Ruthenium-106 eye plaque brachytherapy in the conservative treatment of uveal melanoma: a mono-institutional experience.

BACKGROUND: Traditional treatment for uveal melanoma is the enucleation of the eye with outcomes cosmetically unacceptable and loss of useful vision. Plaque brachytherapy, compared to enucleation, had the advantage to preserve the eye with outcomes cosmetically acceptable and preservation of vision. PATIENTS AND METHODS: From July 1990 to December 2009 one hundred forty-two (142) patients (51 males and 91 females) with small to medium uveal melanoma were treated with 106Ru plaque brachytherapy. The patients underwent a complete staging before brachytherapy with indirect ophthalmoscopy and ultrasounds. Mean tumour thickness was 3.26 mm (1.6-6 mm). The dose scheduled was 80-100 Gy to the apex with a maximum dose of 800 Gy to the sclera. RESULTS: One hundred forty-two have been treated, nine patients had lost the follow-up and drop out; 133 patients were assessed. Mean follow-up was 7.7 years (6 months-18 years). The overall survival at 5, 10 and 15 years was 92%, 85% and 78% respectively. Cancer fee survival was 95%, 90% and 83%, respectively at 5, 10 and 15 year. Radiation-induced toxicity was represented in 47 patients with a 5 year actuarial survival rate free from complications of 54%. CONCLUSIONS: 106Ru plaque brachytherapy is a valid approach for treatment of uveal melanoma. This technique is efficacy and safe, with a low toxicity profile.

Association between facial measurements and polymorphisms in human epidermal growth factor and transforming growth factor ß1.

The aim of the study was to evaluate the association between genetic polymorphisms in human epidermal growth factor (EGF) (rs4444903) and transforming growth factor ß1 - (TGF-ß1) (rs1800470) with facial measurements in patients with dentofacial deformities. A total of 144 adult patients with dentofacial deformities were included. Facial linear and angular measurements were traced in lateral cephalometric radiographs used Dolphin 2D software. Cells from oral mucosa were collected for DNA to be extracted. The polymorphisms were genotyped using real-time polymerase chain reaction (PCR). Probabilites of less than 0.05 were accepted as significant. The rs4444903 heterozygous patients had a decrease in the mandibular length (p=0.043) and the length of the mandibular base (p=0.008), and homozygous A patients also had a reduction in the length of the mandibular base (p=0.013) compared with homozygous G patients. Patients AG had an increase in measurement of the anterior facial height (p=0.032) and in ANS-Me distance (p=0.022) when compared with homozygous A. To the rs1800470, heterozygous patients had an increase in the length of the mandibular base (p=0.043) when compared with homozygous A. Heterozygous AG patients had an increase in angular measurements in TGF-ß1 polymorphism for the upper gonial angle, when compared with the homozygous AA (p=0.032). Genetic polymorphisms in EGF and TGF-ß1 are associated with facial measurements in a Brazilian population of patients with dentofacial deformities.

A combined therapeutic approach in progressive idiopathic pulmonary fibrosis-pirfenidone as bridge therapy for ex vivo lung transplantation: a case report.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial pneumonia of unknown etiology, which is associated with the histopathologic pattern of usual interstitial pneumonia (UIP) and leads to a progressive decrease of respiratory function. The present article describes a case of a 62-year-old ex-smoker referred to our hospital because of IPF. After 2 years of follow-up, the subject experienced a significant worsening of pulmonary function and was enrolled in a lung transplantation program. Afterward, a pharmacological treatment with pirfenidone was started, achieving a stabilization of respiratory function. The patient underwent a single lung transplantation by means of a normothermic ex vivo lung perfusion (EVLP) approach according to the Toronto model. At 20-month evaluation the subject's respiratory function was significantly improved, and quality of life was considerably ameliorated. We believe that an integrated multidisciplinary approach should be considered a key option for the treatment of individuals with IPF.

Predictors of outcome for patients with severe respiratory failure requiring non invasive mechanical ventilation.

OBJECTIVE: Failure to identify patients in whom non-invasive ventilation (NIV) would be unsuccessful may cause inappropriate delay in intubation. Aim of this study was to determine predictors of NIV failure. PATIENTS AND METHODS: We retrospectively evaluated COPD patients, undergoing NIV for at least 12h because of hypercapnic acute respiratory failure. Univariable and multivariable analyses were performed on: age, gender, APACHE II and GCS, gas exchange at admission, during NIV and at discharge/death, length of stay. ROC analysis for pH START and APACHE II were performed. RESULTS: Among 201 individuals enrolled, NIV failed in 50. In the logistic regression model only APACHE II was found to have an independent effect on the outcome (p < 0.0001, OR 1.179, 95% CI 1.101-1.263 as quantitative variable; p < 0.0001, OR 3.753, 95% CI 1.798-7.835, as qualitative variable, > 20.5). CONCLUSIONS: APACHE II may be a crucial parameter in predicting NIV failure; further multicentric studies are needed to better define NIV indications.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

Phenotypic variation in combined granular-lattice (Avellino) corneal dystrophy.

OBJECTIVE: To describe the phenotypic variation exhibited by members of families with combined granular-lattice (Avellino) corneal dystrophy. SETTING: We examined 40 patients (age range, 12 to 85 years) from six unrelated families with Avellino corneal dystrophy. This included the first individuals to ever be examined near the presumed site of origin in Italy. In addition, one family was the first to trace its origins to Germany rather than to Italy. We studied the phenotypic expression of the disease in the cornea, visual acuities, subjective complaints, complications, treatment, and histologic condition of these individuals. RESULTS: The granular stromal lesions reach their mature quantity and size early in life, and appear as either gray and crumb-shaped deposits or superficial with an annular and planar distribution. The lattice component appears gradually, beginning and maturing later in life. The phenotypic variation within families was found to be substantial. Widely variable proportions of lattice and granular changes were found within single sibships. Visual acuities ranged from 20/20 to 20/400. Recurrent corneal erosions were present but infrequent. Subjective complaints included glare and decreased night vision. Penetrating keratoplasty was required in one individual to restore vision. Histopathologic examination revealed typical amyloid and granular deposits. Granular deposits were found replacing Bowman's membrane and extending to the corneal surface. These deposits probably represent the cause of recurrent erosions. CONCLUSIONS: Combined granular and lattice corneal dystrophy may present with substantial phenotypic variation. The disease can be found in individuals who trace their ancestry to both Italy and Germany, a wider geographic distribution than previously proposed.

Hepatitis C virus infection in chronic liver disease in Somalia.

To assess the role of hepatitis C virus (HCV) in liver disease in Somalia, antibody to HCV (anti-HCV) was studied by enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) in 110 patients with chronic liver diseases, in 309 healthy adults, in 179 institutionalized subjects with a high prevalence of intestinal parasites and Schistosoma haematobium, and in 287 children with diseases other than hepatitis. According to the RIBA test, anti-HCV was present in three healthy adults (0.97%), in four institutionalized individuals (2.2%), but in none of the children. The prevalence of anti-HCV was 4.8% in patients with hepatitis B surface antigen (HBsAg)-positive chronic liver diseases and 20.6% in patients with HBsAg-negative chronic liver diseases. Thus, HCV infection appears to play a minor role in HBsAg-positive liver disease in Somalia but may be an important factor in HBsAg-negative chronic liver disease. The low anti-HCV prevalence in individuals with no hepatic disorders is consistent with the fact that HCV does not spread by nonpercutaneous transfer. We found also a large proportion of both patients with hepatic disease and institutionalized individuals who tested positive by ELISA but not confirmed by RIBA. However, the likelihood of a true positive result increases proportionally with the ELISA value; thus, in most cases a low ELISA value probably represents a false-positive reaction, while a high ELISA value probably represents a true positive reaction.

Time-resolved immunofluorescence: a sensitive and specific assay for anti-HIV antibody detection in human sera.

We describe a new immunoassay, time-resolved fluoroimmunoassay (TR-FIA), for detection of anti-HIV antibodies in human sera. This method is based on the use of a crude virus preparation coated on a polystyrene microtitre plate and of a swine anti-human IgG labelled with a rare earth metal, europium, as fluorescent label chelated with EDTA derivatives. A light pulse from a xenon lamp (340 nm) was used to excite the label and after a 400 microseconds delay time the emission fluorescence was counted for 400 microseconds at 613 nm. This cycle was repeated 1000 times during the total counting time of 1 s. TR-FIA presents considerable advantages over other techniques: (a) it avoids time-consuming, expensive and hazardous virus purification steps; (b) it excludes the use of radiotracers or substrates with potential health risks to reveal the reaction; (c) it has high sensitivity and specificity. A total of 475 serum specimens were tested by ELISA and by TR-FIA. The proportions of positivity were 29.6% by ELISA versus 26.7% by TR-FIA. The sensitivity of both systems was 100%. The specificity was 87.5% for ELISA, whereas it reached a value of 99.4% for immunofluorimetric assay.

Idiopathic central retinal vein occlusion in a thrombophilic patient with the heterozygous 20210 G/A prothrombin genotype.

PURPOSE: To report the occurrence of monolateral central retinal vein occlusion in a patient with heterozygous 20210 G/A prothrombin genotype, known to be associated with high thrombophilic risk. METHODS: A monolateral central retinal vein occlusion was diagnosed in a 71-year-old woman, who had suffered from a deep vein thrombosis in her left leg at the age of 36 years. Mutations of the genes involved in the coagulation process were investigated by DNA polymerase chain reaction. RESULT: DNA analysis showed the patient to be heterozygous for the prothrombin 20210 G/A genetic variation. CONCLUSION: The 20210 G/A prothrombin gene mutation may be associated with central retinal vein occlusion.

Hepatitis B virus circulation in three different villages of Somalia.

Hepatitis B virus (HBV) circulation was surveyed in three Somalian villages (Buur-Fuul, Mooda-Moode and Bajuni Islands) in different districts and 52 children living in a closed community, aged under one year, were studied. Of the 331 village subjects aged one to 83 years, 12.08% were HBs positive, 29.9% anti-HBs positive, 43.8% anti-HBc positive and 21.4 anti-HBe positive. Among the HBs-positive subjects, 34.7% had HBeAg and 21.7% had anti-HBcAg-IgM. No statistically significant differences were found for HBs, anti-HBs, anti-HBc and anti-HBe among the three villages. HBeAg prevalence was higher in Buur-Fuul than in Mooda-Moode and in Bajuni Islands. HBsAg prevalence was about the same for each age group studied, whereas the prevalence of anti-HBc showed a continuous rise and reached its maximum level of 43.8% in those aged 39 years and older. The proportion of HBs-positive subjects who also carried HBeAg was high in the youngest children but fell with age. HBs-positive children aged under one year had a high anti-HBc-IgM prevalence. Our finding suggests that perinatal infection may play an important role among the Somalian population in determining the reservoir of virus carriers.

Application of time-resolved fluoroimmunoassay (TR-FIA) for the diagnosis of invasive amoebiasis.

A development of solid-phase immunoassay, time-resolved fluoroimmunoassay (TR-FIA), was used for anti-amoebic antibodies. The test used a chelate of the lanthanide europium as label. The long fluorescent life-time and large Stoke's shift of europium chelates permit sensitive detection in a time-resolved fluorimeter. The TR-FIA was compared with counterimmunoelectrophoresis (CIEP), indirect haemagglutination (IHA) and enzyme-linked immunosorbent assay (ELISA) using 61 sera from patients with invasive amoebiasis, 344 sera submitted routinely for amoebic serology without clinical data, 125 sera from patients with diseases other than amoebiasis, and 86 sera from "healthy" individuals. Overall agreement between TR-FIA and ELISA was 97.1%, between TR-FIA and IHA 93.2%, and between TR-FIA and CIEP 94.0%. Sensitivity, specificity and positive and negative predictive values were calculated to compare the 4 diagnostic methods in invasive amoebiasis. TR-FIA showed a higher validity than other methods. The application of such highly detectable labels in immunometric assays promises to open up entirely new areas of research.

A new serological technique, time-resolved fluoroimmunoassay (TRFIA), for the immunological diagnosis of urinary schistosomiasis.

The application of a new serological method, time-resolved fluoroimmunoassay (TRFIA), is described for the diagnosis of urinary schistosomiasis. A chelate of lanthanides (europium) with a long fluorescent life-time is used as label. The intensity of fluorescence is measured after a delay selected to eliminate almost completely the background fluorescence, which decays rapidly. TRFIA was compared with an established method, enzyme linked immunosorbent assay (ELISA). Using sera from proven cases of Schistosoma haematobium infection, 98.1% of the samples were positive by TRFIA and 86.5% by ELISA. Sera from patients infected with helminths other than schistosomes produced only 1.5% of false positives with TRFIA, compared with 12.3% by ELISA. TRFIA is more sensitive and specific than ELISA.

High prevalence of anti-hepatitis delta virus antibody in chronic liver disease in Somalia.

We have assessed the prevalence of hepatitis delta virus (HDV) infection in people with histologically proven chronic liver disease living in Somalia. Among 104 patients studied (14 with chronic persistent hepatitis, 74 with chronic active hepatitis, and 16 with active cirrhosis), 52 were positive for hepatitis B surface antigen; of these, 26 (50%) carried anti-delta antibodies. HDV infection was detected more frequently in sera from hepatitis B e antigen (HBeAg) negative patients (60.9%) than in HBeAg positive patients (9.1%). Using the dot-blot hybridization technique, serum hepatitis B virus deoxyribonucleic acid was revealed in 73.1% of patients without HDV infection, while it was detected in only 7.7% of anti-delta positive patients. It is concluded that HDV is strongly associated with chronic liver disease in Somalia.

Epidemiological study of parasitic infections in Somali nomads.

In Somali nomads the incidence of intestinal helminths is very low compared with that observed in Somalian closed institutions and practically no Entamoeba infection occurs. Schistosoma haematobium eggs are observed in urine of 50% of adults nomads. Immunological tests reveal that the relative prevalences of leishmaniasis (the lowest), malaria, and toxoplasmosis (the highest) in nomads are similar to those shown by the same techniques in settled communities.

The prevalence and intensity of intestinal parasites in two Somalian communities.

About 85% of the population of two Somali communities harboured soil-transmitted intestinal nematodes and/or protozoa. The commonest parasite (75% in the Lafoole institution and 59% in the Afgoye institution) was Trichuris trichiura. Mixed infections were common. The source of infection is contaminated fields around dwelling quarters, because of indiscriminate defaecation. One of the factors responsible for the higher incidence of hookworm in Lafoole (45%) compared with Afgoye (1.5%) may be the different soil character of the surrounding fields.

Reinfection of Somali children with Trichuris trichiura after chemotherapy: relevance of immunostimulation.

The intestinal helminth status of an age-stratified sample (6 to 20 years old) from a Somalian community has been assessed and the typical pattern of highly aggregated parasite distribution found. A reinfection study on a sample of 40 children (treated and untreated with a pentapeptide identical to the active site of the thymic hormone thymopoietin) seemed to indicate that immunological factors play a significant role in modulating the population dynamics of infection in endemic communities.

Treatment of common ocular allergic disorders; a comparison of lodoxamide and NAAGA.

BACKGROUND/AIMS: Lodoxamide tromethamine and N-acetyl-aspartyl glutamic acid (NAAGA) are mast cell stabilisers, both of which have been shown to be effective in the treatment of allergic conjunctivitis. The aim of this study was to compare the two compounds in patients with common ocular allergic disorders. METHODS: 73 patients participated in a double masked, randomised multicentre study. Diagnoses were chronic allergic conjunctivitis, vernal conjunctivitis, seasonal and atopic conjunctivitis. 36 patients were treated with lodoxamide 0.1% and 37 with NAAGA 4.9%, the drops being instilled four times daily for up to 56 days. RESULTS: The overall opinion of the physicians and the patients was in favour of lodoxamide at day 10 of the study. At this time, 86% of lodoxamide treated and 49% of NAAGA treated patients considered they had improved. The patients' opinion favoured lodoxamide at day 28 and both physicians' and patients' evaluations were in favour of lodoxamide at day 42. Evaluation of signs and symptoms indicated superiority of lodoxamide at days 42 and 56. Both treatments were well tolerated. CONCLUSION: While both lodoxamide and NAAGA treatments are associated with clinical improvements in patients with allergic conjunctivitis, lodoxamide may have an earlier onset of action.

The serological diagnosis of human hydatid disease by time-resolved fluoroimmunoassay.

The use of a new immunoassay, time-resolved fluoroimmunoassay (TR-FIA), in the diagnosis of human hydatid disease has been evaluated. This technique, which is based on the labelling of antibodies with europium (Eu), was compared with a well-established method, the enzyme linked immunosorbent assay (ELISA). Of 102 patients with hydatid disease, 97 (95.1%) were positive according to TR-FIA and 83 (81.4%) according to ELISA. The rate of non-specificity for other parasitic infections (n = 206) was 8.7% for TR-FIA and 17.5% for ELISA. It is concluded that TR-FIA is more sensitive and more specific than ELISA in the diagnosis of human hydatid disease.

An epidemic of Neisseria gonorrhoeae in a Somali orphanage.

Neisseria gonorrhoeae was isolated from 53 young females (6-14 years old) in a Somali orphanage. A male guardian was found to be the effective transmitter having sexually abused the children. All the bacterial isolates were of the same serogroup WI and the same serovar Aedih. This presents an unusual example of a tight geographic cluster of infected people which is often characteristic of gonorrhoea epidemics.

PIP: The physician of an orphanage in Afgoye, 30 km from Mogadishu, Somalia, noticed vaginal discharge in 95 of the 500 girls at the orphanage in September 1987. A Somali-Italian investigative team took vaginal specimens from the 95 girls. Laboratory personnel isolated Neisseria gonorrhoea in 56% of the 95 6-14 year old females (53) who all lived in 2 adjacent dormitories. They found that all the bacterial isolates were of the N. gonorrhoea WI serogroup and Aedih serovar. The physician prescribed penicillin treatment for all the girls. Contact tracing revealed that a male guardian was the source of gonorrhea. Some children had already accused him of sexually abusing them. Orphanage officials had transferred him 1 week before the arrival of the investigative team. His room had been very near to the 2 dormitories for only a few weeks before the investigative team arrived. In this short time, his sexual abuse effected this cluster of infections. This supports the present theory of gonorrhea epidemiology that a core group of infectious people are most likely responsible for most, if not all, of the continuing endemicity of gonorrhea. The infection rate was in range of the estimated probability of transmission (50-70%) during sexual intercourse from an infectious male to a female. The results showed that high resolution typing of gonococci has in addition to its scientific value a more practical value; forensic medicine and illustration that gonorrhea consists of smaller microepidemics.