Subclinical saccadic adduction slowing in patients with monosymptomatic unilateral optic neuritis predicts the development of multiple sclerosis

Parameters of visually guided saccades were studied in 22 patients with monosymptomatic optic neuritis and 21 age-matched control subjects with a precise infrared reflection technique. Follow-up of the patients over 2.2 years, on average, allowed correlations of subclinical saccadic abnormalities, measured at study entry, with the development of clinically definite multiple sclerosis (CDMS). Subclinical adduction slowing defined on statistical grounds was observed in nine patients. Seven of these and four out of five patients with prolonged saccadic latency developed CDMS during the follow-up period. We conclude that subclinical adduction slowing in patients with optic neuritis represents an oculographic finding with pathological significance.     

Endocrinology: Follicle cyst formation after administration of different gonadotrophin-releasing hormone analogues for assisted reproduction

The aim of this study was to examine the occurence of ovariancysts during the administration of three different gonadotrophin-releasinghormone analogues (GnRHa) in the long protocol as well as theircharacteristics, management and outcome compared with patientswith no cyst formation. A total of 172 in-vitro fertilization(IVF) cycles in which GnRHa was administered at menstruationwere analysed. Group B consisted of 72 cycles in which buserelinwas used. Of these, 10 (13.9%) were with cysts (group B1) and62 (86.1%) without cysts (group B2). Group T included 49 cyclesin which triptorelin was injected. Of these, seven (14.2%) werewith cysts (group T1) and 42 (85.7%) without cysts (group T2).Group L comprised 51 cycles in which leuprolide was administered.Of these, eight (15.7%) were with cysts (group L1) and 43 (84.3%)without cysts (group L2). All women with ovarian cysts had higherserum oestradiol concentrations and all except five underwentcyst aspiration with no complication. No differences were observedin the number of follicles and oocytes between groups B, T andL or between the groups with cysts and those without cysts.The pregnancy rate was similar in all groups. In conclusion,follicle cyst formation does not seem to be related to the useof a specific GnRHa, its short- or long-acting form or to themode of administration. In addition, follicle cyst aspirationis a safe and successful solution to the problem of functionallyactive ovarian cysts.     

Tumor cell proliferation in early gastric cancer: biological and clinical behavior

BACKGROUND/AIMS: Recently, early gastric cancers without lymph node metastasis have successfully been removed through a simple endoscopic resection. Tumor cell proliferation may be related to the malignant potential of early gastric cancer. The purpose of this study is to prospectively investigate the relationship between the incorporation rate of bromodeoxyuridine (BrdU) into the DNA of dividing cells, and the main biological and clinical early gastric cancer characteristics. METHODOLOGY: Multiple tumor specimens were taken from 27 early gastric cancers and analyzed through anti-BrdU monoclonal antibody. Tumor BrdU labeling index (LI=% positive cells over 2,000 tumor cells) was determined. Early gastric cancers were evaluated in tumor size, mucosal and submucosal involvement, histologic type and grading, lymphatic and venous invasion, and nodal metastasis. RESULTS: BrdU LI was significantly higher in patients with submucosal neoplastic invasion, Pen A Kodama type, tumor vessel invasion and lymph node involvement. Early gastric cancer patients with over 22% BrdU LI showed a significantly higher incidence of submucosal invasion, lymphatic-venous involvement and a reduced survival when compared to patients with medium (12-22%) or low BrdU LI (<12%). CONCLUSIONS: Our results suggest that BrdU LI may be considered a useful indicator of early gastric cancer aggressiveness.     

Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess

The human microsomal 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) metabolizes active cortisol into cortisone and protects the mineralocorticoid receptor from glucocorticoid occupancy. In a congenital deficiency of 11 beta-HSD2, the protective mechanism fails and cortisol gains inappropriate access to mineralocorticoid receptor, resulting in low-renin hypertension and hypokalemia. In the present study, we describe the clinical and molecular genetic characterization of a patient with a new mutation in the HSD11B2 gene. This is a 4-yr-old male with arterial hypertension. The plasma renin activity and serum aldosterone were undetectable in the presence of a high cortisol to cortisone ratio. PCR amplification and sequence analysis of HSD11B2 gene showed the homozygous mutation in exon 4 Asp223Asn (GAC-->AAC) and a single nucleotide substitution C-->T in intron 3. Using site-directed mutagenesis, we generated a mutant 11 beta HSD2 cDNA containing the Asp223Asn mutation. Wild-type and mutant cDNA was transfected into Chinese hamster ovary cells and enzymatic activities were measured using radiolabeled cortisol and thin-layer chromatography. The mRNA and 11 beta HSD2 protein were detected by RT-PCR and Western blot, respectively. Wild-type and mutant 11 beta HSD2 protein was expressed in Chinese hamster ovary cells, but the mutant enzyme had only 6% of wild-type activity. In silico 3D modeling showed that Asp223Asn changed the enzyme's surface electrostatic potential affecting the cofactor and substrate enzyme-binding capacity. The single substitution C-->T in intron 3 (IVS3 + 14 C-->T) have been previously reported that alters the normal splicing of pre-mRNA, given a nonfunctional protein. These findings may determine the full inactivation of this enzyme, explaining the biochemical profile and the early onset of hypertension seen in this patient.     

A Phase II Study of the Docetaxel–Carboplatin Chemotherapy Regimen in Advanced Non-Small-Cell Lung Cancer

The efficacy of the docetaxel–carboplatin combination chemotherapy was studied in various phase II studies. Based on these data we aimed to test the regimen in previously untreated patients with advanced advanced non-smoking lung cancer (NSCLC) with docetaxel 80 mg/m² a standard dose of carboplatin at AUC = 5, in an attempt to define the efficacy and tolerability of the combination in an open-label phase II study. Patients with histologically confirmed advanced NSCLC stage IIIB and IV were candidates for the present study. Docetaxel was administered at 80 mg/m² over 1 h by intravenous (IV) infusion followed by carboplatin AUC = 5 in 30 min IV infusion, both on day 1, and recycled every 21 days. Sixty patients received 263 courses of therapy in total; 231/263 (88%) were administered according to the planned doses, and 48/60 (80%) patients received chemotherapy without decrement of the dose; 32/263 (12%) of the courses were administered with a 10%–30% dose reduction. Complete responses (CR) were seen in 5 patients (8.3%) and partial responses (PR) in 16 patients (26.7%) for an overall response rate of 35%. Median duration of response was 7.5 months [95% confidence interval (CI)-7.1–7.9], time to progression (TIP) 11.5 months (95% CI-8.2–14.8), median overall survival (OS) 15.0 months (95% CI-10.8–19.2). One-year survival was 61.7%. Toxicity was acceptable; it was calculated according to the administered cycles and was mainly neutropenia: grade 3, 9% and grade 4, 2%; anemia: grade 3, 8%; nausea and vomiting: grade 3, 8%. The outpatient regimen of docetaxel–carboplatin is effective with acceptable toxicity in patients with advanced NSCLC.     

Reactive Oxygen Metabolites (ROMs) as an Index of Oxidative Stress in Obstructive Sleep Apnea Patients

Study Objectives: Obstructive sleep apnea syndrome (OSA) is accompanied by oxygen desaturation and arousal from sleep. Free oxygen radicals are highly reactive molecules which could be produced by the OSA phenomenon of hypoxia/reoxygenation: cyclical alterations of arterial oxygen saturation with oxygen desaturation developing in response to apneas followed by resumption of oxygen saturation during hyperventilation. On the basis of these considerations, it was hypothesized that OSA may be linked to increased oxidative stress. Materials and methods: Twenty-six participants gave an interview during which a physician asked them about their age, smoking habits, and symptoms such as excessive daytime sleepiness and snoring. Physical examination and polysomnography were performed during their hospitalization. Reactive oxygen metabolites (ROMs) were measured in blood samples by the diacron reactive oxygen metabolites (D-ROM) test. Results: Twenty-one out of 26 subjects had an apnea/hypopnea index greater than 5 (OSA group). The measurement of free radicals was high in OSA patients. Furthermore, ROMs values in OSA patients were linearly correlated with the apnea/hypopnea index (R = 0.426; p = 0.042). The predictive value of a positive D-ROM test is 81%. Conclusions: ROMs were elevated in patients with OSA. When OSA was severe, similarly the value of ROMs in blood samples was enhanced, and the probable underlying mechanism for these events is the hypoxia/reoxygenation phenomenon.     

24-Hour Efficacy of Travoprost/Timolol BAK-Free Versus Latanoprost/Timolol Fixed Combinations in Patients Insufficiently Controlled with Latanoprost

Introduction

To compare the 24-h intraocular pressure (IOP) control and tolerability of travoprost/timolol benzalkonium chloride (BAK)-free (TTFC) vs. latanoprost/timolol fixed combination preserved with BAK (LTFC) in open-angle glaucoma patients insufficiently controlled with latanoprost 0.005% monotherapy given once in the evening.

Methods

The authors have conducted a prospective, observer-masked, active-controlled, cross-over, comparison study. Qualified open-angle glaucoma patients who demonstrated a latanoprost-treated morning IOP (10:00 ± 1 h) greater than 20 mmHg on two separate visits were randomized for 3 months to receive either TTFC or LTFC. Patients were then crossed over to the opposite treatment for another 3 months. At the end of the latanoprost run-in and after each 3-month therapy period patients underwent 24-h IOP monitoring in the habitual position using Goldmann applanation tonometry in the sitting position during the day (10:00, 14:00, 18:00 and 22:00) and Perkins tonometry in the supine position at night (02:00 and 06:00). Selected ocular surface parameters were evaluated after each therapy period.

Results

Forty-two open-angle glaucoma patients completed the study. The mean 24-h baseline IOP on latanoprost was 21.5 ± 1.6 mmHg. Both fixed combinations significantly reduced the IOP at each time point, for the mean, peak and fluctuation of 24-h IOP compared with latanoprost monotherapy (P < 0.01). When the two fixed combinations were compared directly, TTFC provided significantly lower mean 24-h IOP (18.9 ± 2.2 mmHg) vs. LTFC (19.3 ± 2.3 mmHg) (P = 0.004) and significantly lower IOP at 18:00 (18.6 ± 2.5 vs. 19.5 ± 2.7 mmHg for LTFC) (P < 0.001). Further, TTFC demonstrated significantly better tear film break-up time (5.15 vs. 4.65 s), corneal stain (1.5 vs. 1.8) and Schirmer I test (9.9 vs. 9.2 mm) compared with LTFC after 3 months of therapy (P < 0.01 for all comparisons).

Conclusion

The mean 24-h IOP lowering of TTFC was statistically more significant compared to LTFC in patients insufficiently controlled with latanoprost monotherapy. Measurement of ocular surface health and tear film status favored the BAK-free TTFC compared to LTFC.     

New Perspectives on Lamellar Keratoplasty

Lamellar (anterior and posterior) keratoplasty entails the surgical replacement of diseased-only corneal tissue, while healthy host corneal tissue is preserved. Selective keratoplasty offers several advantages in comparison to penetrating keratoplasty such as a lower rate of graft rejection, less endothelial cell loss, faster/superior visual rehabilitation and enhanced resistance to closed injury. The surgical approach of “partial corneal transplantation” may be divided into anterior and posterior: techniques including superficial and deep anterior lamellar keratoplasty (SALK and DALK, respectively) and endothelial keratoplasty as well as Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). These novel surgical procedures are rapidly becoming the preferred therapy option for specific corneal dysfunctions involving the corneal stroma (SALK, DALK), or corneal endothelium (DSAEK, DMEK). During the past decade, the continuing advancement of surgical techniques and the development of innovative surgical instruments have significantly enhanced corneal transplantation. Lamellar keratoplasty techniques facilitate corneal surgery, provide patients with superior outcomes and can successfully restore vision in corneal-related blindness. Nevertheless, more long-term evidence is needed to better evaluate these promising new techniques.     

Ultrastructural changes of the palatal mucosa following application of 4-nitroquinoline-l-oxide (4NQO) in rats subjected to major salivary gland excision.

OBJECTIVE: It has been suggested that saliva exerts a protective role against the carcinogenic effect of various substances in the oral cavity. The objective of this study was to examine the ultrastructural changes of the palatal mucosa caused by the application of 4-nitroquinoline-l-oxide (4NQO) in the presence or absence of saliva. STUDY DESIGN: Wistar-Furth rats subjected and not subjected to total bilateral excision of the major salivary glands were either painted with an aqueous solution of 4NQO or with propylene glycol only (controls). Two animals of each group were humanely killed periodically. The areas of the palatal lesions were immediately sliced and processed for TEM examination. RESULTS: Ultrastructurally, the progressive changes to squamous cell carcinoma were observed in the animals painted with 4NQO. In the desalivated animals group, the ultrastructural alterations appeared earlier than in the group with salivary glands. CONCLUSIONS: Saliva appeared to delay but not hinder tumor induction by 4NQO.