Review of patient experience with bilateral sagittal split osteotomies as a day case procedure.

Historically, patients who received bilateral sagittal split osteotomies (BSSO) required an inpatient admission for at least one night. Since March 2015, the Oral and Maxillofacial Department at the Royal Gwent Hospital has performed bilateral sagittal split osteotomies (BSSO) as a day case procedure for their medically and socially fit patients. Our team's service evaluation by Davies et al (2018) for this procedure, demonstrated that this could be done both routinely and successfully, whilst conforming to national day case procedural standards. The aim of this satisfaction survey was to evaluate this procedure from a patient's perspective, to further consolidate our results from 2018. The forty-five patients who underwent day case BSSO (DCBSSO) between February 2015 and February 2020 were retrospectively identified and deemed eligible for inclusion. Participation involved completion of a 10-part questionnaire via telephone consultation. Patients were asked questions focussing on their experience of discharge timing, management of postoperative symptoms, and overall recovery at home. Twenty-four patients consented to partake in the survey (response rate of 73%). Twenty-three (96%) were extremely happy to be discharged the day of their surgery and felt that the timing of discharge was appropriate. Only 17% of patients experienced discomfort overnight and 96% of these stated they could manage their symptoms at home. From this survey, we can confirm that the majority of patients receiving DCBSSO at the Royal Gwent Hospital were happy to be discharged the day of their surgery and recover at home.

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD).

Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated with hypocitrullinemia on NBS and subsequent confirmatory tests. An oral biotin trial is also warranted.

It Takes Two? An Exploration of Processes and Outcomes in a Two-Session Couple Intervention.

Although relationship distress is common, couples often forego professional help due to concerns such as time constraints, financial costs, and stigma. The two-session relationship checkup is an alternative format of couple intervention developed to address these concerns. In this qualitative study, we interviewed 20 coupled participants and six clinicians to examine the checkup's processes and outcomes. The phenomenological themes that emerged revealed sequential processes by which this format works. Couple themes included client motivation, the therapeutic relationship, and therapeutic change in terms of perceptions and behaviors-particularly with regard to communication. Clinician data largely mirrored these themes. The results suggest the intervention addressed barriers to help-seeking and may be a viable selective option for at-risk couples.

The Gulf Coast tick: a review of the life history, ecology, distribution, and emergence as an arthropod of medical and veterinary importance.

The Gulf Coast tick, Amblyomma maculatum Koch (Acari: Ixodidae), is a unique univoltine ectoparasite of seven vertebrate host classes in the Western Hemisphere that is increasingly recognized as a pest of livestock and wildlife, a vector of pathogens to humans and canines, and a putative vector of Ehrlichia ruminantium, the causal agent of heartwater, a fatal foreign animal disease of ruminants resident in the Caribbean. This review assembles current and historical literature encompassing the biology, ecology, and zoogeography of this tick and provides new assessments of changes in cyclical population distribution, habitat associations, host utilization, seasonal phenology, and life history. These assessments are pertinent to the emergence of A. maculatum as a vector of veterinary and medical importance, and its pest management on livestock and other animals.

Retinoid-suppressed phosphorylation of RARalpha mediates the differentiation pathway of osteosarcoma cells.

Although retinoic acid (RA) is a potent agent that coordinates inhibition of proliferation with differentiation of many cell types, RA-mediated signaling pathways in osteosarcoma cell differentiation are uncharacterized. In this study, we show that in human U2OS osteosarcoma cells, decreased phosphorylation of RA receptor alpha (RARalpha) by RA treatment or overexpressing a phosphorylation-defective mutant RARalphaS77A results in the inhibition of proliferation and induction of differentiation, and that U2OS cells transduced with RARalphaS77A suppresses tumor formation in nude mice. Moreover, using different human primary osteosarcoma cells and human mesenchymal stem cells for gene expression analysis, we found that either RA or RARalphaS77A induces many of the same differentiation response pathways and signaling molecules involved in U2OS cell differentiation. In addition, overexpression of the fibroblast growth factor 8f (FGF8f), one of the downstream targets induced by both RA and RARalphaS77A in U2OS cells, inhibits proliferation and induces expression of osteoblastic differentiation regulators. Hence, these data strongly suggest that RA-suppressed phosphorylation of RARalpha induces FGF8f expression to mediate differentiation response pathway in U2OS osteosarcoma cells.

Determination of the biotin content of select foods using accurate and sensitive HPLC/avidin binding.

Assessing dietary biotin content, biotin bioavailability, and resulting biotin status are crucial in determining whether biotin deficiency is teratogenic in humans. Accuracy in estimating dietary biotin is limited both by data gaps in food composition tables and by inaccuracies in published data. The present study applied sensitive and specific analytical techniques to determine values for biotin content in a select group of foods. Total biotin content of 87 foods was determined using acid hydrolysis and the HPLC/avidin-binding assay. These values are consistent with published values in that meat, fish, poultry, egg, dairy, and some vegetables are relatively rich sources of biotin. However, these biotin values disagreed substantially with published values for many foods. Assay values varied between 247 times greater than published values for a given food to as much as 36% less than the published biotin value. Among 51 foods assayed for which published values were available, only seven agreed within analytical variability (720%). We conclude that published values for biotin content of foods are likely to be inaccurate.

Observer agreement in the grading of oral epithelial dysplasia.

OBJECTIVES: To determine the extent of observer agreement in diagnosis of oral epithelial dysplasia (OED). Published studies of OED examiner agreement report relatively low agreement levels; however, these studies were limited by the methodologies employed. METHODS: For this study, 64 slides were each independently examined twice by three oral pathologists. Consistency was assessed by determining intra- and interexaminer agreement. Conformity was assessed by using the modal diagnosis as a gold standard. RESULTS: The group showed moderate interobserver agreement when grading the presence or absence of OED with a group-simple kappa (Ks) of 0.51 (95% CI = 0.42-0.61), and substantial agreement when using a 5-point ordinal scale with a group-weighted kappa (Kw) of 0.74 (95% CI = 0.64-0.85). The group showed fair to substantial intraexaminer agreement when assessing the presence or absence of OED, with Ks ranging from 0.22 to 0.78, and showing almost a perfect agreement using a 5-point ordinal scale, with Kw ranging from 0.82-0.96. Conformity with the comparison standard modal diagnosis was almost perfect, with pairwise Kw ranging from 0.81 to 0.92. CONCLUSION: Overall, there was substantial intra- and interobserver consistency and almost perfect conformity in the grading of OED. Appropriate statistical methods are necessary to determine the degree of observer agreement.

Tuberous sclerosis: clinicopathologic features and review of the literature.

INTRODUCTION: Tuberous sclerosis is a hamartoneoplastic syndrome, which may involve multiple organ systems. Oral hard tissue manifestations of the syndrome have been described in the literature only as recently as 1955. Patients who presented with clinical manifestations of tuberous sclerosis did not routinely undergo oral surveys to rule out 'lesions', and consequently data on 'lesions' in the maxillofacial complex is scant. Ten cases have been found in the English language literature, which describe maxillofacial 'lesions', which may be tumours, new growths, neoplasms or overgrowths occurring in patients diagnosed with tuberous sclerosis. PURPOSE: To review the literature for all maxillofacial lesions associated with tuberous sclerosis and to present an eleventh case of a patient with a maxillofacial lesion diagnosed as having tuberous sclerosis. RESULTS: Eleven cases were found with maxillofacial fibroblastic lesions associated with tuberous sclerosis. These lesions were all fibrous benign neoplasms found in the maxillofacial bony complex. CONCLUSIONS: Maxillofacial fibroblastic lesions in tuberous sclerosis have various histopathological presentations, some of which may be difficult to differentiate. Consequently, close microscopic examination of these lesions is necessary so that adequate surgical treatment is provided.

Certain immune markers are not good indicators of mild to moderate biotin deficiency in rats.

To assess the effects of marginal biotin deficiency on immune function and thereby evaluate immune function as a potential marker for impaired biotin status, we investigated immune function in a rat model during progression from sufficiency to moderate biotin deficiency. As immune function indicators, we assessed the IgG response to a vaccine and the cytokine responses and relative proportions of lymphocyte subpopulations in the immunocytes in blood, spleen and thymus. Neither phenotype nor organ redistribution of lymphocytes differed between biotin-deficient and biotin-sufficient rats. Assessment of immune function by mitogen T cell proliferation, mitogen-induced interferon-gamma and interleukin-4 levels, IgG antibody responses and natural killer cell activity were not significantly different in mild to moderately biotin-deficient rats compared with biotin-sufficient controls. The absence of effects on immune function was not attributable to failure to induce biotin deficiency; the rats exhibited unequivocal evidence of biotin deficiency, including reduced hepatic biotin and impaired leucine metabolism resulting from deficiency of the biotin-dependent enzyme methylcrotonyl-CoA carboxylase. We conclude that the immune markers examined are not promising candidates as indicators of mild to moderate deficiency in humans.

Potential environmental and host participants in the early white matter lesion of adreno-leukodystrophy: morphologic evidence for CD8 cytotoxic T cells, cytolysis of oligodendrocytes, and CD1-mediated lipid antigen presentation.

The 2 most common forms of X-linked adreno-leukodystrophy (ALD) are the juvenile or childhood cerebral form with inflammatory demyelination and the adult adrenomyeloneuropathy (AMN) involving spinal cord tracts without significant inflammation. Modifier genes or environmental factors may contribute to the phenotypic variability. We performed immunohistochemical, an in situ polymerase chain reaction, and TUNEL analyses to identify several viruses, lymphocyte subpopulations, apoptotic cells, and effector molecules, focusing on morphologically normal white matter, dysmyelinative and acute demyelinative lesions. No distinguishing viral antigens were detected. Most lymphocytes were CD8 cytotoxic T cells (CTLs) with the alpha/beta TCR, and they infiltrated morphologically unaffected white matter. Only a few oligodendrocytes were immunoreactive for caspase-3. MHC class II- and TGF-beta-positive microglia were present. CD44, which can mediate MHC-unrestricted target cell death, was seen on many lymphocytes and white matter elements. CD1 molecules, which play major roles in MHC-unrestricted lipid antigen presentation, were noted. Our data indicate that unconventional CD8 CTLs are operative in the early stages of dysmyelination/demyelination and that cytolysis of oligodendrocytes, rather than apoptosis, appears to be the major mode of oligodendrocytic death. The presentation of lipid antigens may be a key pathogenetic element in ALD and AMN-ALD.

Hematocrit correlates well with circulating red blood cell volume in very low birth weight infants.

Although circulating red blood cell (RBC) volume is a better measure of total body oxygen delivering capacity than hematocrit (HCT), circulating RBC volume is more difficult to measure. Thus, the HCT is often used in RBC transfusion decisions. However, several previous studies of low birth weight infants have reported that the correlation between HCT and circulating RBC volume is poor. Using a robust nonradioactive method based on in vivo dilution of biotinylated RBC enumerated by flow cytometry, the present study reexamined the correlation between HCT and circulating RBC volume in very low birth weight infants. Venous and capillary HCT levels were compared with circulating RBC volume measured using the biotin method. Twenty-six stable very low birth weight infants with birth weights less than 1300 g were studied on 43 occasions between 7 and 79 d of life. Venous HCT values correlated highly with circulating RBC volume (r = 0.907; p < 0.0001). However, the mean 95% confidence limits for prediction of circulating RBC volume from venous HCT (the average error of prediction) was +/-13.4 mL/kg. The correlation between HCT and circulating RBC volume is strong in older stable very low birth weight infants. However, clinically important uncertainty exists in estimating circulating RBC volume and the associated RBC transfusion needs of an individual infant based on venous HCT. Because direct measurement of circulating RBC volume is not yet practical, the HCT (or the blood Hb concentration) remains the best available indirect indicator.

A direct streptavidin-binding assay does not accurately quantitate biotin in human urine.

In human urine, the biotin concentration assayed directly using an avidin-binding assay (ABA) apparently overestimates "true" biotin concentration as measured by HPLC separation of biotin from biotin metabolites followed by ABA. Because biotin metabolites account for about half of biotin plus biotin metabolites in human urine, we speculate that the error might arise from biotin metabolites. We sought to test the following hypothesis: biotin measured by direct ABA routinely exceeds true biotin in urine due to biotin metabolites; however, if urinary biotin is quantitated using a streptavidin-binding assay (SABA) that does not detect biotin metabolites, results will agree with true biotin. An assay for biotin that uses europium coupled to streptavidin and time-resolved fluorescence was developed and validated. Urine samples were obtained from biotin-deficient, normal and biotin-supplemented adults. In 133 urine samples from 26 subjects, biotin by direct ABA correlated positively and significantly with biotin measured after HPLC separation (P < 0.001; r = 0.78). However, biotin by direct ABA routinely exceeded true biotin. The magnitude of the overestimate correlated strongly with biotin metabolites; r = 0.80 and P < 0.0001. In 92 samples from nine subjects, biotin by direct SABA correlated positively and significantly with true biotin (P = 0.001; r = 0.73) but exceeded true biotin by more than analytical error in 62 of the 92 samples. The error did not correlate significantly with total biotin metabolites. In 62 samples analyzed by both assays, biotin by direct SABA correlated weakly (r = 0.69) but significantly (P < 0.0001) with biotin by direct ABA. These studies provide evidence that direct SABA does not accurately quantitate biotin. Although the errors from direct ABA arise primarily from metabolites, the errors from direct SABA cannot be attributed primarily to biotin metabolites. Whether these interfering substances are biotin metabolites or other unknown substances, the substances are likely separated from the biotin fraction by HPLC.

Ectoparasite control in small ruminants.

Ectoparasites are a common problem in small ruminants of North America. Management of ectoparasites in small ruminants can be challenging for producers and veterinarians. It is important for the veterinarian to make an accurate diagnosis of the type of ectoparasite that is infesting the animal, then to develop a plan that most effectively and economically controls the ectoparasite. Effective and economic control of an ectoparasite infestation begins with an understanding of the ectoparasite's life cycle and how that life cycle affects the animal. It should be noted that climate and geographical area can affect the life cycle of specific ectoparasites, so it is important for veterinarians to educate themselves about their specific environment. Once the life cycle has been addressed, then the veterinarian should decide which intervention will provide the best control. Intervention possibilities may range from insecticides to environmental management or a combination of several methods. The veterinarian should provide the producer with realistic goals that define specific limitations of ectoparasite control.

Epstein-Barr virus detection in non-Hodgkin's lymphoma of the oral cavity: an immunocytochemical and in situ hybridization study.

OBJECTIVE: The purpose of this study was to histologically characterize a series of oral non-Hodgkin's lymphomas (NHLs) and to investigate latent and lytic Epstein-Barr virus (EBV) infection in these. STUDY DESIGN: The revised European-American Lymphoma classification system (41) was used to categorize 58 cases of oral NHL, which included 9 immunosuppression-related NHLs. EBV infection was determined by in situ hybridization for Epstein-Barr virus-encoded RNA and by immunohistochemistry for the EBV antigens latency membrane protein, Epstein-Barr nuclear antigen-2 (EBNA2) and Z EBV replication activator protein. RESULTS: Most tumors were B-cell lymphomas (78%), but the proportion of T-cell lymphomas was surprisingly high (22%). The most common histologic subtypes were diffuse large B-cell lymphomas (45%), peripheral T-cell lymphomas (19%), and follicle center lymphomas (14%). Two thirds of the known immunosuppression-related NHLs were T-cell lymphomas. All of the immunosuppression-related tumors were EBV-infected, whereas the EBV infection rate in the NHLs of the remaining patients presumed to be immunocompetent was only 9%. Most EBV-positive tumors expressed neither of the latent antigens (ie, latency membrane protein and Epstein-Barr nuclear antigen-2), and coexpression of the 2 was observed only in immunosuppressed patients. Z EBV replication activator protein expression, which is indicative of replicative infection, occurred only in immunosuppressed individuals. CONCLUSIONS: Diffuse large B-cell lymphomas were the most common histologic subtype of oral NHLs, but T-cell lymphomas were relatively common and frequently occurred in states of immunosuppression. EBV may play a limited role in the initiation of lymphoma in the immunocompetent patient, but the virus may be of importance in progression of the disease in those patients with more aggressive tumors, as immunosuppression occurs.

Human herpesvirus 6.

The development of techniques for the culture of lymphoid cells and the isolation of viruses that infect these cells led to the discovery of human herpesvirus (HHV) 6 in 1986. At the time, HHV-6 was the first new human herpesvirus to be discovered in roughly a quarter of a century, and its isolation marked the beginning of an era of discovery in herpesvirology, with the identification of HHV-7 and HHV-8 (Kaposi's sarcoma-associated herpesvirus) during the following decade. Like most human herpesviruses, HHV-6 is ubiquitous and capable of establishing a lifelong, latent infection of its host. HHV-6 is particularly efficient at infecting infants and young children, and primary infection with the virus is associated with roseola infantum (exanthem subitum) and, most commonly, an undifferentiated febrile illness. Viral reactivation in the immunocompromised host has been linked to a variety of diseases, including encephalitis, and HHV-6 has been tentatively associated with multiple sclerosis. This article discusses the major properties of HHV-6, its association with human disease, and the pathobiological significance of viral reactivation.

In vivo biotin supplementation at a pharmacologic dose decreases proliferation rates of human peripheral blood mononuclear cells and cytokine release.

Theoretically, vitamin supplements may either enhance or reduce protein synthesis and proliferation in peripheral blood mononuclear cells (PBMC). In the present study, we determined whether administration of a pharmacologic dose of biotin affects proliferation rates of PBMC and cytokine release. Healthy adults (n = 5) ingested 3.1 micromol biotin/d for 14 d; blood and urine were collected pre- and postsupplementation. PBMC were isolated by density gradient and incubated with the mitogen concanavalin A for up to 3 d. At timed intervals during mitogen stimulation, we measured the following: 1) cellular uptake of [(3)H]thymidine to determine proliferation rates; 2) concentrations of various cytokines released into the medium; and 3) the percentages of PBMC subsets as judged by CD surface markers. Biotin supplementation caused a significant decrease of PBMC proliferation. At 2 d after mitogen stimulation, [(3)H]thymidine uptake by postsupplementation PBMC was 66 +/- 21% of the uptake by presupplementation PBMC (P < 0.05). Similarly, concentrations of interleukin-1beta (2 d after mitogen) and interleukin-2 (1 d after mitogen) in media from postsupplementation PBMC were 65 +/- 28% and 44 +/- 23%, respectively, of those for presupplementation PBMC (P < 0.01). Percentages of PBMC subsets were not affected by 14 d of biotin supplementation. Overall, this study provides evidence that administration of pharmacologic doses of biotin for 14 d decreases PBMC proliferation and synthesis of interleukin-1beta and interleukin-2.

The clearance and metabolism of biotin administered intravenously to pigs in tracer and physiologic amounts is much more rapid than previously appreciated.

Understanding of biotin pharmacokinetics and regulation of metabolism is essential for the determination of the biotin requirement for humans. Using Landrace-Cambrough pigs as a model, we initially demonstrated that biotin binding to protein accounts for only a small percentage of the total biotin in plasma. A physiologic amount of [14C]biotin was administered intravenously to three pigs; nine blood samples were collected over 48 h. Plasma concentrations of 14C-labeled metabolites were negligible for the first 2 h after biotin infusion. Disappearance curves of total 14C and of [14C]biotin were similar; both fit a triexponential function consistent with a three-compartment, open model. To characterize the rapid early phase of disappearance more precisely, a physiologic amount of [14C]biotin was administered intravenously to five pigs; eight blood samples were collected over the first hour and 16 total samples over 48 h. Again a triexponential function provided an excellent fit. The mean half-life values (+/- 1 SD) for the three phases were 0.11 +/- 0.07, 1.43 +/- 0.42 and 22 +/- 4 h. The [14C]biotin accumulated primarily in the liver, kidney and muscle. When administered intravenously at tracer doses to three pigs, [3H]biotin exhibited similar early pharmacokinetics; however, substantial quantities of a 3H-labeled metabolite appeared after 1 h. These studies provide evidence that egress of biotin from plasma is more rapid than previously appreciated. The slower second and third phases may represent transport into the cytosol, biotransformation into intermediates and covalent binding to intracellular proteins. Similar pharmacokinetics are likely to be seen in humans.

Preliminary survey of ticks (Acari: Ixodidae) parasitizing wild turkeys (Aves: Phasianidae) in eastern Kansas.

During the spring and fall turkey hunting seasons of 1999, hunters and Kansas Department of Wildlife and Parks field personnel examined wild turkeys, Meleagris gallopavo L., for ticks and submitted them to us for identification. From springtime hunting, we received 113 ticks from 12 turkeys killed in nine counties, all in the eastern one-third of Kansas. Collectors reported examining three additional wild turkeys on which no ticks were found. All ticks were nymphal lone star ticks, Amblyomma americanum (L.). Of 11 wild turkeys examined in seven counties during October, one was parasitized by 30 A. americanum larvae. Data from this study and accounts from the published literature suggest that parasitism of wild turkeys by immature lone star ticks is commonplace wherever this host and ectoparasite are sympatric. Our study suggests that M. gallopavo may be an important host that supports lone star tick populations.