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PubMed2026

Long-read sequencing reveals a hidden Alu-mediated splice defect in CPLANE1, causing orofaciodigital syndrome type VI.

Orofaciodigital syndrome type VI (OFD VI) is a recessive ciliopathy characterized by excessive polydactyly, molar tooth sign, cleft lip, and developmental delay, caused by pathogenic variants in CPLANE1. Here, we present a patient with OFD VI that remained genetically unexplained after routine genetic testing, including short-read whole genome sequencing (WGS). Using long-read sequencing, we found two biallelic splice-site variants in CPLANE1, c.8633-4_8633-3del, and an Alu element insertion close to an exon-intron boundary. Transcript analysis showed that each variant independently resulted in exon skipping, and quantitative expression studies revealed reduced total CPLANE1 mRNA levels in patient-derived fibroblasts. Based on these findings, we were able to re-classify the c.8633-4_8633-3del variant from a variant of uncertain significance (VUS) to likely pathogenic. The identification of an Alu element insertion missed by short-read WGS highlights the added diagnostic value of long-read sequencing in uncovering cryptic, transposable element-associated pathogenic variants.

Journal Article↗
PubMed2003

An evaluation of pulse oximeters in dogs, cats and horses.

OBJECTIVE: Evaluation of five pulse oximeters in dogs, cats and horses with sensors placed at five sites and hemoglobin saturation at three plateaus. STUDY DESIGN: Prospective randomized multispecies experimental trial. ANIMALS: Five healthy dogs, cats and horses. METHODS: Animals were anesthetized and instrumented with ECG leads and arterial catheters. Five pulse oximeters (Nellcor Puritan Bennett-395, NPB-190, NPB-290, NPB-40 and Surgi-Vet V3304) with sensors at five sites were studied in a 5 x 5 Latin square design. Ten readings (SpO2) were taken at each of three hemoglobin saturation plateaus (98, 85 and 72%) in each animal. Arterial samples were drawn concurrently and hemoglobin saturation was measured with a co-oximeter. Accuracy of saturation measurements was calculated as the root mean squared difference (RMSD), a composite of bias and precision, for each model tested in each species. RESULTS: Accuracy varied widely. In dogs, the RMSD for the NPB-395, NPB-190, NPB-290, NPB-40 and V3304 were 2.7, 2.2, 2.4, 1.7 and 2.7% respectively. Failure to produce readings for the NPB-395, NPB-190, NPB-290, NPB-40 and V3304 were 0, 0, 0.7, 0, and 20%, respectively. The Pearson correlation coefficients for the tongue, toe, ear, lip and prepuce or vulva were 0.95, 0.97, 0.69, 0.87 and 0.95, respectively. In horses, the RMSD for the NPB-395, NPB-190, NPB-290, NPB-40 and V3304 were 3.1, 3.0, 4.7, 3.3 and 2.1%, respectively while rates of failure to produce readings were 10, 21, 0, 17 and 60%, respectively. The Pearson correlation coefficients for the tongue, nostril, ear, lip and prepuce or vulva were 0.98, 0.94, 0.88, 0.93 and 0.94, respectively. In cats, the RMSD for all data for the NPB-395, NPB-190, NPB-290, NPB-40 and V3304 were 5.9, 5.6, 7.9, 7.9 and 10.7%, respectively while failure rates were 0, 0.7, 0, 20 and 32%, respectively. The correlation coefficients for the tongue, rear paw, ear, lip and front paw were 0.54, 0.79,.0.64, 0.49 and 0.57, respectively. For saturations above 90% in cats, the RMSD for the NPB-395, NPB-190, NPB-290, NPB-40 and V3304 were 2.6, 4.4, 4.0, 3.5 and 4.8%, respectively, while failure rates were 0, 1.7, 0, 25 and 43%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Accuracy and failure rates (failure to produce a reading) varied widely from model to model and from species to species. Generally, among the models tested in the clinically relevant range (90-100%) RMSD ranged from 2-5% while failure rates were highest in the V3304.

Anesthesia↗
PubMed1980

The histopathologic features which follow repeated applications of tobacco tar to rat lip mucosa.

The response of rat lip mucosa to two tobacco tar preparations combined with heat was examined histopathologically. It was shown that the magnitude of irritational hyperplasia produced was related to the level of irritation. This was greatest in those rats subjected to the longest period of application of the tobacco extract with the greatest concentration of tar combined with heating the site of application. Neoplastic changes were not produced.

Animals↗
PubMed1999

The use of ultrasound for guiding needle placement for inferior alveolar nerve blocks.

OBJECTIVE: The degree of pulpal anesthesia obtained with an ultrasound-assisted inferior alveolar nerve block was compared to that obtained with a conventional inferior alveolar nerve block for mandibular teeth to determine whether needle placement assisted by ultrasound results in more successful anesthesia. STUDY DESIGN: Through use of a repeated-measures design, each of 40 subjects randomly received an ultrasound-assisted inferior alveolar nerve block and a conventional inferior alveolar nerve block at 2 separate appointments. Mandibular anterior and posterior teeth were blindly tested by means of a pulp tester at 4-minute cycles for 60 minutes postinjection. Anesthesia was considered successful when 2 consecutive readings of 80 were obtained. RESULTS: One hundred percent of the subjects had profound lip numbness with both the ultrasound-assisted inferior alveolar nerve block and the conventional inferior alveolar nerve block. For these 2 techniques, anesthetic success rates for individual teeth ranged from 38% to 92%. There were no significant differences (P > .05) between the 2 techniques. CONCLUSIONS: It was concluded that accurate needle placement with ultrasound for the inferior alveolar nerve block did not result in more successful pulpal anesthesia in the mandible. Therefore, accuracy of needle placement is not the primary reason for pulpal anesthetic failure with this block.

Adult↗
PubMed1977

[Types of apraxia of the articulation apparatus in afferent motor aphasia].

On the basis of the comparative data on physiology and psychology of speech, as well as applied and comparative linguistics, it is known that apraxia of articulation apparatus in patients with afferent motor aphasia is heterogenous. The study of 3 groups of patients with primary apraxia of either a tongue, lips, or pharynx and larynx allowed one to find that in persons whose native language is Russian, written speech, reading and understanding is disturbed to a lesser degree in primary apraxia of glotis and larynx that are not initial phonemoformation organs in the Russian language.

Aphasia↗
PubMed2004

The lack of focused anticipation of verbal information in stutterers: a magnetoencephalographic study.

The motivation of this work was to investigate stuttering--a disorder of speech motor control--in the light of preparatory neural activity of voluntary movements related to speech. To this end, brain activity was recorded with a whole cortex magnetoencephalograph (MEG) in developmental stutterers and nonstutterers while three different tasks of single-word reading were performed. Visually presented words had to be silently read immediately after word presentation (condition 1), spoken aloud immediately after word presentation (condition 2), or spoken aloud after a delay of 1.3 s as indicated by a second visual stimulus (condition 3). Condition 2 clearly showed marked neurophysiological differences between stutterers and nonstutterers. Only nonstutterers showed clear neural activity before speech onset, which is interpreted as being linked to visual word presentation and to reflect focused verbal anticipation. This prespeech activity might reflect the "Bereitschaftsfeld2" (BF2) that is the later component of the "Bereitschaftsfeld", a well-known preparatory activity described for many other voluntary movements. Our results strongly link the lack of such preparatory brain activity at the single-word level to the disability of fluent speech in stutterers. The present results strongly support the notion that stuttering is related to impaired focused attention or anticipation.

Adolescent↗
PubMed2000

Anesthetic efficacy and heart rate effects of the intraosseous injection of 3% mepivacaine after an inferior alveolar nerve block.

OBJECTIVE: The purpose of this study was to determine the anesthetic efficacy and heart rate effects of an intraosseous injection of 3% mepivacaine after an inferior alveolar nerve block. STUDY DESIGN: Through use of a repeated-measures design, each of 48 subjects randomly received 2 combinations of injections at 2 separate appointments. The combinations were (1) an inferior alveolar nerve block (with 1.8 mL of 3% mepivacaine) + intraosseous injection with 1.8 mL of 3% mepivacaine and (2) an inferior alveolar nerve (with 1. 8 mL of 3% mepivacaine) + mock intraosseous injection. The first molar was blindly pulp tested at 2-minute cycles for 60 minutes postinjection. Anesthesia was considered successful with 2 consecutive 80 readings. Heart rate (pulse rate) was measured with a pulse oximeter. RESULTS: All subjects had lip numbness with both of the inferior alveolar nerve + intraosseous techniques. Anesthetic success for the first molar was significantly increased for 30 minutes with intraosseous injection of mepivacaine in comparison with the inferior alveolar nerve block alone (mock intraosseous injection). Subjects receiving the intraosseous injection of mepivacaine experienced minimal increases in heart rate. CONCLUSIONS: The intraosseous injection of 1.8 mL of 3% mepivacaine, when used to augment an inferior alveolar nerve block, significantly increased anesthetic success for 30 minutes in the first molar. The 3% mepivacaine had a minimal effect on heart rate and would be useful in patients with contraindications to epinephrine use.

Adult↗
PubMed2006

Biosynthetic gene cluster for the polyenoyltetramic acid alpha-lipomycin.

The gram-positive bacterium Streptomyces aureofaciens Tü117 produces the acyclic polyene antibiotic alpha-lipomycin. The entire biosynthetic gene cluster (lip gene cluster) was cloned and characterized. DNA sequence analysis of a 74-kb region revealed the presence of 28 complete open reading frames (ORFs), 22 of them belonging to the biosynthetic gene cluster. Central to the cluster is a polyketide synthase locus that encodes an eight-module system comprised of four multifunctional proteins. In addition, one ORF shows homology to those for nonribosomal peptide synthetases, indicating that alpha-lipomycin belongs to the classification of hybrid peptide-polyketide natural products. Furthermore, the lip cluster includes genes responsible for the formation and attachment of d-digitoxose as well as ORFs that resemble those for putative regulatory and export functions. We generated biosynthetic mutants by insertional gene inactivation. By analysis of culture extracts of these mutants, we could prove that, indeed, the genes involved in the biosynthesis of lipomycin had been cloned, and additionally we gained insight into an unusual biosynthesis pathway.

Anti-Bacterial Agents↗
PubMed1996

Spatial acuity of the body surface over the life span.

Spatial acuity over 13 regions of the body was assessed cross-sectionally in 122 male and female subjects between 8 and 87 years of age. Of two measures, the primary one was a threshold for detecting a gap between two points (a refinement of the conventional two-point threshold). The secondary one was a threshold of point localization in 7 of these 13 body regions. The two measures yielded similar pictures of body acuity and age-related changes in acuity, and they agreed in essentials with an early acuity map dating back to Weber in 1835, as cited and confirmed experimentally by Weinstein (1968). To this acuity map, the present study added the dimension of age. The main finding was that aging is much harder on some body regions than on others. Declining acuity with age was found to characterize all regions to one degree or another, but the hands and feet turned out to be far more vulnerable than the more central regions, including the very acute lip and tongue. Deterioration of acuity in the great toe (averaging 400% between youth and advanced age) and fingertip (averaging 130%) may adversely affect such diverse activities as braille reading, grasping, and maintaining balance. The acuity map determined by gap discrimination was essentially the same for males and females; however, males gave significantly smaller localization thresholds than females. In two body regions tested (fingertip and upper lip), children significantly outperformed young adults at gap discrimination.

Adolescent↗
PubMed1999

[Evaluation of the ability of asthmatic children to use a breath-actuated pressurized inhaler].

BACKGROUND: Poor inhaler technique in asthmatics is well documented. The objective of this study was to evaluate the influence of reading the instruction leaflet and the consultant's explanations on the use of the new breath-actuated inhaler (Autohaler 3M). METHODS: In this study were participating 379 asthmatic children and adolescents, aged from four to 17 years (mean age: 10; 64% boys), recruited by 80 pediatricians. The use of the Autohaler device was considered to be correct if the shaking, lip position, deep inhalation and apnea were all properly performed. RESULTS: The Autohaler was used correctly by 42% of the subjects simply after reading the instruction leaflet (phase I), and by 75% of the subjects who, having failed phase I, received the consultant's explanations (phase II). At the end of phases I and II, the device was correctly used by 84% of the subjects. In multivariate analysis, those under the age of nine years and those with no prior use of inhaler systems accounted for a significant amount of the incorrect use of the Autohaler during phase I. In phase II, only the fact of being less than nine years old was significantly related to incorrect use. CONCLUSION: More than four-fifths of the asthmatic children and adolescents properly used the Autohaler after merely reading the instructions and after receiving additional explanation from the consultant. The marked improvement obtained after medical explanations underlines the essential educative role of the physician when prescribing. Young children require specific training and particularly careful attention.

Adolescent↗
PubMed2000

Anesthetic efficacy and heart rate effects of the intraosseous injection of 1.5% etidocaine (1:200,000 epinephrine) after an inferior alveolar nerve block.

OBJECTIVE: The purpose of this study was to determine the anesthetic efficacy and heart rate effects of an intraosseous (IO) injection of 1.5% etidocaine with 1:200,000 epinephrine after an inferior alveolar nerve block. STUDY DESIGN: In a repeated-measures designed study, 48 subjects randomly received 2 combinations of injections at 2 separate appointments. The combinations were an inferior alveolar nerve (IAN) block (with 3% mepivacaine) + IO injection with 1.8 mL of 1.5% etidocaine hydrochloride containing 1:200,000 epinephrine, and an IAN + mock IO injection. The first molar was blindly tested with a pulp tester at 2-minute cycles for 60 minutes after the injection. Anesthesia was considered successful when 2 consecutive 80 readings (no subject response) were obtained. Heart rate (pulse rate) was measured with a pulse oximeter. RESULTS: Lip numbness occurred in 100% of the subjects with both the techniques. For the first molar, anesthetic success for the IAN + mock IO and the IAN + IO etidocaine hydrochloride groups, respectively, were 81% and 100%. The differences were significant (P <.05) when the IAN + IO etidocaine hydrochloride technique was compared with the IAN + mock IO. A mean increase in heart rate of 32 beats/min occurred in 90% of the subjects with the IO injection of the etidocaine hydrochloride solution. In 89% of these subjects, the heart rate returned to within 5 beats of baseline values 4 minutes or less after solution deposition. CONCLUSIONS: The IO injection of 1.8 mL of 1.5% etidocaine hydrochloride with 1:200,000 epinephrine, when used to augment an inferior alveolar nerve block, significantly increased anesthetic success in the first molar. The majority of subjects receiving the IO injection of the etidocaine hydrochloride solution had a transient increase in heart rate.

Adult↗
PubMed1998

Memory span, naming speed, and memory strategies in poor and normal readers.

Eleven-year-old severely impaired poor readers failed to show a word length effect with pictorial presentation, but showed an effect of equal magnitude to that of reading age and chronological age controls with auditory presentation. The lack of a pictorial word length effect was unlikely to be due to slow speed of naming skills, as in one study these were at least as fast as those of the reading age controls. It is possible that the poor readers failed to verbally encode the pictures. However, they reported using verbal rehearsal, and lip movements were often observed during presentation, suggesting that they did verbally encode the items. Therefore they may have failed to show a word length effect because they did not retrieve information from the phonological store at recall. Although the poor readers had impaired naming speed skills for their age on both discrete item identification and articulation rate tasks, they could not be equated with their chronological age controls on memory span or reading when these naming speed differences were controlled. However, the groups were matched on the naming speed measures when differences in reading ability were controlled.

Child↗
PubMed1985

Racial differences in cephalometric measurements and incidence of cleft lip with or without cleft palate.

A study was made to search for the morphological basis and, indirectly, the developmental basis for racial differences in risk of cleft lip with or without cleft palate CL(P) in Hawaii. A total of ten linear and three angular measurements read from anterior-posterior cephalographs were examined on 210 healthy adult Caucasian, Hawaiian, Japanese, Chinese, and Filipino subjects. Racial comparisons were made on these variables after adjusting for age and sex. Generally, the CL(P) high-risk group consisting of Japanese, Chinese, and Filipinos had smaller dimensions than Caucasians and Hawaiians in the variables (S-N, N-Ba) representing size of cranial base and the measurements of face height (N-A, N-ANS), palatal length (ANS-PNS), and mandibular length (Ar-Gn). Facial width relative to palatal length as measured by the ratio of bizygomatic diameter to palatal length showed a marked consistency with the racial differences in CL(P) risk. Possible significance of this finding is discussed in relation to development of the orofacial structure.

Adolescent↗
PubMed2004

Cutaneous and oral eruption from oral exposure to nickel in dental braces.

Oral eruptions due to nickel allergy are rare. A common presentation of intraoral contact dermatitis is the presence of lichenoid plaques on the buccal mucosa adjacent to the offending antigen. We report an unusual case of cutaneous and mucosal nickel allergy arising after placement of dental braces. An 11-year-old boy was referred by his orthodontist to the University of Minnesota Occupational and Contact Dermatitis Clinic to be evaluated for a possible metal allergy. The patient developed an itchy rash on his abdomen and under his wristwatch 1 week after dental braces were placed. He was diagnosed with allergic contact dermatitis from nickel. The patient avoided cutaneous nickel exposure and had a minimal resolution of his symptoms. One year later, the patient developed swelling and burning of the lips. Secondary to extreme discomfort, the braces, which contained nickel, titanium, and zinc, were removed. The patient underwent standard patch testing; the final reading at 96 hours showed a +++ reaction to nickel, palladium, cobalt chloride, and neomycin. The patient experienced relief of his oral symptoms after removal of the braces. No current relevance to palladium, cobalt, or neomycin has been found.

Child↗
PubMed2005

Automatic audiovisual integration in speech perception.

Two experiments aimed to determine whether features of both the visual and acoustical inputs are always merged into the perceived representation of speech and whether this audiovisual integration is based on either cross-modal binding functions or on imitation. In a McGurk paradigm, observers were required to repeat aloud a string of phonemes uttered by an actor (acoustical presentation of phonemic string) whose mouth, in contrast, mimicked pronunciation of a different string (visual presentation). In a control experiment participants read the same printed strings of letters. This condition aimed to analyze the pattern of voice and the lip kinematics controlling for imitation. In the control experiment and in the congruent audiovisual presentation, i.e. when the articulation mouth gestures were congruent with the emission of the string of phones, the voice spectrum and the lip kinematics varied according to the pronounced strings of phonemes. In the McGurk paradigm the participants were unaware of the incongruence between visual and acoustical stimuli. The acoustical analysis of the participants' spoken responses showed three distinct patterns: the fusion of the two stimuli (the McGurk effect), repetition of the acoustically presented string of phonemes, and, less frequently, of the string of phonemes corresponding to the mouth gestures mimicked by the actor. However, the analysis of the latter two responses showed that the formant 2 of the participants' voice spectra always differed from the value recorded in the congruent audiovisual presentation. It approached the value of the formant 2 of the string of phonemes presented in the other modality, which was apparently ignored. The lip kinematics of the participants repeating the string of phonemes acoustically presented were influenced by the observation of the lip movements mimicked by the actor, but only when pronouncing a labial consonant. The data are discussed in favor of the hypothesis that features of both the visual and acoustical inputs always contribute to the representation of a string of phonemes and that cross-modal integration occurs by extracting mouth articulation features peculiar for the pronunciation of that string of phonemes.

Acoustic Stimulation↗
PubMed2004

Photography of cleft audit patients.

The IMI National Guidelines have been prepared as baseline guides on specific aspects of medical illustration practice, and provide auditable standards for the future. They can be implemented in full, or may be amended according to individual requirements. The following, which is the first in the series to be published in this journal, is an abridged version of guidelines prepared by Marie Jones. The full version of this and the other guidelines can be read or downloaded at www.imi.org.uk.

Adult↗
PubMed1992

Cloning, nucleotide sequence and expression in Escherichia coli of a lipase gene from Bacillus subtilis 168.

The gene coding for an extracellular lipase of Bacillus subtilis 168 was cloned and found to be expressed in Escherichia coli. Enzyme activity measurements showed no fatty acid chain length preference. A set of Tn5 insertions which inactivate the gene were localized and used to initiate its sequencing. The nucleotide sequence was determined on two independent clones expressed in E. coli. In one of these clones, the sequence revealed a frameshift, due to the presence of an additional adenine in the N-terminal region, which caused the interruption of the open reading frame, probably allowing translation to initiate at a second ATG codon. The sequence of the wild-type lip gene from B. subtilis was confirmed on the chromosomal fragment amplified by polymerase chain reaction (PCR). When compared to other lipases sequenced to date, the enzyme described here lacks the conserved pentapeptide Gly-X-Ser-X-Gly supposed to be essential for catalysis. However, alignments of several microbial lipase sequences suggest that the pentapeptide Ala-X-Ser-X-Gly present in the lipase B. subtilis may function as the catalytic site. Homologies were found in the N-terminal protein region with lipases from different Pseudomonas species. The predicted M(r) and isoelectric point for the mature protein are 19,348 and 9.7 respectively.

Amino Acid Sequence↗
PubMed1976

Oxygen tension and surface temperature of the endonasal tissues in the goat. Preliminary report.

Measurement of the PO2 in the mucosal cells and at various depths of the lamina propria lining the nasal cavity in five male goats using Silver's special microelectrodes, revealed relative hypoxia in the anterodorsal part of the nasal septum and tips of naso- and maxilloturbinals. In these sites PO2 values varied between 55-65 at the surface and 30-35 in the superficial subepithlial layer while elsewhere in the nose, lip and tongue, PO2 values of 85-90 were obtained. Temperature measurements with the thermistor in two goats yielded readings of 34-34-5 degrees C. in the hypoxic areas against 36-37 degrees C. in the posterior parts, the roof and floor of the nasal cavity. However, the oxygen tension diminished steadily in all areas as the microneedle electrode approached the chondro-osteal tissues but PO2 values of 0-10 in the perichondrium. The significance of these findings in the predilective localization of granulomata and various forms of vasculitis in the anterior endonasal tissues has been discussed.

Animals↗