High-Resolution Transcriptomic Landscape of the Human Submandibular Gland.

Saliva-secreting and transporting cells are part of the complex cellular milieu of the human salivary gland, where they play important roles in normal glandular physiology and diseased states. However, comprehensive molecular characterization, particularly at single-cell resolution, is still incomplete, in part due to difficulty in procuring normal human tissues. Here, we perform an in-depth analysis of male and female adult human submandibular gland (SMG) samples by bulk RNA sequencing (RNA-seq) and examine the molecular underpinnings of the heterogeneous cell populations by single-cell (sc) RNA-seq. Our results from scRNA-seq highlight the remarkable diversity of clusters of epithelial and nonepithelial cells that reside in the SMG that is also faithfully recapitulated by deconvolution of the bulk-RNA data sets. Our analyses reveal complex transcriptomic heterogeneity within both the ductal and acinar subpopulations and identify atypical SMG cell types, such as mucoacinar cells that are unique to humans and ionocytes that have been recently described in the mouse. We use CellChat to explore ligand-receptor interactome predictions that likely mediate crucial cell-cell communications between the various cell clusters. Finally, we apply a trajectory inference method to investigate specific cellular branching points and topology that offers insights into the dynamic and complex differentiation process of the adult SMG. The data sets and the analyses herein comprise an extensive wealth of high-resolution information and a valuable resource for a deeper mechanistic understanding of human SMG biology and pathophysiology.

Cardiac remodelling of Atlantic halibut Hippoglossus hippoglossus induced by experimental anaemia with phenylhydrazine.

Phenylhydrazine injections (0.3 mg kg(-1) , followed by a second injection of 0.1 mg kg(-1) 7 days later) induced a reproducible and stable anaemia in Atlantic halibut Hippoglossus hippoglossus, reducing the haematocrit and haemoglobin by 70.0 and 75.5%, respectively, over 3 weeks. There were no changes in blood electrolyte or lactate concentrations, although anaemic fish showed a 37.5 and 33.0% increase in cardiac somatic index and ventricular somatic index, respectively, compared with dimethyl sulphur oxide (DMSO) and saline vehicle controls. Changes in cardiac somatic indices did not correlate with the ratio of ventricular length:height and length:width did correlate with haematocrit and haemoglobin indicating that changes in cardiac shape may occur as a function of anaemic hypoxemia.

Life-threatening reaction to vancomycin given for noninfectious fever.

OBJECTIVE: To report a case of vancomycin-induced anaphylaxis (or anaphylactoid reaction) in a patient with a fever of unrecognized noninfectious origin. CASE SUMMARY: An 83-year-old white man, who was a patient of the Veterans Affairs Medical Center, developed a serious anaphylactic (or anaphylactoid) reaction while receiving intravenous vancomycin as empiric therapy for a nosocomial fever of unknown origin. The fever was subsequently proved to have been due to acute polyarticular gout rather than an infection. DISCUSSION: This patient developed respiratory distress and an increased serum troponin concentration, suggestive of a myocardial enzymatic leak as a result of vancomycin therapy. Vancomycin was given before the noninfectious cause of his fever was recognized. CONCLUSIONS: Even with cautious slow infusion, intravenous vancomycin can precipitate life-threatening infusion-related reactions in some patients. Because of this, and to reduce selective pressure for vancomycin resistance, sources of fever that do not require treatment with vancomycin should be diligently investigated prior to the institution of empiric vancomycin therapy in febrile patients, particularly when the past medical history is suggestive of an alternative diagnosis.

Screening for extreme postdialysis urea rebound using the Smye method: patients with access recirculation identified when a slow flow method is not used to draw the postdialysis blood.

To look for patients with extreme urea rebound, we drew intradialytic samples one third of the way into dialysis during routine modeling for 3 months. The samples taken postdialysis were obtained after stopping the blood pump, without any slow flow period. Using the Smye equations, the intradialytic urea level was used to predict urea rebound, expressed as Kt/V-equilibrated minus Kt/V-single pool (deltaKt/V). Results were averaged for the 3-month period in 369 patients. Mean estimated deltaKt/V was -0.20 +/- 0.13, which was similar to but slightly higher than the predicted value (-0.6 x K/V + 0.03) of -0.19 +/- 0.04. In 27 patients, extreme rebound (mean deltaKt/V < -0.40) was found. Sixteen of these patients consented to further study, but only after access revision in four patients. In these patients, additional slow flow samples after 15 seconds and 2 minutes of slow flow, respectively, were drawn one third of the way into dialysis and postdialysis, and a sample was drawn 30 minutes after dialysis. On restudy, postdialysis rebound was still high with full flow samples deltaKt/V = -0.40 +/- 25, but was much lower (-0.18 +/- 0.07) and similar to predicted rebound (-0.19 +/- 0.05; P = NS) when based on 15-second slow flow samples. Eight of the 16 had marked (>15%) access recirculation by urea sampling, and deltaKt/V based on full flow post samples correlated with access recirculation (r = -0.91). The results suggest that the Smye method is valuable for identifying patients with aberrantly large postdialysis rebound values. When the postdialysis samples are drawn without an antecedent slow flow period, most patients with extreme rebound values turn out to have marked access recirculation.

Intrasubject reproducibility of growth hormone-releasing hormone-stimulated growth hormone in older women, older men, and younger men.

Intrasubject reproducibility of growth hormone (GH) response to growth hormone-releasing hormone (GHRH) was studied in healthy older women (n = 9), older men (n = 8), and younger men (n = 10). Subjects received IV injections of 0.1 ml/kg saline, 1 micrograms/kg GHRH, and 2 micrograms/kg GHRH, three times each, and blood was sampled at 0, 15, 30, 45, 60, and 120 min for GH concentration. There was no significant difference in peak GH response between the 1- and 2-micrograms/kg GHRH dosages. GH responsiveness, group variance of peak GH, and intrasubject variability were greatest for younger men, less for older men, and least for older women at both dosages of GHRH. Because of the large intrasubject variability observed in this study, it appears necessary to test subjects more than once to obtain a valid characterization of GH responsiveness.

Anonymous cocaine screening in a private obstetric population.

OBJECTIVE: To establish the prevalence of cocaine use in private obstetric patients during their prenatal care and at admission to delivery units. METHODS: Urine samples were collected anonymously during routine sampling from 1425 patients in six private hospitals and four private physicians' offices. RESULTS: Positive cocaine metabolites were identified in three of 555 urine specimens (0.54%) obtained from hospitals and in two of 870 (0.23%) obtained from private offices during prenatal examinations. The total positive urine cocaine results were five of 1425 (0.35%). CONCLUSIONS: Universal screening in a private obstetric population similar to that found in Denver would not be cost-effective. We urge health care providers to ask patients about substance abuse and to screen patients who are at high risk for substance use.

Amniotic fluid glucose concentration as a marker for intra-amniotic infection.

This study evaluated the use of amniotic fluid (AF) glucose concentration as a rapid indicator of intra-amniotic infection. Amniotic fluid glucose concentrations were measured in 86 pregnancies and compared with AF cultures. There were 14 positive cultures with a mean AF glucose of 7.1 mg/dL (range 1-24) and 72 negative cultures with a mean AF glucose of 30.4 mg/dL (range 5-66), a significant difference (P less than .001). An AF glucose of less than or equal to 5 mg/dL had a positive predictive value of 90%; an AF glucose of greater than 20 mg/dL had a 98% negative predictive value. Amniotic fluid glucose can be obtained rapidly and inexpensively, and may be of use in the diagnosis of intra-amniotic infection.

Multifetal reduction of triplets and pregnancy outcome.

Multifetal pregnancy reduction has been suggested as a strategy to improve pregnancy outcome in grand multiple gestations of three or more fetuses. We prospectively investigated multifetal pregnancy reduction in 13 women with triplet pregnancies in the first trimester following ovulation induction, in vitro fertilization, or gamete intrafallopian transfer procedures. Eleven women whose triplet pregnancies followed similar reproductive technologies and who declined or were not offered the procedure were managed expectantly. Mean (+/- standard deviation) infant birth weight was 2227 +/- 478 g in the multifetal reduction group and 2239 +/- 399 g in the group managed expectantly. Gestational age was 35.5 +/- 2.3 weeks in the study group and 35.7 +/- 2.5 weeks in the triplets managed expectantly. Newborn hospital days as well as newborn and maternal complications were not statistically different between the management groups. Maternal interventions included tocolytic medication, home uterine activity monitoring, and extended hospitalization, and were more common in the triplets managed expectantly than in the study group of triplets reduced to twins. Multifetal pregnancy reduction for triplet pregnancies does not necessarily improve pregnancy outcome, though it may be offered on the basis of parental choice.

Selective embryocide in the nonsurgical management of combined intrauterine-extrauterine pregnancy.

Early diagnosis of ectopic pregnancy has provided the opportunity for nonsurgical management in selected cases. We used selective embryocide to manage the ectopic embryo in a patient with a combined intrauterine-extrauterine gestation following in vitro fertilization. The intrauterine pregnancy continued to term without incident.

Single fetal demise in twin gestation.

A single fetal demise in a twin gestation occurs infrequently: it is recognized in fewer than 7% of twins past the first trimester. Increased morbidity is associated primarily with monozygotic twins who have vascular anastomoses associated with diamniotic-monochorionic placentation, and with monoamniotic twins. Morbidity and mortality of these twin gestations potentially can be reduced with identification of the at-risk pregnancy and with intensive antenatal surveillance. The most difficult management problem is the twin-to-twin transfusion syndrome, which will require improved technologic developments to resolve.

Prolongation of premature gestation in women with hemolysis, elevated liver enzymes and low platelets. A report of five cases.

Severe pregnancy-induced hypertension complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) is considered an indication for immediate delivery, often resulting in premature or even previable infants. In five cases, temporary reversal of the HELLP syndrome was achieved using low-dose aspirin and corticosteroids. Pregnancy was prolonged an average of 4 weeks; three pregnancies were prolonged, beginning at less than or equal to 25 weeks, for an average of 5.5 weeks. Two of seven infants died, one from pulmonary hypoplasia due to oligohydramnios and the other from complications of prematurity. No long-term maternal morbidity was encountered, though one patient had peripartum disseminated intravascular coagulation and a seizure. A review of the literature supports the usefulness of low-dose aspirin in this setting; the impact of corticosteroids as part of the reversal strategy has not been discussed previously.

Intrauterine resuscitation with tocolysis. An alternate month clinical trial.

Fifty patients were compared for the purpose of investigating the usefulness of intrauterine resuscitation with tocolysis (IURT). Terbutaline was given, as an intravenous bolus, to 31 women in labor in whom fetal distress was diagnosed and urgent delivery by cesarean section was indicated. In alternate months, a control group of 19 women with similar diagnoses was urgently delivered after standard interventions such as maternal positioning, oxygen administration, hydration, and discontinuation of oxytocin. Improvement in perinatal outcome was shown in infants after IURT. Apgar scores were less than 7 in 42% of the study group and in 71% of the control group at 1 minute (P = .04). Five-minute Apgar scores less than 7 occurred in 7% of the study group and 24% of the control group. A low venous pH was seen in 55% of the control group compared with 29% of the infants resuscitated with terbutaline. Estimated maternal blood loss and hematocrit change was not different in the two groups. Maternal blood pressure and pulse changes following IURT were modest and of doubtful significance. We conclude that intravenous terbutaline administered as a bolus injection at the time of fetal distress in labor improves infant outcome as evidenced by more vigorous Apgar scores and less acidemia without significant adverse physiologic effects on the mother.

Cesarean birth for failed progress in labor.

"Failure to progress" is the leading indication for primary cesarean section and has a major impact on the escalating cesarean birth rate in the United States. We investigated the labor and delivery records of nulliparous women at term with vertex presentations admitted to the clinic and private services of our hospital to determine the importance of different management strategies associated with operative deliveries. Birth weights and immediate neonatal outcome were identical between the clinic and private services. The cesarean birth rate on the clinic service was 5.2%, compared with 17.1% on the private service; 80% of the abdominal deliveries on the private service were for "failure to progress." Epidural use rates were similar on both services and were associated with a 70% incidence of oxytocin augmentation. Once oxytocin augmentation became part of labor management, a 14-fold increase in cesarean sections was observed for the private service, but oxytocin had no impact on the cesarean birth rate in the clinic service. The placement of an intrauterine pressure catheter and an approach to the use of oxytocin that might be characterized as "selective active management" were necessary to achieve efficient uterine action in a timely fashion, permitting a high likelihood of vaginal birth on the clinic service.

Neonatal aortic thrombosis associated with the lupus anticoagulant.

The lupus anticoagulant has been associated with clinical thrombosis and poor pregnancy outcome. There are no published reports of its detection in neonates born to affected mothers. We report such a case associated with neonatal aortic thrombosis.

Prostaglandin E2 in tylose gel for cervical ripening before induction of labor.

Two hundred seventeen women who received 3 mg of prostaglandin E2 (PGE2) gel applied to the cervix followed by adjunctive oxytocin were compared to 94 patients whose labor was induced with oxytocin alone (OA). Postdatism, pregnancy-induced hypertension and rupture of the membranes were the major indications for induction of labor, accounting for 70% of the PGE2 group and 88% of the OA group. Mean initial cervical scores were found to be significantly less favorable among PGE2 patients as compared with OA patients. Though PGE2 was associated with a significant improvement in mean cervical scores, responsiveness of the cervix to PGE2, as determined by clinical examination, was not necessary for a successful induction. Failed inductions were infrequent in both groups. Nulliparous PGE2 patients with unfavorable cervical scores had fewer cesarean sections (CSs) and shorter labors than did their OA counterparts. Complications were uncommon but largely due to the subsequent use of oxytocin. Patients with prior CSs were safely induced following PGE2 cervical ripening.

Use of amniotic fluid analysis in the management of preterm rupture of the membranes.

The management of preterm rupture of the membranes (PROM) must weigh the risks of respiratory distress from immediate delivery against those of expectant management. We divided 115 patients with PROM between 24 and 36 weeks of gestation into interventionist and expectant management groups on the basis of the amniotic fluid maturity. There was no difference between these groups with respect to gestational age and birth weight. Mature amniotic fluid was demonstrated in 41% of the patients. Interventionist management of infants with mature amniotic fluid irrespective of gestational age was associated with an improved outcome when compared to expectant management. Infants with PROM who can be shown to have mature amniotic fluid should be delivered promptly to avoid the small but real risks of expectant management.