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Although most of the poor outcomes with cutaneous squamous cell carcinoma (CSCC) occur in high-stage tumors, 26% of nodal metastases and 8% of disease-specific deaths develop in Brigham and Women's Hospital (BWH) T2a tumors.To determine risk factors associated with poor outcomes (nodal metastasis, distant metastases, and disease-specific deaths) in BWH T2a CSCC.A 17-year retrospective multi-institutional cohort study of primary CSCC BWH T2a tumors. A predictive model based on tumor characteristics was developed to identify those at higher risk of poor outcomes.Presence of 1 major criterion (primary tumor diameter ≥40 mm, invasion depth beyond subcutaneous fat, poor differentiation, or large-caliber perineural invasion) and ≥ 1 minor criterion (invasion depth in subcutaneous fat, moderate differentiation, small-caliber perineural invasion, or lymphovascular invasion) was most predictive of developing poor outcomes (area under the curve, 0.53; C-statistic, 0.60). This model has a sensitivity of 7.7%, specificity of 97.4%, and a positive and negative predictive value of 33.3% and 86.1%, respectively. The 5-year cumulative incidence of poor outcomes in these tumors is 8.0% (95% CI, 5.1-13.7) compared to 2.8% (95% CI, 1.9-4.1) in other T2a tumors (sub-hazard ratio, 3.0; 95% CI, 1.5-5.8).Multi-institutional cohort study was not externally validated.BWH T2a-high CSCCs have an 8% chance of developing poor outcomes.

Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid malignancies; risk of PTC recurrence over a 30-year period is approximately 30%, of which 70% occur as nodal metastases. Patients with nodal disease who are treated with therapeutic dissection are at higher risk for recurrence, but optimal nodal yield has not been defined. We aim to determine variables predictive of nodal recurrence of PTC within the first 5 years of surgery, with a focus on lymph node ratio (LNR), to inform clinical decision-making.Retrospective chart review identified 41 patients with nodal recurrence of PTC and 284 without nodal recurrence following thyroid surgery from 2000 to 2015. Cohorts were compared with regards to clinical history, surgical findings, and tumor characteristics.The fraction of the patients who underwent therapeutic central or lateral lymph node dissection was significantly higher in the nodal recurrence cohort. Maximum tumor size, presence of extrathyroidal extension, largest lymph node focus, LNR, postoperative thyroglobulin level, and administration of postoperative radioactive iodine were significantly increased in the PTC nodal recurrence group. LNR greater than 0.3 held the highest level of significance as a binary cutoff and captured the larger proportion of patients in the nodal recurrence cohort (68.3%).This study demonstrates characteristics to help assess risk of nodal recurrence of PTC and suggests LNR of lower than 0.3 is optimal to reduce risk of recurrence. The next steps include cohort studies to validate findings and weight variable analysis to optimize the extent of surgical therapeutic dissection.4 Laryngoscope, 132:1883-1887, 2022.

This study aimed to evaluate functional and aesthetic patient-reported outcomes using validated metrics after component dorsal hump reduction (DHR) with spreader graft placement, which have not been previously reported.Prospective cohort study.This prospective cohort study was conducted in a tertiary care medical center. Participants underwent septorhinoplasty (SRP) with spreader graft placement with cosmetic, component DHR (cosmetic DHR), or SRP with spreader graft placement without dorsal hump reduction (noncosmetic, non-DHR). The Nasal Obstruction Symptom Evaluation (NOSE) scale and the FACE-Q Satisfaction with Nose, Nostrils, and Social Functioning scales were administered to patients preoperatively and postoperatively (at 2, 4, 6, and/or 12 months). Pre- and postoperative NOSE and FACE-Q scores were compared.A total of 226 patients underwent SRP with spreader graft placement; 113 (50.0%) with cosmetic DHR and 113 (50.0%) noncosmetic, non-DHR (control). Patients who completed the NOSE and FACE-Q surveys preoperatively and at least at one postoperative time point were included. Both cohorts had a statistically and clinically significant improvement in NOSE and FACE-Q scores. There were similar improvements in NOSE scores in both cohorts. Postoperative FACE-Q scores were higher in the cosmetic DHR cohort despite lower preoperative FACE-Q scores when compared to the control cohort.Although there are multiple techniques for DHR, component DHR with spreader graft placement has long been considered the standard. Therefore, it is important to note the significant postoperative cosmetic and functional improvements reported by patients who have undergone this procedure to compare to newer techniques as they evolve.3 Laryngoscope, 132:2157-2161, 2022.

Objectives/hypothesis Although upper lateral cartilages are commonly released from the dorsum of the septum during spreader graft placement in septorhinoplasty (SRP), there has been a focus on maintaining integrity of connections in the middle vault. Avoiding release of upper lateral cartilages in certain patient groups may represent an early step in this paradigm shift. We aim to assess satisfaction with nasal appearance and correction of nasal obstruction in patients who underwent SRP with spreader graft placement without upper lateral cartilage release and compared it to the traditional upper lateral cartilage release cohort. Study design Prospective cohort study. Methods A total of 559 patients who underwent SRP with spreader graft placement with upper lateral cartilage release and 30 patients who underwent SRP with spreader graft placement without release between 2012 and 2020 were administered the Nasal Obstruction Symptom Evaluation (NOSE), FACE-Q Satisfaction with Nose, and FACE-Q Social Functioning scales pre- and postoperatively. Pre- and postoperative NOSE FACE-Q, and negative inspiratory force (NIF) scores and changes were compared between groups. Results Results demonstrated clinically and statistically significant improvement at follow-up for both groups. There was no significant difference between groups in mean improvement of NOSE, FACE-Q, and NIF scores at time of last follow-up. Conclusion SRP with spreader graft placement with and without upper lateral cartilage release provide clinically and statistically significant improvement, and no significant difference in functional outcome. This suggests that upper lateral cartilages do not need to be released to achieve functional improvement and that surgeons should consider whether release is necessary to achieve goals of surgery. Level of evidence 3 Laryngoscope, 2021.

Objective Saddle nose deformity is a well‐described condition that most commonly results from trauma or prior surgery. For larger saddle nose deformity defects, bone grafts are a reconstructive option that provide adequate structure for repair. One new technique for repair of these deformities is a vomerian bone onlay graft. We aim to provide a review of literature on autogenous repair of saddle nose deformities, as well as introduce a new technique in which the vomer bone is used as an onlay bone graft. Methods Literature review and case series. Five cases in which vomer onlay grafts were used for repair of saddle nose deformity were reviewed between January 2013 and December 2015. Aesthetic outcomes and postoperative complications were evaluated at subsequent follow‐up visits in clinic. Results In all cases where vomer bone was harvested, the vomer onlay graft provided adequate structure to traverse the saddle nose deformity. No postoperative complications were observed in an 18 month follow‐up period. Conclusion Vomerian bone onlay grafts are a reconstructive option for saddle nose deformity and nasal dorsum defects. While septal cartilage is commonly used, and ethmoidal bone has been previously described as an option for composite graft reconstruction, vomer bone onlay grafting has not been well described in the literature. This method may be of use when previous nasal surgery has been performed and standard septal cartilage is not possible to harvest. The aesthetic outcomes following nasal dorsum reconstruction using onlay grafts are favorable, but long‐term outcomes of these grafts require further study. Level of Evidence IV., Vomerian bone onlay grafts are a reconstructive option for saddle nose deformity and nasal dorsum defects. While septal cartilage is commonly used, and ethmoidal bone has been previously described as an option for composite graft reconstruction, vomer bone onlay grafting has not been well described in the literature. The aesthetic outcomes following nasal dorsum reconstruction using onlay grafts are favorable, but long‐term outcomes of these grafts require further study.

OBJECTIVES/HYPOTHESIS Standard spreader grafts (SSGs) are commonly used in septorhinoplasty to treat internal nasal valve narrowing and have been shown to improve nasal airway obstruction. Extended spreader grafts (ESGs) have also been proven effective for correcting nasal deviation. To date, the effectiveness of ESGs using patient-reported outcome measures has not been demonstrated, and results of ESGs have not been compared to SSGs. This study aims to assess satisfaction and nasal appearance in patients who have undergone septorhinoplasty with SSG versus ESG. STUDY DESIGN Prospective cohort study. METHODS Five hundred sixty-eight patients who underwent septorhinoplasty with SSGs and 126 patients who underwent septorhinoplasty with ESGs between 2012 and 2018 were administered the Nasal Obstruction Symptom Evaluation (NOSE) scale and FACE-Q Satisfaction With Nose, FACE-Q Satisfaction With Nostrils, and FACE-Q Social Functioning scales pre- and postoperatively. Pre- and postoperative NOSE and FACE-Q scores, negative inspiratory force (NIF), and changes in these values were compared between groups. RESULTS Results demonstrated clinically and statistically significant improvement at follow-up for both groups. There was no significant difference between the SSG and ESG groups in mean improvement of NOSE scores, FACE-Q scores, and NIF at follow-up of 6 months and at 12 months. CONCLUSIONS This study demonstrates that SSGs and ESGs both provide clinically and statistically significant improvement, and no significant difference in functional outcome. Both techniques can be effective. The etiology of the nasal obstruction and/or deformity should be considered when deciding which type of spreader graft to use. LEVEL OF EVIDENCE 3 Laryngoscope, 131:765-772, 2021.

The objective of this paper is to investigate the differences between unilateral and bilateral nasal obstruction with subjective symptomatology in nasal obstruction. This is a retrospective chart review of prospectively collected data of patients with nasal obstruction presenting to a facial plastic and reconstructive surgery clinic for evaluation and treatment. Patient demographics including age and gender were recorded along with nasal physical exam findings. These included internal valve narrowing (IVN), external valve narrowing, internal valve collapse, external valve collapse, and septal deviations (inferior and superior). Findings were reported for the left, the right, and both sides. Nasal valve and septal findings were recorded on 3- and 4-point Likert scales, respectively, for each side of the nose. A total of 1,646 patients were included in the study. On univariate analysis, a significant correlation was seen between Nasal Obstruction Symptom Evaluation (NOSE) scores and all individual exam findings (p

Skull base osteomyelitis (SBO) is an invasive infection of the external auditory canal, with involvement of the skull base, typically in the elderly diabetic population. Diagnosis may be challenging, as it requires a combination of clinical, laboratory, and radiographical findings. The mainstay of treatment is long-term antibiotic therapy, but surgical debridement of the temporal bone may be necessary in refractory cases. Commonly reported complications include cranial neuropathies, meningitis, temporal lobe abscess, and dural venous sinus thrombosis. A rare and life-threatening complication of SBO is petrous internal carotid artery (ICA) blowout, which has been described as presenting with bleeding from the ear. Here, we describe the case of a 77-year-old woman with SBO complicated by a petrous ICA blowout, which presented with fulminant epistaxis. To our knowledge, this is the second reported case of a massive hemorrhage from a petrous ICA blowout secondary to SBO and the first presentation with massive epistaxis. We present this case to raise awareness of this potential impending complication in patients with SBO and recommend consideration of this etiology when assessing patients with massive epistaxis in the appropriate clinical setting. Level of evidence: III

BACKGROUND Increased body mass index (BMI) has been associated with postoperative complications in multiple surgical specialties. In otologic surgery involving the stapes, where appropriate patient positioning and surgical dexterity are necessary for proper prosthesis placement, patients with higher BMI could make surgery more challenging. The purpose of this study is to evaluate the impact of BMI on outcomes after stapes surgery. METHODS Medical records were examined from January 2015 to December 2017 in patients undergoing stapedectomy or stapedotomy at two tertiary care facilities. A retrospective cohort analysis comparing hearing outcomes on postoperative audiogram following procedural intervention with BMI was performed. The primary outcome was postoperative air-bone gap (dB) on audiogram. RESULTS Two hundred sixty three stapedotomy and stapedectomy patients were included in the study. Six percent had BMI less than 18.5 (underweight), 30% had BMI between 18.6 and 24.9 (normal weight), 38% had BMI between 25 and 29.9 (overweight), 24% had BMI above 30 (obese). The mean preoperative and postoperative air-bone gap (ABG) was 27.0 dB (standard deviation [SD] 15) and 10.4 dB (SD 10.6), respectively, with a postoperative ABG less than or equal to 20 dB in 87% of cases. There were no significant differences in postoperative ABG results when comparing the BMI categories (p = 0.11). CONCLUSIONS Stapedotomy and stapedectomy are effective surgeries that can be performed by experienced surgeons with successful hearing improvement. While high BMI patients may be a challenge to position appropriately for their surgery, this does not translate to altered otologic outcomes for these patients.

OBJECTIVE(S) To characterize procedural trends in facial plastic and reconstructive surgery procedures in relation to the United States economy. METHODS Retrospective cohort study examining annual procedure rates were determined from the American Society of Plastic Surgeons (ASPS) National Clearinghouse of Plastic Surgery Procedural Statistics from January 1 2007 to December 30, 2017. Procedures were compared to economic activity of the United States as measured by gross domestic product (GDP) were compared using Kolmogorov-Smirnov goodness of fit testing and piecewise multivariate regression modeling. RESULTS Annual trends in procedural rates showed an overall decrease in the rates of rhinoplasty (284,960 to 218,924), blepharoplasty (240,660 to 209,571), and otoplasty (28,571 to 23,433) from 2007 to 2017. Total cosmetic surgery remained fairly stable, while minimally invasive cosmetic surgery increased in frequency over the study period. On piecewise regression analysis, rhinoplasty (P = .02), rhytidectomy (P = .007), invasive cosmetic surgery (P

OBJECTIVE Burnout is defined as work-related emotional exhaustion, depersonalization, and decreased sense of accomplishment. Virtual reality (VR) has emerged as an effective treatment modality for various conditions related to anxiety, however, few studies have assessed its role for stress management in residents. We hypothesize that VR-based mindfulness meditation can reduce resident burnout in real-world settings. STUDY DESIGN Prospective randomized crossover trial. METHODS Resident participants completed the validated Maslach Burnout Inventory (MBI). One group used a VR-based meditation app; the second group received no intervention. After a 2-month rotation, all subjects completed an MBI and crossed over to the other arm. Wilcoxon rank-sum tests were used to compare MBI scores before and after intervention, and to compare results by gender and postgraduate year. Mann-Whitney U tests were used to assess qualitative differences between participants. RESULTS Eighteen residents completed the study. Five participants were female and 13 were male. Weekly use of VR-guided meditation and paced breathing was associated with a significant decrease in emotional exhaustion (P = .009), and on subgroup analysis, male gender specifically was associated with a decrease in emotional exhaustion (P = .027). In the post-intervention survey, 42.9% subjects reported that VR encouraged them to employ paced breathing techniques, 71.4% reported that they would use the technology if regularly available, and 21.4% reported they would use paced breathing in the future. CONCLUSION VR-based therapy may serve as a successful tool in stress management and reduce the rate of burnout among otolaryngology residents. LEVEL OF EVIDENCE NA Laryngoscope, 131:1972-1976, 2021.

OBJECTIVE Evaluate surgical outcomes in patients with enlarged cochlear aperture (ECA) after cochlear implantation. DATABASES REVIEWED PubMed, EMBASE, and Scopus. METHODS A systematic review was performed using standardized methodology. Studies were included if they included subjects with ECA who underwent cochlear implantation. Exclusion criteria included non-English articles, abstracts, letters/commentaries, case reports, and reviews. Bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. RESULTS Out of 1,688 identified articles, 7 articles representing 23 subjects with ECA were included. Publication rates increased between the period of study from 2009 to 2018. Four studies were level 4 evidence and three studies were level 3 evidence. In total, 20 subjects underwent cochlear implantation. Cerebrospinal fluid gushers were encountered in the majority of cases that reported complications (16/17, 94.1%); one patient developed postoperative meningitis, and another experienced postimplantation facial nerve stimulation. No study provided measurements on cochlear aperture size or defined size criteria used to identify ECA. Four studies recognized X-linked deafness to be associated with ECA, and the most common mutation was in POU3F4 gene. CONCLUSION An association exists between ECA and cerebrospinal fluid gusher, underscoring the importance of reviewing preoperative imaging. Size criteria are not well defined, and there is a paucity of data with respect to normative measurements. Many cases of ECA may give a genetic link. Although level of evidence of current studies remains modest, ECA reports have increased and will likely continue to expand with advancements in imaging and genetic testing.

Background Sialorrhea is a common comorbidity among children with neurologic disorders. Botulinum toxin injections and surgical procedures are recommended for the management of pathological sialorrhea in patients who fail conservative management or with concerns for salivary aspiration. The following review evaluates outcomes following botulinum toxin injections and surgical interventions for sialorrhea over a 10-year period with a focus on treatment options and outcomes for patients with anterior and posterior drooling. Methods The study included all patients less than 25 years of age who underwent a procedure for drooling (Current Procedural Terminology (CPT) codes 42440, 42450, 42509, 42510, 64611 matched with the International Classification of Diseases (ICD)-9 and ICD-10 codes 527.7 and K11.7) from January 1, 2006 to December 31, 2015. A chart review collected demographics, drooling medication use, and type of drooling (anterior, posterior, both). Outcome variables included pre- and post-procedure number of bibs, parent-reported outcomes, post-intervention drooling medication requirement, post-procedure length of stay, and complications. Results Seventy-one patients were included in our analysis, with 88 total procedures performed. The average age at first intervention was 8.9 years; 43 patients were male and 40 patients had cerebral palsy. Thirty-one patients experienced posterior drooling or anterior/posterior drooling. These patients were more likely to undergo surgery as the first invasive intervention. The most commonly performed interventions were botulinum toxin injections (28 patients, 39%) and sublingual gland excision (SLGE) with submandibular duct ligation (SMDL) (36 patients, 51%). Improvement following injections was noted in 56% of patients versus 73% of patients following any surgical intervention. Conclusion Management of drooling is complex with 18 different procedures performed over 10 years. Surgical interventions, specifically SLGE with SMDL and submandibular gland excision (SMGE), result in substantial improvement; these are commonly performed as the first intervention in patients with posterior drooling. By reviewing our experience, we hope to guide management decisions and help manage patient and caregiver expectations.

Capsular contracture is a common adverse outcome following implant breast reconstruction, often associated with radiation treatment. The authors hypothesize that muscle fibrosis is the main contributor of breast reconstruction contracture after radiation. Retrospective chart review identified patients that underwent DTI reconstruction with pre-or post-operative breast irradiation. Signs of capsular contracture were assessed using clinic notes and independent graders reviewing two-dimensional images and anatomic landmarks. Capsular contracture rate was greater in the subpectoral vs. prepectoral group (n = 28, 51.8% vs. n = 12, 30.0%, p = 0.02). When compared to prepectoral DTI reconstruction in irradiated patients, subpectoral implant placement was nearly 4 times as likely to result in capsular contracture (p

IMPORTANCE: By measuring health utility values (HUVs) for patients with nasal obstruction after septorhinoplasty, the association of nasal congestion with overall health can be measured and the functional outcomes of septorhinoplasty can be determined. OBJECTIVE: To use the EuroQol 5-Dimension (EQ-5D) questionnaire to evaluate nasal obstruction outcomes after septorhinoplasty and to determine HUVs. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included patients who underwent septorhinoplasty for nasal obstruction at a single institution by a single surgeon from January 1, 2013, through December 31, 2017. Participants completed the EQ-5D questionnaire immediately before surgery and postoperatively at 2, 4, 6, and 12 months. The EQ-5D scores were converted to HUVs using population-based data for individuals with chronic diseases. Data were analyzed from May 1 through December 31, 2018. EXPOSURE: Functional septorhinoplasty. MAIN OUTCOMES AND MEASURES: Preoperative and postoperative EQ-5D scores were compared to evaluate improvement in overall health after septorhinoplasty. RESULTS: A total of 463 patients (53.8% women; mean [SD] age, 36.8 [15.7] years) who underwent septorhinoplasty and completed EQ-5D surveys at baseline and postoperatively were included in the study population. Overall mean (SD) preoperative HUV was 0.872 (0.01), compared with 1.00 for those with a perfect state of health. On univariate analysis, female sex (mean [SD] HUV, 0.853 [0.01]; P = .004), previous nasal surgery (mean [SD] HUV, 0.85 [0.16]; P = .02), previous septoplasty (mean [SD] HUV, 0.88 [0.15]; P = .02), and previous sinus surgery (mean [SD] HUV, 0.79 [0.20]; P = .009) were associated with significantly lower baseline HUVs. On multivariate regression including these variables, only previous septoplasty was significantly associated with a positive change in mean (SD) HUV (0.88 [0.15] vs 0.85 [0.16]; P = .02). Mean (SD) HUV was significantly improved at 2 months postoperatively to 0.91 (0.14; P = .001) and remained significantly improved from baseline at 12 months, at 0.93 (0.13; P

Introduction A Sistrunk procedure is the standard operative management of patients with thyroglossal duct cysts. Drain placement is commonly employed with the goal of reducing postoperative complications. This study investigates the association between drain use and relevant postoperative complications following pediatric Sistrunk procedures. Methods Retrospective cohort study evaluating 295 pediatric patients treated between 2007 and 2016 at two tertiary care children’s hospitals. Results The mean age of the study population was 5.6 years (SD 4.0). A drain was utilized in 234 cases (79.3%). The mean procedural duration was 108 minutes (SD 48), and significantly longer in patients receiving a drain. Early postoperative complications included seroma (5.8%), secondary infection (3.4%), wound breakdown (2.0%) and hematoma (0.3%). The risk of such complications did not significantly differ between patients without drain placement (9.8%) versus those who underwent surgical drain placement (12.0%) after accounting for age and history of preoperative infection (adjusted RR = 0.86; 95% CI: 0.37, 1.98; p=0.72). In the subgroup analysis, findings were consistent across institutions, age category, history of infection, and primary versus secondary procedure. Conclusion This dual institutional study found drain placement during a Sistrunk procedure may not reduce rates of common postoperative complications, even in longer duration cases in which a drain is more frequently placed. This data suggests a Sistrunk procedure may be safely performed without drain placement in select cases.

Alterations of the lingual frenulum may contribute to oromyofacial dysfunction, speech and swallowing impediments, underdevelopment of the maxillofacial skeleton, and even predispose to sleep breathing disorder. This study aims to assess the utility of existing instruments for evaluation of restricted tongue mobility, describe normal and abnormal ranges of tongue mobility, and provide evidence in support of a reliable and efficient measure of tongue mobility. A prospective cohort study of 1052 consecutive patients was evaluated during a 3-month period. Age, gender, ethnicity, height, weight, BMI, maximal interincisal mouth opening (MIO), mouth opening with tongue tip to maxillary incisive papillae at roof of mouth (MOTTIP), Kotlow’s free-tongue measurement, and presence of severe tongue-tie were recorded. Secondary outcome measures include tongue range of motion deficit (TRMD, difference between MIO and MOTTIP) and tongue range of motion ratio (TRMR, ratio of MOTTIP to MIO). Results indicate that MIO is dependent on age and height; MOTTIP and TRMD are dependent on MIO; Kotlow’s free-tongue measurement is an independent measure of free-tongue length and tongue mobility. TRMR is the only independent measurement of tongue mobility that is directly associated with restrictions in tongue function. We propose the use of tongue range of motion ratio as an initial screening tool to assess for restrictions in tongue mobility. “Functional” ankyloglossia can thus be defined and treatment effects followed objectively by using the proposed grading scale: grade 1: tongue range of motion ratio is >80%, grade 2 50–80%, grade 3 < 50%, grade 4 < 25%.

The aim was to examine cross-cultural variation in linguistic responsiveness to young children in 10 English-speaking mother–child dyads and 10 Italian-speaking mother– child dyads. All 20 children were late talkers who possessed delays in expressive vocabulary development but age-appropriate cognitive and receptive language skills. Dyads were filmed in 15 minute free play contexts, which were transcribed and coded for measures of maternal linguistic input (e.g. rate, MLU, labels, expansions) and child language productivity (e.g. utterances, different words used). The results revealed that the Italian mothers used more utterances, spoke more quickly and used a more diverse vocabulary than the Canadian mothers. The Italian children mirrored their mothers and also used more utterances and a more diverse vocabulary than the Canadian children. Mothers in both groups used similar percentages of responsive labels and expansions. However, Italian mothers responded to fewer of their children's vocalisations, usin...

Elevated plasma vasopressin concentrations have been documented in antipsychotic drug-treated patients as well as drug-free acutely psychotic patients. To evaluate the effects of antipsychotic drugs on plasma vasopressin, we measured vasopressin response to a single dose of intramuscular chlorpromazine or intravenous haloperidol in normal individuals and to 2 weeks of oral antipsychotics in patients with acute schizophrenia. Neither intramuscular chlorpromazine nor intravenous haloperidol affected plasma vasopressin in normals, except in one subject who developed high plasma vasopressin concentrations coincident with marked hypotension following chlorpromazine. Prior to antipsychotics, two acute schizophrenia patients had elevated plasma vasopressin concentrations, which normalized during antipsychotic drug treatment. We conclude that antipsychotics do not directly stimulate vasopressin release, but may indirectly stimulate vasopressin release by well-described baroreceptor reflex mechanisms if hypotension occurs. Also, acute schizophrenia may be associated with increased plasma vasopressin levels in some patients.

The effects of fetal hypoxemia on renal hemodynamics and renal function were studied in two groups of chronically catheterized young (< 120 days of gestation) and near-term lamb fetuses (> 130 days). Fetal hypoxemia produced, in both groups, a significantly decrease in renal blood flow (RBF) and a significant increase in the filtration fraction. However, the glomerular filtration rate (GFR) did not change significantly suggesting that the renal vasoconstriction associated with fetal hypoxemia was more important at the efferent than at the afferent arteriolar level. In the group of near-term fetuses, the decrease in RBF correlated closely with changes in plasma renin activity (PRA) (r = 0.77). No changes in PRA were observed during hypoxemia in the group of young fetuses. After hypoxemia, reactive hyperemia associated with a significant increase in urinary prostaglandin excretion (PGE and PGF2 alpha) was observed in near-term fetuses but not in young fetuses. It also was demonstrated that fetal hypoxemia produced a significant increase in fetal plasma concentrations of vasopressin associated with an antidiuresis in all but one near-term fetus and in 50% of the young fetuses, suggesting that the ability of the fetal kidney to reabsorb free water is more developed in near-term fetuses. Finally, fetal hypoxemia had no effect on mean arterial pressure and heart rate in young fetuses; however, in near-term fetuses, a significant increase in blood pressure and a decrease in heart rate were observed. In summary, it appears that the response of the fetal kidney to hypoxemia depends on the degree of fetal maturation.

To test the effect of opiate receptor blockade on hormone release in man, we administered 10 mg naloxone iv to eight normal subjects and compared the results with those found after saline infusion. Naloxone produced a rise in serum cortisol (P < 0.01), LH (P < 0.01), FSH (P < 0.05), and insulin (P < 0.05) levels but did not alter serum GH, PRL, TSH, arginine vasopressin, glucagon, T3, or T4. Naloxon e had no effect on GH levels in two subjects with active acromegaly or on TSH levels i n six subjects with primary hypothyroidism. In dynamic pituitary function testing, naloxone diminished the GH response to arginine (P < 0.05) without altering the PRL response; naloxone augmented the PRL response to TRH (P < 0.025) without affecting the TSH response. Naloxone did not significantly alter GH or PRL response to L-dopa. Naloxone enhanced the increment in serum cortisol induced by the stress of gastroscopy without changing the GH or PRL response. Naloxone increased glucose response areas (P < 0.05) after an iv gl...

Plasma oxytocin levels in the umbilical artery (UA) exceeded umbilical venous levels in newborn infants delivered by cesarean section (without maternal labor) (p < 0.05) and following labor (NS). There was an initial rapid decrease in oxytocin concentration from UA levels to those in peripheral venous blood by 30 min of age. Plasma oxytocin levels for breast-fed and formula-fed infants remained elevated over adult basal levels (1.7 ± 0.3 μU/ml) throughout the 4-day study period. Mean oxytocin concentration measured in breast milk from 10 mothers 2–4 days following vaginal delivery was 10.0 ± 1.4 μU/ml. The stimulus for fetal and neonatal oxytocin secretion remains obscure, but continues beyond the period of birth.

Baseline plasma oxytocin (OT) concentrations were measured in 25 healthy men, 102 nonpregnant women, and 59 pregnant women from 15-42 weeks gestation. In addition, plasma OT levels were measured at the onset, peak, and immediately after a single uterine contraction in 6 women in the latent phase and 14 women in the active phases of labor, as well as in 19 women at initial presentation of the fetal head on the perineum (+3 station) and 11 women at the time of delivery of the head during a normal vaginal delivery. Baseline plasma OT concentrations did not vary significantly among men (1.5 +/- 0.2 microunits/ml), nonpregnant women (1.4 +/- 0.2 microunits/ml), or pregnant women before labor (1.3 +/- 0.1 microunits/ml) and did not differ in an additional subgroup of 20 women receiving oral contraceptive medication (1.8 +/- 0.7 microunits/ml). In studies conducted during labor, plasma OT concentrations did not correlate with uterine pressure measurements and did not increase significantly over baseline pregnancy concentrations during the latent (1.3 +/- 0.2 microunits/ml) or active (1.6 +/- 0.2 microunits/ml) phases of labor. There was a significant increase in plasma OT levels from the time of initial visualization of the fetal head to the time of delivery of the head (1.1 +/- 0.1 to 4.2 +/- 1.1 microunits/ml, respectively; P less than 0.05). These data support the view that maternal plasma OT levels remain low during pregnancy until late in the second stage of labor.

IN patients with chronic renal failure who are undergoing hemodialysis, arterial oxygen tension (PaO2) falls when a dialysis solution containing acetate is used.1 2 3 4 It has been suggested that hypoxemia results from altered pulmonary ventilation-perfusion ratios in the lung that are consequent to pulmonary sequestration of neutrophils.3 4 5 However, Aurigemma1 and Tolchin2 and their colleagues have proposed that the major cause of the reduced PaO2 is a reduction in carbon dioxide output at the lungs, as a consequence of the carbon dioxide loss through the dialysis bath that leads to reduced ventilation. Such a reduction in ventilation has been . . .

To test the effect of opiate receptor blockade on hormone release in man, we administered 10 mg naloxone iv to eight normal subjects and compared the results with those found after saline infusion. Naloxone produced a rise in serum cortisol (P < 0.01), LH (P < 0.01), FSH (P < 0.05), and insulin (P < 0.05) levels but did not alter serum GH, PRL, TSH, arginine vasopressin, glucagon, T3, or T4. Naloxon e had no effect on GH levels in two subjects with active acromegaly or on TSH levels i n six subjects with primary hypothyroidism. In dynamic pituitary function testing, naloxone diminished the GH response to arginine (P < 0.05) without altering the PRL response; naloxone augmented the PRL response to TRH (P < 0.025) without affecting the TSH response. Naloxone did not significantly alter GH or PRL response to L-dopa. Naloxone enhanced the increment in serum cortisol induced by the stress of gastroscopy without changing the GH or PRL response. Naloxone increased glucose response areas (P < 0.05) after an iv gl...

To study the relationships between fetal and maternal oxytocin (OT) levels and the initiation of labor in sheep, paired maternal and fetal plasma OT concentrations (microunits per ml) were measured by RIA. Samples were obtained daily from pregnant ewes and their fetuses for 5 days before spontaneous delivery and frequently during the first and second stages of labor and during the 3 h after delivery. The mean maternal plasma OT concentration during the first stage of labor was not different from that preceding labor. In contrast, the mean maternal plasma OT level during stage 2 of labor was significantly higher than the earlier baseline maternal values or the mean paired fetal concentration. There was no significant increase in the mean fetal plasma OT concentration before delivery. The newborn plasma OT concentration was elevated 15 min after delivery. From these data, we conclude that in the sheep, 1) the onset of labor is not associated with increased maternal plasma OT levels, 2) cervical or vaginal distension may be the stimulus for maternal OT release during stage 2 of labor, 3) an increase in the fetal plasma OT concentration does not occur before the initiation of labor or during the course of labor, and 4) stress in the final moments of labor or in early neonatal life may be responsible for elevated cord and early neonatal plasma OT levels.

The effect of pain on plasma AVP concentration in man has previously been studied only during major surgery with general anaesthesia. Plasma AVP concentration (pAVP) and plasma osmolality (pOsm) were measured in thirty-six patients seen in a surgical emergency department complaining of pain and in fifty-one control subjects. No significant difference in pOsm was found, but pAVP was significantly higher in the emergency room patients in pain (M +/- SEM = 4.94 +/- 0.98 pmol/1 compared to 2.31 +/- 0.32 pmol/1 in control subjects, P less than 0.01). In the control subjects, age was found to have a low but significant inverse correlation with pAVP (r = 0.37, P less than 0.01). Chronic smoking was associated with significant elevation of pAVP (3.81 +/- 0.99 pmol/1 in smokers vs. 1.89 +/- 0.28 pmol/1 in non-smokers, P less than 0.02). Neither smoking nor age could account for the difference in pAVP between the pain and control groups. Thus, pain is a non-osmolar factor capable of elevating AVP in conscious man.

Despite numerous studies which have characterized the regulation of antidiuretic hormone (ADH), the role of volume in governing ADH release remains incompletely defined. Most studies have examined the quantitative effects of hypovolemia on arginine vasopressin (AVP). In contrast, few have assessed the role of hypervolemia on AVP regulation. Furthermore, there are no data to date on the effect of acute isoosmotic volume expansion on plasma AVP in man. The successful characterization of the water immersion model (NI) and the demonstration that it induces an acute central volume expansion without changes in plasma composition commended its utilization in the present study. Twelve normal subjects were studied after 14 h of dehydration on two occasions: control and during 4 h of NI. Blood was obtained every 30 min for AVP. AVP was unaltered during the control period. In contrast, there was a prompt and sustained suppression of AVP throughout NI (P < 0.05 vs. control). There were no concomitant changes in plasma osmolality. Since the changes in AVP occurred consequent to central volume expansion but in the absence of concomitant changes in plasma composition, the current data support the concept that acute isoosmotic central volume expansion in man results in a suppression of plasma AVP.

Patients undergoing hemodialysis with acetate-containing dialysis solutions develop hypoxemia. To determine the cause of the hypoxemia, we studied and compared the ventilatory, gas-exchange and blood-gas responses in chronic renal failure patients undergoing hemodialysis with acetate and bicarbonate dialysis solutions. Seven stable chronic dialysis patients were dialyzed against acetate and bicarbonate solutions in a random order. Dialysis was carried out using a 1.5 m2 hollow fiber dialyzer at a blood flow rate of 200 ml/min and a dialysate flow rate of 500 ml/min. During acetate dialysis, PaO2 fell within 15 minutes from a mean control predialysis concentration of 84 = 6 (SEM) mmHg to a mean of 70 +/- 7.5 mmHg (P less than 0.05), and remained low throughout the study. PaO2 did not change significantly during bicarbonate dialysis. Total ventilation fell from a predialysis level of 7.2 +/- 0.7 L/min to 5.7 +/- 0.6 L/min within 15 minutes (P less than 0.05). PaCO2 was not significantly changed from predialysis levels with either acetate or bicarbonate dialysis. Measurement of blood concentration of CO2 and bicarbonate across the dialyzer indicated that the total CO2 loss (as CO2 and bicarbonate) through the dialyzer was 3 millimoles per minute or the equivalent of approximately 60 ml of CO2 per minute, i.e., about one third of the patient's metabolic production of CO2.

The MCR and placental permeability to oxytocin were determined in chronically catheterized pregnant sheep. Simultaneous maternal and fetal plasma oxytocin (OT) concentrations were measured by RIA before and during continuous infusion of synthetic OT to steady state conditions. Baseline fetal plasma OT concentrations were significantly higher than simultaneously collected maternal concentrations (1.6 +/- 0.13 vs. 1.1 +/- 0.13 muU/ml, respectively; P less than 0.01). Mean fetal OT MCRs were 12.0 +/- 1.35 and 12.1 +/- 1.09 ml/kg . min at OT infusion rates of 64 and 640 muU/kg . min. Mean maternal MCRs were 12.1 +/- 2.64 and 12.4 +/- 1.38 ml/kg . min at OT infusion rates of 80 and 800 muU/kg . min. Uterine contractions were induced by maternal OT infusion of 800 muU/kg . min but not by lower infusion rates; no uterine contractions were induced by fetal OT infusion. OT did not appear to cross the placenta in either direction under the present study conditions.

Arginine vasotocin, arginine vasopressin, and oxytocin play a critical role in the stimulation of labor and delivery and in salt and water homeostasis in the newborn infant. The authors present information on their chemistry, secretion, and metabolism, and discuss the clinical effects upon target organs of their presence or absence.

who was old enough to be given the Bender-Gestalt test showed highly significant errors suggestive of perceptuomotor difficulties. No association could be found between IQ scores, respiratory distress syndrome, or hyperbilirubinemia. No inordinate delay in the placement of the venous catheter was observed in those with IQ < 90, nor was there any difference in the mean caloric intake of children with IQ < 90 when compared to the caloric intake of Group A as a whole. In Group B, the mean IQ of patients was 99.3, with their control children having a mean IQ of 99.1.

Circulating arginine vasopressin (AVP) and plasma renin activity responses to furosemide (2 mg/kg) and acute hypertonic saline (10 mEq/kg) were studied in the fetal lamb from 100 days gestation to term. The baseline to peak plasma AVP response (delta 3.7 +/- 1.2 uU/ml) and area under the response curve (209 +/- 57 uU/ml/65 min) in the fetal lambs123 days were greater than in those106 days gestation (delta 1.8 +/0 1.1 and (171 +/- 61, respectively), P0.02. The plasma renin activity/AVP ratio after furosemide was similar in the two gestational groups. The log plasma AVP responses corrected for rise in plasma osmolality (0.090 +/- .01 uU/ml) 30 min after infusion, and the area under the response curve (253 +/- 49 uU/ml/30 min) was greater (P0.02) in the fetal lambs120 days than in those under 115 days gestation (.035 +/0 0.01 and 88 +/0 29, respectively), P0.02. These results confirm that the fetal lamb responds to an osmotic stimulus with increased plasma AVP levels and documents that this response significantly matures during the last trimester of gestation. The fetal lamb also manifests a hypothalamus-posterior pituitary AVP response to furosemide that is proportional to the maturing renal renin response.

The effects of alterations of plasma osmolality on plasma arginine vasopressin (AVP) and renin activity (PRA) following graded hemorrhage were studied in conscious dogs who were either euhydrated, dehydrated, water loaded, or infused with hypertonic saline. Base-line plasma osmolality and AVP were significantly different in the four treatment groups; however, following hemorrhage the increases in log AVP did not significantly differ. An unexpected finding was that water loading resulted in significant elevations in PRA and plasma aldosterone concentrations, whereas plasma osmolality and AVP were reduced. Prior to hemorrhage, PRA was significantly greater in the water-loaded and dehydrated groups than in the euhydrated or saline-infused groups; following hemorrhage the increases in log PRA were not significantly different in all four treatment groups. The data suggest that, although alterations in osmolality influence base-line levels of AVP, they have no effect on relative (logarithmic) rises in AVP following hemorrhage. Similarly, alterations in AVP may influence base-line PRA, but do not influence relative rises in PRA following hemorrhage.

Summary: Baseline plasma osmolality (pOsm) and plasma arginine vasopressin (pAVP) were measured in chronically catheterized fetal sheep. Mean baseline pAVP in fetuses from 101–120 days was 1.9 ± 0.46 μU/ml (mean ± SEM) with a pOsm of 293 ± 1.8 mOsm/kg. In fetuses of 121–141 days of gestation, mean pAVP was significantly lower, 0.77 ± 0.19 μU/ml (P < 0.05), with a similar pOsm (293 ± 1.9 mOsm/kg). The logarithmic baseline pAVP values were linearly correlated with pOsm for both groups. Hypertonic saline infusion resulted in a similar increase in the log pAVP corrected for the rise in pOsm in the 101–120-day fetuses and in 121–141-day fetuses. The slope of this response was similar to that of the steady state relationship. The data indicates that the fetal osmoreceptor system for control of arginine vasopressin secretion is fully functional in the last trimester of pregnancy. Speculation: The fetal hypothalamic posterior pituitary system appears to show a relatively heightened response to increases in plasma osmolality during the last trimester of gestation. This may reflect the heightened hypothalamic activity postulated to explain the high circulating growth hormone levels at this time. The higher baseline plasma vasopressin levels in the younger fetuses would support this view. Alternatively, the augmented responsiveness may represent an adaptive response to the immaturity of the fetal kidney with respect to free water clearance or an adaptive response to some extrarenal function of the hormone on salt and water homeostasis in utero.

Haloperidol, a central nervous system dopamine blocker, was given im to seven normal volunteers at a dose level (1.0 mg) known to have central nervous system effects. Plasma PRL levels rose sharply in response to haloperidol, but plasma arginine vasopressin levels did not change significantly. These data do not support the hypothesis of a prominent dopamine neurotransmitter regulation of arginine vasopressin secretion.

The renal reabsorption of water independent of solute is the result of the coordinated function of the collecting duct and the ascending limb of the loop of Henle. The unique juxtaposition of the ascending and descending portions of the loop of Henle and of the vasa recta permits the function of a counter-current multiplier system in which water is removed from the tubular lumen and reabsorbed into the circulation. The driving force for reabsorption is the osmotic gradient in the renal medulla which is dependent, in part, on chloride (followed by sodium) pumping from the thick ascending loop of Henle. Urea trapping is also thought to play an important role in the generation of a hypertonic medullary interstitium. Arginine vasopressin (AVP) acts by binding to receptors on the cell membrane and activating adenylate cyclase. This, inturn, results in the intracellular accumulation of cyclic adenosine monophosphate (AMP) which in some fashion abruptly increases the water permeability of the luminal membrane of cells in the collecting duct. As a consequence, water flows along an osmotic gradient out of the tubular lumen into the medullary interstitium. Diabetes insipidus is the clinical condition associated with either a deficiency of or a resistance to AVP. Central diabetes insipidus is due to diminished release of AVP following damage to either the neurosecretory nuclei or the pituitary stalk. Possible causes include idiopathic, familial, trauma, tumor, infection or vascular lesions. Patients present with polyuria, usually beginning over a period of a few days. The diagnosis is made by showing that urinary concentration is impaired after water restriction but that there is a good response to exogenous vasopressin therapy. Nephrogenic diabetes insipidus can be identified by a patient's lack of response to AVP. Nephrogenic diabetes insipidus is caused by a familial defect, although milder forms can be acquired as a result of various forms of renal disease. Central diabetes insipidus is eminently responsive to replacement therapy, particularly with dDAVP, a long lasting analogue of AVP. Nephrogenic diabetes insipidus is best treated with a combination of thiazide diuretics as well as a diet low in sodium and protein.

The effect of furosemide on plasma renin, vasopressin (AVP), and aldosterone concentrations was studied in 10 control and 6 nephrectomized lambs during the 1st 2 wk of life. In a separate study in 10 newborn lambs, 1-sarcosine-8-alanine-angiotensin II (saralasin acetate, 5 mug/kg per min) was infused alone for 40 min, after which furosemide 2 mg/kg i.v. was injected in association with continuing saralasin acetate infusion. Plasma renin activity increased from a mean (+/-SEM) of 21.3+/-3.4 ng/ml per h in the 10 control lambs to 39.4+/-8.2 ng/ml per h at 8 min (P0.001) and remained high through 120 min after furosemide. Plasma AVP and aldosterone concentrations increased from respective mean values of 2.1+/-0.4 muU/ml and 12.8+/-2.5 ng/dl to 9.8+/-2.0 muU/ml (P0.01) and 23.0+/-7.7 ng/dl (P0.05) at 35 min and 13.8+/-2.1 muU/ml and 23.0+/-4.4 ng/dl at 65 min after furosemide (each P0.01). There was an insignificant AVP response in the 10 lambs treated with angiotensin inhibitor: from a mean base line of 4.7+/-0.9 to 8.3+/-2.0 muU/ml at 35 min, and 7.4+/-2.0 muU/ml at 65 min after furosemide. There was no increase in AVP in the anephric lambs. The mean increment AVP response from base line in the newborn lambs without saralasin, Delta 10.8+/-2.0 muU/ml, was greater than in the lambs with saralasin, Delta4.0+/-1.9 (P0.05), and greater than in the anephric lambs, Delta3.3+/-2.1 muU/ml (P0.05). The mean blood pressure fell 6 mm Hg in the 10 control lambs (P0.05), 7 mm Hg in the anephric lambs (P0.05), and 16 mm Hg in the lambs treated with angiotensin inhibitor (P0.05) by 35 min after furosemide. However, the changes in plasma AVP were not related to the fall in blood pressure. These data support the view that the observed AVP response to furosemide in the newborn lamb was mediated through the renin-angiotensin system.

Plasma antidiuretic hormone (ADH) measured by radioimmunoassay was higher in acutely psychotic subjects than in acutely anxious nonpsychotic subjects or normal subjects. ADH was not elevated in acutely anxious nonpsychotic subjects. ADH was positively correlated with degree of psychosis. Normal osmolar and volume regulatory mechanisms did not seem responsible for the ADH elevations in the psychotic subjects. Because ADH is both produced in the hypothalamus and can be accurately measured in blood, this substance may prove particularly valuable in the study of psychiatric disorders.

Although an impairment in renal water excretion is a commonly encountered clinical problem in cirrhotic patients, the mechanisms responsible for this abnormality are uncertain. ADH levels are elevated in some patients with decompensated cirrhosis, but a causal relationship between these levels and impaired water excretion has not been established. Since in normal man, water immersion to the neck (NI) results in a preferential central hypervolemia (CV), without plasma compositional change, and a resultant suppression of AVP, we designed the present study to determine if the diuretic response of cirrhotic patients to NI is mediated by a decrease in AVP. 17 cirrhotic patients with ascites were studied following 14 h of dehydration on two occasions: during a seated control study (C) and during 4 h of NI. AVP, determined by RIA, was measured every 30 min. 12 of the 17 patients manifested a diuresis that equalled or exceeded that documented in normal hydropenic subjects during immersion. NI did not alter mean AVP as compared with either the pre-study hour or those of the corresponding control study. Furthermore, peak V and CH2O varied independently of prestudy AVP (r = -0.116), mean change in AVP (r = -0.060), as well as nadir AVP levels (r = -0.122). The demonstration of a diuresis in some of the subjects, occurring without concomitant suppression of plasma AVP, suggests that ADH may constitute a permissive rather than pivotal factor in the impaired water excretion of many patients with advanced liver disease.