Granulocyte transfusion experience in pediatric neutropenic fever: Splitted product can be an alternative?

The granulocyte transfusion (GTX) has been used for a long time due to uncontrolled neutropenic fever with antimicrobial agents. In some cases, the product needs to be splitted for using in the next 12 hours. The aim of this study is to evaluate the efficacy of splitted product and clinical response to GTX. In this study, 15 patients with malignancy with 19 neutropenic fever, who had received 56 GTX, were included. Seventeen of 56 GTX were splitted and used in maximum 12 hours during infections which did not respond to antibacterial and antifungal therapy in 7 days. The patients were divided in to response groups as a complete, partial and progressive. The predictive factors for response group were evaluated. GTX were well tolerated in all patients. The median granulocyte dose was 1.26 (0.38-5.22) × 10(9)/kg. Total response rate was 89.5%. The infection-related mortality rate was 10.5%. Although the granulocyte doses are the same in both of the product groups, an hour later ANC increment of primer product was higher than that of splitted product (p = 0.001). Among the products, 48.7% of primer product and 17.6% of splitted product had induced ≥ 1000/mm(3) ANC increment after an hour (p = 0.039). Granulocyte transfusion is safe and effective in controlling the febrile neutropenia attack. GTX should be applied in a short time to provide effective ANC increment. For now, main granulocyte product instead of splitted product should be preferred in case of uncontrolled neutropenic fever with antibacterial/antifungal agents.

A crucial role for IL-6 in the CNS of rats during fever induced by the injection of live E. coli.

Interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 have been established as important mediators of fever induced by lipopolysaccharide (LPS) from Gram-negative bacteria. Whether these pro-inflammatory cytokines are also important in mediating fever induced by live bacteria remains less certain. We therefore investigated the following: (1) the synthesis of TNF-α, IL-1ß, and IL-6 during E. coli-induced fever and (2) the effect of blocking the action of cytokines within the brain on E. coli-induced fever. Body or tail skin temperature (bT or Tsk, respectively) was measured by biotelemetry or telethermometry, every 30 min, during 6 or 24 h. Depending on the number of colony-forming units (CFU) injected i.p., administration of E. coli induced a long-lasting increase in bT of male Wistar rats. The duration of fever did not correlate with the number of CFU found in peritoneal cavity or blood. Because 2.5 × 10(8) CFU induced a sustained fever without inducing a state of sepsis/severe infection, this dose was used in subsequent experiments. The E. coli-induced increase in bT was preceded by a decrease in Tsk, reflecting a thermoregulatory response. TNF-α, IL-1ß, and IL-6 were detected at 3 h in serum of animals injected i.p. with E. coli. In the peritoneal exudates, TNF-α, IL-1ß, and IL-6 were detected at 0.5 and 3 h after E. coli administration. Moreover, both IL-1ß and IL-6, but not TNF-α, were found in the cerebrospinal fluid (CSF) and hypothalamus of animals injected with E. coli. Although pre-treatment (i.c.v., 2 µl, 15 min before) with anti-IL-6 antibody (anti-IL-6, 5 µg) reduced E. coli-induced fever, pre-treatment with either IL-1 receptor antagonist (IL-1ra, 200 µg) or soluble TNF receptor I (sTNFRI, 500 ng) had no effect on the fever response. In conclusion, replicating E. coli promotes an integrated thermoregulatory response in which the central action of IL-6, but not IL-1 and TNF, appears to be important.

Surveillance for healthcare-acquired febrile respiratory infection in pediatric hospitals participating in the Canadian Nosocomial Infection Surveillance Program.

OBJECTIVE: To determine the rates of healthcare-acquired febrile respiratory infection (HA-FRI) in Canadian pediatric hospitals and to determine the vaccination status of patients with healthcare-acquired respiratory syncytial virus (RSV) infection, influenza, or pneumococcal infection who were also eligible for immunoprophylaxis. METHODS: Prospective surveillance was conducted in 8 hospitals from January 1 to April 30, 2005. All hospitalized patients less than 18 years of age were eligible, except for patients housed in standard newborn nurseries or psychiatric units. Infection control professionals reviewed laboratory reports, conducted ward rounds, and reviewed medical records to identify case patients. Descriptive analyses were completed, as well. RESULTS: A total of 96 case patients were identified; 52 (54%) were male, and 48 (50%) were aged 1 year or less. Seventy-two patients (75%) had chronic medical conditions. Respiratory viruses accounted for 72 (71%) of 101 pathogens identified, and RSV was the virus most frequently identified. Of these 96 patients, 9 (9%) died, and 3 (3%) of the deaths were related to the patient's HA-FRI. The mean incidence rate was 0.97 infections/1,000 patient-days (range, 0.29-1.50 infections/1,000 patient-days). Only 2 (15%) of 13 influenza vaccine-eligible children who acquired influenza while hospitalized were reported to have been vaccinated, but influenza vaccination status was unknown for most children. However, 4 (80%) of 5 RSV prophylaxis-eligible children who had healthcare-acquired RSV infection had received immunoprophylaxis with anti-RSV monoclonal antibody. CONCLUSIONS: HA-FRI is mainly caused by viruses such as RSV, and it primarily affects children under 1 year of age and those with chronic medical conditions.

Evaluation by survival analysis on effect of traditional Chinese medicine in treating children with respiratory syncytial viral pneumonia of phlegm-heat blocking Fei syndrome.

OBJECTIVE: To objectively evaluate the clinical effect of traditional Chinese medicine in treating children's respiratory syncytial viral pneumonia (RSVP) of phlegm-heat blocking Fei syndrome (PHBFS). METHODS: A single-blinded multi-center, blocked, randomized and parallel-controlled method was adopted. The clinical study was carried out on 206 children with RSVP-PHBFS who were assigned to two groups, 108 in the test group treated through intravenous dripping of Qingkailing Injection () in combination of oral intake of Er'tong Qingfei Oral Liquid () and 98 in the control group with intravenous dripping of ribavirin injection in combination with oral intake of potassium guaiacol sulfonate oral liquid, all for 10 days. The clinical efficacy was evaluated and compared at the end of the trial from various aspects by three methods including comprehensive efficacy, post-treatment main symptoms score difference and survival analysis of the main symptoms. RESULTS: After treatment, in the test group, 60 patients were cured, 36 markedly alleviated, and 12 improved. In the control group, 41 were cured, 38 markedly alleviated, 18 improved and 1 unchanged. Comparison on the comprehensive efficacy between the two groups shows a better efficacy in the test group (chi(2)=4.4527, P=0.0348). Scores of the main symptoms were lowered after treatment in both groups, the difference was 22.41+/-4.99 scores in the test group and 17.61+/-6.34 scores in the control group, being more significant in the former (t=-5.99, P<0.01). Survival analysis shows that there was significant difference between the two groups in the effect initiating time on such symptoms as fever, cough, copious sputum, shortness of breath, and rales, which was earlier in the test group (P<0.01 or P<0.05). CONCLUSION: Evaluation of the efficacy of traditional Chinese medicine in treating children with RSVP-PHBFS by using the three methods jointly could better show the objectivity of the evaluation.

Compliance with a critical pathway for the management of febrile neutropenia and impact on clinical outcomes.

Febrile neutropenia is associated with significant morbidity and mortality. Managing infectious in neutropenic patients remains a dynamic process, making necessary timely and efficient empirical antibiotic therapy. The implementation of critical pathways has been suggested as a strategy to improve clinical effectiveness. This study evaluated the compliance with an institutional critical pathway for the management of febrile neutropenia and the impact on clinical outcomes at Hospital de Clínicas de Porto Alegre, Brazil (HCPA). We performed a cohort study that prospectively included patients hospitalized from January 2004 to December 2005 and presented febrile neutropenia (190 episodes). Historical controls were selected from March 2001 to April 2003 (193 episodes) before the critical pathway was introduced. This study showed a low rate of full compliance (21.6%; 95% CI 15.7-27.5) with the critical pathway. In most cases, there was partial compliance (67.9%; 95% CI 61.3-74.5). Despite the moderate adherence observed, we recorded a decrease in in-hospital all-cause mortality in the sample studied after protocol implementation (from 24.4 to 14.4%; P = 0.017) and reduction in the length of use of cephalosporin and quinolones. In conclusion, implementation of a critical pathway seems to be an effective strategy to improve clinical outcomes in patients hospitalized with febrile neutropenia.

Ephedrine plus caffeine causes age-dependent cardiovascular responses in Fischer 344 rats.

Human consumption of ephedrine and caffeine in dietary supplements has been associated with a number of adverse effects including changes in the ECG, myocardial infarction, hyperthermia, and, in rare instances, death. The purpose of this study was to investigate the potential mechanisms associated with the cardiotoxicity of combined ephedrine and caffeine ingestion. Seven- and fourteen-week-old Fischer 344 rats treated with ephedrine in combination with caffeine exhibited increases in heart rate (HR), temperature, and corrected QT interval. Of the 14-wk-old rats treated with 25 mg/kg ephedrine plus 30 mg/kg caffeine, 57% died within 3-5 h of treatment, whereas none of the similarly treated 7-wk-old rats nor any of the rats treated with vehicle died. One hour after treatment with this dose of ephedrine plus caffeine, 14-wk-old rats exhibited a larger increase in HR (as % increase over baseline) than 7-wk-old rats. Furthermore, the 14-wk-old rats that died had a higher HR and temperature than the 14-wk-old rats that lived. Histopathological studies suggested interstitial hemorrhage and myofiber necrosis in the 14-wk-old rats treated with the highest concentration of ephedrine and caffeine. This study showed enhanced susceptibility to ephedrine plus caffeine in 14-wk-old rats compared with 7-wk-old rats. The greater mortality in the 14-wk-old rats was associated with increases in body temperature, HR, and myocardial necrosis.

Randomized controlled trial of the effect of daily supplementation with zinc or multiple micronutrients on the morbidity, growth, and micronutrient status of young Peruvian children.

BACKGROUND: Zinc supplements reduce childhood morbidity in populations in whom zinc deficiency is common. In such populations, deficiencies in other micronutrients may also occur. OBJECTIVE: The objective was to determine whether the administration of other micronutrients with zinc modifies the effect of zinc supplementation on children's morbidity and physical growth. DESIGN: Two hundred forty-six children aged 6-35 mo with persistent diarrhea were randomly assigned to 1 of 3 groups to receive a daily supplement of 10 mg Zn alone (Zn; n = 81), zinc plus vitamins and other minerals at 1-2 times recommended daily intakes (Zn+VM; n = 82), or placebo (n = 83) for approximately 6 mo after the diarrhea episode ended. Morbidity information was collected on weekdays. Weight, length, and other anthropometric indicators were measured monthly, and plasma zinc and other indicators of micronutrient status were measured at baseline and 6 mo. RESULTS: Supplement consumption was high ( approximately 90%) in all groups, although slightly more vomiting was reported in the Zn+VM group (P < 0.0001, analysis of variance). The change in plasma zinc from baseline to 6 mo was greater in the 2 zinc groups (6.1, 27.3, and 16.2 micro g/dL in the placebo, Zn, and Zn+VM groups, respectively; P < 0.0001, analysis of variance). The Zn group had fewer episodes of diarrhea, dysentery, and respiratory illness and a lower prevalence of fever and cough than did the Zn+VM group and a lower prevalence of cough than did the placebo group (P = 0.05). No significant effects of supplementation on growth were observed. CONCLUSION: Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone.

[High risk febrile neutropenia in acute leukemia. The experience of a public hospital. National Program of Antineoplastic Drugs in Adult, Hospital del Salvador, 1991-2001]. / Neutropenia febril de alto riesgo en leucemia aguda. Experiencia en un hospital público. Programa Nacional de Drogas Antineoplásicas del Adulto (PANDA), Hospital del Salvador, 1991-2001.

BACKGROUND: Febrile neutropenia is one of the most important problems to face during the treatment of acute leukemia. AIM: To assess the results of a standardized protocol for the treatment of febrile neutropenia and compare it with a period in which treatment was not standardized. PATIENTS AND METHODS: One hundred and eight episodes of febrile neutropenia in 69 patients, treated with a standardized antimicrobial protocol between 1996 and 2001, were analyzed. The protocol consisted in the use of a combination of antimicrobial whose spectrum was broadened progressively according to the isolated microorganisms and the involved foci. These were compared with 83 episodes in 54 patients, treated without standardized protocols between 1990 and 1995. RESULTS: Both groups of patients were comparable. Their ages ranged from 15 to 65 years old. The male/female ratio was 1.3 and the lymphoblastic/myeloid leukemia ratio was 1.4. Sixty one percent of episodes occurred during induction chemotherapy and mean duration of neutropenia was 17 days. A clinically significant focus was identified in 72% of episodes and a microorganism was isolated blood culture in 35% of them. There was a predominance of gram negative organisms. The mortality decreased from 18 to 9% in the period 1996-2000 (p = 0.094). CONCLUSIONS: The use of a standardized antimicrobial protocol reduced the mortality in febrile neutropenia, even when colony stimulating factors and filtered air rooms are unavailable.

Neutropenia febril de alto riesgo en leucemia aguda. Experiencia en un hospital público. Programa Nacional de Drogas Antineoplásicas del Adulto (PANDA), Hospital del Salvador, 1991-2001 / High risk febrile neutropenia in acute leukemia. The experience of a public hospital. National Program of Antineoplastic Drugs in Adult, Hospital del Salvador, 1991-2001

BACKGROUND: Febrile neutropenia is one of the most important problems to face during the treatment of acute leukemia. AIM: To assess the results of a standardized protocol for the treatment of febrile neutropenia and compare it with a period in which treatment was not standardized. PATIENTS AND METHODS: One hundred and eight episodes of febrile neutropenia in 69 patients, treated with a standardized antimicrobial protocol between 1996 and 2001, were analyzed. The protocol consisted in the use of a combination of antimicrobial whose spectrum was broadened progressively according to the isolated microorganisms and the involved foci. These were compared with 83 episodes in 54 patients, treated without standardized protocols between 1990 and 1995. RESULTS: Both groups of patients were comparable. Their ages ranged from 15 to 65 years old. The male/female ratio was 1.3 and the lymphoblastic/myeloid leukemia ratio was 1.4. Sixty one percent of episodes occurred during induction chemotherapy and mean duration of neutropenia was 17 days. A clinically significant focus was identified in 72 per cent of episodes and a microorganism was isolated blood culture in 35 per cent of them. There was a predominance of gram negative organisms. The mortality decreased from 18 to 9 per cent in the period 1996-2000 (p = 0.094). CONCLUSIONS: The use of a standardized antimicrobial protocol reduced the mortality in febrile neutropenia, even when colony stimulating factors and filtered air rooms are unavailable.

Effect of nitric oxide on mortality of mice after whole body hyperthermia.

The objective of this study is to find the role of nitric oxide (NO) in the haemodynamics of mice subjected to heat stress caused by Whole Body Hyperthermia (WBH) treatment. L-arginine (L-arg), a natural substrate for NO synthase (NOS), N-nitro-L-arginine methyl ester (L-NAME), a preferential inhibitor of endothelial NOS, and dexamethasone, a preferential inhibitor of inducible NOS, have been used to study the role of NO in thermal injury caused by WBH treatment. Nitrite in plasma and mortality of Swiss male mice subjected to WBH treatment induced by radiant heat (40 degrees C fo 1 h at 50-55% relative humidity), were monitored in mice pre-treated with either L-NAME, dexamethasone or L-arg. A batch of mice subjected to 24 h fasting prior to WBH treatment was also used to study the above parameters. Injections with 1.5 mg/kg or above of L-NAME just before WBH treatment, induced mortality in mice, with a corresponding drop in plasma nitrite values. L-arg (8 mg/kg) pre-treatment reversed the killing caused by L-NAME in WBH treated mice. L-arg (60 mg/kg) pre-treatment induced mortality in mice subjected to WBH treatment. In the fasted group, a very low dose of L-arg (8 mg/kg) given before WBH treatment led to a significant increase in plasma nitrite levels. In both the normal and fasted groups of mice, 120 mg/kg of L-arg pre-treatment resulted in a sharp increase in plasma nitrite values and subsequent death of mice. The results throw up an important finding, in that the interaction of elevated body temperature, with either a decrease or over production of nitrite oxide, leads to modulation of thermal injury of mice, caused by WBH treatment.

Empiric antimicrobial therapy of febrile neutropenic patients undergoing haematopoietic stem cell transplantation.

This study was conducted to assess the efficacy and toxicity of intravenous (i.v.) ceftazidime and ciprofloxacin in neutropenic febrile patients undergoing high dose myeloablative therapy and hematopoietic stem cell transplantation (HSCT). All patients undergoing HSCT for leukaemia, lymphoma, multiple myeloma and solid tumours received open-label ceftazidime 2 g i.v. every 8 h and ciprofloxacin 400 mg i.v. every 12 h if they developed fever while they were neutropenic. Success with or without modification of this regimen was defined as survival through the neutropenic period; failure was defined as death secondary to infection. Of 106 patients treated with this regimen, the success rate was 99%. Sixty-one of the patients (57.5%) defervesced within 48-72 h and remained afebrile without regimen modification. In 41.5% of the cases (44/106), the regimen was modified because of persistent fever. One patient died secondary to sepsis. The combination of ceftazidime and ciprofloxacin as initial empiric antibacterial therapy in febrile neutropenic patients undergoing myeloablative therapy and HSCT is highly effective and is associated with minimal toxicity.

[The role of cAMP phosphodiesterase inhibitors in the pharmacotherapy of the hypoxic syndrome]. / Rol' ingibitorov fosfodiésterazy tsAMF v farmakoterapii gipoksicheskogo sindroma.

The authors studied the pharmacotherapeutic activity of drugs belonging to various pharmacological groups which are inhibitors of cAMP phosphodiesterase in the hypoxic syndrome. The increase in the level of the secondary intermediate of the adenylate cyclase path in transmission of the intracellular signal from the outer surface of the cell to the nucleus, the hypoxia protector cAMP, under the effect of the drugs under study favorably influenced survival and the course of hypoxic hypoxia in overheating. A combination of quercetin bioflavonoid with acetylsalicylic acid demonstrated stronger antihypoxic and thermoprotector properties. The results were less marked with the use of the calcium channel blocker cinnarizine and an agent of the xanthine pentoxyfelline group. The possible mechanisms of the antihypoxic activity of the drugs under study are discussed.

[A comparative evaluation of the efficacy of pharmacotherapeutic agents in hypoxia in the presence of hyperthermia]. / Sravnitel'naia otsenka éffektivnosti farmakoterapevticheskikh sredstv pri gipoksii na fone gipertermii.

In conditions of acute hypoxia in the presence of hyperthermia drugs were shown to exhibit various degrees of protective activity. Antihypoxic action coupled with thermoprotective activity is manifested by beneficial affect on the course of the pathological process. It is quercitrol that proved to be the most effective drug; it is capable of correcting simultaneously the disturbances emerging in different links of the pathological process: effect on the processes of lipid peroxidation and metabolism of arachidonic acid as well as on the activity of enzymes belonging to the monooxigenaze system in the experiment.

Hyperthermia deaths in Finland in 1970-86.

All cases in which hyperthermia had been determined as the basic cause of death during the period 1970-86 were collected from the records of the Central Statistical Office of Finland. Of the total of 230 cases, 228 were included in the present study; the two remaining victims died abroad, and no autopsy was performed in Finland. Most of the hyperthermia deaths occurred while the decedent was taking a sauna bath; most decedents were men aged 42-62 years. An increase in the total number of hyperthermia deaths, and of male victims, was noted from the beginning of the 1970s onward; the number of female victims remained at a relatively steady level throughout, with the exception of a slight rise in 1986. Acute alcohol consumption was detected in most of the victims; in some cases there was also a reference to chronic alcoholism or recent long-term heavy drinking. The findings suggest that in addition to the acute hazardous effect of ethanol on thermoregulatory mechanisms, the long-term consumption of alcohol may have promoted fatal hyperthermia in these subjects.

Prevention of hyperthermia-induced seizures in immature rats by a hydantoin derivative of naloxone.

The non-specific opiate antagonist naloxone protects immature rats from hyperthermic seizures which occur when the animals are exposed to an environment of 40 degrees C and 55% humidity. Most of the currently used antiepileptic therapeutic agents can be said to contain either a hydantoin or a moiety stereochemically closely related to one. We have added a hydantoin group to naloxone and created a new combined chemical, naloxyl-6-alpha spirohydantoin. The new compound was ten times as effective as naloxone against hyperthermic seizures in 15-day old rat pups. Unlike naloxone, the new naloxone-hydantoin derivative retained a protective effect 24 hrs after injection.

Fever and survival: the role of serum iron.

1. The effects of bacterial infection and temperature on serum iron levels were investigated in the lizard Dipsosaurus dorsalis. 2. Changes in body temperature from normal (38 degrees C) to febrile (41 degrees C) did not alter serum iron levels. Injection with Aeromonas hydrophila led to a significant reduction in serum iron levels, comparable to that found in mammals. This reduction in serum iron level was independent of the lizard's body temperature. 3. When grown in vitro, A. hydrophila grew equally well at afebrile (38 degrees C) and febrile (41 degrees C) temperatures. When the iron levels of the growth medium were reduced, the bacterial growth was diminished at the febrile temperature but was not significantly affected at the afebrile temperature. 4. The addition of iron supplements to bacterially infected lizards led to an increase in the percent mortality. 5. These results indicate that one of the mechanisms behind the beneficial, or adaptive value of fever in D. dorsalis is the decrease in iron available to the pathogenic micro-organisms.

Extreme pyrexia.

Twenty-eight cases of extreme pyrexia seen in a five-year period were analyzed retrospectively. All of the patients had temperatures between 41.1 C (106 F) and 42.2 C (108 F) with a mean maximum temperature of 41.4 C (106.6 F). Infection, thermoregulatory defects, or a combination thereof accounted for fever in these patients. There was little evidence of direct tissue damage caused by fever, and standard therapy with aspirin or acetaminophen, vigorous surface cooling, and volume expansion was generally sucessful. Mortality could be related to the extreme pyrexia in only 7% (2) but an additional 21% (6) of these patients later died from serious underlying diseases.