Liters Of Normal Saline Research Articles

Pulmonary edema and respiratory failure associated with clenbuterol exposure

Background: Clenbuterol is a long-acting β 2-adrenergic agonist used outsidethe United States for treating pulmonary disorders and within the United States in veterinary medicine. Due to itspromotion of muscle growth and lipolysis ( β 3 effects), clenbuterol is illicitly exploited for livestock growth promotion and by bodybuilders. Recently, there have been reports of clenbuterol contamination of heroin and cocaine, resulting in prolonged tachycardia, hypokalemia, hypophosphatemia, and myocardial injury. We report a case of clenbuterol toxicity causing pulmonary edema and respiratory failure. Case report: The patient was a 33-year-old man who inhaled an unknown white powder and developed immediate onset of chest pain, palpitations, tremors, headache, nausea and vomiting. He presented to the emergency department, where the following initial vital signs were recorded: sinus tachycardia, 146 bpm; wide pulse pressure, 116/27 mm Hg; respiratory rate, 20/min; room air oxygen saturation, 99%. He was diaphoretic with a fine tremor and enlarged, reactive pupils. His electrocardiogram showed 1-millimeter ST depressions laterally. A working diagnosis of cocaine toxicity was made, and he was treated with 5 milligrams of intravenous lorazepam and 3 liters of normal saline without significant change in vital signs. Laboratory results were as follows: hypokalemia, 1.9 mmol/L; hypophosphatemia, 0.4 mg/dL; hyperglycemia, 230 mg/dL; lactate, 7.2 mmol/L; anion gap, 18. The patient was admitted to the intensive care unit, and treated with benzodiazepines and haloperidol for agitation, chest pain, and persistent tachycardia. Six hours after presentation, he desaturated to 64% on 100% oxygen. He was intubated for respiratory failure and CXR showed bilateral pulmonary edema. Ultrasound revealed bilateral oculated pleural effusions; creatinine kinase, 8880 U/L (normal rate, 25-185 U/L); creatinine kinase myocardial band, 57 ng/mL (normal rate, <5 ng/mL); troponin I, 1.18 ng/mL (normal rate, <0.4 ng/mL). He was extubated on hospital day 4 and discharged 9 days after initial presentation. His toxicology screen was negative for cocaine. His serum and urine analysis confirmed the presence of clenbuterol, at 6 and 874 ng/mL, respectively. Conclusion: Pulmonaryedema is a known complication of intravenous β 2-adrenergic agonists with a reported incidence of 5% in the obstetrics literature. The etiology is unknown but likely multifactorial, and can include cardiogenic mechanisms such as fluid overload and catecholamine-induced myocardial necrosis, and noncardiogenic mechanisms such as direct toxicity and increased pulmonary vessel permeability. This is the first documented case of pulmonary edema after inhalational β 2-adrenergic agonist exposure. Based on the recent epidemic of clenbuterol exposure, clinicians should be aware of the possibility of pulmonary edema and consequent respiratory failure.

Acute kidney injury following proton pump inhibitor therapy

A 63-year-old male with a past medical history significant for hypertension for 12 years, stage 3 chronic kidney disease (baseline serum creatinine concentration, 1.4 mg/dl; estimated glomerular filtration rate, 54ml/min) secondary to hypertensive nephrosclerosis presented with generalized malaise and weakness for 2 weeks. He was referred for admission to the hospital for evaluation of renal dysfunction. Three months before this admission, he was treated with naproxen 500 mg per day for bilateral knee pain owing to degenerative joint disease. After 2 weeks of therapy, he developed epigastric pain with anorexia, vomiting, and hematemesis. He underwent upper endoscopy, which revealed esophageal, gastric, and duodenal erosions and ulcerations. Serum creatinine concentration was 2.3 mg/dl. Naproxen was discontinued, esomeprazole 40 mg per day was initiated as anti-acid therapy and a liter of normal saline was administered intravenously. Two days later, the serum creatinine concentration returned to baseline (1.4mg/dl) and the patient was discharged home on esomeprazole and tramadol/acetaminophen. On presentation to the hospital, blood pressure was 142/88mm Hg, pulse 100/min, temperature 98.9 degrees F, and respiratory rate 18/min. The conjunctivae were pale with anicteric sclera. Heart and lung examination was unremarkable except for a grade 1/6 systolic ejection murmur over the left sternal border. The abdomen had minimal epigastric tenderness, and there was trace edema in the ankles. There was no skin rash, petechiae, or purpura. Medications included amlodipine 10mg daily, esomeprazole 40 mg daily, diazepam 2.5 mg daily, tramadol/acetaminophen 100 mg twice daily, and calcitriol 1 mcg every other day. Admission laboratory data are noted in Table 1. The remaining laboratory values, including liver function tests and coagulation profile were within normal range. There was no peripheral eosinophilia. Urinalysis was notable for specific gravity, 1.015; pH, 6.0; trace blood; 1 + protein; and trace leukocyte esterase. Examination of the urine sediment revealed 2-5 dysmorphic red blood cells/high-power field, 2-5 white blood cells/high-power field; few renal tubular epithelial cells; no cellular or granular casts were present. Urine eosinophils (Wright stain) were negative. Fractional excretion of sodium was 1.8% whereas spot urine protein/creatinine ratio was 0.65 mg/g. A sonogram of kidneys demonstrated slightly echogenic but normal-sized kidneys without hydronephrosis. The patient was administered 2 Liters of normal saline and all medications except amlodipine were held. Despite this, the serum creatinine concentration rose the next day to 5.2 mg/dl, whereas urine output was 550 ml for the day. A kidney biopsy was performed for non-oliguric acute kidney injury.

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Surgical strategy and management of infected pancreatic necrosis.

Infected pancreatic necrosis and sepsis are the leading causes of death in patients with necrotizing pancreatitis. Between 1986 and 1993, 123 patients with infected pancreatic necrosis were treated; in all cases the infected necrosis extended to the retroperitoneal area. Surgical treatment was performed a mean of 18.5 days after the onset of acute pancreatitis. Operative management consisted of wide-ranging necrosectomy through all the affected area, combined with continuous widespread lavage and suction drainage applied for a mean of 39.5 days, with a median of 6.5 litres of normal saline per day. In 56 cases (46 per cent), another surgical intervention (distal pancreatic resection, splenectomy, cholecystectomy, sphincteroplasty or colonic resection) was also performed. Bacteriological findings revealed mainly enteric bacteria, but Candida infection was detected in 21 per cent of patients. The overall hospital mortality rate was 7 per cent (nine patients died). Infected pancreatic necrosis responds well to aggressive surgical treatment, continuous, long-standing lavage and suction drainage, together with supportive therapy combined with adequate antibiotic and antifungal medication.

Urethral Injury Following Genital Mutilation in Pregnancy: A Rate Cause of Postpartum Haemorrhage

OBJECTIVE: To reveal the danger in genital mutilation in pregnancy METHOD:The authors present the case of a 20-year old primigravida who was subjected to this ritual in the third trimester, sustained focal injuries to the urethra which initially healed, but during delivery 4 weeks later, and resulted in significant primary postpartum haemorrhage. RESULTS: Her pregnancy was unsupervised; she received 2 doses of tetanus toxoid 4 weeks apart in a local health center. The pregnancy was uneventful until she was subjected to the genital cutting 4 weeks earlier by an appointed lady in the community whom she recognized as a health assistant who gave her the tetanus toxoid injection. The aim was to enable her achieve “a safe vaginal delivery and be accepted as a woman in her Community”. The procedure involved slicing of the upper part of her urethral region along with the clitoris with a “sharp object”, a local herb was applied and there was no significant bleeding as her thighs were strapped together for about 2 hours when the ritual singing was completed Her cervix could barely admit two fingers; there was neither evidence of laceration nor active haemorrhage from the uterus. A diagnosis of primary post partum haemorrhage due to genital injuries secondary to female genital mutilation in pregnancy in imminent shock was made. Immediate resuscitation included rapid infusion of 1 liter of normal saline; she received two units of compatible whole blood at a pre transfusion packedcell volume of 18%. CONCLUSION: There is the need to establish National Policies and Programmes that will be effectively backed with legal instruments to abolish female genital mutilation. Health care providers and policy makers in the mean time should be aware and well trained in the management of FGM complications to decrease the risks of mortality and serious morbidity. The obvious danger of this barbaric ritual in pregnancy labour and pueperium is highlighted for increased sanctions and advocacy at all level of healthcare. Nig Jnl Orthopaedics & Trauma Vol.2(2) 2003: 130-133

FINISH LINE FATIGUE IN TRIATHLON - AN EXERCISE IN DIFFERENTIALS

1729 HISTORY - LF, a 30 yo WF high level triathlete, presented to the finish line of an Olympic Distance Championship Triathlon disoriented and unable to ambulate further without assistance. She was immediately supported, but after several steps was unable to ambulate further. She was subsequently carried immediately to the finish line medical tent. Ambient Weather: Wet Bulb Globe Temperature 81 F.; Sunny skies with haze; minimal breeze. PHYSICAL EXAMINATION: Temp. (rectal) Deferred (agitation). HR: 150. R: 30, deep. BP 110/60. Skin was warm and moist (sweaty); Turgor: Fair. MS: Awake, confused, agitated; Oriented to person, season, month; Monosyllabic. Exercise Associated Collapse Exertional Hyperthermia Dehydration INITIAL TREATMENT & FOLLOW UP: Six-point ice packs; free-flow garden hose. Two liters of normal saline given intravenously. Mental status steadily improved; HR steadily normalized. Began to take oral fluids; eventually able to ambulate unassisted. Conversation lucid and appropriate. Voided clear yellow urine. LF, a resident physician, was discharged to the care of family and friends. Subsequent to release from the Medical Tent, LF returned home, continued with dry heaves, developed frequent watery diarrhea, remained fatigued, and did not void again. She proceeded to the Emergency Room after 3 hours. Persistent Dehydration Rhabdomyolysis Acute Renal Failure / Acute Tubular Necrosis (?)Hyponatremia (?)Bowel Ischemia TEST & RESULTS IN ER: LABS: WBC = 30.45 with Left Shift; Hgb 12.9; CPK 744; Na 142, K 3.9, Cl 111, CO2 20, BUN 20, Cr 1.7; UA: Yellow, Clear, SpG 1.020, pH 5.0, Keto 15; Myoglobin - NEG. CXR: Bibasilar atelectasis/infiltrate; B/L pleural effusions. WORKING DIAGNOSIS: Dehydration; Mycoplasma pneumonia. 10-12 L NS given in ER Azithromycin LAB FOLLOW UP: Legionella: Negative. Mycoplasma: Negative (CF 1:8). Exertional Heat Injury with Dehydration & Mild Acidosis. Viral vs Other Bacterial pneumonia vs Pulmonary Congestion (Fluid Overload) Other Potential Underlying / Precipitating Process(es) • Leptospirosis; Overtraining Syndrome; Anemia vs "Sports Anemia"

High pressure pulsatile lavage of contaminated human tibiae: an in vitro study.

This study was designed to examine the effect of high pressure pulsatile lavage (HPPL) on bone destruction and propagation of bacteria in experimentally contaminated human tibiae. Using an in vitro model, nine human tibiae from above-knee amputations were tested. A mid-diaphyseal tibial shaft fracture was created, and each end of the fracture was contaminated with bacteria (six tibiae with Staphylococcus aureus, three tibiae with Escherichia coli). The proximal end was designated as the control and the distal end was the test site. The test site was debrided by HPPL (seventy pounds/square inch, 1,200 milliliters/minute, 1,050 cycles/minute) with three liters of normal saline, whereas the control site did not receive any form of irrigation. Serial sections at increasing distance from the fracture site were cultured and the numbers of bacterial colony-forming units (CFUs) were determined at each level. The degree of macroscopic architectural change in each serial section was graded on an ordinal scale. Analysis of culture data revealed a reproducible pattern of bacterial propagation into the intramedullary canal. Peak bacterial seeding occurred at two to three centimeters from the fracture site (p = 0.023, Wilcoxon signed rank test). The degree of bone destruction varied proportionally with the depth into the canal and was found to be predictive of the extent of bacterial propagation determined by culture data. In an in vitro model of a contaminated fracture, HPPL resulted in bacterial seeding into the intramedullary canal and significant damage to the architecture of the bone. These observations might have clinical significance.

High pressure pulsatile lavage irrigation of intraarticular fractures: effects on fracture healing.

To evaluate the effects of pulsatile lavage and bulb syringe irrigation on fracture healing in vivo. Randomized prospective trial in an animal model. Medical school orthopaedic department. Thirty New Zealand white rabbits. The control group (C) underwent osteotomy of the medial femoral condyle, stabilization, and closure. The bulb syringe and pulsatile lavage groups underwent the same procedure as group C, with the addition of irrigation with one liter of normal saline via a bulb syringe (B) or a pulsatile lavage system (P). Animals were administered two fluorescent bone stains: xylenol orange at the time of operation, and calcein green one week postoperatively. Animals were euthanized two weeks postoperatively and femurs were retrieved for histological analysis. Union was determined by examination of microradiographs under light microscopy. The viability of bone along the fracture site was determined by evaluation of xylenol orange and calcein green staining under fluorescent microscopy. The density of new bone formed in the osteotomy site was assessed by computerized digitization of standardized regions of the proximal and distal osteotomy. Xylenol orange bands were present a mean of 66 +/- 8 percent (mean +/- standard error of the mean), 65 +/- 6 percent, and 44 +/- 5 percent of the distance along the osteotomy in groups C, B, and P, respectively (p < 0.001). Calcein green bands were present throughout the osteotomy site in all specimens. Calcified new bone was present in 62 +/- 4 percent, 58 +/- 7 percent, and 41 +/- 9 percent of the area measured in groups C, B, and P, respectively (p = 0.07). Twenty percent of the osteotomies in groups C and B did not unite, compared with 30 percent in group P (p > 0.5). Pulsatile lavage irrigation of fresh intraarticular fractures in rabbits has a detrimental effect on early new bone formation; this effect, however, is no longer apparent two weeks following irrigation. While this study evaluated the effects of pulsatile lavage irrigation in noncontaminated fractures without extensive soft tissue injury, the detrimental effects observed on early new bone formation may translate to an increased risk of nonunion in the setting of a contaminated open fracture with extensive soft tissue injury. Based on the results of this investigation, the selective use of pulsatile lavage irrigation appears warranted. In the absence of gross wound contamination, irrigation with a bulb syringe appears less likely to impair fracture healing than does pulsatile lavage irrigation. Expansion of the model used in this study to include bacterial contamination and soft tissue crushing may further elucidate the effects of pulsatile lavage irrigation on fracture healing.

Study of the Knowledge about Crystalloid Solutions in Medical Personnel: A case report

Background : The clinicians frequently use crystalloid solutions to manage inpatients and outpatients. Recently Normosol becomes available but there is little understanding of Normosol. So we surveyed residents to assess the level of knowledge about three crystalloid solutions. Methods : The respondents were 46 residents of internal medicine, general surgery, pediatrics, and anesthesiology. The questionnaire asked for the following information: To list the constituents and their concentrations in each 1 litre of normal saline, Hartmann's solution, and Normosol; to match correct pH and osmolality to each solutions; to describe the metabolism and role of lactate in Hartmann's solution. Results : All 46 (100%) knew that both sodium and chloride ions were present in normal saline. Twenty six (57%) of them knew correct concentration of sodium and chloride. The presence of sodium ion in Hartmann's solution was known by 44 (96%) and its concentration was recognized by 20 (43%). Chloride ion and potassium ion in Hartmann's solution were recognized by 43 (93%) and 42 (91%), respectively. Fifteen (33%) knew correct constituents of Hartmann's solution. Only three (7%) knew correct constituents and their concentration of Hartmann's solution. Thirty six (76%) knew that bicarbonate is formed by metabolism of lactate. No one accurately recorded the correct constituents of Normosol. Conclusions : The constituents and their concentrations of normal saline are well known to residents but those of Hartmann's solution and Normosol are not. Our survey reveals that there was little understanding of the reasons for including lactate in Hartmann's solution and even less of presence of acetate in Normosol. (Korean J Anesthesiol 1998; 34: 403∼408)

Intraperitoneal Chemotherapy with Mitoxanthrone in Ovarian Cancer

Ovarian carcinoma remains confined to the peritoneal cavity for the greater part of its natural history, so intraperitoneal (i.p.) administration of chemotherapy could result in greater total drug exposure of the tumor and minimize systemic antiblastic drug side effects. The aim of this study was to evaluate the therapeutic efficacy and toxic effects of intraperitoneal mitoxanthrone in patients affected by ovarian carcinoma with macroscopic absence of disease or minimal residual disease. Ten patients were enrolled (stage II and III) who had been previously treated with neoadjuvant systemic chemotherapy (CDDP or CBDCA + CTX) and radical surgery resulting in macroscopic absence of disease or minimal residual disease (< 1 cm). Mitoxanthrone (25 mg/m2) was instilled in 2 liters of normal saline every four weeks for 2-4 cycles. A total of 26 courses was administered; two patients discontinued i.p. therapy, one for chemoperitonitis and another for bowel perforation requiring catheter removal. Of the 10 patients receiving i.p. chemotherapy, 7 are alive at 5 years from radical surgery, and 3 had relapses at 13, 14 and 57 months, respectively, from radical surgery. Intraperitoneal mitoxanthrone appears to be an effective second-line therapy in ovarian cancer; it is well tolerated as far as toxic effects are concerned, allowing cost reduction and improved patient compliance. For those cases requiring a limited number of peritoneal accesses traditional percutaneous systems have a more favorable cost/benefit ratio.

Percutaneous anterior discectomy under ultrasound guidance.

The object of this experiment was to demonstrate that, by using a peritoneal fluid infusion coupled with ultrasound guidance, a safe anterior entry into the L5-S1 disc of the pig could be made. The goal was to develop a procedure with the advantages of a laparoscopic approach to the disc which has been published to allow removal of extruded herniations, that a neurosurgeon could perform without a general surgeon in attendance. The procedure was carried out under general anesthesia and fluoroscopic control. One liter of normal saline was then infused into the abdomen of a pig. Under ultrasound guidance and laparoscopic confirmation, a Nucleotome was placed into the L5-S1 disc and the disc was aspirated. The results showed that the disc was safely entered in all 5 pigs. The disc was successfully removed in 4 of 5 pigs. In all animals the bowel floated out of the pelvis, obviating the need for bowel manipulation. Laparoscopic ultrasound was needed for visualization in 3 pigs, while external ultrasound was used in two. Our conclusion is that peritoneal fluid infusion and ultrasound guidance, when applied to laparoscopic anterior discectomy, eliminates the need for retroperitoneal dissection and bowel manipulation, significantly simplifying the laparoscopic discectomy procedure.

Computerized Tomography of the Abdomen and Pelvis with Peritoneal Administration of Soluble Contrast (IPC-CT) in Detection of Residual Disease for Patients with Ovarian Cancer

Forty-five ovarian cancer patients were submitted to abdominopelvic computed tomography after intraperitoneal administration of soluble contrast in large fluid volumes (3 liters of normal saline) (IPC-CT), for a total of 66 exams. In all cases standard abdominopelvic CT scanning had previously missed the presence of disease. Peritoneal access was achieved by a temporary Teflon catheter inserted blindly. No major complications related to peritoneal access or fluid administration occurred. Laparotomy was performed in all cases to evaluate accuracy of this new diagnostic procedure. Overall, 32/66 exams showed no abnormal findings. In 9/32 cases persistence of disease was demonstrated by laparotomy. The remaining 34 exams were suggestive of persistence of tumor. In 19 cases CT scan showed nodular images or peritoneal thickness. Persistence of disease was confirmed by laparotomy in all instances. In 15 cases only an abnormal diffusion of soluble contrast into peritoneum (suprahepatic, anterior, or parietocolic region) was demonstrated. In 11/15 persistence of tumor was found at laparotomy. To summarize, IPC-CT revealed persistence of tumor in 30/39 cases (77% sensitivity). Positive results were predictive of persistence of disease in 30/34 cases (88% specificity). This new procedure was able to detect persistence of disease in most of our patients showing negative standard CT (30/39 vs 0/39; P < 10E-8) and its diagnostic accuracy was even better than standard CT+serum tumor markers (30/39 vs 16/39; P < 0.001). In conclusion, IPC-CT could be very effective in monitoring response to treatment and could markedly reduce the number of ovarian cancer patients requiring second-look laparotomy.

Salvage Intraperitoneal Mitoxantrone Therapy of Ovarian Cancer: Influence of Increasing the Volume of Treatment

Despite the demonstrated activity of intraperitoneal mitoxantrone in patients with small volume-platinum-refractory ovarian cancer, previous reports have revealed that many patients fail to achieve adequate distribution of the cytotoxic drug throughout the peritoneal cavity when delivered in a "standard" 2-liter treatment volume. In an effort to improve the distribution and therapeutic efficacy of intraperitoneal mitoxantrone, 22 patients with platinum-refractory ovarian cancer were treated with the drug at a dose of 10 mg/m2 given in 2 liters of normal saline followed by an additional 1-2 liters every 2 weeks for eight cycles. The surgically defined complete response rate in 17 patients evaluable for response with platinum-refractory ovarian cancer was 24%, with an overall response rate of 29%. Of 18 in which the influence of treatment volume could be examined (4 patients developed catheter failure), 12 (67%) were able to tolerate a 4-liter treatment volume for >80% of courses, with a total of 15 patients (83%) receiving treatment with a minimum of a 3-liter treatment volume. We conclude that it is possible to safely increase the intraperitoneal treatment volume to 3-4 liters in most patients undergoing this therapeutic strategy. While the impact on therapeutic efficacy of expanding the volume employed for cytotoxic drug delivery remains to be defined, in theory this approach may optimize the opportunity for agents achieving high-intraperitoneal concentrations to produce their maximal cytotoxic effect.

Characteristics of red cell concentrates subjected to a viricidal procedure and stored for 35 days

Several approaches have been proposed to inactivate contaminating viruses in cellular blood products. Efforts to sterilise red cell concentrates have had limited success at the red cell and protein concentrations encountered in transfusion practice. We have studied the invitro properties of red cells exposed to a viricidal solution containing sodium chlorite and lactic acid, where the generation of chlorous acid acts as the sterilisation mechanism. Red cell concentrates (RCC's) were washed with one litre of normal saline containing 63 mG of lactic acid and 11.5 mG of sodium chlorite, concentrations previously shown to inactivate > 5 logs of Human Immunodeficiency Virus in 5 minutes. Total contact time of the sterilising solution with the red cells was 10 minutes, after which they were washed with one litre of normal saline followed by 500 mL of an additive solution (AAS - TUTA) formulated to preserve red cell metabolism. Red cell haemolysis, potassium leakage. Adenosine Tri-Phosphate (ATP), 2,3 DiPhosphoglycerate (2,3 DPG) and pH were measured over the 35 day storage period (Table).ATPuM/G HbFree HbmG/unitFree K+mmol/unitHCT%QC limit1.5<500<9.055±5RCC's2.3±0.3180±453.5±0.448±11 Mean+SD for 6 RCC's treated with sterilant, all results at Day 35. All parameters measured showed adequate maintenance over storage. Red cells which had been frozen in liquid nitrogen were similarly treated after thawing and deglycerolisation. No significant differences from control units were observed, with AAS - TUTA as a final suspending medium. While further invivo studies as well as more extensive viral inactivation data are required, these findings indicate that this method shows promise as a procedure to sterilise red cells.

Are heat stroke patients fluid depleted? Importance of monitoring central venous pressure as a simple guideline for fluid therapy

During pilgrimage season (Hajj) in Saudi Arabia 34 patients with heat stroke (HS) were centrally cannulated to assess their state of hydration and fluid requirement during cooling period. Central venous pressure (C.V.P.) measurements indicated that most victims of heat stroke had normal C.V.P. on arrival at heat stroke centres and may not be fluid depleted. Twenty-two patients (64.7%) had normal or above normal C.V.P. Twelve patients (35.3%) had zero or below zero C.V.P. Six patients (17.6%) had above 10 cmH2O (range 10-26 cmH2O) and could have developed acute congestive heat failure and pulmonary edema if they had been transfused at the standard recommended rate of 3-4 litres of fluid during an average cooling time of 1 h as has been practiced in the heat stroke centres to date. This study also showed that heat stroke patients should not be briskly transfused because the heart may be affected by heat stroke per se and an unmonitored challenge by brisk i.v. therapy during cooling (which on its own increases preload on the heart due to peripheral vasoconstriction) can lead to acute overload problems. An average of 1 litre of normal saline or Ringer's lactate (crystalloids) was sufficient to normalize C.V.P. during the cooling period and to restore an optimal state of hydration without predisposing to congestive cardiac failure and pulmonary edema--the potential to develop disastrous adult respiratory distress syndrome and disseminated intravascular coagulopathy.

Cisplatin induced emesis: preliminary results indicative of changes in plasma levels of 5-hydroxytryptamine

Nauseaandvomiting induced bychemotherapy isa variable responserelated tothenatureandintensity oftreatment and patient susceptility. Themechanism whereby chemotherapy evokes nausea andvomiting isuncertain butrecently, the ability of5-HT3receptor antagonists toantagonise chemotherapy induced emesis inanimals (Costall etal., 1986; Miner & Sanger, 1986) andman (Cunningham etal., 1987; Leibundgut & Lancranjan, 1987; Krisetal., 1989) hasfocused interest on theroleof5-hydroxytryptamine (5-HT). Ithas beenhypothesised thatemetogenic chemotherapeutic agents may release 5-HTtotrigger theemetic reflex via5-HT3 receptors located atcentral sites or on theafferent vagus nerve(Andrews etal., 1988; Hawthorne etal., 1988; Higgins etal., 1989). 5-HTisfoundinhighconcentration inthe enterochromaffin cells andplatelets anda release of5-HT fromsuchsites wouldbeexpected toelevate thecirculating levels of5-HT(Verbeuren, 1989). Thepresent studies were designed toinvestigate whether plasma 5-HTlevels areincreased during chemotherapy inpatients receiving thepotent emetogencisplatin. Tenmalepatients agedbetween 20and39years(median 30years) undergoing cisplatinum-containing cytotoxic therapy formetastatic germ cell tumourofthetestis (teratoma eight patients, seminoma twopatients) were studied during thefirst 24hofa 5-day courseoftreatment. Commonlyused schedules oftreatment were employed, mainlytheBEP regime (bleomycin, etoposide andcisplatinum). Allpatients received pre-chemotherapy antiemetics. Although there were minorvariations intheantiemetic regime tosuit individual patients, thecommonly usedschedule was lorazepam 2mg, metoclopramide 1Omg anddexamethasone 8mg, allgiven intravenously athour0,together withfurther dosesof appropriate drugs on demandinthecaseofnauseaorvomitingdeveloping after theinitiation oftherapy. Indwelling cannulae (standard 22gaugeneedle or a 22 gaugeVenflon) were inserted intoa surface veinon the dorsumofthehandandsealed withattachable rubber caps. Intravenous cisplatin (20mg m-2)was administered in1 litre ofnormalsaline over4h viaa surface veinoftheopposite forearm using an IMED 960volumentric infusion pump. Bloodsamples weretakenimmediately before theinfusion of cisplatin andthenat2,4,6,8,16and24hafter thestart of treatment. Eachsampling involved theremovalof5 ml of bloodprior tothecollection ofa 2.7mlsample intoa 2.7ml monovettevial(Startedt). The contentsofthevialwere immediately mixed.Within5-15minof collection 1ml aliquots ofthesamples were removedandcentrifuged at 15,000 g for3minto separate thebloodcells fromthe plasma. Aliquots of200jil ofplasma were thenremoved, immediately frozen andstored inliquid nitrogen before analysis. Fortheextraction of5-HT,8 of20mg ml-'

Volume homeostasis in calves with artificial atria and ventricles

We examined whether replacement of cardiac atria and ventricles with total artificial hearts (TAH), a procedure that removes cardiac nerves and all sources of atrial natriuretic factor (ANF), would cause alterations in volume homeostasis in awake calves. Preoperatively, extracted plasma immunoreactive (ir)ANF levels were 13.3 +/- 0.6 and remained postoperatively at 10.5 +/- 0.4 pg/ml (P less than 0.01). TAH implantation caused systemic and pulmonary hypertension (P less than 0.01), salt retention, edema, and significant elevations of plasma renin, aldosterone, and arginine vasopressin. In intact calves rapid infusion of 6 liters of normal saline raised irANF levels to 73.7 +/- 6.5 pg/ml (P less than 0.01) and elicited a large natriuresis and diuresis. No such response to 6 liters of normal saline was obtained after calves had recovered from TAH implantation. Reduction of cardiac output (CO) by 50% caused further salt retention and no change in irANF levels. Elevation of CO back to and 33% above base line produced only a diuresis, whereas salt retention persisted and irANF levels remained unchanged. The same maneuvers elicited in surgical control calves (artificial ventricles only, largely intact atria) a significant increase in irANF levels and a diuresis and natriuresis. In conclusion, alterations in volume homeostasis observed after TAH implantation seem to be the consequence of at least two pathophysiological mechanisms: 1) functional ANF "deficiency," characterized by apparently unregulated ANF secretion from noncardiac sites, and 2) cardiac denervation.

Atrial natriuretic factor in the elderly: diminished response to epinephrine

We have previously found that epinephrine (EPI) increases plasma immunoreactive atrial natriuretic factor (irANF) in young human subjects. Because elderly humans have decreased sensitivity to adrenergic stimulation, we compared plasma irANF responses to intravenous infusion of EPI, 5 micrograms/min for 80 min in six young (ages 20-29) and nine old (ages 62-75) healthy subjects. In addition, we measured plasma irANF responses of the nine old subjects to 1 liter of normal saline infused over 30 min. Young and old subjects had similar basal EPI levels [108 +/- 18 vs. 106 +/- 10 (SE) pg/ml], but basal irANF levels tended to be higher in the old (32 +/- 7 vs. 50 +/- 8 pmol/l, P = 0.15). The young subjects had a significant increase in irANF levels after the EPI infusion (32 +/- 7 vs. 59 +/- 11 pmol/l, P less than 0.02), but there was no change in irANF in the old (50 +/- 8 vs. 48 +/- 7 pmol/l) despite similar plasma EPI levels in young and old (1,125 +/- 57 vs. 1,183 +/- 52 pg/ml). In contrast, the irANF response of the old subjects to saline infusion was striking: all nine subjects demonstrated a rise in irANF (P less than 0.01); mean levels increased from 54 +/- 4 pmol/l to a peak of 122 +/- 23 pmol/l. We conclude that healthy elderly subjects have a defect in EPI-stimulated ANF secretion, a finding compatible with other evidence for diminished sensitivity to adrenergic stimulation in aging.(ABSTRACT TRUNCATED AT 250 WORDS)

A phase I–II trial of cisplatin, hyperthermia and radiation in patients with locally advanced malignancies

A Phase I–II trial testing the addition of systemic cisplatin (CDDP) to local hyperthermia and radiation was conducted to determine the dose of cisplatin that is tolerable once weekly for 6 weeks and to estimate the therapeutic potential of this trimodality combination in patients with locally advanced malignancies. Cisplatin at 20 mg/m 2 (4 patients), 30 mg/m 2 (8 patients), and 40 mg/m 2 (12 patients) was given rapidly (over 5–10 min) i.v. after prehydration with 1 liter of normal saline. After approximately two-thirds of the cisplatin dose had been delivered, microwave hyperthermia was begun and continued for 60 min; the target minimum tumor temperature was 43°C. Following hyperthermia, a 400 cGy fraction of radiation was delivered to the tumor. On other days during the treatment weeks, additional 200 cGy fractions were given to total doses of 6,000–6600 cGy in patients with full radiation tolerance or 2400–3600 cGy in patients with limited radiation tolerance. The 24 patients in this trial had a median age of 57 years and the predominant sites/tumor types were head and neck/squamous cell carcinoma (9) and chest wall/breast adenocarcinoma (9). Seventeen of the 24 treated tumors (70%) had previously been irradiated. Eighteen patients (75%) had received prior chemotherapy and nine patients (38%) had previously been treated with cisplatin. Bone marrow suppression was dose limiting in patients heavily pretreated with chemotherapy and chest wall radiation. No significant toxicities were observed at the 20 and 30 mg/m 2 dose levels, but 5 of the 12 patients (42%) treated at 40 mg/m 2 required modification of the cisplatin dose because of blood count suppression in four patients and mild renal dysfunction in one patient. Each of the patients with bone marrow suppression, however, had been heavily pretreated except for one patient with thrombocytopenia due to hypersplenism. Nausea and vomiting were mild with use of a standard, multiagent antiemetic regimen. Twelve patients (50%) attained a complete regression (CR) and 12 patients (50%) a partial regression (PR). Complete regression appeared to correlate with smaller tumor volumes (115 cc for CR versus 199 cc for PR patients) and higher tumor temperatures (4.6 average minimum equivalent minutes at 43°C in CR versus 2.0 min in PR patients). Local toxicities included second degree burns in 12 patients (50%) and third degree burns in 6 (25%), but all burns healed in 4–12 weeks without surgical intervention. There was no significant increase in acute radiation reactions. This protocol proved feasible and effective, although time consuming. A cisplatin dose of 30 mg/m 2 i.v. weekly for 6 weeks appears tolerable even in heavily pretreated patients. The dose of cisplatin that is tolerable in untreated patients is at least 40 mg/m 2 weekly for 6 weeks and may well be higher but has yet to be determined.

Ceftizoxime prophylaxis in major gynaecological surgery

SummarySixty women who were due to undergo major gynaecological surgery consented to enter the trial. Thirty six abdominal and twenty four vaginal procedures were performed for a wide range of gynaecological conditions. The patients were divided randomly into two groups. One group was given an intravenous infusion of 4g of ceftizoxime in one litre of normal saline, starting pre‐operatively to run in continuously over 24 hours. The other group was used as a control. There was no significant difference in post‐operative infection rate between the two groups of patients.