.

BACKGROUND: Despite advances in pump technology, thromboembolic events/acute pump thrombosis remain potentially life-threatening complications in patients with continuous-flow left ventricular assist devices (CF-LVAD). We sought to determine early signs of thromboembolic event/pump thrombosis in patients with CF-LVAD, which could lead to earlier intervention. METHODS: We analysed all HeartMate II recipients (n = 40) in our centre between December 2006 and July 2013. Thromboembolic event/pump thrombosis was defined as a transient ischaemic attack (TIA), ischaemic cerebrovascular accident (CVA), or pump thrombosis. RESULTS: During median LVAD support of 336 days [IQR: 182-808], 8 (20 %) patients developed a thromboembolic event/pump thrombosis (six TIA/CVA, two pump thromboses). At the time of the thromboembolic event/pump thrombosis, significantly higher pump power was seen compared with the no-thrombosis group (8.2 ± 3.0 vs. 6.4 ± 1.4 W, p = 0.02), as well as a trend towards a lower pulse index (4.1 ± 1.5 vs. 5.0 ± 1.0, p = 0.05) and a trend towards higher pump flow (5.7 ± 1.0 vs. 4.9 ± 1.9 L m, p = 0.06). The thrombosis group had a more than fourfold higher lactate dehydrogenase (LDH) median 1548 [IQR: 754-2379] vs. 363 [IQR: 325-443] U/L, p = 0.0001). Bacterial (n = 4) or viral (n = 1) infection was present in 5 out of 8 patients. LDH > 735 U/L predicted thromboembolic events/pump thrombosis with a positive predictive value of 88 %. CONCLUSIONS: In patients with a CF-LVAD (HeartMate II), thromboembolic events and/or pump thrombosis are associated with symptoms and signs of acute haemolysis as manifested by a high LDH, elevated pump power and decreased pulse index, especially in the context of an infection.

Functional outcome of unstable pelvic ring injuries after iliosacral screw fixation: single versus two screw fixation.

INTRODUCTION: A clinical series of patients was studied to compare the functional score after the use of a single versus two percutaneous iliosacral screws for unstable posterior pelvic ring fractures with or without anterior fixation with the aim to explore if the addition of a second screw would provide better results regarding the functional outcome score. MATERIALS AND METHODS: This case series includes 77 patients with an average of 32.6 years who suffered unstable posterior pelvic ring fractures. Forty-six were Tile type C and 31 were Tile type B. Patients underwent closed reduction and were fixed using percutaneous fluoroscopic-guided iliosacral screws in the supine position with 1 screw in 50 fractures, 2 screws in 37 fractures, 2 fractures were fixed with plates after ORIF, and in 6 cases (out of the bilateral cases) the undisplaced side was unfixed. Postoperatively three patients were lost to follow up and 74 patients (84 posterior fractures fixed with screws) were followed up for a mean of 37.4 months (range 6-151 months) and were evaluated using the Majeed score (1989). RESULTS: Clinical union occurred in all the patients, although in two cases posterior fixation failed and was revised. Radiologically excellent reduction was achieved in 55 patients (71.4%), good in 16 (20.8%), fair in 6 (7.8%) and none had poor reduction. Statistically; among 62 cases that completed the Majeed score evaluation at the last follow-up session, there was no significant difference p value 0.051 between two groups. We also compared Majeed score in Tile B and C fractures fixed with one versus two screws. CONCLUSION: The addition of a second screw for posterior fixation did not show any statistically significant difference regarding functional outcome. LEVEL OF EVIDENCE: Level IV clinical trial.

Under-coracoid-around-clavicle (UCAC) loop in type II distal clavicle fractures.

In Neer type II (Robinson type 3B) fractures of the distal clavicle the medial fragment is detached from the coracoclavicular ligaments and displaced upwards, whereas the lateral fragment, which is usually small, maintains its position. Several fixation techniques have been suggested to treat this fracture. The aim of this study was to assess the outcome of patients with type II distal clavicle fractures treated with coracoclavicular suture fixation using three loops of Ethibond. This prospective study included 14 patients with Neer type II fractures treated with open reduction and coracoclavicular fixation. Ethibond sutures were passed under the coracoid and around the clavicle (UCAC loop) without making any drill holes in the proximal or distal fragments. There were 11 men and three women with a mean age of 34.57 years (29 to 41). Patients were followed for a mean of 24.64 months (14 to 31) and evaluated radiologically and clinically using the Constant score. Fracture union was obtained in 13 patients at a mean of 18.23 weeks (13 to 23) and the mean Constant score was 96.07 (91 to 100). One patient developed an asymptomatic fibrous nonunion at one year. This study suggests that open reduction and internal fixation of unstable distal clavicle fractures using UCAC loops can provide rigid fixation and lead to bony union. This technique avoids using metal hardware, preserves the acromioclavicular joint and provides adequate stability with excellent results.

Interferon-gamma +874 T/A and interleukin-10 -1082 A/G single nucleotide polymorphism in Egyptian children with tuberculosis.

The aim was to investigate the association of interferon-gamma (IFN-γ) +874 T/A and interleukin-10 (IL-10)-1082 A/G single nucleotide polymorphisms with tuberculous infection and post-BCG lymphadenitis in Egyptian children. IFN-γ +874 T/A and IL-10 -1082 A/G polymorphism detection by amplification refractory mutation system technique was carried out for 110 patients with TB, 40 patients with post-BCG lymphadenitis and 118 healthy controls. IFN-γ +874 A allele was higher in TB and post-BCG patients than those in healthy controls (Pc=0.006 and 0.002, respectively). IFN-γ +874 genotype AA was significantly higher in patients with TB than that in control (Pc=0.015), in extrapulmonary than patients with pulmonary TB (PTB) (Pc=0.009), and young children with TB below 5 years (Pc=0.024). No statistically significant differences were observed between patients with TB and controls for the frequency of IL-10(-1082) alleles or genotypes (P>0.05); however, a statistically significant difference in the frequency of IL-10 (-1082) GG genotype was found between patients with pulmonary and extrapulmonary TB (Pc=0.003). Low producer IFN-γ +874 A/A genotype is associated with post-BCG lymphadenitis and TB disease especially in younger children below 5 years. IL-10-1082 G/G genotype did not exhibit significant association except for increased GG frequency in PTB. Both cytokine polymorphisms have no relation to tuberculin reaction in patients with TB.

Contrast echocardiography: mechanism of action, safety and clinical applications.

Since its initial description by Gramiak and Shah in 1968, contrast echocardiography has become an established practice world-wide. Microbubbles have the unique property of being pure intravascular tracers. The basic rationale behind bubble imaging is the characteristic responses to ultrasound power that results in enhanced ultrasound images from the blood pool. Therefore, whenever there is blood pool there is a potential application for contrast ultrasound. Clinical applications of contrast echocardiography have been vastly grown from diagnostic applications such as detection of a persistent foramen ovale to drug delivery. This article reviews the mechanism of action, safety and clinical applications of contrast echocardiography.

Candidal colonization, strain diversity, and antifungal susceptibility among adult diabetic patients.

BACKGROUND AND OBJECTIVES: Candidal colonization in diabetics is a matter of debate. The aim of this study is to investigate oral candidal colonization, strain diversity, antifungal susceptibility, and the influence of local and systemic host factors on candidal colonization in adult diabetics. METHODS: We conducted a case-control study that compared 150 diabetics (49 type 1, 101 type 2) with 50 healthy controls. Two salivary samples were collected, using the oral rinse sampling method: one for salivary flow rate and pH determination, and the other for candidal colonization assessment. The candidal isolates were identified and tested in vitro for antifungal susceptibility using the commercial kit, Candifast. The relationship between specific host factors and candidal colonization was also investigated. RESULTS: Diabetics had a higher candidal carriage rate compared to controls, but not density. Candida albicans was the most frequently isolated species, but diabetics had a variety of other candidal species present. None of the control samples were resistant to any tested antifungal, while the diabetic samples had differing resistances to azole antifungals. Although there was a significant positive correlation between glycemic control and candidal colonization in type 2 diabetics, there was a negative correlation between salivary pH and candidal carriage in the controls versus density in type 2 diabetics. CONCLUSIONS: Diabetic patients not only had a higher candidal carriage rate, but also a variety of candidal species that were resistant to azole antifungals. Oral candidal colonization was significantly associated with glycemic control, type of diabetes, and salivary pH.

Influence of the pattern of hypertrophy on left ventricular twist in hypertrophic cardiomyopathy.

BACKGROUND/OBJECTIVE: Left ventricular (LV) twist has an important role in LV function. The influence of the pattern of LV hypertrophy on LV twist in hypertrophic cardiomyopathy (HCM) patients is unknown. This study sought to assess LV twist in a large group of HCM patients according to the pattern of LV hypertrophy. METHODS: The final study population consisted of 43 patients with HCM (mean age 43 (15) years, 31 men) and a typical sigmoidal (n = 16) or reverse septal curvature (n = 27) and 43 age-matched and gender-matched healthy control subjects. LV peak systolic rotation (Rot(max)), LV peak systolic twist (Twist(max)) and untwisting at 5%, 10% and 15% of diastole were determined by speckle tracking echocardiography (STE). RESULTS: Compared to control subjects, HCM patients had increased basal Rot(max) (-5.5 degrees (2.3 degrees ) vs -3.4 degrees (1.7 degrees ), p<0.001) and comparable apical Rot(max) (7.3 degrees (3.1 degrees ) vs 7.0 degrees (2.2 degrees ), p = NS), resulting in increased Twist(max) (12.4 degrees (4.0 degrees ) vs 9.9 degrees (2.7 degrees ), p<0.01). Untwisting at 5%, 10% and 15% of diastole was decreased in HCM patients (all p<0.05). There was a striking difference in apical Rot(max )(9.4 degrees (2.8 degrees ) vs 6.0 degrees (2.6 degrees ), p<0.01) and Twist(max) (15.3 degrees (3.2 degrees ) vs 10.6 degrees (3.3 degrees ), p<0.01) between HCM patients with a sigmoidal and reverse septal curvature. CONCLUSIONS: STE may provide novel non-invasive indices to assess LV function in patients with HCM. Apical Rot(max) and Twist(max) in HCM patients are dependent on the pattern of LV hypertrophy.

Cardiac evaluation in children and adults with Pompe disease sharing the common c.-32-13T>G genotype rarely reveals abnormalities.

BACKGROUND AND OBJECTIVE: Pompe disease is an inherited metabolic disorder caused by deficiency of acid alpha-glucosidase. All affected neonates have a severe hypertrophic cardiomyopathy, leading to cardiac failure and death within the first year of life. We investigated the presence and extent of cardiac involvement in children and adults with Pompe disease with the common c.-32-13T>G genotype to determine the usefulness of cardiac screening in these patients with relatively 'milder' phenotypes. METHODS: Cardiac dimensions and function were evaluated through echocardiography, electrocardiography and Holter monitoring. The total group comprised 68 patients with Pompe disease, of whom 22 patients had disease onset before the age of 18. RESULTS: Two patients (3%) had cardiac abnormalities possibly related to Pompe disease: Electrocardiography showed a Wolff-Parkinson-White pattern in an 8-year-old girl, and one severely affected adult patient had a mild hypertrophic cardiomyopathy. This hypertrophy did not change during treatment with recombinant human alpha-glucosidase. In addition, four adult patients showed minor cardiac abnormalities which did not exceed the prevalence in the general population and were attributed to advanced age, hypertension or pre-existing cardiac pathology unrelated to Pompe disease. CONCLUSIONS: Cardiac involvement is rare in Pompe patients with the common c.-32-13T>G genotype. The younger patients were not more frequently affected than the adults. Electrocardiographic evaluation appears to be appropriate as initial screening tool. Extensive cardiac screening seems indicated only if the electrocardiogram is abnormal or the patient has a history of cardiac disease.

Dobutamine stress MRI versus threedimensional contrast echocardiography: It's all Black and White.

Dobutamine stress magnetic resonance imaging is considered the superior stress modality to detect wall motion abnormalities. In this report we demonstrate the strengths of a newly developed stress modality: dobutamine stress contrastenhanced real-time three-dimensional echocardiography. This stress modality may become a competitor of stress magnetic resonance imaging allowing fast acquisition and an unlimited number of left ventricular cross sections. Unfortunately, at the moment adequate imaging with stress realtime three-dimensional echocardiography is only possible in a minority of cardiac patients. (Neth Heart J 2008;16:217-8.).

Cardiac involvement in adults with Pompe disease.

BACKGROUND: Glycogen storage disease type II or Pompe disease is a neuromuscular disorder caused by deficiency of lysosomal acid alpha- glucosidase. Classic infantile Pompe disease results in massive left ventricular (LV) hypertrophy and failure. Although Pompe disease is often included in the differential diagnosis of LV hypertrophy the true frequency of cardiac involvement in adults with Pompe disease is not known. METHODS: Forty-six consecutive adult patients (mean age 48 +/- 12, 22 men) with Pompe disease were included. Each patient underwent a clinical examination, electrocardiography, and rest and low-dose dobutamine (in 20 patients) two-dimensional echocardiography including contrast and tissue Doppler imaging. RESULTS: All patients had limited exercise tolerance; a rollator walking aid was used in seven patients (15%), a wheelchair in 13 patients (28%), and assisted ventilation in 14 patients (30%). Prior to this study, one patient was known with permanent atrial fibrillation, His-bundle ablation and a VVI pacemaker and another patient was known with fluid retention. The first patient had increased LV end-diastolic diameter, impaired LV ejection fraction, low systolic mitral annular velocities and diastolic dysfunction grade II. The patient with fluid retention was wheelchair bound and dependent on 24-h assisted ventilation and showed right ventricular and LV hypertrophy (septum 16 mm, posterior wall 15 mm). LV hypertrophy was not seen in any of the other patients. One woman of advanced age had isolated low systolic mitral annular velocities. Mean global systolic LV function, including contractile reserve, was not decreased in patients with Pompe disease. Eight patients (17%) had mild diastolic dysfunction grade I, related to hypertension in four and advanced age in seven. CONCLUSIONS: In adult patients with Pompe disease without objective signs of cardiac affection by 12-leads electrocardiography or physical examination, echocardiographic screening for LV hypertrophy seems not effective.

Is there alteration in aortic stiffness in Leber hereditary optic neuropathy?

PURPOSE: Leber hereditary optic neuropathy (LHON) is recognized as the most common cause of isolated blindness in young men. The current study was designed to test whether LHON as a mitochondrial disease is associated with vascular functional alterations characterized by aortic elastic properties during echocardiography. METHODS: A total of 19 patients with typical features of LHON aged 42+/-13 years (10 males) were included. Their results were compared to 19 age- and gender-matched healthy controls. Aortic stiffness index was calculated from the echocardiographically derived aortic diameters and the clinical blood pressure data. RESULTS: In this patient population, the point mutation was present in 3460G>A position in five cases, in 11778G>A position in five cases, and in 14484T>C position in nine patients. Diastolic aortic diameter (26.0+/-2.5 mm vs 28.4+/-4.1 mm, p<0.05) and aortic stiffness index (5.1+/-2.6 vs 12.0+/-7.9, p<0.05) were significantly increased in LHON patients compared to controls. CONCLUSIONS: Aortic stiffness can be increased in LHON disease, but further studies are warranted to confirm these findings in a larger LHON patient population with a more reliable method focusing on the pathophysiologic background.

Cardiac abnormalities in adults with the attenuated form of mucopolysaccharidosis type I.

BACKGROUND: Cardiac involvement in mucopolysaccharidosis type I (MPS I) has been studied primarily in its most severe forms. Cardiac involvement, particularly left ventricular (LV) systolic and diastolic function, in the attenuated form of MPS I is less well known. METHODS: Cardiac function was prospectively investigated in 9 adult patients with the attenuated form of MPS I. All patients underwent 12-lead electrocardiography, 24 h Holter monitoring and two-dimensional echocardiography including tissue Doppler imaging (TDI). Eighteen age- and sex-matched healthy volunteers served as a control group. RESULTS: Aortic, mitral and tricuspid valve thickening was seen in, respectively, 5 (56%), 4 (44%) and 2 (22%) patients. Moderate mitral valve stenosis was seen in 1 patient and moderate aortic stenosis in 2 patients. All patients had mild-to-moderate aortic and mitral valve regurgitation and 6 patients (67%) had mild-to-moderate tricuspid valve regurgitation. Despite normal LV dimensions, ejection fraction and mass index, MPS patients had lower mean systolic mitral annular velocities (6.1 +/- 0.6 vs 9.1 +/- 1.4 cm/s, p < 0.01) compared to normal control subjects. Similarly, mean early diastolic mitral annular velocities were lower in MPS patients (7.8 +/- 0.9 vs 13.3 +/- 3.3 cm/s, p < 0.01). CONCLUSION: MPS I patients with the attenuated phenotype have not only valvular abnormalities but also LV diastolic and systolic abnormalities.

The role of hepatitis C in hepatocellular carcinoma: a case control study among Egyptian patients.

BACKGROUND: Egypt has one of the highest prevalence rates of hepatitis C virus (HCV) infection in the world; however, the risk and attribution related to HCV in Egyptian patients with hepatocellular carcinoma (HCC) remains unknown. GOALS: The current study was undertaken to estimate the risk of HCC in relation to HCV in Egypt. STUDY: Thirty-three patients with HCC and 35 healthy controls who had a similar socioeconomic status were prospectively enrolled at the University of Cairo National Cancer Institute. RESULTS: Anti-HCV antibodies were present in 75.8% of the patients and in 42.9% of the controls (p = 0.01); hepatitis B surface antigen (HBsAg) was present in 15.2% of the patients and in 2.9% of the controls (p = 0.03). In addition, the sex-and age-adjusted odds ratio (OR) for anti-HCV antibodies was 5.1 (95% CI = 1.5-17.4) and for HBsAg was 13.2 (95% CI = 1.2-148.2). Concurrent Schistosoma mansoni and anti-HCV was associated with an OR of 10.3 (95% CI = 1.3-79.8), which was higher than that for anti-HCV (6.5; 95% CI = 1.6-26.6) and S. mansoni infection (0.2; 95% CI = 0.1-6.2) alone. Finally, we estimated the attributable fraction of HCC to HCV to be 64% in this study population and 48% in the general Egyptian population. CONCLUSIONS: Both HCV and hepatitis B virus infection increase the risk of HCC in Egyptian patients, whereas isolated Schistosoma infection does not. Because of the very high prevalence rate of HCV in the general Egyptian population, it accounts for most HCC cases in Egypt.

Biological monitoring of occupational exposure to contraceptive drugs.

The present study was carried out for screening some biochemical changes due to occupational exposure to contraceptive drugs. It included 18 male workers and 22 female workers involved in the manufacture of contraceptive pills and 34 female workers manufacturing contraceptive ampoules. The levels of some sex hormones and gonadotropins were evaluated. Some parameters of blood picture, blood coagulation, liver and kidney functions, lipid profile and trace elements metabolism were assessed. Results were compared with those of a control group composed of 19 males and 27 females. Increased levels of estrogen among exposed workers was the main finding. It has been attributed to liver rather than pituitary dysfunction. A less atherogenic lipid profile has also been found. Referral to preventive measures has been recommended.

Postoperative radiotherapy of carcinoma in bilharzial bladder: improved disease free survival through improving local control.

Two hundred thirty-six patients with T3 bladder cancer who survived radical surgery and proved to have P3a, P3b, or P4a tumors were randomized in two phases into three groups: (a) no further treatment (83 patients); (b) postoperative radiotherapy multiple daily fractionation (MDF), using 3 daily fractions of 1.25 Gy each, with 3 hr between fractions, up to a total dose of 37.5 Gy in 12 days (75 patients); and (c) postoperative radiotherapy conventional fractionation (CF), for a total dose of 50 Gy/5 weeks (78 patients). The tolerance of the patients to postoperative radiotherapy was quite acceptable, with equal acute reactions in MDF and CF groups. The 5-year disease-free survival (DFS) rates amounted to 49 and 44% in MDF and CF postoperative radiotherapy groups, respectively, compared to 25% in the cystectomy-alone group. The 5-year local control rates were 87% and 93% for those treated with multiple daily fractionation and conventional fractionation while it was 50% in the surgery-alone group. The therapeutic benefit of postoperative irradiation was consistent for all tumor types, histological grades, and pathological stages for both the disease-free survival and local control. Patients with nodal metastases demonstrated lower recurrence rates in the postoperative radiotherapy groups, but this was not associated with improved disease-free survival. Multivariate analysis using the Cox Model confirmed these results. The independent prognostic factors affecting both disease-free survival and local control were the addition of postoperative radiotherapy, the nodal status, the pathological stage, and the tumor grade. Late complications of radiotherapy in the skin, small intestine, rectum, and the anastomotic site of the urinary division were lower with MDF than with conventional fractionation.

Postoperative radiotherapy of carcinoma in bilharzial bladder using a three-fractions per day regimen.

Patients with T3 bladder cancer who survived surgery and proved to have P3a, P3b or P4a tumors were randomized to either no further treatment (61 patients) or postoperative total pelvic irradiation (55 patients). A three-fraction per day regime was adopted with a dose per fraction of 125 cGy and an interval of 3 h between fractions. The total dose amounted to 3750 cGy divided into 30 fractions over 12 days. Patients of the postoperative radiotherapy group were re-randomized to radiotherapy alone or radiotherapy plus misonidazole (MISO) in a daily dose of 1 g/m2 given orally 2 h before the first daily fraction. The 2-year disease-free survival rate in the cystectomy alone group was 33 +/- 6% compared to 65 +/- 6% in the postoperative radiotherapy group. The therapeutic benefit applied to the two cell types, all histological grades and stages and to patients with or without nodal metastases. The benefit of postoperative irradiation was also verified by the Cox's multivariant analysis which adjusts for the relative representation of the important prognostic factors particularly pathological stage and nodal involvement. MISO did not seem to add to the therapeutic gain. No late complications were encountered in the wall of the rectum, small bowel or uretero-intestinal anastomotic sites. This is suggested to be due to the small dose per fraction used. However, early small bowel reactions were dose-limiting.

Misonidazole in the preoperative and radical radiotherapy of bladder cancer.

Measurement of intercapillary distances suggests the presence of significant cell hypoxia in Bilharzial bladder cancer. This tumor seems to be capable of reoxygenation in view of the existence of a correlation between prognosis and immediate tumor shrinkage after irradiation. Two programs are presented: 1) Use of misonidazole with concentrated preoperative irradiation where the reoxygenation properties are not used fully. A prospective randomized study is presented whereby cystectomy alone is compared with cystectomy plus preoperative irradiation (6.5 Gy X 2F/1 week) with or without misonidazole. the drug is given either orally (in two doses 3 g/m2 each given 3.5 hours prior to each fraction; blood levels: 90-110 micrograms/ml) or intravesically. The intravesical administration is designed in the light of penetration studies and seems to have the advantage of the complete lack of systemic drug toxicity. Twenty-eight patients were included in this study and no drug toxicity was recorded. A second preoperative irradiation study is presented whereby cystectomy alone is compared with cystectomy plus preoperative irradiation (4.0 Gy X 5F) with or without misonidazole in individual doses of 2 g/m2. 2) Two radical radiotherapy regimes are presented. One protocol involves a split course (SC) protracted regime making full use of spontaneous reoxygenation. The drug is given in 0.5 g/m2 daily doses (total dose 14 g/m2 spread over 61 days, blood level: 15-20 micrograms/ml). A second protocol involves hyperfractionation stimulating continuous low-dose-rate irradiation. Higher blood levels are attained (60-80 micrograms/ml) after daily doses of 2 g/m2 (total dose: 14 g/m2 spread over 35 days). In a phase II study using SC technic, reversible grade 1 peripheral neuropathy was encountered in 5 of 22 patients. Complete tumor regression 3 months after irradiation was achieved in 18 of 22 patients with 3T tumors. No neuropathy was encountered in four patients subjected to the HF regimen who also showed complete tumor regression.