Neurotoxicity of immunotoxins

Immunotoxins are being tested for the therapy of systemic cancer and brain tumors. Neurotoxicity has been dose limiting for several of these antibody conjugates given systemically. We review the animal and clinical data related to the neurotoxicity of immunotoxins in attempt to understand the molecular basis for the unexpected neural involvement and to prevent or minimize this toxicity in future clinical trials.     

AUGMENTATION DURACYSTOPLASTY IN NEUROGENIC BLADDER DYSFUNCTION

Background
Augmentation cystoplasty is the treatment of choice for patients with neurogenic bladder dysfunction in cases that are unresponsive to other medical treatment. Although intestinal segments as bladder substitutes are preferred over the other alternatives at present, they are not ideal bladder replacements due to several potential hazards. The purpose of this study was to determine whether or not augmentation duracystoplasty can be an afternative to augmentation enterocystoptasties.
Methods:
Ten patients with neurogenic bladder dysfunction unresponsive to conservative measures, underwent augmentation duracystoplasty by using the modified Bramble-Clam technique. The follow-up period was T-28 months.
Results:
At present, seven of 10 patients are completely continent for with clean intermittent catheterization. The remaining three patients required oral oxybutinin therapy, postoperatively, to achieve continence although lower dosages than those required in the preoperative period. We did not observe any serious pre- or postoperative complications.
Conclusions:
Based on these preliminary findings we think that duracystoplasty can be considered as a treatment alternative for hyperreflexic and/or low compliant neurogenic bladders.     

Statistical description of microcirculatory flow as measured with an MR method

Quantification of microcirculatory flow is important for the functional assessment of biologic systems. The authors describe a method of analyzing the dependence of the magnetic resonance (MR) signal intensity on microcirculatory flow. A gel bead phantom was used to simulate the randomly oriented flow capillaries, and the MR signal intensity of the phantom was studied at different flow velocities by using velocity-sensitized and -compensated spin-echo pulse sequences. A theoretical model based on the spin-phase phenomenon is proposed to elucidate the effect of flow on signal intensity. The velocity phase of a spin depends on its path and the corresponding velocity-encoding gradients. A Monte Carlo simulation was used to generate the path of a spin on the basis of a statistical model for flow through a random capillary network. From the velocity-phase distribution of a group of spins within a voxel, the signal attenuation due to flow can be calculated. The results of the statistical model and experimental measurements agreed well. Also, T1 and T2 effects in MR flow measurements were investigated. The current study provides a theoretical framework for understanding MR measurements of micro-circulatory flow.     

Leptin in corneas from keratoconus and infectious keratitis patients.

PURPOSE: Leptin is produced primarily by adipose tissue. More recent studies have shown extra sites of leptin production in physiologic and ill human tissues. However, whether leptin originates from human corneas in infectious keratitis and keratoconus is not known. The aim of this study was to demonstrate and quantitate leptin expression in corneas with infectious keratitis and keratoconus and make comparisons to control corneas. METHODS: We examined the immunohistochemical staining of leptin in nine corneas surgically excised from patients with infectious keratitis (3 patients), keratoconus (3 patients), and donor corneas (3 patients). RESULTS: The results were analyzed using a semiquantitative scoring system of mild, moderate, and strong. Cells of the infectious keratitis group had the strongest leptin staining intensity, the control group had moderate, and the keratoconus group had mild staining intensity. The more vascular corneas in the infectious keratitis group were also associated with the greatest leptin staining. CONCLUSIONS: Our findings indicate that leptin expression was present in all three sources of corneas (infectious keratitis, keratoconus, and normal control). Quantitative scoring would imply it may play a role in infectious keratitis, although further experiments are necessary to establish any causal relationship.     

Occult cystobiliary communication presenting as postoperative biliary leakage after hydatid liver surgery: are there significant preoperative clinical predictors?

BACKGROUND: Occult cystobiliary communication (CBC) presents with biliary leakage, if the cystobiliary opening cannot be detected and repaired at operation. We investigated the clinical signs associated with the risk of occult CBC in the preoperative period by studying patients who developed biliary leakage after hydatid liver surgery. METHODS: We analyzed the records of 191 patients treated for hydatid liver cyst. Postoperative biliary leakage developed in 41 patients (21.5%). Independent predictive factors were established by logistic regression analysis using clinical parameters, whose cutoff values were determined by receiver operating characteristic (ROC) curves. RESULTS: Postoperative biliary leakage presented as external biliary fistula in 31 (75.6%) of 41 patients, as biliary peritonitis in 6 (14.6%) and as cyst cavity biliary abscess in 4 (9.8%). Independent clinical predictors of occult CBC, represented by biliary leakage, were alkaline phosphatase > 250 U/L, total bilirubin > 17.1 micromol/L, direct bilirubin > 6.8 micromol/L, gamma-glutamyl transferase > 34.5 U/L, eosinophils > 0.09 and cyst diameter > 8.5 cm. Multilocular or degenerate cysts increased the risk of biliary leakage (p = 0.012). Postoperative complication rates were 53.7% in the patients with biliary leakage, and 10.0% (p < 0.001) in those without. The mean postoperative hospital stay was longer in patients with biliary leakage (14.3 [and standard deviation {SD} 1.9] d) than in those without (7.3 [SD 2.3] d) (p < 0.001). Nineteen (61.3%) of 31 biliary fistulae closed spontaneously within 10 days. The remaining 12 (38.7%) fistulae closed within 7 days after endoscopic sphincterotomy. CONCLUSION: Factors that predict occult CBC due to hydatid liver cyst were identified. These factors should allow the likelihood of CBC to be determined and, thus, indicate the need for additional procedures during operation to prevent the complications of biliary leakage.     

Follow-up of 366 ears after tympanostomy tube insertion: why is it draining?

OBJECTIVE: Tympanostomy tube insertion is one of the most frequently performed procedures in otolaryngology. Complications, such as otorrhea, tympanosclerosis, and cholesteatoma, have been reported in the literature after its application. STUDY DESIGN: This study reports the complications encountered with 239 children (439 ears) with a follow-up of 7 to 73 months (median, 29 months) after tympanostomy tube insertion. Hearing results and middle ear pressures were compared and complications were noted in 366 ears that were available for the study. RESULTS: Otorrhea developed in 3 (0.8%) cases. Tympanosclerosis was seen in 74 (20.2%) cases. Tympanic membrane perforation, retraction pocket, granulation tissue, and atelectasis were seen in 4.6%, 5.2%, 1.1%, and 6%, respectively. No patients developed cholesteatoma after tube insertion. Hearing results were improved postoperatively in 93.4% of patients (median, 14.2 dB) and worse in 6.6% of patients (median, 8.3 dB). The average extrusion time was 7.3 months for grommet and 16.3 months for T-tubes. CONCLUSION: Multifactor etiologies show some unsolved or misunderstood underlying pathology, or unmentioned environmental factor such as atopy due to rich flora and humidity might exist to consider in the pathophysiology of the otorrhea.     

Effects of tamoxifen on spinal bone density in women with breast cancer

Bone densitometry (L2-L4) was performed on 10 postmenopausal women with breast cancer after 0, 6, and 12 months of tamoxifen treatment; the results were compared with data from 10 normal controls. The patients and controls differed significantly at 6 (P less than .05) and 12 (P less than .003) months. The tamoxifen group showed a nonsignificant mean gain in bone mineral density after 6 and 12 months of treatment (+0.024 +/- 0.014 and +0.022 +/- 0.018 g/cm2, respectively), whereas the controls showed a nonsignificant mean loss of bone mass at 6 months (-0.012 +/- 0.018 g/cm2) and a statistically significant loss of bone density after 12 months (-0.024 +/- 0.01 g/cm2). These preliminary data suggest that tamoxifen use is associated with preservation of bone mass during the first year of treatment.     

Bromocriptine-induced cerebrospinal fluid fistula in patients with macroprolactinomas: Report of three cases and a review of the literature

Bromocriptine therapy for macroprolactinoma induced cerebrospinal fluid (CSF) rhinorrhea in three patients. The tumor had extended well beyond the sella turcica and caused bony erosion in all the cases. All three patients responded to bromocriptine therapy rapidly. CSF fistula occurred concomitantly with the reduction of tumor size and caused meningitis in two of the patients. Withdrawal of bromocriptine resulted in cessation of the leakage. One of the patients underwent transsphenoidal repair. Two patients refused surgery. This potentially lethal complication encountered in these three cases demonstrates the need for close supervision of macro-prolactinoma patients with skull base erosion placed under bromocriptine therapy.