Cryotherapy for trichiasis in ocular cicatricial pemphigoid

Trichiasis is a common and potentially sight threatening complication of ocular cicatricial pemphigoid and is usually secondary to cicatricial entropion. This study aimed to assess the success and complications of eyelid cryotherapy for trichiasis in a group of patients with long term follow up. The case records of all patients with ocular cicatricial pemphigoid that attended the external disease clinic at Moorfields Eye Hospital from 1980 to 1992 were reviewed. Each eyelid was divided into three horizontal zones. Cryotherapy was delivered with an Amoilette cryoprobe for approximately 30 seconds. Failure of the cryotherapy was defined as a regrowth of the eyelashes within the treated zone that either required epilation for symptom control or caused keratopathy. Ninety two lid zones were treated, involving 25 lids of 12 patients. The cumulative chance of success decreased rapidly to 40% over the first year. Thereafter, the chance of success declined slowly to 34% at 4 years. Complications included lid notching (n = 2), tarsal atrophy (n = 1), altered lid contour (n = 1), and temporarily raised intraocular pressure (n = 1). All patients had quiescent disease at the time of the cryotherapy and no patients showed increased conjunctival disease activity after treatment. Six patients were taking systemic immunosuppression medication. When ocular cicatricial pemphigoid is quiescent, lid cryotherapy has an acceptable complication rate. The major reason for recurrence of the trichiasis was attributed to inadequate follicle freezing.     

Costimulatory molecules in ocular cicatricial pemphigoid

PURPOSE: To examine normal and inflamed conjunctiva from patients with ocular cicatricial pemphigoid (OCP) for the presence of costimulatory molecule CD28 and its ligands B7-1 (CD80) and B7-2 (CD86). METHODS: Conjunctival biopsy specimens from 12 patients with OCP and from five healthy persons undergoing cataract surgery were analyzed by light microscopy and immunohistochemical examination with monoclonal antibody probes for CD28, B7-1, and B7-2 molecules and for mononuclear cell subtypes. RESULTS: Epithelium of OCP conjunctiva showed more Langerhans' cells, B7-1-positive (+) cells, and B7-2 expression (ratio of B7-2-positive cells to antigen-presenting cells). In the substantia propria, OCP specimens showed significantly increased numbers of T cells (CD3 +), macrophages (CD68+), CD28+ cells, B7-2+ cells (CD86+), Langerhans' cells (CD1a), and B7-1+ cells (CD80). Most of the B7-2+ cells, macrophages, and Langerhans' cells were located subepithelially. B7-2 expression was significantly higher in OCP conjunctival substantia propria compared with normal conjunctiva. CONCLUSIONS: The results of this study indicate that the expression of the costimulatory molecule B7-2 is upregulated in conjunctiva of patients with active OCP. This increased subepithelial B7-2 expression may contribute to the sustained immune activation in OCP conjunctiva.     

Immunohistopathologic testing in patients suspected of ocular cicatricial pemphigoid

PURPOSE: Optimizing the sensitivity of immunopathologic methods in detecting target antigens in immune-mediated cicatrizing conjunctivitis. Methods: Immunofluorescence was performed on normal and salt-split conjunctival biopsies in fifteen patients with clinical evidence of ocular cicatricial pemphigoid, and results were compared with immunoperoxidase, a technique thought to be more sensitive although more expensive and more difficult technically to perform. RESULTS: Ten of fifteen biopsies (67%) were positive when conventional and salt-split immunofluorescence results were combined. Four of eight patients with positive conventional immunofluorescence showed more marked immunofluorescence with the salt-split method. All patients were positive with immunoperoxidase (100%). CONCLUSION: Immunoperoxidase was more sensitive than conventional or salt-split immunofluorescence in detecting immunoreactant deposition along the basement membrane of the conjunctiva. Salt-split immunofluorescence demonstrated more intense staining of conjunctival samples when compared with conventional immunofluorescence, without however increasing the yield of positive biopsies. Finding solutions for the proper handling of conjunctival tissue in salt may improve the diagnostic yield of salt-split immunofluorescence.     

Differences in the anti-basement membrane zone antibodies in ocular and pseudo-ocular cicatricial pemphigoid

Dupuytren's contracture (DC) is a disease of the palmar fascia resulting in thickening and contracture of fibrous bands on the palmar surface of the hands and fingers. For decades, a controversy has existed regarding whether acute traumatic injury or cumulative biomechanical work exposure can contribute to the development of this disorder. To address this controversy, this review considers the following questions: Is there evidence that DC is associated with 1) frequent or repetitive manual work; and 2) hand vibration? The published literature was searched for studies meeting the following criteria: 1) in English or having an English abstract; 2) controlled studies; 3) DC an identified health outcome studied; and 4) the study group exposed to repetitive or frequent manual work, vibration, or acute traumatic injury. Relevant non-English articles identified through English abstracts were translated. The validity of studies meeting the selection criteria was assessed using a series of questions adapted from those of Stock [1991: Am J Ind Med 19:87-107]. Studies that met a priori minimum levels of methodologic quality were taken into account to reach conclusions with respect to the above questions. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each study. Ten studies met the initial selection criteria. Of these, four studies met the criteria for methodologic quality, one addressing the relationship between manual work and DC, and three studies of vibration and DC. No controlled studies of acute trauma and DC were identified. Bennett [1982: Br J Ind Med 39:98-100] found the prevalence of DC at a British PVC bagging and packing plant in which workers were exposed to repetitive manual work to be 5.5 times that at a local plant without packing, and twice the expected prevalence in a U.K. working population previously studied by Early [1962: J Bone Joint Surg 44B:602-613]. DC was observed more frequently among vibration white finger claimants than controls by Thomas and Clarke [1992: J Soc Occup Med 42:155-158] (OR, 2.1; 95% CI, 1.1-3-9), and more frequently among vibration-exposed workers than controls by Bovenzi et al. [1994: Occup Environ Med 51:603-611] (OR, 2.6 95% CI, 1.2-5.5). Cocco et al [1987: Med Lav 78:386-392] found that a history of vibration exposure occurred more frequently among cases of DC than among controls (OR, 2.3; 95% CI, 1.5-4.4). The latter two studies presented some evidence of a dose-response relationship. There is good support for an association between vibration exposure and DC.     

Autoantigens of cicatricial pemphigoid and their pathogenetic significance

Cicatrical pemphigoid (CP) comprises a group of patients with a chronic subepidermal blistering disease which primarily involves mucous membranes; lesions characteristically heal with scarring. Immunofluorescence investigations typically demonstrate deposits of tissue bound and circulating immunoreactants of the IgG and less frequently of the IgA class in a linear pattern along the basement membrane zone. These autoantibodies are thought to play an important role in the blister formation of CP. Most patients show binding to the bullous pemphigoid antigen 2 (BPag2), collagen type XVII, with a molecular-weight of 180 kD. A smaller group of patients with CP have autoantibodies to laminin 5. Animal models confirm that autoantibodies binding to these two adhesion molecules (BPag2 and laminin 5) are important in blister formation. There are other autoantigens described in CP; however, they are only found in small groups of CP patients and most of them are not further characterised. The described molecules are part of the hemidesmosomal adhesion complex. Impaired function of any component of this complex may lead to a separation of the epidermis from the dermis; better knowledge about the single molecules and the exact localisation of epitopes within these molecules may lead to further understanding of the clinical picture.     

Stenosis of the esophagus in cicatricial pemphigoid resolved by colon interposition: report of a case

OBJECTIVE: To examine the extent of sun exposure, sun protection and experience of sunburn among young New Zealand children on summer weekends. METHODS: In a telephone survey of 1243 respondents, those with children in the household were asked about sun exposure and protection for the youngest child in the family. Information was obtained for 285 children aged from infancy to 10 years. RESULTS: Over 90% of the children were reported to be outside on the preceding Saturday and/or Sunday; 7% of those outside experienced some degree of sunburn. The worst burning was on the face, head, neck or ears. On either day about half the children were wearing sunscreen and 60% were wearing a hat. Parental use of sun protection was the strongest predictor of sun protection among the children. CONCLUSIONS: While reports of sun protection among young children were encouraging, many children in the community are still at high risk of sunburn. Efforts to promote sun protection as a family responsibility may reduce the experience of burning among the young.     

Surgical treatment of cicatricial biliary strictures

BACKGROUND/AIMS: Cicatricial biliary strictures are usually associated with high morbidity and mortality rates, frequently related to technical difficulties of their surgical repair, mainly in hilar lesions. Interference with bile duct blood supply during surgical attempts for correction is a major factor for unsuccessful results. The aim of this study is to evaluate, after an extended follow-up period, the results obtained with a modified technique for surgical correction of cicatricial biliary strictures. METHODOLOGY: The medical records of 57 patients surgically treated for cicatricial biliary strictures between January 1984 and July 1995 were reviewed and the immediate and long term results retrospectively analyzed. Patients consisted of 46 females and 11 males. The average age was 43 years. The etiology of the biliary lesion was: cholecystectomy alone (23); cholecystectomy with duct exploration (8); T tube CBD drainage (6); Biliary-enteric anastomosis stricture (16); choledochoplasty (2) and trauma (2). In 28 cases (49.1%) the stricture was located in the upper third of the bile duct, in 28 (49.1%) in the middle third and in one case (1.7%) it was low. All patients were submitted to longitudinal Roux-en-Y hepaticojejunostomy with mucosa apposition after dissection of the anterior aspect of the biliary tract. No transanastomotic stents were used. RESULTS: Ten patients (17.5%) presented 11 postoperative complications: biliary fistula (4), duodenal fistula (1), wound infection (5), and acute pancreatitis (1). Average hospital stay was 11 days and there were no postoperative mortalities. The follow-up study was possible in 54 patients and ranged from one to ten years, with an average of 2.9 years. Four patients of 28 (14%) with hilar lesions developed stricture recurrence and cholangitis episodes, whereas no patients bearing lesions below the biliary junction had such complications. CONCLUSION: Roux-en-Y hepaticojejunostomy with mucosa apposition without transanastomotic stent performed after minimal dissection of the biliary duct, thus avoiding major interference with the bile duct blood supply, is a safe and efficient method for the surgical repair of cicatricial biliary strictures. Using this technique excellent results can be obtained in the lesions below the biliary junction and acceptable results may be achieved in patients with hilar lesions.     

Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid

To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate analysis identified the importance of age at presentation and histological subtypes. When all causes of death were considered, the multivariate analysis identified age as the only significant factor. The length of initial disease-free interval had no influence on prognosis after relapse, but the 169 patients with nodal relapse had a higher cause-specific survival than those with an extranodal component of relapse (74% versus 51% at 10 years, P < 0.005). Thus, the important factors for outcome after initial treatment with radiotherapy are those factors predicting the risk of relapse after initial treatment together with those predicting outcome after relapse, namely age, histologic subtype and extent of disease at relapse.     

Operative treatment of the endobronchial tuberculosis with cicatricial bronchiarctia

OBJECTIVE: The experience of surgical treatment in 32 patients with cicatricial brochiarctia by endobronchial tuberculosis was reported. METHOD: The modes of surgical treatment in the series include: sleeve resection was done in 19 cases, lobectomy in 4 cases, pneumonectomy in 7, and left principal bronchial reconstruction in 2 cases. RESULTS: The results were excellent and without operative death. Serious postoperative complication was bronchopleural fistula in one case. The patient was treated by surgical repair of the bronchial stump and buttressed with vascularized pedicle flaps of omentum in the second operation. 2 cases of 32 patients were affected with mild stenosis of bronchial anestomosis after a follow-up of 12 to 18 months. CONCLUSIONS: It was suggested that when the patient developed the endobronchial tuberculosis with cicatricial bronchiarctia, corrective operation should be performed as early as possible, and the sleeve resection should be the first choice.     

Pharmacological determinants of the antitumour activity of mitomycin C

Raspberries were epidemiologically associated with cyclosporiasis outbreaks during 1996 and 1997. The 18S rRNA genes of Cyclospora cayetanensis and several species of a closely related genus, Eimeria, were sequenced and primers for a nested PCR developed in a previous study. The ability to distinguish amplified products of Cyclospora sp. from those of Eimeria spp. is important for testing food and environmental samples. Therefore, an RFLP analysis of amplified products was used to differentiate Cyclospora cayetanensis from Eimeria spp. PCR inhibitors and the low levels of Cyclospora oocysts present in raspberries make template preparation for PCR challenging. Several approaches for PCR template preparation from raspberry samples were evaluated. Template preparation methods using various washing and concentration steps, oocyst disruption protocols, resin matrix treatment, DNA precipitation, and/or the addition of nonfat dried milk solution to a PCR using modified primers were evaluated first with oocysts of Eimeria tenella then refined with oocysts of C. cayetanensis. Approximately 10 E. tenella oocysts per PCR or approximately 19 C. cayetanensis oocysts per PCR were detected with the optimized template preparation method. The addition of 20 microliters of raspberry wash sediment extract and nonfat dried milk solution did not inhibit the amplification of DNA from as few as 10 E. tenella and 25 C. cayetanensis oocysts in a 100-microliter PCR. The nucleotide sequences of C. cayetanensis and the Eimeria spp. are 94 to 96% similar in the amplified region, but the amplification products from the two genera were distinguished using an RFLP analysis with the restriction enzyme MnlI.     

Subconjunctival adipose hernias of the orbit

Clinical report of three cases of subconjunctival fat prolapse. Differential diagnoses are discussed. Subconjunctival orbital fat prolapse is a benign entity with a fat herniation through defective Tenon's capsule.     

Incidence of delayed onset infection after trabeculectomy with adjunctive mitomycin C or 5-fluorouracil treatment

AIMS/BACKGROUND: The introduction of the adjunctive use of antiproliferatives to trabeculectomy has greatly improved the success rate of this operation. Trabeculectomy with antiproliferative treatment, however, is usually associated with a cystic and thin walled filtering bleb, which may be more susceptible to infection. The objective of this study was to evaluate the incidence, clinical findings, and risk factors of delayed onset, bleb related infection after trabeculectomy with adjunctive mitomycin C (MMC) or 5-fluorouracil (5-FU) treatment. METHODS: The records of 632 glaucoma patients who underwent 966 trabeculectomies, with and without the use of adjunctive MMC or 5-FU treatment, between January 1985 and February 1995 were analysed. The mean follow up period was 3.5 (2.4) years (range 0.1 to 11.2 years). The mean patient age was 54.8 (18.8) years (range 0 to 88 years). RESULTS: Bleb related infection occurred in one of 76 trabeculectomies that did not receive antiproliferatives (1.3%), three of 228 treated with 5-FU (1.3%) trabeculectomies, and seven of 662 treated with MMC (1.1%). Five eyes developed blebitis; six eyes developed endophthalmitis. Bleb related infection developed an average of 3.1 (1.6) (range 0.4 to 6.0) years after trabeculectomy. All eyes had avascular or hypovascular blebs that were cystic in shape before infection and all eyes had reduced intraocular pressure. Early wound leaks and chronic, intermittent bleb leaks were identified to be risk factors for the bleb related infection. CONCLUSION: The incidence of delayed onset, bleb related infection after trabeculectomy with antiproliferative treatment is similar to that after trabeculectomy without antiproliferatives.     

Topical mitomycin C chemotherapy for conjunctival melanoma and PAM with atypia

Increasing parental participation in their child's health and health care is an important process by which the health care system can effectively address and service the needs of its patients. Clinicians need to have an appreciation of parental understanding, beliefs, and expectations. This paper reviews the recent literature regarding parental needs, concerns, decision-making strategies, and expectations for their children's health and health care.     

Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Intraperitoneal hyperthermic perfusion with mitomycin C for colorectal cancer with peritoneal metastases

In 94 our of 2570 individuals vaccinated against tick-borne encephalitis (TBE) with FSME-Immun the level of IgG antibodies to TBE virus were tested. The examination was performed before and 2.5 years after the first dose of full cycle vaccination, which according to the manufacturer, consists of three doses. The maintenance of specific seroconversion was detected in 91.9% of the studied subjects. No statistically significant differences in antibody levels were found in the different age groups. None of the immunized subject developed TBE up to the present time.     

Spermatogenic cell apoptosis induced by mitomycin C in the mouse testis

Spermatogenic cell degeneration in the mature mammalian testis occurs both spontaneously during normal spermatogenesis and in response to cytotoxic agents. Mitomycin C (MC) is an antibiotic that affects DNA synthesis. In the present study, we examined the induction of mouse spermatogenic cell apoptosis by MC, using TdT-mediated dUTP-biotin nick end labeling (TUNEL) to detect high levels of DNA fragmentation in situ, transmission electron microscopy (TEM) to observe nuclear chromatin condensation, and molecular methods to detect DNA ladders. This study shows that in the testis of MC-treated mice: (i) apoptotic cell death with fragmentation of nuclear DNA is induced by MC dose-dependently, (ii) apoptotic cell death is most commonly found in the spermatogonia and less frequently in spermatocytes, and (iii) apoptotic cell death induced by MC is not specific for the seminiferous stage of the tubules. The present study suggests that the spermatogenic cell apoptosis induced by MC might be involved in its testicular toxicity.