Validation of the bag-mediated filtration system for environmental surveillance of poliovirus in Nairobi, Kenya.

AIMS: This study compared the bag-mediated filtration system (BMFS) and standard WHO two-phase separation methods for poliovirus (PV) environmental surveillance, examined factors impacting PV detection and monitored Sabin-like (SL) PV type 2 presence with withdrawal of oral polio vaccine type 2 (OPV2) in April 2016. METHODS AND RESULTS: Environmental samples were collected in Nairobi, Kenya (Sept 2015-Feb 2017), concentrated via BMFS and two-phase separation methods, then assayed using the WHO PV isolation algorithm and intratypic differentiation diagnostic screening kit. SL1, SL2 and SL3 were detected at higher rates in BMFS than two-phase samples (P < 0·05). In BMFS samples, SL PV detection did not significantly differ with volume filtered, filtration time or filter shipment time (P > 0·05), while SL3 was detected less frequently with higher shipment temperatures (P = 0·027). SL2 was detected more frequently before OPV2 withdrawal in BMFS and two-phase samples (P < 1 × 10-5 ). CONCLUSIONS: Poliovirus was detected at higher rates with the BMFS, a method that includes a secondary concentration step, than using the standard WHO two-phase method. SL2 disappearance from the environment was commensurate with OPV2 withdrawal. SIGNIFICANCE AND IMPACT OF THE STUDY: The BMFS offers comparable or improved PV detection under the conditions in this study, relative to the two-phase method.

Bilateral versus unilateral botulinum toxin injections for chronic anal fissure: a randomised trial.

BACKGROUND: Botulinum toxin injected into the internal anal sphincter is used in the treatment of chronic anal fissure but there is no standardised technique for its administration. This randomised single centre trial compares bilateral (either side of fissure) to unilateral injection. METHODS: Participants were randomised to receive bilateral (50 + 50 units) or unilateral (100 units) Dysport® injections into the internal anal sphincter in an outpatient setting. Injection-related pain assessed by visual analogue scale was the primary outcome measure. Secondary outcomes were healing rate, fissure pain, incontinence, and global health scores. RESULTS: Between October 2008 and April 2012, 100 patients with chronic anal fissure were randomised to receive bilateral or unilateral injections. Injection-related pain was comparable in both groups. There was no difference in healing rate. Initially, there was greater improvement in fissure pain in the bilateral group but at 1 year the unilateral group showed greater improvement. Cleveland Clinic Incontinence score was lower in the unilateral group in the early post-treatment period and global health assessment (EuroQol EQ-VAS) was higher in the unilateral group at 1 year. CONCLUSIONS: Injection-related pain was similar in bilateral and unilateral injection groups. Unilateral injection was as effective as bilateral injections in healing and improving fissure pain without any deterioration in continence.

[What Surgeons Need to Know About Forensic Medicine]. / Was muss der Chirurg von der Rechtsmedizin wissen?

Background: Forensic medicine finds more and more resonance due to requests and queries from clinicians and acts as a mediator between the individual medical disciplines, in particular with regard to legal issues, and as an interface between the fields of medicine, police and judiciary. The aim of this short narrative overview is to make surgeons aware of the forensic aspects of their work, which is usually focused on clinical and curative aspects. Crucial points: Traditionally, the basic work in forensic medicine comprises sudden and unexpected deaths, for which it is important to definitely clarify the mode of death based on the detected cause of death. In addition to violent and unnatural deaths, there are sudden natural deaths, which are natural, but also unsolved. Clinical forensic medicine basically concentrates on the examination of victims of violence, which may comprise various types of bodily harm including sexual crime, child maltreatment and traffic accidents. The investigational results (autopsy findings, injury patterns, results from the investigation of traces) need to be presented and interpreted in public procedures at court by forensic medicine specialists, who act as experts answering questions while retaining a neutral position. Conclusion: Specialists in forensic medicine should not only be consulted for issues related to the inspection of corpses and to issue a death certification. Much rather, they should also be consulted as specialised partners of surgeons and other clinicians, e.g. for the documentation of specific findings and the description of injury patterns in injured persons who are still alive.

[What a surgeon needs to know of the work of a medical ethics committee/institutional review board]. / Was muss ein Chirurg von der Arbeit einer medizinischen Ethik-Kommission wissen?

Ethical committees or institutional review boards are interdisciplinary committees to assess the ethical, social, legal and medical aspects of research involving human subjects. The ethics commission is to protect both the patient as well as the investigators and other personnel involved in the implementation of scientific projects. According to the professional code (Berufsordnung) every physician is obliged to consult an ethics committee to get a an approval before carrying out a research project. Concerning the Declaration of Helsinki, the advice of physicians is an international standard before carrying out a research project. In addition to the advisory function the ethics committee has an authorisation function within the pharmaceutical and medical device law. In the present publication the advisory and authorisation functions of an German ethics committee are briefly explained.

The efficacy of psychosocial intervention for pain in breast cancer patients and survivors: a systematic review and meta-analysis.

Persistent pain after breast cancer treatment is prevalent, and not all patients respond sufficiently to pharmacological treatment. Pain is recognized as a multi-dimensional phenomenon, which includes psychological and social components, and several clinical trials have investigated the efficacy of psychosocial interventions on pain in cancer patients and survivors. Our aim was to systematically review and quantify the existing research on the effect of psychosocial interventions on pain in breast cancer patients and survivors. Two independent raters reviewed 474 abstracts for eligibility, leading to the identification of 26 independent and eligible studies published between 1983 and 2012, which were assessed for their methodological quality and subjected to meta-analytic evaluation. A total of 1786 participants were included in the analyses. A statistically significant and robust overall effect size was found across all included studies (Hedges g = 0.37, 95 % CI: 0.20-0.40; p < 0.001). However, the effect size was considerably smaller (0.21), when adjusted for possible publication bias. Furthermore, the results were heterogeneous, and when exploring the sources of heterogeneity, studies of higher methodological quality were found to yield a more conservative effect size (g = 0.21, 95 % CI: 0.02-0.41) than studies of poorer quality (g = 0.65, 95 % CI: 0.25-1.04). The results also indicated that patient educational approaches yielded a larger effect size (g = 0.64) than relaxation-based interventions (g = 0.31, 95 % CI: -0.05-0.67) and supportive group therapy (g = 0.17, 95 % CI: 0.02-0.32). Taken together, while suggestive of psychosocial intervention as an effective tool in the management of pain among breast cancer patients and survivors, the results should be interpreted as preliminary. The methodological quality of the existing research varied considerably, and only few studies had selected patients on the basis of the presence of pain and included pain as the primary outcome.

The global distribution of oral and maxillofacial surgeons: a mixed-methods study.

Despite its role in treating the most dominant non-communicable diseases worldwide, the global workforce of oral and maxillofacial (OM) surgeons is not well-characterized. To address the current deficit in understanding of the global OM surgeon workforce and to elevate oral and maxillofacial surgery (OMS) in the global health discourse, we join other surgical specialties in evaluating global surgical capacity with a descriptive analysis of the distribution of OM surgeons worldwide. A mixed-methods study was implemented using a combination of literature review, in-country contacts, internet searches, and survey data. The survey was distributed globally from January to June 2022. Data regarding OM surgeon workforce estimates were obtained for 104 of 195 United Nations-recognized countries (53.3%). Among countries with available estimates, the median global workforce density was 0.518 OM surgeons per 100,000 population. Twenty-eight countries (26.9%) were reported to have two or fewer OM surgeons. The median OM surgeon workforce density for low-income countries was 0.015 surgeons per 100,000 population, compared to 1.087 surgeons per 100,000 population in high-income countries. low and middle-income countries countries have the least workforce density as well as the least data coverage. More work is needed to better understand the capacity of the global OM surgeon workforce and access to OMS care.

Evaluation of tooth preparations - a comparative study between faculty members and pre-clinical students.

INTRODUCTION: Preparation of teeth is a basic technique for dental treatment and plays an essential role in pre-clinical education. The purpose of this study was to evaluate whether undergraduate students' evaluations of prepared teeth were consistent with faculty assessments and correlated with students' performance in test preparations. MATERIALS AND METHODS: Thirty four of 52 dental students having attended a pre-clinical course on basic prosthodontic topics including tooth preparation volunteered to participate in this study. The students were given 10 casts each containing one tooth with an intentionally applied preparation fault of a certain type prepared by an experienced clinician. The students were asked to mark on a list the fault type found in every tooth. The association of students' ratings with their performance during the course was analysed by means of a contingency table, and a generalised linear model was used to compare students' and faculty ratings (α = 0.05). RESULTS: No significant difference between students' and faculty ratings could be found by analysis of deviance (P = 0.953). Significant deviations of fault detection probabilities from their group mean were found for six of ten fault types. No significant association between students' performance in test preparations and students ratings could be found (P = 0.564). DISCUSSION: It was possible to achieve a level of calibration within the group of students, which was comparable to that in the group of faculty members. CONCLUSIONS: Calibration of both students and examiners remains to be an issue with the teaching concepts applied in this study.

Student attitudes towards computer-aided testing.

INTRODUCTION: Computer-aided learning (CAL) is a viable alternative to traditional teaching methods. While CAL is used for teaching only, computer-aided testing (CAT) can be applied as a computer-based examination method. The aim of the present study was to evaluate students' attitude towards CAT as compared to written multiple choice tests. MATERIALS AND METHODS: Forty-one undergraduate dental students underwent a mock examination consisting of 15 written multiple choice questions and 15 questions delivered using the interactive MobiTed® system. A questionnaire based on an eight-item seven-point Likert scale was used to evaluate the students' attitude towards CAT. The students' performance in both tests was analysed using paired t-tests. Correlations between test performance and questionnaire were expressed by Pearson correlation coefficients. RESULTS: Despite study-design-related differences, students' test performance between written multiple choice and MobiTed® was comparable. No correlations between test results and questionnaire could be set up. Students rated MobiTed® to be equivalent to written multiple choice and had no difficulties with the CAT set up. The pre-defined sequence of questions with each question being shown only once was considered to be a major disadvantage of the CAT system. Complex questions should be displayed longer compared to short questions. DISCUSSION: Computer-aided testing appeared to be equivalent to written multiple choice tests not only in terms of student performance but also to their perception. This is consistent with previous studies. CONCLUSIONS: Interactive multiple choice tests may provide an alternative to written tests, but should allow examinees to have control over the sequence, as well as the length of time the questions are displayed.

Inactivation of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) on various environmental surfaces by mist application of a stabilized chlorine dioxide and quaternary ammonium compound-based disinfectant.

Contaminated environmental surfaces are important reservoirs in the transmission of many human pathogens. Although several options exist for disinfecting contaminated environmental surfaces, few are compatible with use on both hard smooth non-porous (hard) and soft porous surfaces (soft) while still offering significant disinfection of the contaminating organisms. This study evaluated the efficacy of mist application of a stabilized chlorine dioxide and quaternary ammonium compound-based disinfectant (Cryocide20) for inactivation of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) on various environmental surfaces. MRSA and VRE were applied to hard and soft surfaces (glass, steel, tile, carpet, and cotton fabric), allowed to dry, and exposed to a uniform mist application of the disinfectant solution. After 1 hr of contact time, the residual disinfectant was neutralized, and the bacteria were recovered and enumerated on brain heart infusion (BHI) agar. Reduction of both test bacteria was observed on most of the hard and soft surfaces tested. Log(10) reduction of the organisms tended to be higher on steel, tile, and carpet than glass or cotton. Overall, these results suggest that mist application of Cryocide20 disinfectant may be an effective option for reduction of low levels of infectious bacterial pathogens from contaminated environmental surfaces.

[Partial allotransplantation of the face including the mandible: a feasibility study]. / Allotransplantation partielle de face incluant l'os mandibulaire: étude de faisabilité.

OBJECTIVE: Facial grafts are useful in that they allow the repair of severe facial defects in one step in contrast to the actual available techniques which require staged procedures with limited cosmetic and functional results. The aim of our study was to determine whether it would be possible to include part of the mandible in a partial allotransplant of the face. MATERIAL AND METHODS: An anatomical study on the arterial and venous vascularisation of the face and the mandible was performed on 7 heads. Then nine heads were used to describe an anatomical model of harvesting two-thirds of the lower face. RESULTS: The study determined that a graft could be viable with a facial artery, inferior dental artery and two veins facial. Thus, a reliable method for harvesting hemi-mandible and total mandible is developed. The average sampling time was 4 hours and thirty minutes. Harvesting a total mandibular graft was more tedious because of the loss of joint laxity caused by the absence of mandibular osteotomy. CONCLUSION: Partial allotransplant of the face including the mandible is feasible. In such transplantations, functional difficulties related to the temporo-mandibular joint and orthognathic problems need to be overcome.

Impact of health care organization on surgical lung cancer care.

OBJECTIVES: Organization and governance of national healthcare might play an important role in decision-making and outcomes in patients with lung cancer. Both Denmark and the Netherlands have a high level of healthcare but a different financial coverage, governance and level of centralization. By using both national databases we analyzed the consequences of these differences on patterns of care and outcomes with a focus on morbidity, mortality and clinical staging. MATERIALS AND METHODS: General numbers on both healthcare systems were requested. All patients who had surgery for lung cancer from 2013 to 2016 were included. Mortality, morbidity and clinical staging were analyzed for patients with NSCLC without metastases, only one operation and no neo-adjuvant therapy. RESULTS: In 2016 annual budget as share of gross national product was 10.4% for both countries. In Denmark 4 hospitals performed lung surgery in 2016, compared to 43 hospitals in the Netherlands. We included 4030 Danish and 8286 Dutch patients. In the subgroup 30-day mortality was 1.5% in Denmark compared to 1.9% in the Netherlands. The percentage of patients with a complicated course was 24.4% and 34.8% respectively (p < 0.05). Accuracy between cTNM and pTNM was 53.0% in Denmark and 52.9% in the Netherlands. CONCLUSION: Surgery for lung cancer is at a high level in both countries, reflected by low mortality-rates. Centralization has been implemented successfully in Denmark, which might explain the lower rate of patients with a complicated post-operative course, although different definitions preclude firm conclusions. In both countries correct clinical staging of lung cancer remains a challenge.

[Acute group A beta-hemolytic streptococcus membranous laryngotracheobronchitis in an adult]. / Laryngotrachéobronchite aiguë membraneuse à streptocoque bêta-hémolytique du groupe A de l'adulte.

OBJECTIVE: To describe the first case of a group A beta-hemolytic streptococcus laryngotracheobronchitis as well as the other possible etiologies in a case of acute dyspnea. METHODS: We report the case of a 46-year-old woman with a doubtful vaccination status who presented clinical features of croup (laryngotracheobronchitis). She developed respiratory distress and required endotracheal intubation. RESULTS: The endoscopy demonstrated a great deal of crust and pseudomembrane detachment. Bacterial culture grew group A beta-hemolytic streptococcus. Progression was good with antibiotics and corticosteroid treatment. CONCLUSION: Bacterial acute pseudomembranous croup (laryngotracheobronchitis) is rare. We must search for the most frequent diagnoses such as diphtheria and epiglottitis. This is the first case to be reported in the literature.

Hospital variation and the impact of postoperative complications on the use of perioperative chemo(radio)therapy in resectable gastric cancer. Results from the Dutch Upper GI Cancer Audit.

BACKGROUND: Dutch national guidelines on the diagnosis and treatment of gastric cancer recommend the use of perioperative chemotherapy in patients with resectable gastric cancer. However, adjuvant chemotherapy is often not administered. The aim of this study was to evaluate hospital variation on the probability to receive adjuvant chemotherapy and to identify associated factors with special attention to postoperative complications. METHODS: All patients who received neoadjuvant chemotherapy and underwent an elective surgical resection for stage IB-IVa (M0) gastric adenocarcinoma between 2011 and 2015 were identified from a national database (Dutch Upper GI Cancer Audit). A multivariable linear mixed model was used to evaluate case-mix adjusted hospital variation and to identify factors associated with adjuvant therapy. RESULTS: Of all surgically treated gastric cancer patients who received neoadjuvant chemotherapy (n = 882), 68% received adjuvant chemo(radio)therapy. After adjusting for case-mix and random variation, a large hospital variation in the administration rates for adjuvant was observed (OR range 0.31-7.1). In multivariable analysis, weight loss, a poor health status and failure of neoadjuvant chemotherapy completion were strongly associated with an increased likelihood of adjuvant therapy omission. Patients with severe postoperative complications had a threefold increased likelihood of adjuvant therapy omission (OR 3.07 95% CI 2.04-4.65). CONCLUSION: Despite national guidelines, considerable hospital variation was observed in the probability of receiving adjuvant chemo(radio)therapy. Postoperative complications were strongly associated with adjuvant chemo(radio)therapy omission, underlining the need to further reduce perioperative morbidity in gastric cancer surgery.

Factors contributing to variation in the use of multimodality treatment in patients with gastric cancer: A Dutch population based study.

BACKGROUND: Substantial variation in the use of (neo) adjuvant treatment in patients with gastric cancer exists. The aim of this study was to identify underlying (organizational and process) factors associated with the use of perioperative therapy. PATIENTS AND METHODS: Patients with resectable gastric cancer who underwent surgery between 2012 and 2014 were selected from the Dutch Upper gastrointestinal Cancer Audit (DUCA). The proportion of perioperatively treated patients was defined per hospital. Five hospitals with the lowest percentage (LP group) and 5 hospitals with the highest percentage (HP group) of perioperative therapy were identified. In the selected hospitals additional information was obtained from patients' medical records using a structured list with predefined variables. RESULTS: In total, 429 patients (231 in LP group, 198 in HP group) from 9 different hospitals were included. Perioperative therapy was given in 16.0% of patients in the LP group compared to 40.4% in the HP group. In the LP group, patients were enrolled in a clinical trial less frequently (10.8% versus 26.8%, P<.001), and a higher percentage grade III-IV toxicity was observed during neoadjuvant treatment (25.7% versus 46.3%, P=.007). Multivariable analysis showed that, besides known casemix factors, consultation with ≥3 upper GI specialists prior to treatment decision was positively associated with initiating perioperative therapy (OR 2.08, 95% CI 1.19-3.66). CONCLUSION: Results of this study confirm considerable hospital variation in the use of perioperative therapy in patients with gastric cancer. Besides known casemix factors, use of perioperative therapy was associated with the level of involvement of multidisciplinary care.

Pathogenic role of cyclic AMP in the impairment of urinary concentrating ability in acute hypercalcemia.

A possible association between the impairment of urinary concentrating ability and an impairment of the vasopressin-dependent cyclic AMP system in hypercalcemia was investigated in rat kidneys both in vivo and in vitro. The increases of urinary osmolality and negative free water clearance and the increase of urinary cyclic AMP excretion by vasopressin injection were significantly less in the hypercalcemic rats than in the control rats. The increase of cyclic AMP concentration by vasopressin in renal medullary tissue was significantly less in the slices obtained from the hypercalcem'c rats than in those obtained from the control rats. The activation of adenylate cyclase by vasopressin was significantly less in the group with an increased concentration of calcium in media than the control group, but phosphodiesterase activity was not affected by calcium concentration in the media. These data suggest that the impaired urinary concentrating ability in hypercalcemic kidneys is due at least in part to the direct inhibitory effect of calcium on the vasopressin-dependent cyclic AMP system at the level of adenylate cyclase in renal medulla.

Direct inhibitory effect of hypercalcemia on renal actions of parathyroid hormone.

The effects of calcium on the renal actions of parathyroid hormone (PTH) were studied in vivo and in vitro. In parathyroidectomized rats, variable levels of blood calcium concentration were induced by intravenous infusion of calcium. The renal responses to the injected PTH, i.e. phosphate and cyclic AMP excretion, were compared in these animals. After PTH injection, the increases of both phosphate and cyclic AMP excretion were less in the calcium-infused animals than in the control group without calcium infusion. There was an inverse correlation between the renal responses to PTH and plasma calcium concentration of 4.2-13.5 mg/100 ml. But calcium had no effect on phosphate excretion induced by infusion of dibutyryl cyclic AMP. In the in vitro experiments, the increase of cyclic AMP concentration in response to PTH was less in renal cortical slices taken from the calcium-infused animals than in ones from the control group without calcium infusion. Calcium also inhibited the activation of renal cortical adenylate cyclase in response to PTH, but calcium had no effect on phosphodiesterase. The data indicate that calcium directly inhibits renal actions of PTH both in vivo and in vitro. Such inhibitory mechanism is probably at or before the step of PTH-dependent cyclic AMP generation in the kidney.

Effects of catecholamines and their interaction with other hormones on cyclic 3',5'-adenosine monophosphate of the kidney.

Catecholamines have several physiological effects on the kidney. These include: (a) stimulation of renin synthesis in the cortex: (b) antidiuresis by beta adrenergic agents; and (c) diuresis by alpha adrenergic stimulation. The role of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in the renal actions of catecholamines was evaluated by measuring the effects of several adrenergic agents on cyclic AMP concentration in the dog kidney. Beta adrenergic activity increased cyclic AMP concentration in the renal cortex, a finding consistent with the hypothesis that beta-adrenergic stimulation augments renin synthesis by increasing cyclic AMP generation. Beta adrenergic stimulation, like vasopressin, increased cyclic AMP concentration in the renal medulla. This suggests that beta adrenergic stimulation causes antidiuresis by augmenting cyclic AMP generation in the renal medulla. Alpha adrenergic activity inhibited the effect of vasopressin to stimulate cyclic AMP generation. These results support the hypothesis that the diuretic effect of alpha adrenergic stimulation is mediated by inhibition of the effect of vasopressin to increase cyclic AMP generation.

Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.

It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method. Incubation of cortical homogenates with PTH for 10 min at 37degreesC inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg++-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100degreesC abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex. Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg++ dependent and temperature dependent, and required preincubation at 37degreesC. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase. All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of carbonic anhydrase, and that inhibitory effect is mediated through the cyclic AMP system.

Effects of vasopressin and prostaglandin E 1 on the adenyl cyclase-cyclic 3',5'-adenosine monophosphate system of the renal medulla of the rat.

Vasopressin increased adenyl cyclase activity in homogenates of both inner and outer renal medulla of the rat. It also increased the concentration of cyclic 3',5'-adenosine monophosphate (AMP) in slices of both inner and outer medulla but not in renal cortex. In the inner medulla, a concentration of prostaglandin E(1) (PGE(1)), which was ineffective by itself significantly reduced the stimulation of adenyl cyclase activity and cyclic AMP concentration induced by vasopressin. These results are consistent with the hypothesis that PGE(1) can compete with vasopressin for adenyl cyclase-binding sites. However, the findings in the outer medulla suggest the situation is more complex. Although 10(-8) M PGE(1) had no effect by itself and inhibited the vasopressin-induced elevation of cyclic AMP, larger amounts of PGE(1) increased both adenyl cyclase activity and cyclic AMP levels. The maximum effect on the latter parameter was at least 6 times as great as that of maximum amounts of vasopressin.

"Essential" hypernatremia due to ineffective osmotic and intact volume regulation of vasopressin secretion.

A physiological explanation for sustained hyperosmolality was sought in a patient with histiocytosis. During 23 days of observation with only sodium intake regulated at 100 mEq daily, elevation (mean 310 mOsm/kg of water) and fluctuation (range 298-323) of the fasting plasma osmolality were recorded. The presence of endogenous vasopressin was indicated by the patient's ability to concentrate the urine to as high as 710 mOsm/kg of water with a creatinine clearance of 84 cc/min, and by dilution of the urine in response to alcohol. The failure of increasing fluid intake to as high as 6.2 liters daily to lower the plasma osmolality indicated that deficient fluid intake was not solely responsible for the elevated plasma osmolality. Hypertonic saline infusion during water diuresis resulted in the excretion of an increased volume of dilute urine. The water diuresis continued despite a rise in plasma osmolality from 287 to 339. An isotonic saline infusion initiated during hydropenia resulted in a water diuresis which continued despite a rise in the plasma osmolality from 303 to 320. Stable water diuresis induced during recumbency by either oral ingestion of water or intravenous infusion of normal saline was terminated by orthostasis and resumed with the return to the recumbent position. Antecedent alcohol ingestion blocked the antidiuresis of orthostasis. The data are interpreted as indicating impairment of the osmoreceptor mechanism as the primary cause of the hyperosmolar syndrome. They also indicate that vasopressin secretion was regulated primarily by changes in effective blood volume. Chlorpropamide was found to be an effective treatment for the syndrome.