Intravenous Infusion Of Mannitol Research Articles

The comparison of post-dural puncture headache treatment with acetaminophen-caffeine capsule and intravenous mannitol infusion: A randomized single-blind clinical trial

Background: Post-dural puncture headache (PDPH) is a common problem after spinal anesthesia. Depending on the severity of PDPH, there are both invasive and non-invasive treatments. Caffeine has been used for the treatment of PDPH since 1949, but the administration of mannitol is a novel management to tackle PDPH. This study was conducted to compare the effectiveness of acetaminophen-caffeine and mannitol in the treatment of PDPH. Methods: We enrolled 80 patients with PDPH in the present clinical trial and observed them during 72 hours after cesarean section. Participants were randomly and equally allocated to two groups for treatment with intravenous (IV) mannitol or oral acetaminophen-caffeine. The effects of treatment were evaluated using the visual analogue scale (VAS) questionnaire at hours of 1, 2, 3, 4, 6, 12, 18, 24, and 48. SPSS software was used. Results: Forty patients in each group completed the study. There was a significant reduction in the pain scores of the both groups after treatment, but the interaction between time and group demonstrated that mannitol administration was superior to acetaminophen-caffeine in pain reduction of the patients undergoing spinal anesthesia (P = 0.028). Patients’ satisfaction in the mannitol group was significantly higher than the caffeine group (P = 0.001). Conclusion: This study suggests that IV mannitol infusion affects faster and earlier for the treatment of PDPH than acetaminophen-caffeine capsule. Mannitol could be probably more effective for treatment of PDPH.

Sequential occurrence of eclampsia-associated posterior reversible encephalopathy syndrome and reversible splenial lesion syndrome (a case report): proposal of a novel pathogenesis for reversible splenial lesion syndrome

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a rare clinic-radiological entity characterized by headache, an altered mental status, visual disturbances, and seizures. Reversible splenial lesion syndrome (RESLES) is a new clinic-radiological syndrome characterized by the presence of reversible lesions with transiently restricted diffusion (cytotoxic edema) in the splenium of the corpus callosum (SCC) on magnetic resonance (MR) images. Here we report a rare case involving a 23-year-old pregnant woman with eclampsia who sequentially developed PRES and RESLES.Case presentationThe patient, a 23-year-old pregnant woman, presented with sudden-onset headache, dizziness, and severe hypertension (blood pressure, 170/110 mmHg). Brain MR imaging (MRI) revealed T2 hyperintense lesions in the posterior circulation territories. Immediate cesarean section was performed, and the patient received intravenous infusion of mannitol (125 ml, q8h) for 8 days for the treatment of PRES. Ten days later, or 1 day after the discontinuation of mannitol, T2-weighted MRI showed that the hyperintense lesions (vasogenic edema) had disappeared. However, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping revealed an isolated lesion in the splenium of the corpus callosum (SCC) that was accompanied by restricted diffusion (cytotoxic edema); these findings indicated reversible splenial lesion syndrome (RESLES). Five days after the discontinuation of mannitol, she had no abnormal symptoms and was discharged from our hospital. Brain MRI performed 29 days after the clinical onset of symptoms showed no abnormalities.ConclusionThe sequential occurrence of the two reversible diseases in our patient prompted us to propose a novel pathogenesis for RESLES. Specifically, we believe that the vasogenic edema in PRES was reduced with mannitol treatment, which increased the hyperosmotic stress and opened the blood–brain barrier; meanwhile, upregulation of aquaporin-4 expression secondary to the increased osmotic pressure resulted in cytotoxic edema in the astrocytes in SCC (RESLES). Further research is necessary to confirm this possible pathogenesis.

Cerebral influx of Na+ and Cl\u2212 as the osmotherapy-mediated rebound response in rats

BackgroundCerebral edema can cause life-threatening increase in intracranial pressure. Besides surgical craniectomy performed in severe cases, osmotherapy may be employed to lower the intracranial pressure by osmotic extraction of cerebral fluid upon intravenous infusion of mannitol or NaCl. A so-called rebound effect can, however, hinder continuous reduction in cerebral fluid by yet unresolved mechanisms.MethodsWe determined the brain water and electrolyte content in healthy rats treated with osmotherapy. Osmotherapy (elevated plasma osmolarity) was mediated by intraperitoneal injection of NaCl or mannitol with inclusion of pharmacological inhibitors of selected ion-transporters present at the capillary lumen or choroidal membranes. Brain barrier integrity was determined by fluorescence detection following intravenous delivery of Na+-fluorescein.ResultsNaCl was slightly more efficient than mannitol as an osmotic agent. The brain water loss was only ~ 60% of that predicted from ideal osmotic behavior, which could be accounted for by cerebral Na+ and Cl− accumulation. This electrolyte accumulation represented the majority of the rebound response, which was unaffected by the employed pharmacological agents. The brain barriers remained intact during the elevated plasma osmolarity.ConclusionsA brain volume regulatory response occurs during osmotherapy, leading to the rebound response. This response involves brain accumulation of Na+ and Cl− and takes place by unresolved molecular mechanisms that do not include the common ion-transporting mechanisms located in the capillary endothelium at the blood–brain barrier and in the choroid plexus epithelium at the blood–CSF barrier. Future identification of these ion-transporting routes could provide a pharmacological target to prevent the rebound effect associated with the widely used osmotherapy.

Comparative study between hydrocortisone and mannitol in treatment of postdural puncture headache: A randomized double-blind study

BackgroundPostdural puncture headache (PDPH) is a common complication after lumbar puncture. Anesthesiologists are the most likely to be consulted for the treatment. PDPH may be debilitating for a patient and can interfere with daily activities and quality of life.MethodsFifty patients of both sexes, aged 18–50 years and ASA I and II undergoing elective lower abdominal and pelvic surgery under spinal anesthesia were included in this randomized double-blind study. Patients were randomly divided into 2 groups 25 each: hydrocortisone group received intravenous hydrocortisone 100 mg every 8 h for 48 h and mannitol group received intravenous infusion of mannitol 20% 100 ml over 30 min followed by 100 ml every 12hours. Mean (±SD) of headache intensity at 0, 6, 12, 24 and 48 h after beginning of treatment was assessed using visual analogue scale.ResultsThere was no significant difference regarding headache intensity between two groups before beginning of treatment. The VAS was significantly reduced in hydrocortisone group than in mannitol group at 6, 12, 24 h with P-value 0.030, 0.007, 0.004 respectively. At 48 h, both groups had nearly the same VAS of headache intensity, with P-value 0.305.ConclusionBoth intravenous hydrocortisone and mannitol intravenous infusion were efficient in reducing postdural puncture headache within 48 h. Hydrocortisone showed earlier and significant relief of headache.

Clinical Outcomes of Wulingsan Subtraction Decoction Treatment of Postoperative Brain Edema and Fever as a Complication of Glioma Neurosurgery.

Objective. To evaluate the efficacy of Wulingsan subtraction (五苓散加减 WLSS) decoction in the treatment of postoperative brain edema and fever as a complication of glioma neurosurgery. Methods. This retrospective study was conducted at the Department of Neurosurgery of Liaocheng People's Hospital. Patients hospitalized between March 2011 and December 2014 were divided into three groups: Group A received WLSS oral liquid (50 mL), twice a day; Group B received an intravenous infusion of mannitol; and Group C received WLSS combined with mannitol (n = 30 patients per group). All patients were treated for 10 days continuously. Therapeutic efficacy was evaluated by measuring body temperature and indicators of renal function before and 3, 5, and 10 days after treatment. Results. Compared to the other two groups, significantly greater clinical efficacy was observed in the patients treated with mannitol (Group B; P < 0.05), although marked clinical efficacy was also observed over time in patients treated with WLSS (Group A). After 5 days, the quantifiable effects of the WLSS and mannitol combination group (Group C) were substantial (P < 0.05). The renal damage in Group B was more obvious after 5 days and 10 days. Conclusion. Compared with mannitol treatment alone, WLSS combined with mannitol induced a more rapid reduction in body temperature. Our findings suggest that patients should be started on mannitol for 3 days and then switched to WLSS to achieve obvious antipyretic effects and protect renal function. This method of treatment should be considered for clinical applications.

Preoperative mannitol infusion improves perioperative cerebral oxygen saturation and enhances postoperative recovery after laparoscopic cholecystectomy.

Objectives:To test the effect of preoperative mannitol infusion on perioperative decreased cerebral oxygen saturation (rSO2) during laparoscopic cholecystectomy.Methods:Forty patients scheduled for laparoscopic cholecystectomy were enrolled in this study conducted at Dammam Hospital of the University, Dammam, Kingdom of Saudi Arabia from December 2013 to June 2014. Patients received either 0.5 g/kg of 20% intravenous mannitol infusion over 10 minutes before induction of anesthesia (group M), or an equal volume of normal saline instead (group C). Primary outcome variable was rSO2. Other variables included extubation time, clinical assessment of consciousness recovery using the Modified Observer’s Assessment of Alertness/Sedation Scale (OAA/S), and the mini-mental state examination (MMSE) for cognitive evaluation.Results:Anesthesia induction increased rSO2 in both groups. Pneumoperitoneum decreased rSO2 in group C, but not in group M. This drop in rSO2 in the group C reached its maximum 30 minutes after extubation, and was significantly less than the preinduction value. Time to extubation in group M was significantly shorter compared to group C (p=0.007). The OAAS in group M at 10 min after extubation was significantly higher compared to group C. No differences were found between the 2 groups in cognitive function as measured by MMSE score.Conclusion:Preoperative mannitol infusion maintains perioperative rSO2 during laparoscopic cholecystectomy and shortens extubation time with earlier resurgence of OAAS.

Shadow in front of the left eye for 8 months, headache for one month, blurred vision and tinnitus for 2 weeks

A 19-year-old female was admitted to our department, complaining of shadow in front of the left eye for 8 months, headache for one month, blurred vision and tinnitus for 2 weeks. Bilateral papilledema was the presumed diagnosis. Neurological examination revealed modest left abducens nerve palsy, diplopia, nystagmus and a stiff neck. Lumbar puncture demonstrated marked intracranial hypertension (>330 mmH 2 O, normal range 70-180 mmH 2 O), modestly elevated protein (0.61 g/L, normal range 0.15-0.45 g/L), low concentration of glucose (1.90 mmol/L, normal range 2.80-4.50 mmol/L) and moderate pleocytosis (116/uL, normal range 0-8/uL). CSF cytology suggested lymphocyte-dominant inflammation with elevated ratio of eosinophils (5%, normal range 1-2%). Cranial MRI demonstrated a subarachnoid cystic lesion located at the right temporal lobe, 2 round-like cystic lesions located at the prepontine region. The positive antibodies to T. solium in serum and CSF further confirmed the diagnosis of neurocysticercosis. The patient received oral administration of antiparasitic drug (albendazole 0.40 g twice a day), intravenous infusion of mannitol (125 ml 2-4 times a day) and steroids (dexamethasone 5 mg twice a day) for 3 weeks. The patient experienced a febrile headache as the dose of steroids was reduced, but was rapidly resolved after resuming the steroids as well as intravenous antibiotics (ceftriaxone sodium, 1 g twice a day). After treatment, repeated cranial MRI demonstrated that the subarachnoid cystic lesion located at the right temporal lobe was modestly resolved, while lesions located at the prepontine region remained almost unchanged. The patient was then discharged, and was told to repeat the regimen 2-3 times at an interval of one month. DOI: 10.3969/j.issn.1672-6731.2015.06.016

Use of Electrical Impedance Tomography to Monitor Regional Cerebral Edema during Clinical Dehydration Treatment

ObjectiveVariations of conductive fluid content in brain tissue (e.g. cerebral edema) change tissue impedance and can potentially be measured by Electrical Impedance Tomography (EIT), an emerging medical imaging technique. The objective of this work is to establish the feasibility of using EIT as an imaging tool for monitoring brain fluid content.Designa prospective study.SettingIn this study EIT was used, for the first time, to monitor variations in cerebral fluid content in a clinical model with patients undergoing clinical dehydration treatment. The EIT system was developed in house and its imaging sensitivity and spatial resolution were evaluated on a saline-filled tank.Patients23 patients with brain edema.InterventionsThe patients were continuously imaged by EIT for two hours after initiation of dehydration treatment using 0.5 g/kg intravenous infusion of mannitol for 20 minutes.Measurement and Main ResultsOverall impedance across the brain increased significantly before and after mannitol dehydration treatment (p = 0.0027). Of the all 23 patients, 14 showed high-level impedance increase and maintained this around 4 hours after the dehydration treatment whereas the other 9 also showed great impedance gain during the treatment but it gradually decreased after the treatment. Further analysis of the regions of interest in the EIT images revealed that diseased regions, identified on corresponding CT images, showed significantly less impedance changes than normal regions during the monitoring period, indicating variations in different patients' responses to such treatment.ConclusionsEIT shows potential promise as an imaging tool for real-time and non-invasive monitoring of brain edema patients.

Management of hypotony after glaucoma filtering surgery

A 39-year-old male with open angle glaucoma in both eyes visited our clinic. The intraocular pressure (IOP) of both eyes fluctuated between 15 mmHg and 25 mmHg. The best corrected visual acuity (BCVA) was 20/20 in the right eye and 20/100 in the left eye. He underwent trabeculectomy with an adjunctive agent (mitomycin C; concentration, 0.2 mg/mL) smoothly on the right eye. After the removal of releasable sutures, the filtering bleb was prominent over the superior limbus for 3 consecutive clock hours with an IOP of about 4–5 mmHg. The Seidel test result was negative, and the anterior chamber depth was moderate to deep. The BCVA of the right eye decreased to 20/100, and optical coherence tomography revealed macular edema. We injected sodium hyaluronate (Healon, Abbott Medical Optics, Santa Ana, CA, USA) into the anterior chamber 2 months after the operation, and repeated the same procedure 4 days later. After each injection, the IOP spiked up to 50 mmHg, and an intravenous infusion of mannitol was required. Sodium hyaluronate was found migrating into the bleb on post-injection day 1. Then we decided to revise the bleb by suturing the scleral flap at two sides. The IOP of the right eye returned to 10 mmHg 4 days after the revision surgery. The BCVA of the right eye recovered to 20/20 6 months after the revision. Optical coherence tomography also showed recovery from macular edema. One IOP-lowering agent (1% brinzolamide ophthalmic suspension) was required for IOP control after bleb revision. Early revision of the scleral flap may resolve hypotony and associated serious complications.

Clinical observation on secondary glaucoma after silicone oil tamponade

Objective To investigate the risk factors and treatment of silicone oil glaucoma (SOG).Methods Ninety-five eyes of 93 patients who underwent pars plana vitrectomy and silicone oil tamponade were evaluated in this study. The lens was removed in 58 eyes in which intraocular lens (IOL) was implanted in 10 eyes, so 48 eyes were aphakic. Silicone oil tamponade time was ≤6 months in 32 eyes,and ＞6 months in 63 eyes. The follow-up time ranged from 2 to 25 months, with a mean of (9.5±5.1)months. The fundus and intraocular pressure (IOP) were evaluated at 1 week, 2 weeks and 1 month after surgery. The diagnosis of SOG was established if the one-month postoperative IOP ＞ 21 mm Hg (1 mm Hg=0.133 kPa), and primary and neovascular glaucoma were excluded. After the diagnosis of SOG, carteolol hydrochloride and brinzolamide solution were immediately applied to the eye, and intravenous mannitol infusion was performed. If the IOP still can not be controlled after 1 week of such treatment, silicone oil removal surgery will be performed. If removal of silicone oil can not control the IOP,trabeculectomy surgery will be performed. Results SOG occurred in 21 eyes (22.1%), including 5 phakic eyes (10.6% of 47 phakic eyes) and 16 aphakic eyes (33.3% of 48 aphakic eyes) , 3 eyes (9.4% of 32 eyes)with short tamponade time (≤6 months) and 18 eyes (28.6% of 63 eyes) with long tamponade time (＞6months). The average silicone oil tamponade time was (10.8±5.1) months. Emulsification of the silicone oil occurred in 17 eyes (81.0%). After silicone oil removed, IOP was controlled in 17 eyes (81.0%) within one week. Conclusions Aphakic eye and the duration of silicone oil tamponade are the risk factors of SOG.Emulsification of silicone oil is the main cause. Silicone oil removal is an effective way to treat SOG. Key words: Vitrectomy; Silicone oils/adverse effects; Glaucoma/secondary; Risk factors

High-resolution optical coherence tomography imaging of the living kidney

Optical coherence tomography (OCT) is a rapidly emerging imaging modality that can provide non-invasive, cross-sectional, high-resolution images of tissue morphology in situ and in real-time. In the present series of studies, we used a high-speed OCT imaging system equipped with a frequency-swept laser light source (1.3 μm wavelength) to study living kidneys in situ. Adult, male Munich–Wistar rats were anesthetized, a laparotomy was performed and the living kidneys were exposed for in situ observation. We observed the kidneys prior to, during and following exposure to renal ischemia induced by clamping the renal artery. The effects of intravenous mannitol infusion (1.0 ml of 25%) prior to and during renal ischemia were also studied. Finally, living kidneys were flushed with a renal preservation solution, excised and observed while being stored at 0–4°C. Three-dimensional OCT data sets enabled visualization of the morphology of the uriniferous tubules and the renal corpuscles. When renal ischemia was induced, OCT revealed dramatic shrinkage of tubular lumens due to swelling of the lining epithelium. Three-dimensional visualization and volumetric rendering software provided an accurate evaluation of volumetric changes in tubular lumens in response to renal ischemia. Observations of kidneys flushed with a renal preservation solution and stored at 0–4°C also revealed progressive and significant loss of tubular integrity over time. Intravenous infusion of mannitol solution resulted in thinning of the tubular walls and an increase in the tubular lumen diameters. Mannitol infusion also prevented the cell swelling that otherwise resulted in shrinkage of proximal tubule lumens during ischemia. We conclude that OCT represents an exciting new approach to visualize, in real-time, pathological changes in the living kidney in a non-invasive fashion. Possible clinical applications are discussed.

Mannitol-induced Metabolic Alkalosis

Mannitol is an osmotic diuretic agent useful in a variety of clinical conditions. This study is based on acid-base and electrolyte changes seen after the intravenous infusion of hypertonic mannitol for the prevention of cerebral edema. The study subjects were divided into 3 groups: for group A, an amount of 300-900 mL 15% mannitol was intravenously infused over the period of 60 to 90 minutes; for group B, 1,200-2,600 mL over 12 to 24 hours; and for group C, 3,200-4,900 mL over more than 24 hours. In group A, blood pH is increased from 7.43±0.07 to 7.46±0.04, and plasma HCO3- from 25.3±2.1 to 28.9±2.9 mEq/L, but plasma K+ is decreased from 4.3±0.6 to 3.7±0.8 mEq/L. In group B, blood pH is increased from 7.42±0.02 to 7.47±0.06, and plasma HCO3- from 25.2±1.8 to 29.1±2.9 mEq/L, but plasma K+ is decreased from 4.2±0.3 to 3.8±0.5 mEq/L. In group C, blood pH is increased from 7.41±0.01 to 7.52±0.04, and plasma HCO3- from 24.9±1.2 to 27.7±2.5 mEq/L, but plasma K+ is decreased from 4.2±0.1 to 3.9±0.2 mEq/L. These results showed that intravenous infusion of mannitol could induce metabolic alkalosis and hypokalemia, regardless of its dose. The mannitol induced metabolic alkalosis may be due to increased renal HCO3- production.

Self-complementary adeno-associated virus serotype 2 vector: global distribution and broad dispersion of AAV-mediated transgene expression in mouse brain

The blood–brain barrier is the main obstacle to efficient delivery of therapeutic reagents, including viral vectors, into the central nervous system (CNS) for treating global CNS diseases. In this study, the effects of mannitol infusions on global brain gene expression of a novel AAV vector were examined after intravenous (iv) or intracisternal injection. Initially, a self-complementary adeno-associated virus serotype 2 vector (scAAV) was compared to traditional single-stranded AAV2 vector for reporter gene expression in the brain of adult mice with or without pretreatment of an iv mannitol infusion. One to two months postinjection, analysis of vector-transduced green fluorescent protein (GFP) expression in the brain revealed that vector delivery to the CNS via iv injection required pretreatment with mannitol. This expression was observed only when scAAV vectors were used. Using these conditions, transgene expression was observed in various neurons and glial cells throughout the brain. The peripherally administered scAAV vectors also transduced the cells in multiple somatic tissues with efficient expression in liver (20–30% of hepatocytes), but was less efficient in other somatic tissues. Intracisternal injection of scAAV vector produced a broad and intense transgene expression in both neurons and glial cells in the CNS of injected mice ranging from the olfactory area to the brain stem and spinal cord. More than 50% of the Purkinje cells in the cerebellum expressed GFP. Intravenous infusion of mannitol before intracisternal injection of the scAAV vector enhanced the dispersion of the vector in the CNS. Further optimization of these steps combining peripheral and intracisternal scAAV gene delivery should facilitate the development of treatments for global CNS diseases, especially diseases involving both the somatic system and the CNS, such as lysosomal storage disorders.

Ciguatera poisoning

Human ciguatera poisoning has a circumtropical distribution and a close association with coral reef fish. Cases of poisoning have been reported along the tropical coast of Queensland and in the Northern Territory. The largest single outbreak of ciguatera poisoning, in Australia, occurred in Sydney in 1987. Human intoxication follows consumption of a variety of tropical fish which contain a potent toxin, ciguatoxin, in their tissues. Ciguatoxin is believed to be elaborated by a benthic dinoflagellate Gambierdiscus toxicus and passed through the food chain to higher level carnivores such as Coral Trout. Human victims of Ciguatoxin usually present with gastrointestinal symptoms within six to twelve hours of ingestion of fish. Following the onset of gastrointestinal disturbances a variety of neurological symptoms are manifested. The duration and type of symptoms displayed by the Sydney victims of ciguatera poisoning will be presented. Ciguatoxin is believed to exert a fundamental physiological action on the voltage dependent sodium channels in nerve fibres. Electrophysiological studies performed on rat and human nerves indicate that ciguatoxin slows conduction velocity and prolongs the absolute and relative refractory periods. The duration and magnitude of the supernormal period is also increased. Identical changes in these nerve conduction parameters have also been recorded from fish nerves. Fish nerves, in vivo, may be protected from Ciguatoxin by Inherent partitioning mechanisms. Until recently there was no effective therapy for the ciguatera syndrome. Intravenous Infusion of mannitol has been reported to effectively alleviate symptoms by a number of workers, however the physiological mechanisms underlying this treatment are as yet not elucidated. Human ciguatera poisoning has a circumtropical distribution and a close association with coral reef fish. Cases of poisoning have been reported along the tropical coast of Queensland and in the Northern Territory. The largest single outbreak of ciguatera poisoning, in Australia, occurred in Sydney in 1987. Human intoxication follows consumption of a variety of tropical fish which contain a potent toxin, ciguatoxin, in their tissues. Ciguatoxin is believed to be elaborated by a benthic dinoflagellate Gambierdiscus toxicus and passed through the food chain to higher level carnivores such as Coral Trout. Human victims of Ciguatoxin usually present with gastrointestinal symptoms within six to twelve hours of ingestion of fish. Following the onset of gastrointestinal disturbances a variety of neurological symptoms are manifested. The duration and type of symptoms displayed by the Sydney victims of ciguatera poisoning will be presented. Ciguatoxin is believed to exert a fundamental physiological action on the voltage dependent sodium channels in nerve fibres. Electrophysiological studies performed on rat and human nerves indicate that ciguatoxin slows conduction velocity and prolongs the absolute and relative refractory periods. The duration and magnitude of the supernormal period is also increased. Identical changes in these nerve conduction parameters have also been recorded from fish nerves. Fish nerves, in vivo, may be protected from Ciguatoxin by Inherent partitioning mechanisms. Until recently there was no effective therapy for the ciguatera syndrome. Intravenous Infusion of mannitol has been reported to effectively alleviate symptoms by a number of workers, however the physiological mechanisms underlying this treatment are as yet not elucidated.

Tandem Scanning Confocal Microscopy (TSCM) of normal and ischemic living kidneys

Tandem Scanning Confocal Microscopy (TSCM) allows one to section optically into and record real-time images of living organs and tissues in a noninvasive fashion. In this paper, we will present some initial TSCM observations of subcapsular nephrons in the living, intact kidneys of Munich-Wistar rats and evaluate the nephron's responses to temporary ischemia and to intravenous infusion of mannitol. The rats were anesthetized with Inactin and a laparotomy performed to expose the kidneys. Using a TSCM equipped with a 20 x water-immersion objective, we optically sectioned through the intact kidney capsule and recorded real-time images of living subcapsular glomeruli and uriniferous tubules. The proximal tubule brush border was highly reflective and allowed us to distinguish between the first and second segments of the proximal tubules as well as the distal tubules. Cellular elements of the blood could be seen passing rapidly through peritubular capillaries and individual glomerular capillary loops. With fluorescent filters in place, intravenously injected carboxyfluorescein was seen to pass through the glomerular capillary loops and then progressively through the different segments of the uriniferous tubules. Ligation of the renal artery resulted in rapid swelling of proximal tubule cells into the tubular lumens, loss of reflectiveness of the microvillous brush borders, and closure of the peritubular capillary spaces. Upon release of the ligature, the proximal tubule lumens again became patent, often opening up abruptly and in a zipper-like fashion down the length of the tubules. Increasing the glomerular filtration rate by intravenous infusion of mannitol resulted in increases in tubular luminal and perimeter dimensions. Mannitol also acted as an effective impermeant osmotic agent and prevented most of the cellular swelling which was otherwise seen in response to renal ischemia.

Treatment of Pediatric Ciguatera Fish Poisoning

Sir .—Ciguatera fish poisoning is a serious public health and economic problem concentrated in the Caribbean and Indo-Pacific areas. Ciguatera poisoning is a clinical syndrome that follows ingestion of fish containing ciguatoxin. Ciguatoxin is a biotoxin produced by a dinoflagellate, Gambierdiscus toxicus , and concentrated in the food chain of predator reef fish. 1 Symptoms consist primarily of distinctive neurologic and gastrointestinal manifestations. Historically, treatment has been supportive. Recently, while reviewing our work in the Marshall Islands, we reported successful treatment of a series of adult patients using an intravenous infusion of mannitol. 2 We here describe successful treatment with mannitol infusion of a young child affected by ciguatera poisoning. Report of a Patient .—A 23-month-old, 9.2-kg Marshallese girl presented in the late evening to the emergency department of Majuro Hospital, Majuro, Marshall Islands, with a chief complaint of persistent crying, severe irritability of 5 hours duration, and inability to sleep.

Pronounced increases in brain levels of calcitonin gene-related peptide after kainic acid induced seizures

Changes in immunoreactivity of calcitonin gene-related peptide (CGRP) were investigated in the brains of rats subsequently to seizures induced by intraperitoneal injection of kainic acid (10 mg/kg, i.p.). Increased levels of the neuropeptide were observed in the frontal cortex (increase of 1300% of control value), striatum (900%), dorsal hippocampus (400%) and amygdala/pyriform cortex (135%) three days after injection of the neurotoxin. Intravenous infusion of mannitol (1.5 g/kg, under thiopental anesthesia) which prevents seizures and post-seizure brain damage suppressed the changes in CGRP-like immunoreactivity. Injection of pentylenetetrazol causing generalized motor seizures resulted in no change of CGRP-immunoreactivity after three days. The pronounced but reversible increases of brain CGRP levels suggest a strong but short-lasting activation of the peptide system. The failure of pentylenetetrazol to produce a similar effect and the protective action of mannitol suggest that sustained seizures and/or post-seizure brain damage may be required to produce the rise in peptide levels.

Abuse of a fire‐extinguishing agent and sudden death in adolescents

Two cases of abuse of bromochlorodifluoromethane (BCF - a fire-extinguishing agent) by inhalation are reported. In the first case, a 15-year-old youth presented in ventricular fibrillation; the second youth was dead on arrival at hospital. Port-mortem toxicological investigations confirmed BCF inhalation in the latter patient. Management of the surviving patient included cardioversion, controlled mandatory hyperventilation, intravenous infusions of mannitol, and barbiturate protection against cerebral ischaemia. He had completely recovered after eight days. Community agencies report that BCF inhalation occurs frequently on the Gold Coast, Queensland. This behaviour can be associated with sudden death from ventricular arrhythmias after cardiac sensitization to endogenous adrenaline. The "lone sniffer" is at greatest risk, and identification of such individuals may prevent a fatal outcome.

Bulk flow of amniotic fluid water in response to maternal osmotic challenge

Amniotic fluid volume is regulated by a complex system of fluid exchanges with fetal and maternal fluid compartments. To assess possible hormonal control of amniotic fluid water exchange with the maternal vascular compartment, we studied the effect of intra-amniotic injections of prolactin, vasopressin, or vasotocin on the amniotic to maternal water flux induced by the acute intravenous infusion of mannitol to the pregnant ewe. This mannitol stimulus increased amniotic fluid osmolality secondary to a shift of free water to the maternal vascular/extracellular compartments. Prior intra-amniotic injection of prolactin but not vasopressin or vasotocin blunted the amniotic fluid osmolar response to maternal mannitol infusion. These results suggest that resorption of amniotic fluid water may occur at the chorioamnion and that amniotic fluid prolactin may have a regulatory function in amniotic fluid volume and osmolar homeostasis.

Injection of hypertonic saline or mannitol accelerates the dehydration-induced activation of dopamine synthesis in the neurointermediate lobe of the rat hypophysis.

The rate of dopamine (DA) synthesis (DOPA accumulation after the administration of an inhibitor of aromatic L-amino acid decarboxylase) was determined in terminals of tuberohypophyseal DA neurons in the neurointermediate lobe (NIL) of the rat hypophysis at various times after the presentation of osmotic stimuli. DA synthesis in the NIL, but not in median eminence or striatum, was increased 24 h but not 4 h after an injection of hypertonic saline (5 ml 15% NaCl/kg, s.c.), provided the animals were not permitted access to water after the injection; 24 h of water deprivation per se was without effect on the rate of DA synthesis. DOPA accumulation in the NIL was also increased after an intravenous infusion of mannitol (25 ml 20% mannitol/kg) plus 24 h of water deprivation. These results suggest that the dehydration-induced activation of tuberohypophyseal DA neurons which is normally seen after 2-3 days of water deprivation can be accelerated if water deprivation is preceeded by injections of hypertonic saline or mannitol.