Prostate cancer: evaluation with endorectal MR imaging and three-dimensional proton MR spectroscopic imaging

PURPOSE: To establish the additional value of MR Spectroscopy (3D CSI MRS Three-dimensional Chemical Shift Imaging Magnetic Resonance Spectroscopy) to endorectal MR in the diagnosis and grading of prostate cancer. MATERIALS AND METHODS: MR and 3D CSI MR spectroscopy were performed in 53 patients with suspicion of prostate cancer on the basis of rectal exploration and/or transrectal ultrasound and/or the PSA levels. All the examinations were performed with a 1.5 T imager using an endorectal coil. We acquired axial and coronal T2-weighted FSE sequences, axial T1-weighted SE sequences and PRESS 3D CSI (Point Resolved Spectroscopy 3D Chemical Shift Imaging) sequences localized on the axial T2 images so as to include the prostatic gland while excluding the periprostatic fat. The MR examinations were evaluated by two radiologists unaware of the clinical data, transrectal ultrasound findings, PSA levels and histological findings. The MR and 3D CSI MRS findings were compared with the biopsy findings in 22 cases and with material obtained from laparoscopic prostatectomy in 31 cases. RESULTS: The histological examination revealed adenocarcinoma in 37 cases, prostatitis in 2 cases and no alterations in the remaining 14 cases. The morphologic MR scan showed a sensitivity of 76%, a specificity of 56%, an accuracy of 70%, a PPV of 80% and a NPV of 50%. By combining MR and 3D CSI MRS we obtained a sensitivity of 95%, a specificity of 81%, an accuracy of 91%, a PPV of 92% and a NPV of 87%. Elevated choline concentrations were found both in tumours with a low Gleason score (18 cases) and in those with a high Gleason score (19 cases); instead we found markedly reduced (n=9) or absent (n=4) citrate only in the tumours with a high Gleason score, while we found normal citrate levels in the 18 tumours with a low Gleason score. CONCLUSIONS: The 3D CSI MRS improved the reliability of endorectal MR in the diagnosis and characterisation of prostatic cancer. Moreover, the 3D CSI MRS findings demonstrated a linear correlation with tumour grade.     

Cerebellar ataxia and coenzyme Q10 deficiency

The authors measured coenzyme Q10 (CoQ10) concentration in muscle biopsies from 135 patients with genetically undefined cerebellar ataxia. Thirteen patients with childhood-onset ataxia and cerebellar atrophy had markedly decreased levels of CoQ10. Associated symptoms included seizures, developmental delay, mental retardation, and pyramidal signs. These findings confirm the existence of an ataxic presentation of CoQ10 deficiency, which may be responsive to CoQ10 supplementation.     

Role of gabapentin in spinal muscular atrophy: results of a multicenter,randomized Italian study

Recent studies suggest that gabapentin has a neuroprotective effect in experimental models of motoneuron disease. We carried out a multicenter, randomized, controlled trial of gabapentin versus no treatment in 120 patients with type II or III spinal muscular atrophy for 12 months. We assessed maximum voluntary isometric contraction with a handheld myometer and calculated an arm megascore (summing elbow flexion, hand grip, and three-point pinch scores), and a leg megascore (summing knee flexion, knee extension, and foot extension scores). Forced vital capacity and timed tasks were also evaluated. Arm megascore improved by at least 30% in 24.6% of treated and 16.9% of untreated patients (relative risk = 1.45; 95% confidence interval = 0.71-2.97). The leg megascore improved by at least 30% in 37.7% of treated and 20.3% of untreated patients (relative risk = 1.85; 95% confidence interval = 1.02-3.37). We conclude that gabapentin produced a significant improvement in leg megascore at 6 months, which was more evident at 12 months, with a trend for improvement in arm megascore at 12 months. The treatment had no effect on forced vital capacity or timed functional tests.     

Interscalene brachial plexus anesthesia and analgesia for open shoulder surgery: a randomized,double-blinded comparison between levobupivacaine and ropivacaine

We compared the onset time and quality of interscalene brachial plexus block produced with levobupivacaine and ropivacaine in 50 patients undergoing open shoulder surgery randomly allocated to receive 30 mL of 0.5% levobupivacaine (n = 25) or 0.5% ropivacaine (n = 25) injected through a 20-gauge catheter placed into the interscalene sheath using a 18-gauge insulated and stimulating Tuohy introducer. The block was also prolonged after surgery using a patient-controlled interscalene analgesia with 0.125% levobupivacaine or 0.2% ropivacaine, respectively (basal infusion rate, 6 mL/h; bolus, 2 mL; lockout period, 15 min; maximum boluses per hour, three). Three patients (two with levobupivacaine [8%] and one with ropivacaine [4%]) failed to achieve surgical block within 45 min after the injection and were excluded. The onset time of surgical block was 20 min (10-40 min) with levobupivacaine and 20 min (5-45 min) with ropivacaine (P = 0.53). Rescue intraoperative analgesia (0.1 mg of fentanyl IV) was required in eight patients in each group (34%) (P = 0.99). Forty-two patients completed the 24-h postoperative infusion (22 with levobupivacaine and 20 with ropivacaine). Postoperative analgesia was similarly effective in both groups. Total consumption of local anesthetic infused during the first 24 h was 147 mL (144-196 mL) with levobupivacaine and 162 mL (144-248 mL) with ropivacaine (P = 0.019), with a ratio between boluses received and requested of 0.8 (0.4-1.0) and 0.7 (0.4-1.0), respectively (P = 0.004). The degree of motor block of the operated limb was deeper with levobupivacaine than ropivacaine when starting postoperative analgesia; however, no further differences in degree of motor function were observed between the two groups. We conclude that 30 mL of levobupivacaine 0.5% induces an interscalene brachial plexus anesthesia of similar onset and intensity as the one produced by the same volume and concentration of ropivacaine. Postoperative interscalene analgesia with 0.125% levobupivacaine results in similar pain relief and recovery of motor function with less volume of local anesthetic than with 0.2% ropivacaine. IMPLICATIONS: This prospective, randomized, double-blinded study demonstrates that 30 mL of 0.5% levobupivacaine produces an interscalene brachial plexus block of similar onset and quality as the one produced by the same volume of 0.5% ropivacaine. When prolonging the block after surgery, 0.125% levobupivacaine provides adequate pain relief and recovery of motor function after open shoulder surgery, with less volume infused during the first 24 h after surgery than 0.2% ropivacaine.     

Effect of clotting factors concentrates on lymphocyte and neutrophil function in vitro

Immunological abnormalities have been reported in haemophiliacs. Although infections with HIV, hepatitis and other viruses may contribute to these abnormalities, immune defects are detectable also in HIV seronegative haemophiliacs. It is likely that chronic exposure to extraneous proteins in clotting factor concentrates (CFCs) may play a role in immunomodulation, but the underlying mechanisms remain unclear. The results of the present paper show that: a) soluble HLA class I (sHLA-I), soluble Fas-ligand (sFas-L) and transforming growth factor beta 1 (TGF-beta1) are detectable in plasma derived but not in recombinant CFCs; b) the level of sHLA-I and sFas-L is proportional to the grade of CFCs purity whereas TGF-beta1 showed very variable levels; c) soluble molecules detected in CFCs exert immunomodulatory effects in vitro like apoptosis induction in Jurkat cells and inhibition of mixed lymphocyte reaction response, antigen-specific lymphocyte cytotoxic activity and neutrophil chemotaxis.     

Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients

BACKGROUND: The effects of pancreas transplant alone (PTA) on cardiovascular risk factors (CRF) and cardiac function in type 1 diabetes mellitus (T1DM) patients are still unsettled. METHODS: We studied 13 T1DM patients who received PTA with portal drainage and 11 matched control patients. Parameters of glucose and lipid metabolism and several additional classic CRF were assessed before and up to 6 months posttransplant. Cardiac morphology and function were assessed by Doppler echocardiographic examination. RESULTS: Insulin independence was promptly achieved and then maintained after PTA. Total and low-density lipoprotein cholesterol levels were significantly lower after transplantation, whereas high-density lipoprotein cholesterol and triglyceride concentrations did not change. Both systolic and diastolic blood pressure values and fibrinogen levels improved significantly. In addition, PTA determined a significant amelioration of several morphologic and functional cardiac indices. None of the measured parameters changed in the control patients. CONCLUSIONS: PTA with portal drainage induces an early improvement of CRF and ameliorates cardiac function in patients with T1DM.     

Transitional cell carcinoma of the urinary bladder metastatic to the orbit

We report a rare case of transitional cell carcinoma of the urinary bladder metastatic to the orbit, review the histopathology, and highlight characteristics of the few previously reported cases. A 68-year-old man with a remote history of transitional cell carcinoma of the urinary bladder presented with decreased visual acuity, afferent pupillary defect, and limited extraocular motility OS. Computed tomography scan of the orbits showed a diffuse infiltrate surrounding the left globe and optic nerve. Biopsy revealed metastatic transitional cell carcinoma. The patient expired one month later. With only seven cases previously reported, we conclude that transitional cell carcinoma of the urinary bladder rarely metastasizes to the orbit. When present, orbital metastases signify aggressive disease and a poor prognosis. Mean survival following orbital diagnosis is 2.2 months in the cases reported.     

Interaction of polyhalogenated compounds of appropriate configuration with mammalian or bacterial CYP enzymes. Increased bilirubin and uroporphyrinogen oxidation in vitro

Polyhalogenated compounds, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, are associated with toxic Uroporphyria and cause alleviation of jaundice in the Gunn rat. These effects have been attributed to a microsomal oxidation of uroporphyrinogen and bilirubin for which supportive evidence has been obtained in vitro. CYP1A1 required planar polyhalogenated biphenyls for these oxidative reactions, while CYP1A2 was capable of oxidation in their absence.We have now used rat CYP1A1 and confirmed with the pure enzyme that increased bilirubin oxidation was caused by the addition of 3,4,3',4'-tetrachlorobiphenyl. CYP1A2 was more active than CYP1A1 at oxidizing bilirubin in presence of NADPH alone and reacted to addition of 3,4,3',4'-tetrachlorobiphenyl with a depression rather than a stimulation of bilirubin oxidation.We have also tested a bacterial enzyme, CYP102. Dodecanoic acid and its polyhalogenated analogue (perfluorododecanoic acid) both stimulated NADPH oxidation by CYP102, but only the perfluoro analogue stimulated markedly bilirubin oxidation. The analogue exhibited much greater potency than the normal substrate in stimulating NADPH and bilirubin oxidation and also showed greater affinity for CYP102, as measured by the binding constant, Ks. The molar stoichiometry ratio between NADPH and O(2) consumption was 1 in the case of the substrate, but approximated 2 with the perfluoro analogue. We conclude that halogenated substrate analogues can interact with different CYPs to increase production of oxidative species, probably by an uncoupling mechanism. A role of the ferryl-oxygen intermediate is suggested in the oxidation of biologically important molecules, with possible implications for the therapy of jaundice and for toxic oxidative reactions, such as uroporphyria and cancer.