The intraoperative use of mitomycin-C in excision of ocular surface neoplasia with or without limbal autograft transplantation.

PURPOSE: To evaluate the efficacy of intraoperative mitomycin-C in excision of ocular surface neoplasia for prevention of recurrence. METHODS: Seven patients (eight eyes), three men and four women, aged 56 to 87 years (mean, 73.8 years), with lesions suspicious for corneal or conjunctival neoplasia, were operated on between October 1998 and March 2000. During excision of the lesion, mitomycin-C 0.02% was applied intraoperatively for 5 minutes. In two cases, excision was combined with conjunctival limbal autograft transplantation. All excised lesions were sent for histopathologic evaluation. RESULTS: During the follow-up period ranging from 6 to 28 months (mean, 16 months) one patient (one eye) died of an unrelated cause. Histopathologic study showed four cases of squamous cell carcinoma, one case of carcinoma in situ, two cases of dysplasia, and one case of actinic keratosis. Of the eight eyes, no clinical recurrence of the lesion occurred in seven eyes, whereas one eye with squamous cell carcinoma showed mild recurrence 5 months after surgery and was successfully treated with topical mitomycin-C. Up to the last follow-up of this case 10 months later, the lesion did not recur. CONCLUSION: The excision of conjunctival and corneal epithelial neoplasia combined with the intraoperative use of mitomycin-C seems to reduce the recurrence rate. The combined use of mitomycin-C and conjunctival limbal autograft transplantation in two cases did not alter the surgical outcome. More cases and a longer follow-up are needed to establish the efficacy of such an approach.     

ARTHROSCOPIC EVALUATION AND MANAGEMENT OF MENISCAL INJURIES OF THE KNEE

50 cases of isolated meniscal injuries of the knee were evaluated and managed arthroscopically. 56% of the cases were in 25–35 year age group. In 80% of the cases military training and contact sports was the mode of injury. Maximum (42%) patients reported late (> 2 years) after the injury. On presentation, they had an average Lysholm knee score of 53.76. Medial meniscal lesion was seen in 74%. Commonest pattern of tear encountered was a longitudinal tear (40%). Depending on pattern and extent of lesion, partial meniscectomy (60%), subtotal meniscectomy (14%) and total meniscectomy (26%) were performed. Patients were followed up at six months and one year. The average Lysholm score at 6 months was 83.3 and at one year 79.5. At one year, the patient satisfaction level was 82% and patients who underwent partial meniscectomy had the best results.KEY WORDS: Arthroscopy, Meniscal tear     

Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1

Background and purpose:

Airway remodelling in asthma is manifested, in part, as increased airway smooth muscle (ASM) mass, reflecting myocyte proliferation. We hypothesized that calcitriol, a secosteroidal vitamin D receptor (VDR) modulator, would inhibit growth factor-induced myocyte proliferation.

Experimental approach:

Human ASM cell cultures were derived from bronchial samples taken during surgery. ASM cells were treated with platelet-derived growth factor (PDGF) (10 ng·mL⁻¹) for 24 h in the presence of calcitriol, dexamethasone or a checkpoint kinase 1 (Chk1) inhibitor (SB218078). The effects of calcitriol on PDGF-mediated cell proliferation were assessed by thymidine incorporation assay, propidium iodide-based cell cycle analysis, caspase-3 assay and immunoblotting for specific cell cycle modulators.

Key results:

Calcitriol, but not dexamethasone, inhibited PDGF-induced ASM DNA synthesis concentration dependently (IC₅₀= 520 ± 52 nM). These effects were associated with VDR-mediated expression of cytochrome CYP24A1 with no effects on ASM apoptosis. Calcitriol substantially inhibited (P < 0.01) PDGF-stimulated cell growth in ASM derived from both normal (59 ± 8%) and asthmatic subjects (57 ± 9%). Calcitriol inhibited PDGF-induced phosphorylation of retinoblastoma protein (Rb) and Chk1, with no effects on PDGF-mediated activation of extracellular signal-regulated kinases 1/2, PI3-kinase and S6 kinase, or expression of p21^Waf/Cip-1, p27^Kip1, cyclin D and E2F-1. Consistent with these observations, SB218078 also inhibited (IC₅₀= 450 ± 100 pM) PDGF-induced cell cycle progression.

Conclusions and implications:

Calcitriol decreased PDGF-induced ASM cell growth by inhibiting Rb and Chk1 phosphorylation.This Research Paper is the subject of a Commentary in this issue by Clifford and Knox (pp. 1426–1428). To view this article visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Spontaneous release of acetylcholine from autonomic nerves in the bladder

Background and purpose:

Bladder contractility is regulated by intrinsic myogenic mechanisms interacting with autonomic nerves. In this study, we have investigated the physiological role of spontaneous release of acetylcholine in guinea pig and rat bladders.

Experimental approach:

Conventional isotonic or pressure transducers were used to record contractile activity of guinea pig and rat bladders.

Key results:

Hyoscine (3 µmol·L⁻¹), but not tetrodotoxin (TTX, 1 µmol·L⁻¹), reduced basal tension, distension-evoked contractile activity and physostigmine (1 µmol·L⁻¹)-evoked contractions of the whole guinea pig bladder and muscle strips in vitro. ω-Conotoxin GVIA (0.3 µmol·L⁻¹) did not affect physostigmine-induced contractions when given either alone or in combination with ω-agatoxin IVA (0.1 µmol·L⁻¹) and SNX 482 (0.3 µmol·L⁻¹). After 5 days in organotypic culture, when extrinsic nerves had significantly degenerated, the ability of physostigmine to induce contractions was reduced in the dorso-medial strips, but not in lateral strips (which have around 15 times more intramural neurones). Most muscle strips from adult rats lacked intramural neurones. After 5 days in culture, physostigmine-induced or electrical field stimulation-induced contractions of the rat bladder strips were greatly reduced. In anaesthetized rats, topical application of physostigmine (5–500 nmol) on the bladder produced a TTX-resistant tonic contraction that was abolished by atropine (4.4 µmol·kg⁻¹ i.v.).

Conclusions and implications:

The data indicate that there is spontaneous TTX-resistant release of acetylcholine from autonomic cholinergic extrinsic and intrinsic nerves, which significantly affects bladder contractility. This release is resistant to blockade of N, P/Q and R type Ca²⁺ channels.British Journal of Pharmacology (2009) 157, 607–619; doi:10.1111/j.1476-5381.2009.00166.x; published online 3 April 2009