Citations

Objective To evaluate the horizontal and vertical stability of the quadrangular Le Fort I in patients with congenital cleft lip and palate. Design Prospective longitudinal study. Patients A total of 15 congenital cleft lip and palate patients treated with the maxillary quadrangular Le Fort I were enrolled. Intervention Lateral cephalometric radiographic examinations were obtained preoperatively, early postoperatively, and late postoperatively for four dental and skeletal landmarks. A questionnaire regarding patients' satisfaction with treatment and functional/cosmetic outcomes (airway, speech, mastication) was administered. Main Outcome Measures Surgical horizontal and vertical movement, late postsurgical horizontal and vertical movement, and surgical and postsurgical movement in relation to age and cleft type were evaluated using Spearman correlation coefficients, Wilcoxon signed rank tests, and Mann-Whitney tests. Results Surgical horizontal movements of all measured points showed significant changes. Significant differences of postsurgical horizontal movement were observed in younger patients versus adult patients. Significant differences of postsurgical horizontal movement were observed in unilateral cleft patients versus bilateral cleft patients. A high percentage of patients showed significant functional improvement in nasal airflow, speech, mastication, temporomandibular joint function, and mouth versus nose breathing. Conclusions The quadrangular Le Fort I is a functionally stable and a surgically predictable procedure for cleft lip and palate patients who present with midface deficiency. Patients under the age of 18 at the time of the osteotomy had a higher relapse rate than patients over 18 years of age. Younger patients who need surgery should be advised regarding the increased risk of skeletal relapse. Patients' satisfaction was high in all aesthetic- and function-related items on the questionnaire.

Introduction: Secure messages and electronic visits (“e-visits”) through patient portals provide patients with alternatives to face-to-face appointments, telephone contact, letters, and e-mails. Limited information exists on how portal messaging impacts face-to-face visits in primary care. Materials and Methods: We conducted a retrospective cohort study of 2,357 primary care patients who used electronic messaging (both secure messages and e-visits) on a patient portal. Face-to-face appointment frequencies (visits/year) of each patient were calculated before and after the first message in a matched-pairs analysis. We analyzed visit frequencies with and without adjustments for a first message surge in visits, and we examined subgroups of high message utilizers and long-term users. Results: Primary care patients who sent at least one message (secure message or e-visit) had a mean of 2.43 (standard deviation [SD] 2.3) annual face-to-face visits before the first message and 2.47 (SD 2.8) after, a nonsignificant difference ( p =0.45). After adjustment for a first message surge in visits, no significant visit frequency differences were observed (mean, 2.35 annual visits per patient both before and after first message; p =0.93). Subgroup analysis also showed no significant change in visit frequency for patients with higher message utilization or for those who had used the messaging feature longer. Conclusions: No significant change in face-to-face visit frequency was observed following implementation of portal messaging. Secure messaging and e-visits through a patient portal may not result in a change of adult primary care face-to-face visits.

Objective To identify the clinical and laboratory predictors of clinical improvement in a cohort of myositis patients treated with rituximab. Methods We analyzed data for 195 patients with myositis (75 with adult polymyositis [PM], 72 with adult dermatomyositis [DM], and 48 with juvenile DM) in the Rituximab in Myositis trial. Clinical improvement was defined as 20% improvement in at least 3 of the following 6 core set measures of disease activity: physician's and patient's/parent's global assessment of disease activity, manual muscle testing, physical function, muscle enzymes, and extramuscular disease activity. We analyzed the association of the following baseline variables with improvement: myositis clinical subgroup, demographics, myositis damage, clinical and laboratory parameters, core set measures, rituximab treatment, and myositis autoantibodies (antisynthetase, anti–Mi‐2, anti–signal recognition particle, anti–transcription intermediary factor 1γ [TIF‐1γ], anti‐MJ, other autoantibodies, and no autoantibodies). All measures were univariately assessed for association with improvement using time‐to‐event analyses. A multivariable time‐dependent proportional hazards model was used to evaluate the association of individual predictive factors with improvement. Results In the final multivariable model, the presence of an antisynthetase, primarily anti–Jo‐1 (hazard ratio [HR] 3.08, P < 0.01), anti–Mi‐2 (HR 2.5, P < 0.01), or other autoantibody (HR 1.4, P = 0.14) predicted a shorter time to improvement compared to the absence of autoantibodies. A lower physician's global assessment of damage (HR 2.32, P = 0.02) and juvenile DM (versus adult myositis) (HR 2.45, P = 0.01) also predicted improvement. Unlike autoantibody status, the predictive effect of physician's global assessment of damage and juvenile DM diminished by week 20. Rituximab treatment did not affect these associations. Conclusion Our findings indicate that the presence of antisynthetase and anti–Mi‐2 autoantibodies, juvenile DM subset, and lower disease damage strongly predict clinical improvement in patients with refractory myositis.

Abstract A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any known mutation. DNA from three affected members was subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were used to identify shared coding mutations. Sanger sequencing was performed within the extended family and ethnically matched controls. Subsequent genotyping was performed in a multi-ethnic case–control series consisting of 2928 patients and 2676 control subjects from Canada, Norway, Taiwan, Tunisia, and the USA. A novel mutation in receptor-mediated endocytosis 8/RME-8 (DNAJC13 p.Asn855Ser) was found to segregate with disease. Screening of cases and controls identified four additional patients with the mutation, of which two had familial parkinsonism. All carriers shared an ancestral DNAJC13 p.Asn855Ser haplotype and claimed Dutch–German–Russian Mennonite heritage. DNAJC13 regulates the dynamics of clathrin coats on early endosomes. Cellular analysis shows that the mutation confers a toxic gain-of-function and impairs endosomal transport. DNAJC13 immunoreactivity was also noted within Lewy body inclusions. In late-onset disease which is most reminiscent of idiopathic PD subtle deficits in endosomal receptor-sorting/recycling are highlighted by the discovery of pathogenic mutations VPS35, LRRK2 and now DNAJC13. With this latest discovery, and from a neuronal perspective, a temporal and functional ecology is emerging that connects synaptic exo- and endocytosis, vesicular trafficking, endosomal recycling and the endo-lysosomal degradative pathway. Molecular deficits in these processes are genetically linked to the phenotypic spectrum of parkinsonism associated with Lewy body pathology.

Telemedicine practitioners are familiar with multiple barriers to delivering care at a distance. Licensing and reimbursement barriers are well known and are being addressed at national and state levels by the American Telemedicine Association. Another telemedicine barrier comes in the form of quality measures for diabetes. Minnesota medical practices are currently being compared on the proportion of their patients with diabetes who have attained goals for blood pressure, low-density lipoprotein cholesterol, and hemoglobin A1C. The quality measure for blood pressure specifically excludes measurements taken by the patient, thus precluding blood pressure telemonitoring as a way to meet the blood pressure goal. To counter this barrier, advocacy in telemedicine is needed so that telemonitoring as a data collection tool is included in quality measures.

NIDDM is associated with excessive rates of endogenous glucose production in both the postabsorptive and postprandial states. To determine whether this is due to an intrinsic increase in hepatic sensitivity to glucagon, 9 NIDDM and 10 nondiabetic subjects were studied on three occasions. On each occasion, glycogen was labeled the evening before the study with subjects ingesting meals containing [6-3H]galactose. Beginning at 6:00 A.M. on the following morning, somatostatin was infused to inhibit endogenous hormone secretion. Insulin concentrations were maintained constant at basal levels (defined as that necessary to keep glucose at ∼5 mmol/l) in each individual. On one occasion, glucagon was infused at a rate of 0.65 ng ∼ kg−1 · min−1 throughout the experiment, resulting in glucagon concentrations of ∼130 pg/ml and a slow but comparable fall in endogenous glucose production with time in both groups. On the other two occasions, the glucagon infusion was increased at 10:00 A.M. to either 1.5 or 3.0 ng · kg−1 · min−1, resulting in an increase in glucagon concentrations to ∼180 and 310 pg/ml, respectively. The increment in endogenous glucose production (i.e., area above basal) did not differ in diabetic and nondiabetic subjects during either the 1.5 ng · kg−1 · min−1 (0.75 ± 0.055 vs. 0.78 ± 0.048 mmol/kg) or 3.0 ng · kg−1 · min−1 (1.06 ± 0.066 vs. 1.10 ± 0.073 mmol/kg) glucagon infusions. In contrast, the amount of [6-3H]glucose released from glycogen was lower (P &lt; 0.05) in the diabetic than nondiabetic subjects during both glucagon infusions. The specific activity of glycogen, calculated as the integrated release of [6-3H]glucose divided by the integrated release of unlabeled glucose, was lower (P &lt; 0.05) in diabetic subjects than in nondiabetic subjects during both the 1.5 ng · kg−1 · min−1 (19.0 ± 3.9 vs. 41.4 ± 5.7 dpmμmol) and 3.0 ng · kg−1 · min−1 (19.1 ± 3.1 vs. 36.5 ± 7.2 dpm/μmol) glucagon infusions, implying that a greater portion of the glucose released from glycogen was derived from the indirect pathway. We concluded that although NIDDM is not associated with an intrinsic alteration in hepatic sensitivity to glucagon, it does alter the relative contributions of the direct and indirect pathways to nocturnal glycogen synthesis.

It is well established that patients with non-insulindependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previous studies of impure isotopes to measure glucose turnover. To determine hepatic and extrahepatic responses to insulin in the absence of these errors, steady-state glucose turnover was measured simultaneously with [6-3H]- and [6-14C]glucose during sequential 5- and 4-h infusions of insulin at rates of 0.4 and 10 mil · kg−1 · min−1 in diabetic and nondiabetic subjects. At low insulin concentrations, [6-3H]- and [6-14C]glucose gave similar estimates of glucose turnover. Hepatic glucose release was equal to but not below zero in the nondiabetic subjects, but persistent glucose release (P &lt; 0.001) and decreased glucose uptake (P &lt; 0.001) was observed in the diabetic patients. At high insulin concentrations, both isotopes underestimated glucose turnover during the 1st h after initiation of the highdose insulin infusion. More time (P &lt; 0.05) was required to reachieve steady state in NIDDM than nondiabetic subjects. At steady state, [6-3H] but not [6-14C]glucose systematically underestimated (P &lt; 0.05) glucose turnover in both groups due to the presence of a tritiated nonglucose contaminant. The percentage of radioactivity in plasma due to tritiated contaminants was linearly related to turnover. When plasma [6-3H]glucose specific activity was corrected for the presence of the contaminant in each subject, both [6-3H]- and [6-14C]glucose indicated that diabetic patients had hepatic and extrahepatic insulin resistance. We conclude that in these experiments, although the presence of a low percentage of tritiated nonglucose contaminant in the tracer may alter estimates of the severity of hepatic and extrahepatic insulin resistance in patients with NIDDM, it does not obscure their presence

To determine the effects of acute metabolic acidosis and alkalosis on leucine metabolism in vivo, mongrel dogs were infused with [1-14C] leucine for 8 h, along with NaCI, HCI, or NaHCO3 over the last 4 h. Arterial pH did not change from the basal value during NaCI infusion but decreased (P &lt;.01) and increased (P &lt;.01) during HCI and NaHCO3 infusions, respectively. Total leucine carbon entry did not change from the basal value during saline infusion but increased (P &lt;.01) with acidosis and decreased (P &lt;.05) with alkalosis. Compared with saline controls, acidosis increased (P &lt;.01) leucine oxidation, whereas alkalosis decreased (P &lt;.01) leucine oxidation. During acidosis, total plasma essential and nonessential amino acid concentrations increased (P &lt;.05), whereas during alkalosis, total plasma essential and nonessential amino acid concentrations decreased (P &lt;.05). These studies suggest that acute alterations in arterial pH may affect the regulation of protein metabolism in vivo and must be considered in the interpretation of results from experiments in which alterations of acid-base homeostasis may have occurred.