INTU-related oral-facial-digital syndrome type VI: A confirmatory report.

Oral-facial-digital (OFD) syndromes are a subgroup of ciliopathies distinguished by the co-occurrence of hamartomas and/or multiple frenula of the oral region and digital anomalies. Several clinical forms of OFD syndromes are distinguished by their associated anomalies and/or inheritance patterns, and at least 20 genetic types of OFD syndromes have been delineated. We describe here a child with preaxial and postaxial polydactyly, lingual hamartoma, a congenital heart defect, delayed development and cerebellar peduncles displaying the molar tooth sign. Whole-exome sequencing and SNP array identified compound heterozygous variants in the INTU gene, which encodes a protein involved in the positioning of the ciliary basal body. INTU is a subunit of the CPLANE multiprotein complex essential for the assembly of IFT-A particles and intraflagellar transport. This report of a second patient with INTU-related OFD syndrome and the further delineation of its neuroimaging and skeletal phenotype now allow INTU-related OFD syndromes to be classified within the OFD syndrome type VI group. Patients display a phenotype similar to that of mice with a hypomorphic mutation of Intu, but with the addition of a heart defect.

Forces created by mandibular advancement devices in OSAS patients: a pilot study during sleep.

BACKGROUND: The aim of this study was to measure forces created by progressive mandibular advancement with an oral device, during natural sleep, in a sample of adult patients with obstructive sleep apnea syndrome (OSAS). METHODS: A pressure transducer system was placed on the acrylic arms of a two-piece oral appliance (Herbst type) used by nine moderate to severe OSAS patients, in addition to all captors routinely used for polysomnography. Strains on the left and right sides were collected, during stable sleep stages without arousal, for each step of 1 mm advancement. RESULTS: The mean force in this sample was 1.18 N/mm and showed an almost linear evolution. Measurements showed intra- and inter-individual variability. CONCLUSION: The force values recorded in this study may explain the occlusal and skeletal side effects associated with long-term use of these oral appliances. They illustrate the influence of the extent of mandibular advancement, and indicate a possible dose-dependent effect.

Head and neck skin expansion: assessment of efficiency for the treatment of lesions in the lower half of the face.

The treatment of sequelae for burns or other loss of perioral tissues is complex due to the site where they occur, its functional importance, and social and esthetic aspects. Functional consequences of burns to this area are cutaneous retraction and a lack of skin that can lead to an inability to close the oral aperture, compromising the provision of dental hygiene and intubation procedures. The aim of the present publication was to evaluate the efficacy of chin, labial and jugal cutaneous expansions for the treatment of perioral lesions and lesions of the lower half of the face in our retrospective series of patients. We collected data and photography from digital files for each patient. Proportion of scarred skin that could be treated by one or several expansion procedures was evaluated. The main outcome was the resection of 50% or more initial lesions. Side effects were assessed. Out of a total of 33 expanders, 28 were at the jugal level, 5 were chin expanders, and none were labial expanders. This equated to the inclusion of fourteen patients. The average percentage of the lesion that was removed after the perioral expansion protocol was 68.9% (40%-100%). 85% of patients had a positive outcome. 12% of procedures were complicated by hematoma, infection or prosthesis exposure. Each time that the lesional area could be fully (i.e. 100%) treated, only a single expansion was used. Head and neck expansion is the technique of choice for reconstruction of the lower half of the face and the horizontal part of the neck in terms of efficiency and safety.

Le traitement des séquelles de brûlures ou d'autres pertes de substances tissulaires de la région péri buccale est complexe du fait de l'importance fonctionnelle de cette région et des conséquences esthétiques et sociales. Les conséquences des brûlures de cette région sont les rétractions ou la rigidité cutanées entrainant une limitation de la fermeture buccale et de ce fait compromettant l'état dentaire et les procédures d'intubation. Le but de ce travail est d'évaluer l'efficacité de l'expansion cutanée du menton, des lèvres et des joues dans le traitement des lésions de la région péribuccale ou de la face basse par une étude rétrospective de notre série. Nous avons repris les données cliniques et les photographies à partir des dossiers informatisés pour chaque patient. Nous avons évalué la quantité de peau cicatricielle traitée en un ou plusieurs temps. Le résultat principal est que plus de 50% de la lésion initiale a été traitée. Les effets secondaires ont été évalués. 14 patients ont été inclus. 33 expandeurs ont été posés, 28 étaient au niveau de la joue, 5 sur le menton et aucun sur les lèvres. Le pourcentage moyen de lésion excisée après expansion cutanée de la région péribuccale était de 68,9% (40%-100%). 85% des patients ont eu un résultat satisfaisant. 12% des procédures d'expansion se sont compliquées d'hématome, d'infection ou d'exposition de la prothèse. A chaque fois que la lésion pouvait être traitée totalement, une seule procédure a été réalisée. L'expansion cutanée de la tête et du cou est la technique de choix pour la reconstruction de la face basse et de la portion horizontale du cou en termes de résultats et de complications.

[The set-up of obstructive sleep apnea treatment]. / Mise en place du traitement du SAHOS.

The therapeutic strategy of obstructive sleep apnea syndrome (OSAS) is dependent on the illness severity, which is influenced by several factors as the presence of comorbidities (particularly cardiovascular comorbidities), the importance of diurnal drowsiness and the number of abnormal respiratory events. Whereas the treatment is most often palliative and uncomfortable, its success is closely dependent on its compliance. The way of starting the treatment of OSAS is therefore an essential topic, which will condition its long-term acceptance.

Efficacy, Tolerability, and Safety of Low-Volume Bowel Preparations for Patients with Inflammatory Bowel Diseases: The French Multicentre CLEAN Study.

BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.

Efficacy and compliance of mandibular repositioning device in obstructive sleep apnea syndrome under a patient-driven protocol of care.

OBJECTIVE: To assess the efficacy and compliance of a traction-based mandibular repositioning device (MRD) for treatment of moderate to severe obstructive sleep apnea syndrome (OSAS) under a patient-driven protocol in a routine outpatient care setting. METHODS: Forty patients, 10 severe and 30 moderate OSAS sufferers (apnea-hypopnea index [AHI] >30 and between 15 and 30, respectively), were enrolled by four sleep centers. Nocturnal polygraphy, quality of life, and quality of sleep questionnaires were used to measure the effect of treatment after 45 days. RESULTS: Thirty-five patients completed the study. Frequency of respiratory events, daytime sleepiness, snoring, patient assessment of sleep quality, specific short-form multipurpose health survey (SF-36) and the Pittsburgh Sleep Quality Index (PSQI) improved significantly with the MRD. Sixty percent of patients were "responders" (>50% decrease in AHI); 46% of patients were "full responders" (>50% decrease and AHI <10). Observance of treatment was high; 80% of patients wore the MRD every night. Side effects and patient complaints were minor and transitory. No serious side effects or cases of pathology aggravation were reported. CONCLUSION: Efficacy on respiratory and somnolence parameters of this innovative traction-based MRD was validated under a simple protocol of care with response rates similar to those published in the literature. This study shows consistent significant improvement by the MRD in quality of life and quality of sleep parameters across several tests. Treatment with the MRD under a simple, patient-driven protocol of care with control of efficacy by nocturnal polygraphy is appropriate in routine outpatient practice for moderate OSAS patients.

[Pediatric obstructive sleep apnea syndrome: Treatment strategy]. / Syndrome d'apnée obstructive du sommeil de l'enfant : stratégie thérapeutique.

Pediatric obstructive sleep apnea syndrome (OSAS) has a multifactorial origin. For the child with no dysmorphic disorders or comorbidities, its main etiology is pharyngeal soft tissue hypertrophy, a dimensional reduction of the facial skeletal frame restricting the airway, an anomaly of muscular tone, or a combination of these factors. Consequently, proper diagnosis and treatment planning for these children can require several medical specialties, according to the complexity, severity, and persistence of OSAS: ear-nose-throat specialists (ENT), pneumologists/allergologists, dentofacial orthopedists/orthodontists, and physical therapists/speech therapists. A workshop was organized so as to establish the treatment strategy for these young patients, the majority of whom cannot access multidisciplinary teams (as very few exist in France), and to create guidelines for specialists in the field. The workshop comprised an orthodontist, a pediatric ENT specialist, and a physical therapist, who led a working group of about 50 physicians. They exchanged experience, discussed publications, and established decision trees about pediatric OSAS. Three main areas were studied, and conclusions are presented in this article: (1) multidisciplinary diagnosis strategy, (2) therapy according to the patient's age, and (3) treatment modality for patients combining adenotonsillar hypertrophy and maxillary transverse deficiency.

Photodynamic killing of human squamous cell carcinoma cells using a monoclonal antibody-photosensitizer conjugate.

We have developed procedures in which the photosensitizer benzoporphyrin derivative monoacid ring A (BPD) can be covalently linked to carrier molecules of modified polyvinyl alcohol (PVA) to produce water-soluble PVA-BPD conjugates with a molecular mass in the range of 30 kd. These carriers can subsequently be covalently linked to monoclonal antibodies (MoAbs) using heterobifunctional linking agents. We describe here such a conjugate in which the MoAb (5E8) has specificity for a glycoprotein detected on human squamous cell carcinomas of the lung. We provide evidence that the conjugates produced were covalently linked and retained both their photosensitizing and antigen-binding activities. We show further that the MoAb-PVA-BPD conjugate, in the presence of 10% fetal calf serum, exhibited highly enhanced phototoxic killing of the target cell line (A549) over that exhibited by free BPD or a control MoAb-PVA-BPD conjugate. These results demonstrate, therefore, both the selectivity and specificity of this MoAb conjugate.

Bone calcification and calcium homeostasis in rats with non-insulin-dependent diabetes induced by streptozocin.

The effect of mild, non-insulin-dependent diabetes (NIDDM) on bone calcification and calcium (Ca) homeostasis was studied in growing rats (males and females). The diabetic state was characterized by mild insulin deficiency, plasma levels being 73% of controls, and mild hyperglycemia, with nonfasting plasma glucose levels of 1.5 times normal. There was no difference in plasma levels of Ca, phosphate (Pi), magnesium (Mg), alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), calcitonin, 25-(OH)vitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D), and 24,25-dihydroxyvitamin D (24,25[OH]2D) between the NIDDM rats and their controls of either sex. Metabolic Ca and Pi balance studies revealed that the experimental animals of both sexes were in positive Ca and Pi balance similar to that of their controls. Histologic studies of the kidney and intestinal slices from the experimental group were normal. Ca and Pi bone content calculated per gram bone ash of the femur, mandible, and second and fourth caudal vertebrae, and the organic content in the bones of the NIDDM animals showed no difference from their controls. Femur bone density and tibial epiphyseal growth plate width and morphology were similar histologically in the experimental and control rats. No decreased osteoid content in the tibial bone was found in the diabetic rats compared with controls. Physiologic sex differences, consisting of lower plasma Pi, higher plasma calcitonin levels, increased ratio of femur dry bone weight to total body weight, and increased percentage of mineralized and total bone volume at the tibial metaphysis seen in female compared with male control rats were also seen in the diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular cloning of alpha-amylase genes from Drosophila melanogaster. I. Clone isolation by use of a mouse probe.

A cloned alpha-amylase cDNA sequence from the mouse is homologous to a small set of DNA sequences from Drosophila melanogaster under appropriate conditions of hybridization. A number of recombinant lambda phage that carry homologous Drosophila genomic DNA sequences were isolated using the mouse clone as a hybridization probe. Putative amylase clones hybridized in situ to one or the other of two distinct sites in polytene chromosome 2R and were assigned to one of two classes, A and B. Clone lambda Dm32, representing class A, hybridizes within chromosome section 53CD. Clone lambda Dm65 of class B hybridizes within section 54A1-B1. Clone lambda Dm65 is homologous to a 1450- to 1500-nucleotide RNA species, which is sufficiently long to code for alpha-amylase. No RNA homologous to lambda Dm32 was detected. We suggest that the class B clone, lambda Dm65, contains the functional Amy structural gene(s) and that class A clones contain an amylase pseudogene.

Does HIV cause salivary gland disease?

HIV-associated salivary gland disease (HIV-SGD) is characterized by enlargement of the major salivary glands and/or xerostomia. HIV does not appear to play a direct role in this disease since it was detected by immunohistochemistry in only occasional lymphocytes in labial salivary glands in two out of six patients; it was not found in the salivary gland epithelial cells. Moreover, HIV was not found in any of 21 saliva samples from seven patients. We conclude that HIV-SGD is not caused by direct infection of the salivary glands with HIV.

Polyglutaraldehyde: a new reagent for coupling proteins to microspheres and for labeling cell-surface receptors.

Glutaraldehyde polymerized in basic aqueous solutions was found to react with low molecular weight amines, immunoglobulins and hemoglobin. The polyglutaraldehyde was covalently bound to hypdrophilic microspheres. The rate of addition of proteins to the polyglutaraldehyde-derivatized microspheres was investigated spectrophotometrically as a function of pH and temperature. The reaction of polyglutaraldehyde was found to be faster than that of the monomer. The findings led to successful labeling of human lymphocyte subpopulations.

Development of technology for linking photosensitizers to a model monoclonal antibody.

A procedure is described whereby the photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA) was covalently linked to a model monoclonal antibody in a manner which is reproducible, quantifiable, and retains both the biological activity of the antibody and the cytotoxicity of the photosensitizer. Preliminary steps involved the linkage of BPD-MA to a modified polyvinyl alcohol (PVA) backbone, followed by conjugation to the antibody using heterobifunctional linking technology. Briefly, polyvinyl alcohol (MW ca. 10,000) was modified with 2-fluoro-1-methyl pyridinium toluene-4-sulfonate and 1,6-hexanediamine to produce side chains containing free amino groups. The free carboxyl group of BPD-MA was utilized to conjugate photosensitizer molecules to modified PVA using a standard carbodiimide reaction. Final linkage of the PVA-BPD to a model monoclonal antibody involved further substitution of the carrier with 3-mercaptopropionic acid and carbodiimide to introduce 3-4 sulfhydryl residues per carrier molecule, and introduction of sulfo-m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester residues to the monoclonal (3-4 residues/molecule). Conjugation was effected by reaction of the two species at pH 5.5 for 18 h. Detailed methodology and tests for efficacy of the procedure are provided.

Effect of bile acid composition and manipulation of enterohepatic circulation on leptin gene regulation.

In the rat, the ob gene product, leptin, putatively regulates energy balance via appetite control and energy expenditure. Bile acids in the intestinal lumen are necessary for efficient absorption of dietary lipids and may trigger the release of regulatory peptides. To investigate whether bile acids play a role in leptin gene expression, we altered the bile acid pool and then measured leptin mRNA levels in adipose tissue. Rats fed cholic acid (1% of chow wt/wt) for 2 weeks did not gain weight as rapidly as pair-fed control animals. Despite the lower weight, normalized leptin mRNA levels were 24% greater in cholic acid-fed rats compared with controls. Conversely, cholestyramine, a bile acid sequestrant, in chow (5% wt/wt) resulted in a 26% decline in leptin mRNA. Ligation of the common bile duct or chronic biliary diversion, experimental manipulations that decreased the intestinal concentration of bile salts, decreased leptin gene expression by 30% and 50%, respectively. A fluid and electrolyte (F/E) solution with and without taurocholate (36 micromol/h x 100 g rat[-1]) was then infused for 12 hours into the duodenum in animals with chronic biliary diversion. Taurocholate infusion resulted in a fourfold increase in steady-state adipocyte leptin mRNA levels compared with F/E infusion. Intravenous infusion of taurocholate or incubation of cultured adipocytes with taurocholate had no effect on leptin mRNA levels. We conclude that bile acids upregulate leptin gene expression indirectly, probably via effects on the absorption of dietary lipids or the release of neurohumoral mediators.

Enamel silicon and fluoride relationships demonstrating a surface silicon effect that facilitates fluoride uptake.

This study indicated that a clear relationship exists between silicon and fluoride. We have also demonstrated a probable surface enamel silicon effect that increases fluoride uptake. The complex set of relationships described in the surface chemistry of calcium, tin, and zirconium with fluoride, hydroxide, phosphate, and other surface-occurring ions need not be considered to confuse the specific silicon-fluoride relationship presented here because in this computation we are relating the changes in the silicon and fluoride ion values only. We have, however, considered the thermodynamics of such reactions and intend to elaborate on it in a later publication. We are aware of the small depth of fluoride penetration into enamel after topical treatment Health Foundation, Research Unit at the National Bureau of Standards, Washington, DC 20034, USA.

Osteocartilaginous tumors in the parapharyngeal space arising from bone exostoses.

Three osteocartilaginous tumors that arose from bone stalks were diagnosed by the demonstration, on multiplanar cross-sectional CT and MR images, of the site of stalk attachment to the adjacent mandible (one), skull base (one), and cervical vertebra (one). All three patients presented with signs and symptoms related to mass effect in the parapharyngeal region. Mass effect was more pronounced in the two cases of malignant degeneration (osteosarcoma, chondrosarcoma) than in the single case of benign osteocartilaginous exostosis. Differentiation of benign from malignant osteocartilaginous tumor may be accomplished by appreciating characteristic CT and MR features of the cartilage cap. The differential diagnosis of mass lesions of the parapharyngeal space should include tumors of osteocartilaginous origin.

Liposomal delivery of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD), to tumor tissue in a mouse tumor model.

Biodistribution studies were carried out on 14C-labeled benzoporphyrin derivative monoacid ring A (BPD), which had been formulated as a unilamellar liposome or taken from a stock solution in dimethyl sulfoxide diluted into phosphate-buffered saline immediately before intravenous injection into DBA/2 mice. By and large the general distribution of BPD to various organs and tissues was comparable for both formulations. It was noted, however, that liposomal material appeared to enter tissues more rapidly and to be cleared more rapidly, as demonstrated by shorter half-lives for a number of tissues including skin, lung and fat, and generally lower levels in most tissues 24 h following administration. Accumulation in tumor tissue was slightly higher with liposomal BPD, and clearance rates for this tissue were equivalent (half-lives 16.1 h for liposomal BPD and 16.9 h for aqueous BPD). When the two preparations were tested in a bioassay in tumor-bearing mice, photodynamic therapy (PDT) with liposomal BPD proved to be superior to the aqueous preparation when PDT was administered 3 h following intravenous administration of BPD. Plasma distribution studies in vitro demonstrated that 91.1 +/- 0.3% of the liposomal BPD distributed to the lipoprotein fraction within the first hour of mixing, whereas only 49.1 +/- 2.6% of nonliposomal BPD was associated with lipoprotein under the same conditions. Furthermore, while lipoprotein-associated liposomal BPD distributed evenly between all three types of lipoprotein (high, low and very low density), a majority of nonliposomal BPD associated with the high-density lipoprotein fraction.

Modified polyvinyl alcohol-benzoporphyrin derivative conjugates as phototoxic agents.

Photosensitizing and biodistribution characteristics of a photosensitizer (benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight = 10,000) were tested in vitro and in vivo. Modified PVA was loaded with BPD at molar ratios 1:12, 1:25, 1:50, 1:75 and 1:100. Most of the work was carried out with a conjugate having a 1:25 molar ratio. In vitro photosensitization was tested using A549 (human lung carcinoma), A432 (human epidermoid carcinoma) and P815 (mastocytoma of DBA/2 mice) cell lines. Photosensitization of M1 (rhabdomyosarcoma of DBA/2 mice) tumors was tested in an in vivo/in vitro assay, in which tumor-bearing mice were injected intravenously with free or conjugated 3H-BPD and 3 h later light activation of tumor cells was carried out in vitro. Biodistribution studies were carried out using M1 tumor-bearing DBA/2 mice and 3H-BPD either free or conjugated to M-PVA. The results of these studies showed that the conjugation of BPD to M-PVA resulted in the formation of a macromolecular photosensitizer that retained full photosensitizing activity of the photosensitizer molecules and at the same time gained new characteristics, advantageous for photodynamic treatment, especially in vivo. In vitro M-PVA-BPD conjugates were at least as efficient in photosensitization of tumor cells as an equivalent number of free BPD molecules, both in the presence and in the absence of serum. Although the biodistribution was in general comparable to free BPD, the conjugate (1:25) reached slightly higher levels in the blood, kidney, lung and spleen, and lower levels in the liver, brain, skin and muscle in comparison with free BPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Delivery of benzoporphyrin derivative, a photosensitizer, into atherosclerotic plaque of Watanabe heritable hyperlipidemic rabbits and balloon-injured New Zealand rabbits.

In this study we compared the plasma distribution and arterial accumulation of a photosensitizer, benzoporphyrin derivative (BPD), in two models of atherosclerosis: the spontaneous lesions of the Watanabe heritable hyperlipidemic (WHHL) rabbit and induced lesions of the balloon-injured, cholesterol-fed New Zealand white (NZW) rabbit. Selective uptake and retention of a photosensitizer by the abnormal portion of a vessel is a necessity in order for photodynamic therapy to become a successful modality for inhibition of intimal hyperplasia, selective removal of atherosclerotic tissue or imaging of diseased arteries. Liposome-based formulations were compared to freshly isolated native low density lipoprotein (LDL) and acetylated-LDL (Ac-LDL) as delivery vehicles for BPD. Plasma distribution of the photosensitizer was analyzed by KBr density gradient ultracentrifugation. Although the delivery vehicle influenced plasma distribution immediately postinjection, BPD subsequently partitioned according to the plasma concentration of the lipoproteins. Photosensitizer level in plaque and normal artery specimens was determined by ethyl acetate extraction and spectrofluorometric measurement. The measurement of BPD in normal and atherosclerotic arterial tissue demonstrated a selective accumulation in atherosclerotic tissue. Preassociation with LDL and Ac-LDL enhanced accumulation of BPD in atherosclerotic tissue when compared with normal artery (mean ratios of 2.8 and 4.1 were achieved, respectively). These results indicate that the preferential uptake of BPD by atherosclerotic plaque can be enhanced by preassociation with plasma lipoproteins, suggesting that light activation could lead to a highly selective destruction of diseased vascular tissue.