Toxicity of preserved and unpreserved beta-blocker eyedrops in an in vitro model of human conjunctival cells

PURPOSE: To compare the toxicity of a short-time application of timolol with benzalkonium chloride (timolol-BAC+) and unpreserved timolol (timolol-BAC-) in an in vitro model of human conjunctival cells. METHODS: Chang's conjunctival cell line (ATCC CCL 20.2) was treated for 15min. with 0.1%, 0.25% or 0.4% timolol-BAC(+) or BAC(-) and then examined immediately or 24h later. Cell viability, chromatin condensation, mitochondrial mass and activity, free radicals production were studied by microplate cold light cytometry. Moreover, relative cell number was evaluated by crystal violet colorimetric test. In addition, cell size and the expression of an apoptotic marker Apo2.7 were studied by flow cytometry. RESULTS: Timolol-BAC(+) induced a rapid decrease in cell viability ranging from 40% immediately after treatment to 85% 24h later. A small, significantly less important decrease in cell viability was also observed with all tested concentrations of timolol-BAC(-). 24h after treatment with 0.25% timolol-BAC(+), the relative cell number was reduced by 55% whereas it did not vary after 0.25% timolol -BAC(-) treatment. Only timolol-BAC(+) induced chromatin condensation, decrease in mitochondrial membrane potential and cell size reduction. Moreover, cells treated with timolol-BAC(+) overexpressed the apoptotic marker Apo2.7. Also reactive oxygen species (ROS) production was significantly more important after cell exposure to timolol-BAC(+). CONCLUSION: In our model of conjunctival cells in vitro, timolol-BAC(+) induced irreversible cytotoxic damage with some characteristics of apoptosis. The active compound of timolol-BAC(-) could be responsible for ROS production and for cell viability variations. Oxidative stress could also play a role in timolol-BAC(+)-induced toxicity. In vitro toxic effects of antiglaucoma drugs could, in part, explain some ocular surface disorders in long-term treated patients.     

Antiepileptic effect of high-frequency stimulation of the subthalamic nucleus (corpus luysi) in a case of medically intractable epilepsy caused by focal dysplasia: a 30-month follow-up: technical case report

OBJECTIVE AND IMPORTANCE: Currently, some forms of epilepsy are resistant to both pharmacological and surgical interventions. As a result, there is a need for new therapeutic strategies. Because the nigral system modulates neuronal excitability in animal models of epilepsy, we considered therapeutic high-frequency stimulation of the subthalamic nucleus (STN). We were encouraged by the known relationship between the STN and the nigral system, as well as by our experience with high-frequency stimulation of the STN in Parkinsonian patients. CLINICAL PRESENTATION: A 5-year-old girl with pharmacologically resistant, inoperable epilepsy caused by focal centroparietal dysplasia underwent implantation with a permanent electrode in the left STN and was chronically stimulated. To date, we have followed up this patient for 30 months postoperatively. TECHNIQUE: High-frequency stimulation of the STN induced a significant voltage-dependent reduction (by 80%) in the number and severity of seizures. In addition, consistent improvement in both motor and cognitive functions was noted as a result of reduced postictal states. The effect was more prominent for seizures occurring in clusters (89% reduction) and during the day (88% reduction) than for those that occurred during sleep (53% reduction). CONCLUSION: This is the first report of epilepsy control using chronic high-frequency stimulation of the STN. Preliminary observations in three other operated patients (at 2, 12, and 18 mo) confirm these data. We think that high-frequency stimulation of the STN may hold significant future potential as a treatment for epilepsy, similar to its established role in the treatment of Parkinson's disease. This finding opens completely new experimental and therapeutic avenues for the treatment of surgically and medically intractable epilepsy.     

Laparoscopic retroperitoneal nephrectomy for Aspergillus-infected polycystic kidney

BACKGROUND AND PURPOSE: The management of polycystic kidney disease is mostly restricted to conservative measures. However, nephrectomy may be indicated in particular cases, especially when there are infective complications. To decrease the morbidity of the procedure, the laparoscopic approach has become appealing. We present a laparoscopic retroperitoneal approach to complicated polycystic kidney disease in a high-risk patient. CASERESPORT: We performed right retroperitoneal laparoscopic nephrectomy in a 39-year-old man who had autosomal polycystic kidney disease and had undergone heart transplantation. The immunosuppressed patient presented with severe flank pain, generalized signs of infection, and acute renal insufficiency. With the patient in the right lateral decubitus position, the retroperitoneal space was entered by the open technique, and the posterior pararenal space was developed with finger dissection. Five trocars were used. After the renal vessels had been secured and divided, the cysts were successively punctured, gradually shrinking the operative specimen. The kidney was placed in an Endo-catch and removed after morcellation, with no need to enlarge the 2-cm lumbotomy. The operating time was 80 minutes, and the hospital stay was 4 days. Histologic examination revealed a polycystic kidney with Aspergillus infection. CONCLUSION: The laparoscopic approach is a less-invasive option for removing a polycystic kidney when nephrectomy is indicated. The retroperitoneal route has the advantage of minimizing infection risks because of the absence of peritoneal opening.     

Cornea in Marfan disease: Orbscan and in vivo confocal microscopy analysis

PURPOSE: To investigate corneal thickness, curvature, and morphology with the Orbscan Topography System I (Bausch & Lomb, Inc., Salt Lake City, UT) in patients with Marfan syndrome (MFS) and to study MFS with in vivo confocal microscopy. METHODS: This prospective, clinical, comparative case series included 60 eyes of 31 patients with MFS and 32 eyes of 17 control subjects. First, biomicroscopic examination was conducted to search for ectopia lentis. Then, mean keratometry and ocular refractive power were calculated by the autokeratorefractometer. In each group, the Orbscan System I mean (and mean simulated) keratometry and pachymetric measurements (at the central location and at eight midperipheral locations) were obtained and compared, and correlations were established. In vivo confocal microscopy was performed to evaluate tissue morphology and Z-scan analysis of 14 thin MFS corneas compared with 14 control corneas. RESULTS: A significant decrease (ANOVA, P < 0.0001) of mean simulated keratometry measurement appeared in the MFS group (sim K, 40.8 +/- 1.4 D) compared with the control group (42.9 +/- 1.1 D). Pachymetry in the MFS group was significantly decreased (P < 0.0001) compared with that in the control group, in the center (respectively, 502 +/- 41.9 microm and 552 +/- 23.6 microm) and the eight midperipheral locations. Ectopia lentis was highly linked with mean keratometry and pachymetry (P < 0.0001). Confocal microscopy performed on MFS-affected thin corneas confirmed the corneal thinning and showed an opaque stromal matrix, and Z-scan profiles were abnormal with increased stromal back scattering of light. CONCLUSIONS: MFS is known to be associated with a flattened cornea. This study demonstrated an association with corneal thinning and described confocal microscopy findings in this syndrome.     

Cellular angiofibroma of the vulva: a clinicopathological study of two cases with documentation of some unusual features and review of the literature

BACKGROUND: Cellular angiofibroma (CA) of the vulva is a recently described condition, whose clinical and pathological features are poorly known. METHODS: We have encountered two cases of this very unusual tumor. Their clinical and pathological features were analyzed and compared to those reported in the literature. RESULTS: Both patients were middle-aged women. In each case, the lesion had the clinical appearance of a vulvar cyst, located in the lateral aspect of the clitoris and the right labium majus, respectively. Microscopically, the lesions were well circumscribed but not truly encapsulated. Both were composed of small spindle cells arranged in short fascicles and mixed up with relatively abundant small- or medium-sized rounded vessels. While mitotic activity was perceptible in both cases, no cellular atypia could be demonstrated. A striking feature seen in one case was the presence of pseudoangiomatous changes in the stroma, similar to those occasionally found in spindle cell lipoma. Phenotypically, the tumor cells consistently expressed vimentin, CD99, and both estrogen and progesterone receptors. A discrete CD34 or smooth muscle actin immunoreactivity was also found in one case. No expression of S-100 protein, Bcl-2 protein, CD117 (c-kit gene product), epithelial membrane antigen, desmin, or h-caldesmon could be demonstrated. CONCLUSION: This study further illustrates that CA of the vulva has distinct clinical and pathologic features that set it apart from the other soft tissue conditions involving this area. However, like many soft tissue neoplasms, this tumor also exhibits some variation in its histological or immunohistochemical features.     

Shifting costs from high-cost to low-cost diagnosis-related groups?

Hospitals are commonly compared with each other within diagnosis-related group (DRG) categories. Administrators infer that hospitals with a higher cost per case within a DRG are less efficient than hospitals with a lower cost per case after case mix and severity adjustment. The authors assess whether hospitals that carry a heavy load of high-cost DRGs potentially distribute the added expenses of treating these patients onto their lower cost DRGs using data gathered from the 47 hospitals in the University Hospital Consortium database between January 1994 and December 1995. The results indicate that given standard hospital allocation practices, some of the costs associated with high-cost patients were likely shifted downward, thereby inflating the cost per case for less expensive patients. As researchers adopt more benchmarking methodologies, it is important to recognize that standard accounting practices in which cost shifting from one class of patient to another may impair the ability to understand the actual cost structure for classes of patients.     

Focal cortical dysplasia possibly related to a probable prenatal ischemic injury

Focal cortical dysplasias are a frequent etiology of partial seizure disorders refractory to medical treatment. We report the case of a patient with focal cortical dysplasia, confirmed by surgery, in association with ischemic cerebral lesions that possibly occurred during the intra-uterine development. This observation reinforces the hypothesis of a possible factor of causality between prenatal ischemia and anomalies of cortical development.     

Subclinical speckled perifollicular melanosis of the scalp

Based on the clinical presentation of some skin pigmentation disorders it is thought that a bicompartmental functional system exists in the epidermal melanocyte population. It corresponds to the perifollicular and interfollicular compartments, respectively. The present study was undertaken looking for the presence of such a system on scalp unaffected by pigmentary disorders. The scalps of 100 men with incipient to severe androgenic alopecia were examined using a videocamera equipped with an internal ultraviolet light-emitting unit. The face, trunk and limbs were similarly examined in 45 of these adults and in 13 children of both sexes. In 92 men, a subclinical hypermelanosis was found as a speckled pattern centered on every single follicle. With increasing baldness severity, another epidermal hyperpigmentation pattern involving the interfollicular area was superimposed to the perifollicular pattern. These stereotyped patterns of subclinical melanoderma were also disclosed on the face of adults, but not in children. In addition, the spotty perifollicular pattern was discrete or not apparent on the other parts of the body. It is concluded that the perifollicular subclinical melanotic pattern is a regional characteristic of cephalic skin, perhaps related to the local production of melanocortins, particularly alpha-MSH by the pilosebaceous unit.     

Preoperative coagulation tests in former preterm infants undergoing spinal anaesthesia

BACKGROUND: Clinical history is insufficient to detect disorders of haemostasis in infants aged less than 1 year and laboratory coagulation testing is recommended in infants before perimedullar anaesthesia. METHODS: We designed a retrospective study to assess the preoperative coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time, platelet count] performed in 141 former preterm infants who underwent spinal anaesthesia for elective inguinal hernia repair. All the infants had recovered from any significant medical event (necrotizing enterocolitis, intracranial haemorrhages, transfusions of blood products, sepsis, etc.) when they were scheduled for surgery. RESULTS: Mean values for aPTT were frequently abnormal (60.4%) in infants with a postconceptional age of less than 45 weeks. No complication related to the puncture or abnormal perioperative bleeding was detected. CONCLUSIONS: Other coagulation tests should be evaluated to assess the coagulation status in infants with a postconceptional age of less than 45 weeks.