Melanoma of the conjunctiva and its treatment

37 cases of conjunctival melanomas treated in the University Eye Clinic of Lausanne are analysed. This total is made of 20 men and 17 women aged between 19 and 81 years with a mean age of 54.7 years. Tumors were localized in the bulbar conjunctival in 27 cases, in the palpebral conjunctival in 2 cases and were diffuse in 8 cases. Cornea was infiltrated in 19 cases. In 21 cases, the first treatment was made in our service and 16 cases were recurrences following a treatment made elsewhere. The mortality rate to 5 years was 20%. In a multivariant analysis using the COX Model, the height of the tumor was the only significant parameter (p = 0.035) for life expectancy. Recurrence of the tumor (p = 0.060) and presence of a PAM (p = 0.652) were not significant parameters. Benefits of cryocoagulation and indications for a proton beam irradiation are discussed.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

Prognostic factors in malignant melanoma patients with solitary or multiple brain metastases. Is there a role for surgery?

BACKGROUND: The aim of this study is to evaluate the prognostic parameters and treatment modalities of malignant melanoma patients with brain metastases. METHODS: Experimental design: a retrospective study with a mean follow-up of 46 months. Setting: specialized Cancer Center. Patients: the charts of 136 patients, treated in Roswell Park Cancer Institute, for melanoma brain metastases, were analyzed. Interventions: all patients were treated surgically and in the majority adjuvant therapy was applied. Measures: survival and time of recurrence of patients and possible prognostic factors. RESULTS: Patients who were treated surgically had a better one-year survival rate (28.3%), than patients who received radiotherapy and/or chemotherapy (6.67%) or patients who refused any kind of treatment (3.45%), (p=0.006). Prolonged survival after surgical treatment was found in patients with single metastatic lesions and in patients with multiple metastatic lesions. CONCLUSIONS: Melanoma patients with single metastatic lesions to the brain seem to do better after surgical treatment. The role of surgical intervention in patients with multiple brain metastases needs re-evaluation from a big multicenter, prospective trial.     

An adult patient with a mixed germ cell tumor of the spermatic cord

Tumors of the spermatic cord are very rare, and approximately one half of all primary spermatic cord tumors are malignant. We report the presentation and treatment of an adult (36-year-old) patient with a mixed germ cell tumor that originated in the spermatic cord. No similar cases of mixed tumors of the spermatic cord in adults have been reported.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents

Glucocorticoid suppressible hyperaldosteronism (GSH) is an uncommon form of dominantly inherited hypertension. Presentation with hypertension and complications such as stroke in early life are well recognised. The use of a simple genetic test carried out on blood or placenta facilitates the detection of infants and children with GSH before the development of hypertension, allowing prompt treatment of hypertension if it occurs, and an opportunity to study the effects of growth and environmental influences on the progression of the condition.     

COVID-19 vaccination and recurrent anterior uveitis

A 35-year-old Asian Indian female previously diagnosed with bilateral anterior uveitis and on oral methotrexate developed bilateral anterior uveitis following first/second dose of coronavirus disease 2019 (COVID-19) vaccination. She had skipped her weekly dose of oral methotrexate following first dose of vaccination. Following the second dose, she reduced her oral methotrexate from 25 to 15 mg on her own, but did not stop like the previous occasion. She had extensive workup for her uveitis in the past with only positive severe acute respiratory syndrome coronavirus (SARS-CoV-2) antibodies. She developed unilateral anterior uveitis after she had COVID-19 in July 2022, which resolved with topical steroids and continuation of immunosuppression. This report illustrates that COVID-19 or its vaccination may presumably play a role in triggering the immune system and can cause recurrent ocular inflammation even in the absence of an extraocular inflammation.     

Real-world evidence: Patient views on asthma in respiratory specialist clinics in America

BackgroundApproximately 30% to 50% of patients with moderate/severe asthma have inadequately controlled disease despite adherence to inhaled corticosteroid (ICS)/long-acting β₂-agonist (LABA) therapy. Data on prevalence and burden of uncontrolled asthma in specialty settings are lacking.ObjectiveTo evaluate the prevalence and burden of uncontrolled asthma in respiratory specialist clinics in the United States.MethodsAdults with physician-diagnosed asthma attending pulmonary and allergy clinics with self-reported ICS use in the previous 4 weeks completed an electronic questionnaire including the Asthma Control Test and St George’s Respiratory Questionnaire. Additional information was collected using an electronic case report form.ResultsOf 774 patients attending 12 pulmonary and 12 allergy clinics, 53% were not well controlled (mean [SD] Asthma Control Test, 14.3 [3.6] vs 22.4 [1.6] in well-controlled patients). Among ICS/LABA users, 56% were not well controlled, which increased with increasing ICS dose (low-dose 45.7%; high-dose 59.7%). The not well-controlled group reported more respiratory illnesses, more comorbidities, and poorer health-related quality of life (mean [SD] St George’s Respiratory Questionnaire, 46.1 [18.9] vs 19.8 [12.9] in the well-controlled group). These patients also had more asthma exacerbations (≥1 exacerbation, 68.9% vs 43.1%) and increased health care resource utilization (≥1 asthma-related hospitalization, 10.7% vs 2.7%); 27.3% were also receiving systemic corticosteroids. Approximately 40% of the population were eligible for step-up to ICS/LABA/long-acting muscarinic antagonist triple therapy, and 20% were eligible for biologic therapy.ConclusionSubstantial unmet needs exist among patients with inadequately controlled asthma managed in United States specialist settings, which may be addressed by improved patient and physician education, better guideline implementation, and improved adherence.