Diabetes Insipidus (DI) is a heterogeneous clinical syndrome of disturbance in water balance, characterized by polyuria (urine output > 4 ml/kg/hr), polydypsia (water intake > 2 L/m(2)/d) and failure to thrive. In children, Nephrogenic DI (NDI) is more common than Central DI (CDI), and is often acquired. The signs and symptoms vary with etiology, age at presentation and mode of onset. Neonates and infants with NDI are severely affected and difficult to treat. Diagnosis is based on the presence of high plasma osmolality and low urinary osmolality with significant water diuresis. Water deprivation test with vasopressin challenge, though has limitations, is done to differentiate NDI and CDI and diagnose their partial forms. Measurement of urinary aquaporin 2 and serum copeptin levels are being studied and show promising diagnostic potential. Magnetic Resonance Imaging (MRI) pituitary helps in the etiological diagnosis of CDI, absence of posterior pituitary bright signal being the pathognomic sign. If pituitary stalk thickening of < 2 mm is present, these children need to be monitored for evolving lesion. Neonates and young infants are better managed with fluids alone. Older children with CDI are treated with desmopressin. The oral form is safe, highly effective, with more flexibility of dosing and has largely replaced the intranasal form. In NDI besides treatment of the underlying cause, use of high calorie low solute diet and drugs to ameliorate water excretion (thiazide, amelioride, indomethacin) are useful. Children with NDI however well treated, remain short and have mental retardation on follow up.

Patients with intracranial germ cell tumor (IGCT) often present with pituitary dysfunction, including diabetes insipidus (DI). Recent protocols have used pre-radiation chemotherapy with combinations of etoposide, carboplatin and/or cisplatin, and ifosfamide. Management of DI in these patients requires monitoring of electrolytes and fluids during chemotherapy and hyperhydration. All consecutive patients treated with chemotherapy for an IGCT during the period 1990-2007 at the Hospital for Sick Children, Toronto were reviewed. Out of 32 patients who received chemotherapy, 21 had DI. Only cycles containing cisplatin and/or ifosfamide and hyperhydration were considered. DI and non-DI patients were compared for each cycle of chemotherapy. Patients were studied for number of days in hospital per chemotherapy course, daily fluid input and output, changes in dose, schedule and route of administration of desmopressin (DDAVP) during chemotherapy, daily variations in sodium level, electrolyte monitoring requirements per day, and complications related to fluid and electrolyte disturbances. Fifty-four cycles of chemotherapy in DI patients were compared to 25 cycles in non DI patients. All 21 patients with DI required daily change in dosage and schedule of DDAVP. Marked variations in daily sodium level were observed in the DI group. Seventeen courses required prolonged admission in the DI group (one in non DI patients) and 6 patients experienced serious complications. In conclusion, DI is a risk factor for complications when cisplatin and/or ifosfamide based protocols are used. The role of these agents in the management of ICGT should be carefully evaluated and guidelines for management of DI established.

Alzheimer's disease and related neurodegenerative disorders are prevalent among the elderly and might be considered as the plague of the 21st century. It is thus imperative to find cures for these conditions. The use of nerve growth factor proteins as neuroprotective therapeutics is limited by their hindered mobility through the blood-brain barrier. Peptides provide an attractive alternative. However, do peptide derivatives retain the activity of the entire protein? Are they stable? Would peptides cross the blood-brain barrier and what are the potential side effects? Examples are put forth to strengthen our opinion that peptides are important candidates for future drug development.

Conventional therapy for intracranial germinomas is craniospinal irradiation. In 1990, the Société Française d'Oncologie Pédiatrique initiated a study combining chemotherapy (alternating courses of etoposide-carboplatin and etoposide-ifosfamide for a recommended total of four courses) with 40 Gy local irradiation for patients with localized germinomas. Metastatic patients were allocated to receive low-dose craniospinal radiotherapy. Fifty-seven patients were enrolled between 1990 and 1996. Forty-seven had biopsy-proven germinoma. Biopsy was not performed in ten patients (four had diagnostic tumour markers and in six the neurosurgeon felt biopsy was contraindicated). Fifty-one patients had localized disease, and six leptomeningeal dissemination. Seven patients had bifocal tumour. All but one patient received at least four courses of chemotherapy. Toxicity was mainly haematological. Patients with diabetus insipidus (n = 25) commonly developed electrolyte disturbances during chemotherapy. No patient developed tumour progression during chemotherapy. Fifty patients received local radiotherapy with a median dose of 40 Gy to the initial tumour volume. Six metastatic patients, and one patient with localized disease who stopped chemotherapy due to severe toxicity, received craniospinal radiotherapy. The median follow-up for the group was 42 months. Four patients relapsed 9, 10, 38 and 57 months after diagnosis. Three achieved second complete remission following salvage treatment with chemotherapy alone or chemo-radiotherapy. The estimated 3-year survival probability is 98%(CI: 86.6-99.7%) and the estimated 3-year event-free survival is 96.4%(CI: 86.2-99.1%). This study shows that excellent survival rates can be achieved by combining chemotherapy and local radiotherapy in patients with non-metastatic intracranial germinomas.

Gonadal aromatase expression has been demonstrated in human Leydig, granulosa, and thecal cells, but never in human germ cells. In an attempt to explain the unique occurrence of isosexual precocious puberty in a young girl with a hCG-secreting suprasellar germinoma, we demonstrated the presence of aromatase expression in the germ cell component of this tumor. Immunohistochemical staining for P450-aromatase and hCG using a peroxidase-labeled streptaviden-biotin technique was performed on tumor specimens from the above patient and from four other subjects with central nervous system germinoma. Cytoplasmic aromatase staining was present in the germinoma cells of four of five cases of central nervous system germinoma studied. Staining was absent in the lymphocytic element within the tumor and in negative control tissues. The demonstration of aromatase activity in the malignant element of human germinomas indicates that aromatase expression can occur in human germ cells after malignant transformation. This parallels the finding that the transformation of Sertoli cells to sex cord tumor with annular tubules in Peutz Jeghers syndrome is associated with the induction of marked aromatase expression and systemic estrogen effect. We propose that tumor aromatase played a similar role in the unique occurrence of isosexual precocity in a girl with a suprasellar germinoma.

Previous research has demonstrated that adipokines influence blood pressure (BP). Limited data exist in healthy adolescents, who are in a critical period for preventing the development of high BP. This study investigated the association of leptin, adiponectin and the leptin-to-adiponectin ratio (LAR) with BP in rural Chinese adolescents. This report included 1245 adolescents (average body mass index: 19.3 kg m(-2)) aged 13-21 years from an established twin cohort. We examined gender-specific associations between plasma adipokines and BP, with adjustment for measures of adiposity and insulin resistance (IR). We estimated the genetic contribution to adipokines using the twin design and Cholesky decomposition models. There was no correlation between leptin and adiponectin levels. Leptin was positively associated with systolic blood pressure (SBP) in males and diastolic blood pressure in females, but the association disappeared after adjusting for adiposity and IR. LAR was positively associated with SBP (β(s.e.): 1.94(0.45)), P<0.01), adiponectin was negatively associated with SBP (β(s.e.):-2.18(0.63)), P<0.001) only in males, and such associations were independent of adiposity and IR. A test of gender × adiponectin interaction was significant (P=0.01). Heritability estimation showed that both environmental and genetic factors contribute to variance in adipokines. In these relatively lean Chinese adolescents, leptin was positively associated with BP in both genders, but was adiposity/IR dependent. Adiponectin was negatively associated with SBP in males, independent of adiposity/IR.Journal of Human Hypertension advance online publication, 30 June 2011; doi:10.1038/jhh.2011.64.

PURPOSE The risk of infection can be reduced in hemodialysis (HD) patients with central venous catheters (CVCs) by using prophylactic intranasal mupirocin or polysporin at the exit site. However, there are concerns about the potential emergence of resistant microorganisms. The purpose of our study was to determine if the use of polysporin double in the treatment of exit site infections was associated with the emergence of yeast positive exit site cultures. METHODS In this case control study, we evaluated the risk of developing yeast positive exit site cultures after introducing a polysporin medical directive for the treatment of presumed exit site infections in our HD units. All HD patients using a CVC for blood access at the Ottawa Hospital were eligible for study. Demographic variables, use of polysporin, antibiotics and immunosuppressive medications were compared between those patients with yeast positive exit site cultures and controls. RESULTS There was no differences in age, gender or diabetic status between the cases and controls. However, the use of polysporin, antibiotics and immunocompromised status were associated with an increased risk of yeast positive exit site cultures. The relative importance of each of these factors could not be determined using this study design and requires future prospective study. CONCLUSIONS The emergence of yeast positive exit site cultures after the introduction of a new medical directive at a tertiary care hospital highlights the difference between medications used for prophylaxis and those used for treatment of CVC infections in high risk dialysis patients.

The spin precession frequency of muons stored in the (g-2) storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for a nonzero delta omega a(=omega a mu+- omega a mu-) and a sidereal variation of omega a mu+/-). No significant effect is found, and the following limits on the standard-model extension parameters are obtained: bZ =-(1.0+/-1.1) x 10(-23) GeV;(m mu dZ0 + HXY)=(1.8+/-6.0) x 10(-23) GeV; and the 95% confidence level limits b perpendicular mu+<1.4 x 10(-24) GeV and b perpendicular mu-<2.6 x 10(-24) GeV.

There are no reports in the literature describing any tumours, and specifically sarcoids, in zebras. The equine sarcoid, a locally aggressive, fibroblastic skin tumour, is the most common dermatological neoplasm reported in horses. The Cape mountain zebra (CMZ) has been described as one of the most vulnerable mammals in South Africa with current populations existing in isolated units. All South African CMZ are descendants from no more than 30 individual animals originating from 3 populations, namely the Mountain Zebra National Park, and Kammanassie and Gamka Mountain Nature Reserves near Cradock. The possibility therefore exists that the existing populations arose from a very small gene pool and that they are considerably inbred. A reduction in major histocompatibility complex diversity due to genetic bottlenecks and subsequent inbreeding probably contributed to uniform population sensitivity and the subsequent development of sarcoid in two CMZ populations, namely in the Bontebok National Park and Gariep Nature Reserve. The entire population of CMZ in the Bontebok National Park was observed and sampled during 2002 to document the prevalence and body distribution of sarcoids. During the same year, a comparative study was carried out on an outbred population of Burchell's zebra in the Kruger National Park. The prevalence in CMZ in the Bontebok National Park was 53 %, while the Burchell's zebra in Kruger National Park had a prevalence of 1.9 %. The most common sites for sarcoid in CMZ were the ventral abdomen and limbs. Prevalence of sarcoids in horses recorded in the literature varies between 0.5 % and 2 %. The Gariep Nature Reserve recently reported a prevalence of almost 25 % in CMZ in the reserve.

Diabetes insipidus is a rare endocrine disorder in paediatric patients. Polyuria is a cardinal manifestation that is extremely difficult to recognize in diapered infants. Careful urine quantification is the key to diagnosis in appropriate clinical setting. We report a case of a 4 months old infant presenting with an acute life threatening event following an episode of vomiting and decreased oral intake. She had profound hypernatremia which persisted after stabilization. Polyuria unrecognized by the mother was revealed by 24-hour urine output measurement. A diagnosis of diabetes insipidus was made after appropriate laboratory investigations including serum and urine osmolality. The central nature of the disease was confirmed by neuroimaging which showed holoprosencephaly.

The key question answered by this study is whether it is possible to deliver a pharmacokinetic and pharmacodynamic duration of antidiuretic action long enough to ensure adequate antidiuresis with two daily administrations of desmopressin in patients with central diabetes insipidus (CDI). We studied the efficacy and safety of desmopressin i.v. in 13 CDI patients using two 3-way crossover designs, in the doses 30, 60, 125 ng, and 125, 250 and 500 ng. Duration of action, minimum output rate, max osmolality and average osmolality during action (AUC osmolality) were measured every 30 min for the first 2 h during the infusion, and then every hour or every second hour until the urine output rate was greater than 2 ml/kg/30 min. The duration of antidiuretic action was 4, 8 and 11 h, respectively, for 125, 250, and 500 ng, increasing from 250 to 500 ng but for the remaining secondary dynamic efficacy parameters no difference could be detected based on descriptive statistics between the doses 250 and 500 ng, indicating that the upper plateau region of the dose-response curve had been reached. All treatment emergent adverse events were classified as unrelated or unlikely related to trial medication. No serious adverse events occurred. Data on duration of action indicates that it is possible to achieve antidiuretic control with 500 ng i.v. corresponding to 160 μg orodispersible tablets twice daily in CDI patients. Today, the Minirin Melt label recommends the majority of CDI patients a dose of 60 to 120 μg t.i.d.

Moyamoya disease associated with a germinoma has never yet been reported in the literature. This report describes a case of a cystic neurohypophysial germinoma associated with moyamoya disease. A 15-year-old girl with central diabetes insipidus was admitted to the hospital. Radiological examination revealed a suprasellar tumor and moyamoya disease. Surgery and pathological study confirmed pure germinoma. After the patient was treated with radiation and chemotherapy, the tumor was controlled without any effect on the moyamoya vessels. This report describes a rare incidental combination of moyamoya disease and a suprasellar germinoma. In the management of such cases, physicians should be aware of the symptoms, course, and natural history of both diseases and the effects and side effects of each type of therapy.

We determined if low dose fenoldopam in neonates already receiving conventional diuretics improves urine output, fluid balance, acute kidney injury incidence (AKI) and time to extubation. A prospective controlled clinical trial in a pediatric cardiac intensive care unit on 40 neonates undergoing cardiac surgery with cardiopulmonary bypass, excluding simple ventricular septal defect and atrial septal defect. Fenoldopam was infused at a low dose of 0.1 microg/kg/min soon after anesthesia induction and infusion prolonged for 72 h in 20 patients. 20 neonates with standardized perioperative therapy except fenoldopam administration served as controls. Demographic, hemodynamic, daily urine output, creatinine, creatinine clearance, serum and urinary sodium, potassium were recorded. Inotropic score (IS) was calculated as a surrogate for the degree of hemodynamic impairment. Low dose fenoldopam infusion did not show beneficial effects in renal function. The treatment did not significantly affect IS value, AKI incidence, fluid balance control, time to sternal closure, time to extubation and time to intensive care unit discharge. Low dose fenoldopam in neonates undergoing cardiac surgery with CPB did not produce effects on urine output, fluid balance and AKI incidence. Fenoldopam was well tolerated and did not negatively affect hemodynamics and vasopressor support. Keywords: Fenoldopam; Acute kidney injury; Cardiopulmonary bypass; Congenital heart disease.

BACKGROUND A 28-year-old woman presented with new-onset vertigo and diplopia that had started 2 weeks previously. An MRI scan of the brain revealed an 11 x 9 x 9 mm sellar mass that extended into the suprasellar region. Evaluation of pituitary function showed mild central hypothyroidism and secondary adrenal insufficiency. The patient underwent trans-sphenoidal resection of the mass without any significant intraoperative complications. On postoperative day 1 she abruptly developed polyuria, hypernatremia and urine hypo-osmolality. INVESTIGATIONS Measurements of plasma and urine osmolality, urine specific gravity, and serum sodium levels. DIAGNOSIS Postoperative diabetes insipidus with a triphasic pattern. MANAGEMENT The patient's diabetes insipidus was initially treated with intravenous desmopressin, and her fluid status, serum sodium levels, and serum and urine osmolality were carefully monitored. During the second, antidiuretic phase, desmopressin was discontinued and the patient's fluid intake was restricted. After recurrence of diabetes insipidus during the third phase, the patient was treated with intranasal desmopressin and was discharged. She remains on desmopressin therapy for chronic diabetes insipidus.

BACKGROUND A negative fluid balance during bed rest (BR) is accompanied by decreased plasma volume (PV) which contributes to cardiovascular deconditioning. HYPOTHESIS We hypothesized that increasing dietary sodium while controlling fluid intake would increase plasma osmolality (POSM), stimulate fluid conserving hormones, and reduce fluid/electrolyte (F/E) losses during BR; conversely, decreasing dietary sodium would decrease POSM, suppress fluid conserving hormones, and increase F/E losses. METHODS We controlled fluid intake (30 ml x kg(-1) x d(-1)) in 17 men who consumed either a 4.0 +/- 0.06 g x d(-1)(174 mmol x d(-1))(CONT; n = 6), 1.0 +/- 0.02 g x d(-1)(43 mmol x d(-1))(LS; n = 6), or 10.0 +/- 0.04 g x d(-1)(430 mmol x d(-1))(HS; n = 5) sodium diet before, during, and after 21 d of 6 degrees head-down BR. PV, total body water, urine volume and osmolality, POSM, and F/E controlling hormone concentrations were measured. RESULTS In HS subjects, plasma renin activity (-92%), plasma/urinary aldosterone (-59%;-64%), and PV (-15.0%; 6.0 ml x kg(-1); p < 0.05) decreased while plasma atrial natriuretic peptide (+34%) and urine antidiuretic hormone (+24%) increased during BR (p < 0.05) compared with CONT. In LS, plasma renin activity (+166%), plasma aldosterone (+167%), plasma antidiuretic hormone (+19%), and urinary aldosterone (+335%) increased with no change in PV compared with CONT (p < 0.05). Total body water did not change in any of the subjects. CONCLUSIONS Contrary to our hypothesis, increasing dietary sodium while controlling fluid intake during BR resulted in a greater loss of PV compared with the CONT subjects. Reducing dietary sodium while controlling fluid intake did not alter the PV response during BR compared with CONT subjects.

STUDY DESIGN Case report. OBJECTIVE To present a case of central diabetes insipidus (CDI) that developed after a gunshot injury to the thorax and thoracic spinal cord and to discuss the disease process in light of the relevant literature. SUMMARY OF BACKGROUND DATA Antidiuretic hormone (ADH) abnormalities may develop after spinal trauma and/or surgery. Although there are published reports of inappropriate ADH syndrome arising in this clinical picture, CDI is rare. METHODS A 33-year-old woman with hemopneumothorax and a gunshot wound to her thoracic spine was treated with chest tube drainage. No surgery was performed for the spinal injury. The patient was paraplegic on admission and rapidly developed excessive urine output. Testing revealed that her serum ADH level was low, consistent with CDI. Desmopressin acetate nasal spray was the prescribed treatment. RESULTS The patient responded well to the desmopressin acetate spray. CONCLUSIONS CDI is a complicated hormonal disorder characterized by excessive urine output. It is typically linked to an abnormality in the hypothalamohypophyseal axis that markedly reduces ADH production. The most common inciting causes are craniocerebral trauma, brain tumor and/or surgery, and central nervous system infection. Although uncommon, CDI should be considered when a spinal trauma patient develops excessive urine output.

Acid generation and elimination processes compared to titratable non-metabolizable base (NaOH equivalents, NB) turnover in end-stage renal disease patients are examined in the light of the Law of electroneutrality. The application over 2 days of the whole-body NB balance technique to 18 patients undergoing continuous ambulatory peritoneal dialysis is evaluated. The results show that the mean rate of NB loss with peritoneal effluent (as bicarbonate and organic acid anions) exceeded the mean rate of NB gain with the dialysis fluid (as salts of lactic acid) by 24 (27), m (SD), mmol per 2 days. In spite of this, the bicarbonate and pH of the plasma remained stable and within normal limits. The concurrent mean rate of the intestinal NB absorption was about 61 (27) mmol per 2 days, as calculated from the whole body balances of the several electrolytes in the metabolic steady-state. This intestinal absorption was more than sufficient to restore the body base consumed in neutralizing endogenous acid generation: 37 (14), 2H2SO4 mmol per 2 days, the remaining NB being eliminated as bicarbonate and organic acid anions. The ample spectrum of plasma acid-base (A B) values appears to some extent influenced by patient-related factors, such as the rate of drinking water intake and the set point deviation for organic acid turnover.

We report the successful repair of a distal aortic arch aneurysm in a patient with chronic renal failure following aneurysmectomy for a ruptured abdominal aorta. Perioperative use (during and up to 47 hrs after the operation) of continuous hemodiafiltration was useful for controlling fluid balance and uremia without any complicating hemodynamic instability. However, this should be restricted to the first two or three days after the operation, since it poses risk of significant thrombocytopenia.

Both central diabetes insipidus (DI) and a high rate of excretion of sodium (Na) and chloride (Cl) contributed to the development of polyuria and dysnatremia in two patients during the acute postoperative period after neurosurgery. To minimize difficulties in diagnosis and projections for therapy, two available (but not often used) clinical tools were helpful. First, the osmole excretion rate early on revealed the co-existence of central DI and an osmotic diuresis. The osmoles excreted were largely Na salts; after antidiuretic hormone acted, this electrolyte diuresis caused the urine flow rate to be much higher than otherwise anticipated. Interestingly, part of this saline diuresis occurred when the extracellular fluid volume was contracted. The tool to explain the basis for the dysnatremias was a tonicity balance. Hypernatremia, which developed before treatment of central DI, was primarily a result of a positive balance for Na rather than a large negative balance for water. Moreover, hyponatremia that developed once antidiuretic hormone acted was primarily a result of a negative balance for Na; the urine volume was large and its Na concentration was hypertonic. To prevent a further decline in the plasma Na concentration, either the Na concentration in the urine should be decreased by provision of urea or a loop diuretic while replacing all unwanted water and electrolyte losses; alternatively, the fluid infused should have a similar Na concentration and volume as the urine (infuse hypertonic saline).