Sleep-related breathing disorders in amyotrophic lateral sclerosis.

Sleep-related breathing events in patients with amyotrophic lateral sclerosis (ALS) have been reported in small case series, but the association with the clinical presentation--with (B) or without (nonB) bulbar symptoms--or the relevance for prognosis have not been investigated. We retrospectively analyzed sleep studies of 114 (46 nonB) ALS patients, aged 54 +/- 11 years. Respiratory function was better in nonB patients: forced vital capacity was 76 +/- 20% vs 55 +/- 23% in the bulbar group (p < 0.001); PaCO2 41 +/- 5 vs 44 +/- 6 mm Hg p < 0.05. The mean apnea/hypopnea index (AHI) was higher in nonB patients (22 +/- 12 vs 15 +/- 16 events per hour- p < 0.05); in this group 21 out of 46 patients (46%) had more than 20 events/hour versus 14 out of 68 (21%) in the nonB group (p < 0.005). On the contrary the oxygen desaturation index (ODI) was similar (10 +/- 11 vs 9 +/- 12 events per hour, p = NS). Most events had a central genesis and obstructive events were usually erratic, except in 7 patients (6 in group B) who had more than 10 obstructive events/hour. Data were stratified in three groups: with a disease duration below 1 year (< 1 yr), between 1 and 2 years (1-2 yr), and more than 2 years (> 2 yr). The occurrence of sleep-related respiratory disorders decreased with the increase of disease duration (23 +/- 15; 18 +/- 14; and 16 +/- 15 events per hour respectively), the decrease being significantly lower in the > 2 yr group than in the < 1 yr (p < 0.05). Again ODI was similar in the three groups. In conclusion the present study shows that sleep-related breathing events are more common than previously described in ALS patients, particularly in the first year following onset of the disease. Obstructive events occur rarely, although the prevalence of obstructive sleep apnea is higher than predicted, particularly when bulbar symptoms are present. Patients without bulbar signs show a higher prevalence of central events. The progressive decrease of events with the increase of disease duration could be due to a progressive weakness of respiratory muscles, but it could also suggest an independent role for nocturnal events which could be linked to a worse prognosis or to a more rapid decay of clinical status.

Celiac disease and epilepsy: favorable outcome in a child with difficult to control seizures.

We report the case of a child with difficulties to control epilepsy and celiac disease, diagnosed soon after the onset of the seizure disorder. Seizure frequency and pattern, in addition to electroencephalogram record were suggestive of Lennox-Gastaut syndrome. Diagnosis of celiac disease was determined by positive anti-endomysium and anti-transglutaminase tests, and abnormal jejunal biopsy. Gluten-free diet, started soon after the diagnosis, led to progressive seizure control, allowing significant decrease in dosage of anti-epileptic drugs. This case corroborates the importance of serological screening tests for celiac disease, at least in patients with difficult to control epilepsy.

Prevalence of coeliac disease: unexplained age-related variation in the same population.

BACKGROUND: The aims of this work were (a) to evaluate the prevalence of coeliac disease (CD) in a large sample of the Brazilian general population and (b) to compare CD prevalence between children and adults. METHODS: The study group comprised 4405 subjects (2629 F and 1776 M). Age distributions were 2034 (1-14 years), 848 (15-29), 584 (30-44), 667 (45-59) and 272 above 60. The immunoglobulin A antiendomysial antibody (IgA-EMA) test was used as the serological screening tool. All sera were submitted to turbidimetric measurement of IgA levels and those with IgA deficiency to the IgG antigliadin (IgG-AGA) test. The small intestinal biopsy was recommended for subjects showing either (a) IgA-EMA positivity or (b) selective IgA deficiency (SigAD) and IgG-AGA positivity. RESULTS: There were 16 EMA positive out of 4405 sera tested. SigAD was found in five cases (one adult and four children). Two of these children tested positive for IgG-AGA and underwent jejunal biopsy that, in both cases, disclosed a normal mucosa. Overall, 17 out of 18 eligible subjects performed the small intestinal biopsy. The prevalence of biopsy-proven CD in this study group was 3.41 per 1000 individuals. If all 18 EMA-positive patients were included, the overall prevalence would become 3.63 per 1000. The prevalence in adults and children was 2.11 per 1000 and 5.44 per 1000, respectively. CONCLUSION: This work supports previous findings showing that CD is not a rare disorder in Brazil and that there is an unexplained difference in the prevalence of CD between adults and children.

Phototherapy with turquoise versus blue light.

Preterm jaundiced infants were treated by phototherapy with a new turquoise fluorescent lamp. This was more effective in reducing plasma total bilirubin in relation to light irradiance than the ubiquitously used blue fluorescent lamp.

Antiendomysial antibody test reliability in children with frequent diarrhea and malnutrition: is it celiac disease?

BACKGROUND: The aim of this study was to evaluate the specificity of the immunoglobulin A (IgA) antiendomysial antibody test in the diagnosis of celiac disease in a group of malnourished children with acute diarrhea, chronic diarrhea, or parasitosis, because the reliability of this test has been questioned when applied to this specific group of patients. METHODS: Serum IgA level, IgA antiendomysial antibody (EMA) test, and stool examination were performed in 315 children, ranging in age 6 months to 13 years (range, 41 +/- 2.9 months), affected by malnutrition, isolated or in association with diarrhea or parasitosis. Independent of results, 33 children with a strong suspicion of celiac disease, also underwent IgA antitransglutaminase antibody test and jejunal biopsy. RESULTS: The EMA test was negative in 313 children, including the 43 with parasitosis, being positive in two patients in whom biopsy disclosed typical celiac mucosal abnormalities (1:157). The 31 children with negative EMA test who underwent biopsy also showed negative antitransglutaminase antibody results. Their biopsies disclosed normal mucosa in 1 patient, variable degree of jejunal atrophy (grade 1 and 2) in 27 patients, and grade 3 abnormalities in 3 patients. One of these three children, showing severe jejunal atrophy, died. The diagnosis of celiac disease was apparently not confirmed by a protracted gluten challenge in the other two children. CONCLUSIONS: The specificity of the EMA test seems to be high also in children with chronic malnutrition and diarrhea. However, the possibility of false-negative tests among immunologically compromised children cannot be excluded. In doubtful cases, the gluten challenge is required in malnourished children with clinical picture, biopsy finding, and evolution suggestive of celiac disease.

Prevalence of celiac disease among blood donors in Brazil.

OBJECTIVE: There are no studies on the prevalence of celiac disease (CD) in either Brazil or, as far as we know, South America. The aim of this study was to determine the prevalence of CD in healthy blood donors in the city of Brasilia, Brazil. METHODS: Sera were obtained, independently of age and gender, from an unselected group of 2045 blood donors attending the Hematological Center of Brasilia. An IgG antigliadin antibody (AGA) test was used as a first-level screening step, followed by IgA-AGA test, serum IgA antiendomysium (EMA), and total serum IgA determination performed in all sera showing abnormally high IgG-AGA results. Jejunal biopsy was suggested for all subjects showing at least one of the following: IgA-EMA positivity; IgG-AGA and IgA-AGA positivity; IgG-AGA positivity and selective IgA deficiency. AGA was determined by an enzyme-linked immunosorbent assay (ELISA) technique and IgA-EMA was ascertained by indirect immunofluorescence on cryostat sections of monkey esophagus. Jejunal mucosa samples were obtained with a Watson capsule. RESULTS: Sixty-two (3.03%) blood donors had IgG-AGA above the cut-off values. Fifty-eight individuals showed isolated high values of IgG-AGA, whereas four had simultaneously increased IgG and IgA-AGA. Three patients had positive IgA-EMA test (one with both IgG- and IgA-AGA and two with only IgG-AGA) and underwent jejunal biopsies that disclosed complete villous atrophy associated with an increased number of intraepithelial lymphocytes and hypertrophic criptae. In this study group, the prevalence of biopsy-proven celiac disease was 1.47 +/- 1.66 in 1000 subjects. CONCLUSIONS: We found a prevalence of undiagnosed CD of 1:681 among apparently healthy blood donors. These preliminary results support the view that CD is not a rare disease in Brazil.

Why is coeliac disease endemic in the people of the Sahara?

The prevalence of antiendomysial antibody (AEA) in 989 Saharawi children was 5.6%. Intestinal biopsies in a subsample confirmed that AEA is a marker of coellac disease in people living in a developing country.

Serum IgA antibodies from patients with coeliac disease react strongly with human brain blood-vessel structures.

BACKGROUND: Our objective was to determine the possible presence of IgA antibodies directed against human central nervous system (CNS) structures in sera from coeliac disease (CD) patients. METHODS: Serum samples were collected from 4 patients with active CD on a gluten-containing diet, 11 biopsy-proven CD patients on a gluten-free diet (GFD), and 52 non-coeliac gastrointestinal controls. In all patients IgA antigliadin antibody (AGA) titres were determined with enzyme-linked immunoassay (ELISA), and IgA antiendomysium antibodies (EMA) with indirect immunofluorescence on human umbilical cord. Cryostat sections of human brain occipital cortex were incubated with the patients' sera and subsequently labelled with anti-human IgA fluorescein conjugate. RESULTS: All sera from patients with active CD on a gluten-containing diet yielded positive results in both the IgG-AGA and EMA test and in indirect immunofluorescence on brain tissue, disclosing a strong fluorescence over blood-vessels structures. All sera from CD patients on a GFD and from non-coeliac gastrointestinal controls gave a negative result on both the EMA test and the immunofluorescence reaction on human brain. CONCLUSIONS: Sera from patients with active CD contain IgA antibodies that react with human brain vessel structures, giving intense fluorescence. These antibodies are not present in sera from coeliac patients on a GFD or non-coeliac controls. This finding might be involved in the abnormal nervous system manifestations frequently described in association with coeliac disease.

Costello syndrome in two Brazilian children.

The increasing number of children with Costello syndrome described world wide has helped in delineating further the characteristic features of this condition. We report here two children, seen in the Genetic Division of the Brasilia University Hospital, showing the main features of the syndrome: "coarse" face, redundant skin on the feet and hands, hyperextensible hand and finger joints, curly hair, growth and psychomotor retardation, and feeding problems. In addition, one of the patients developed hydrocephalus during the evolution of the disease, making the third published patient with this complication. We discuss the appropriateness of serial brain imaging studies in Costello syndrome in light of the relative frequency of central nervous system malformations.

Enzyme-assisted cell photosensitization: a proposal for an efficient approach to tumor therapy and diagnosis. The rose bengal fluorogenic substrate.

Rose bengal, a xanthene derivative among the most efficient producer of singlet oxygen, was submitted to a chemical modification consisting in the introduction of an acetate group into the aromatic ring fluorophore structure. The acetate group acts as a quencher, thus inactivating both fluorescence and photosensitization properties of the molecule. In the modified structure, rose bengal acts as a fluorogenic substrate giving rise to the cellular reaction termed fluorochromasia. The acetate group is recognized by a carboxylic esterase activity that splits it. Removal of the quencher group results in restoring the native structure of photosensitizer inside the cells. The intracellular turnover of rose bengal acetate was studied in rat glioma-derived cultures cells, in terms of the balance of the processes of influx and enzyme hydrolysis of the fluorogenic substrate, and of the efflux of the fluorescent product. A large intracellular accumulation of photosensitizer is obtained when treatments are performed with the fluorogenic substrate, even at the drug concentration at which rose bengal does not enter the cells. The intracellular localization allows rose bengal to exert a more effective photosensitization effect. Provided that the quencher group is selected according to the metabolic properties of the tumor cells, the use of fluorogenic substrates as photosensitizer precursors could improve fluorescence diagnosis and the photodynamic therapy of tumors, exploiting the biological properties that distinguish pathological from normal conditions.

Molecular genetic analysis of mentally retarded males with features of the fragile-X syndrome.

The fragile-X[fra(X)] or Martin-Bell syndrome is the most common familial cause of mental retardation and is characterized by the presence of an Xq27.3 chromosome fragile site. Unstable DNA sequences representing large increases in the number of CGG trinucleotide DNA base repeats of the FMR-1 gene are located at the fragile site and responsible for the fra(X) syndrome. In order to identify whether cytogenetically normal yet mentally retarded males without a known cause of their retardation had expansion of the CGG repeat segment of the FMR-I gene, molecular genetic studies using Southern hybridization were performed with two DNA probes (fxa241 and Ox1.9) following digestion of genomic DNA from each patient with restriction enzymes Pstl and EcoRl/Eagl, respectively. DNA studies were performed on 20 (12.3%) out of 162 (122 white and 40 black people) cytogenetically normal mentally retarded males without a known cause of their retardation, but with high anthropometric discriminant values and/or clinical checklist scores identified previously and consistent with the fra(X) syndrome. None of the 20 males showed expansion of the CGG repeat of the FMR-1 gene detectable with the two probes used in this study. While heterogeneous single base pair substitutions, or small deletions or insertions in the FMR-I gene could exist in our patients, aberrations in other X-linked mental retardation genes, not identified to date but whose gene product can produce a phenotype similar to fra(X), either independently or in conjunction with the recently identified FMR-I protein, should be considered and are under investigation. Our study supports the idea that major FMR-I gene expansion detectable with Southern hybridization is rare in cytogenetically normal mentally retarded males, including those with physical and behavioural features seen in the fra(X) syndrome.

Natural fluorescence of white blood cells: spectroscopic and imaging study.

Autofluorescence has been proved to be an intrinsic parameter of biological substrates that may aid in both the characterization of the physiological state and the discrimination of pathological from normal conditions of cells, tissues and organs. In this work, the fluorescence properties of human white blood cells have been studied in suspension and on single cells at microscopy. The results indicate that suspensions of agranulocytes and granulocytes differ in the amplitude of the fluorescence signal on excitation at wavelengths in the range 250-370 nm. The differences are particularly enhanced when excitation is performed in the 250-265 nm range. Microspectrofluorometric analysis, performed on single cells, allows several leukocyte families to be characterized. Lymphocytes, monocytes, neutrophils and eosinophils can be distinguished according to the intensity and spectral shape of the autofluorescence emission in the visible range from 440 to 580 nm. Both the nature and extent of the differences change when the excitation wavelength is moved from 366 to 436 nm. Differences in the intrinsic metabolic engagement, rather than in the cell dimensions, seem to be responsible for the differences observed between the leukocyte populations. The results identify interesting perspectives for autofluorescence as a discriminating parameter in the differential counting of human white blood cells.

[Sedation with benzodiazepine in ophthalmologic surgery: comparative study of diazepam and midazolam]. / Sedazione con benzodiazepine in chirurgia oftalmologica: studio comparativo tra diazepam e midazolam.

INTRODUCTION: To evaluate the effect of giving diazepam and midazolam, respectively 0.1 mg/kg and 0.03 mg/kg on: PAS, PAD, PAM, HR, SaO2 and sedation level at 10, 30, and 50 minutes from injection. These drugs were utilized as sedatives during retrobulbar blockade as anaesthetics technique in cataract surgery. Randomized double blind in operating room for opthalmic surgery in general hospital. MATERIALS AND METHODS: 40 patients (ASA II, III) with mean age 78 +/- 7 divided in two groups with homogeneous morphological and clinic parameters, scheduled for elective cataract surgery. During retrobulbar blockade as anaesthetic technique the patients received diazepam and midazolam in equipotent quantities. Serial measurements of PAS, PAD, PAM, HR, SaO2 and sedation level. RESULTS: Both drugs proved significantly depressant on PAS, PAD, PAM, HR, SaO2. Midazolam proved more depressant than diazepam on SaO2 at 10 minutes from injection; the depression was the same for both drugs at 50 minutes. Sedation level seems higher for midazolam group than diazepam at 10 and 30 minutes, approximately the same for both groups at 50 minutes. CONCLUSIONS: Our results agree with there in the literature. The data show that midazolam is more depressant than diazepam on SaO2 at 10 minutes from injection and the necessity of a controlled "tritation" in small doses for intravenous use of midazolam.

[Excessive reabsorption of irrigation fluid during operative hysteroscopy for uterine myoma]. / Eccessivo riassorbimento di liquido di irrigazione durante isteroscopia operativa per mioma uterino.

Operative hysteroscopy procedures can present complications connected to necessity of kneeping, usually with low viscosity fluids, an uniform distension of uterine cavity. The instilled solutions are reabsorbed through the peritoneum and open uterine venous channels producing a hyperhydration syndrome. The case report shows the rising up of tis syndrome during a hysteroscopy for an uterine myoma resection. The physiopathology includes cardiovascular overload and haemodilution, causing pulmonary, cerebral and tissutal oedema. In this case report the volumes of arterial oxygen saturation and end tidal carbon dioxide obtained on line were the first warning signals. A high CVP value, a plasmatic reduction of Na, albumin, proteins, haemoglobin, haematocrit and osmolarity reflected the excessive fluid reabsorption. For this reason the necessity, during these surgical methods, of considering some practical indications and the absolutely necessary use of clinical and biochemical monitoring systems for these patients.

Photodynamic therapy of B16 pigmented melanoma with liposome-delivered Si(IV)-naphthalocyanine.

The possibility of extending photodynamic therapy to the treatment of highly pigmented neoplastic lesions was tested by using Si(IV)-naphthalocyanine (SiNc) as a tumor-localizing agent. Si(IV)-naphthalocyanine displays intense absorbance at 776 nm (epsilon = 5 x 10(5) M-1 cm-1), where melanin absorption becomes weaker. As an experimental model we selected B16 pigmented melanoma subcutaneously transplanted to C57BL mice. Upon injection of 0.5 or 1 mg kg-1 of liposome-incorporated SiNc, maximal accumulation of the photosensitizer in the tumor was observed at 24 h with recoveries of 0.35 and 0.57 microgram g-1, respectively. However, the tumor targeting by SiNc shows essentially no selectivity, since the photosensitizer concentrations in the skin (peritumoral tissue) were very similar to those found in the tumor at all postinjection times examined by us. Irradiation of SiNc-loaded melanoma with 776 nm light from a diode laser at 24 h postinjection induces tumor necrosis and delay of tumor growth. The effect appears to be of purely photochemical nature at dose rates up to 260 mW cm-2; at higher dose rates, thermal effects are likely to become important.

Anthropometric and craniofacial patterns in mentally retarded males with emphasis on the fragile X syndrome.

Anthropometric and craniofacial profile patterns indicating the percent difference from the overall mean were developed on 34 physical parameters with 31 white, mentally retarded males (23 adults and 8 children) with the fra(X) syndrome matched for age with 31 white, mentally retarded males without a known cause of their retardation. The fra(X) syndrome males consistently showed larger dimensions for all anthropometric variables, with significant differences for height, sitting height, arm span, hand length, middle finger length, hand breadth, foot length, foot breadth, and testicular volume. A craniofacial pattern did emerge between the two groups of mentally retarded males, but with overlap of several variables. Significant differences were noted for head circumference, head breadth, lower face height, bizygomatic diameter, inner canthal distance, ear length and ear width, with the fra(X) syndrome males having larger head dimensions (head circumference, head breadth, head length, face height and lower face height), but smaller measurements for minimal frontal diameter, bizygomatic diameter, bigonial diameter, and inner canthal distance. Several significant correlations were found with the variables for both mentally retarded males with and without the fra(X) syndrome. In a combined anthropometric and craniofacial profile of 19 variables comparing 26 white fra(X) syndrome males (13 with high expression (> 30%) and 13 with low expression (< 30%), but matched for age), a relatively flat profile was observed with no significant differences for any of the variables. Generally, fra(X) syndrome males with increased fragile X chromosome expression have larger amplifications of the CGG trinucleotide repeat of the FMR-1 gene. No physical differences were detectable in our study between fra(X) males with high expression and apparently larger amplifications of the CGG trinucleotide repeats compared with those patients with low expression. Our research illustrates the use of anthropometry in identifying differences between mentally retarded males with or without the fra(X) syndrome and offers a comprehensive approach for screening males for the fra(X) syndrome and selecting those individuals for cytogenetic and/or molecular genetic testing.

Experimental diode laser-assisted microvascular anastomosis.

An experimental study to evaluate a diode-laser approach to microvascular end-to-end anastomoses is reported. Studies were carried out on the femoral arteries and veins of Wistar rats, and effective welding of vessel tissue was obtained at low laser power, by enhancing laser absorption with indocyanine green (Cardio-green) solution. The histologic and surgical effects of this laser technique were examined and compared with those of conventional microvascular sutured anastomoses.

Quantum yield and skin filtering effects on the formation rate of lumirubin.

Photocyclization of bilirubin to lumirubin in the skin of jaundiced infants exposed to blue-green light irradiation is considered to be the most important process for bilirubin elimination from the organism. The quantum yield phi LR of the bilirubin-->lumirubin photoreaction has been recently measured and found to vary with the excitation wavelength, with a peak at about 520 nm. The quantum yield phi ZE for the strongly competing reversible configurational photoisomerization of bilirubin has also been recently shown to be wavelength dependent and to decrease significantly in the long-wavelength part of the absorption band of bilirubin. These new data are taken into account to model the bilirubin photochemistry in vivo by using a simplified skin optical model based on the Kubelka-Munk theory. The rate kappa LR of formation of lumirubin has been evaluated for the case of a four-layer skin and for monochromatic and narrow-band coloured fluorescent lamps. The effects of long-wavelength increase in phi LR, decrease in phi ZE and skin optical losses all combine to shift significantly the optimal rate of formation of lumirubin towards the green. These results suggest that a significant improvement in phototherapy might be obtained with the introduction of new lamps emitting in the blue-green spectral region between 490 and 510 nm.