Passive-active immunization in infants of hepatitis Be antigen-positive mothers. Comparison of the efficacy of early and delayed active immunization

OBJECTIVE: To assess the efficacy of late active immunization against hepatitis B concomitant with diphtheria, pertussis, tetanus, and polio vaccine in high-risk infants receiving hepatitis B immune globulin at birth. DESIGN: Randomized study of infants born to mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis Be antigen (HBeAg). SETTING: Three large city hospitals and one rural area providing prenatal care and obstetric services. SUBJECTS: Eighty neonates of HBsAg- and HBeAg-positive carrier mothers received 0.5 mL/kg of body weight hepatitis B immune globulin within 2 hours of birth and hepatitis B vaccine (10 micrograms) at 0, 1, 2, and 11 months of age (group A) or at 3, 4, 5, and 11 months of age concomitant with diphtheria, pertussis, tetanus, and polio immunization (group B). A second dose of hepatitis B immune globulin was given to infants on schedule B at 3 months. MAIN OUTCOME MEASURES: Blood samples were collected at 0, 3, 6, 11, and 12 months of age and tested for antibodies against hepatitis B core antigen and HBsAg. Follow-up visits were scheduled annually up to 5 years of age. RESULTS: Eight infants were excluded from analysis. During the study period, six children became HBsAg carriers, three in each group, which corresponds to a 5-year incidence of infection of 9% and 8% for groups A (three of 35) and B (three of 37), respectively. Subclinical infections (persistent anti-HBc positivity beyond month 12 or appearance of anti-HBc) were encountered in another eight infants (four in each group). CONCLUSION: Late active immunization starting at 3 months of age appears to provide similar protective efficacy as active immunization starting at birth when combined with hepatitis B immune globulin at 0 and 3 months of age.     

The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin Study Group

BACKGROUND: Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions. METHODS: We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward. RESULTS: The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02). CONCLUSIONS: Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.     

A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants

BACKGROUND: Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. METHODS: We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 g) who had respiratory index scores (mean airway pressure x the fraction of inspired oxygen) of 52.4 at two weeks of age. One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory-index score of > or =2.4 on treatment day 14) or additional placebo for two weeks. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose was then tapered. RESULTS: The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks' postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P< 0.001) in both groups. CONCLUSIONS: Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of ages.     

Aluminum neurotoxicity in preterm infants receiving intravenous-feeding solutions

BACKGROUND: Aluminum, a contaminant of commercial intravenous-feeding solutions, is potentially neurotoxic. We investigated the effect of perinatal exposure to intravenous aluminum on the neurologic development of infants born prematurely. METHODS: We randomly assigned 227 premature infants with gestational ages of less than 34 weeks and birth weights of less than 1850 g who required intravenous feeding before they could begin enteral feeding to receive either standard or specially constituted, aluminum-depleted intravenous-feeding solutions. The neurologic development of the 182 surviving infants who could be tested was assessed by using the Bayley Scales of Infant Development at 18 months of age. RESULTS: The 90 infants who received the standard feeding solutions had a mean (+/-SD) Bayley Mental Development Index of 95+/-22, as compared with 98+/-20 for the 92 infants who received the aluminum-depleted solutions (P=0.39). In a planned subgroup analysis of infants in whom the duration of intravenous feeding exceeded the median and who did not have neuromotor impairment, the mean values for the Bayley Mental Development Index for the 39 infants who received the standard solutions and the 41 infants who received the aluminum-depleted solutions were 92+/-20 and 102+/-17, respectively (P=0.02). The former were significantly more likely (39 percent, vs. 17 percent of the latter group; P=0.03) to have a Mental Development Index of less than 85, increasing their risk of subsequent educational problems. For all 157 infants without neuromotor impairment, increasing aluminum exposure was associated with a reduction in the Mental Development Index (P=0.03), with an adjusted loss of one point per day of intravenous feeding for infants receiving the standard solutions. CONCLUSIONS: In preterm infants, prolonged intravenous feeding with solutions containing aluminum is associated with impaired neurologic development.     

A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group

BACKGROUND: Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha, specifically chimeric monoclonal antibody cA2, in the treatment of Crohn's disease. METHODS: We conducted a 12-week multicenter, double-blind, placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn's disease that was resistant to treatment. All had scores on the Crohn's Disease Activity Index between 220 and 400 (scores can range from 0 to about 600, with higher scores indicating more severe illness). Patients were randomly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight, 10 mg per kilogram, or 20 mg per kilogram. Clinical response, the primary end point, was defined as a reduction of 70 or more points in the score on the Crohn's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications. RESULTS: At four weeks, 81 percent of the patients given 5 mg of cA2 per kilogram (22 of 27 patients), 50 percent of those given 10 mg of cA2 per kilogram (14 of 28), and 64 percent of those given 20 mg of cA2 per kilogram (18 of 28) had had a clinical response, as compared with 17 percent of patients in the placebo group (4 of 24) (p<0.001 for the comparison of the cA2 group as a whole with placebo). Thirty-three percent of the patients given cA2 went into remission (defined as a score below 150 on the Crohn's Disease Activity Index), as compared with 4 percent of the patients given placebo (P=0.005). At 12 weeks, 41 percent of the cA2-treated patients (34 of 83) had had a clinical response, as compared with 12 percent of the patients in the placebo group (3 of 25) (P=0.008). The rates of adverse effects were similar in the groups. CONCLUSIONS: A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease.     

Respiratory syncytial virus infection in childhood

Respiratory syncytial virus is the most frequent cause of respiratory tract infections in infants and is responsible for annual winter epidemics of acute bronchiolitis. Over the last decades medical therapy has remained unchanged and controversial, despite intensive research. Inhaled bronchodilators are often not effective and should be discontinued if no beneficial response can be documented. Steroids and ribavirin are not indicated in previously healthy infants with acute RSV bronchiolitis. There is some evidence, however, that certain risk groups may benefit from their use. With good supportive care the mortality from RSV infection is now low. Postinfectious alterations in lung function are usually transient and reversible. High-risk infants can be protected from severe RSV infections by monthly infusions of RSV immune globulins. This treatment modality has, however, not gained wide acceptance because of the benign nature of the disease and the high costs and side effects of regular immune globulin infusions. An international consensus statement on the treatment of RSV bronchiolitis may help to reduce the wide differences in clinical practice.     

Nutritional outcome of 207 very low-birth-weight infants in an intensive care unit

Growth and feeding outcomes during the first weeks of life were prospectively evaluated in 207 critically ill, very low-birth-weight (VLBW) infants (birth weight less than 1,500 gm). Maximal weight loss occurrd by day 9, averaging 13 percent of birth weight, while birth weight was regained by day 18. Energy intake during initial weight gain (19 gm. per day) averaged 100 kcal per kilogram. Feeding and growth outcome were highly correlated (p of less than 0.001) with severity of illness but were not significantly related to sex, birth weight, or appropriateness of weight for gestational age.     

Weakness of biochemical markers of nutritional and inflammatory status as prognostic indices for growth retardation and morbidity of young children in central Africa

BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss. METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy. RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.     

Legal rights of veterinarians under veterinary Good Samaritan statutes and equine liability statutes

OBJECTIVE: To determine the prevalence and clinical features of Candida species in hospital-acquired urinary tract infections (UTI) in a neonatal intensive care unit. DESIGN: A retrospective study was conducted of hospital-acquired UTI occurring in infants admitted to a neonatal intensive care unit between January 1, 1989, and June 30, 1995. Hospital-acquired infection was defined as one occurring in an infant who was at least 7 days of age and hospitalized since birth. Urinary tract infection was defined by a urine culture yielding a single organism with > 1000 colony-forming units/ml from a suprapubic aspiration or > 10,000 colony-forming units/ml via urethral catheterization. RESULTS: Fifty-seven infants had 60 UTI during the study period. Candida spp. were responsible for 25 of 60 (42%) UTI. The median gestational age of infants with candidal UTI was 26 weeks (range, 23 to 37) which was significantly less than that for infants with bacterial UTI, 28 weeks (range, 23 to 40) (P = 0.04). Candidemia was present in 13 of 25 (52%) candidal UTI which was significantly more often than bacteremia with bacterial UTI, 3 of 35 (8%) (odds ratio, 11.6; 95% confidence interval, 2.8 to 47.8). The median age of infection for candidal UTI was 34 days (range, 9 to 228), which was significantly earlier than for bacterial UTI, 79 days (range, 7 to 247) (P = 0.003). Renal pelvis fungus balls were present in 7 of 20 (35%) infants with candidal UTI who had renal ultrasound studies. CONCLUSIONS: Candida spp. were the pathogens identified in 42% of hospital-acquired urinary tract infections in a neonatal intensive care unit. Candidemia was associated with 52% of candidal UTI and bacteremia with 8% of bacterial UTI. Candidal UTI occurred significantly earlier than bacterial UTI. Renal fungus balls were present in 35% of infants with candidal UTI.     

Very low birth weight children at school age: comparison of neonatal management methods

The outcome of 293 infants born to a geographically defined community and weighing 501-1500 g was investigated. Medical intervention in the newborn period had been avoided. Morbidity was assessed at school age. Of the infants, 236 had been live born in the labour ward of this hospital; of these, 117 (49.6%) died in the neonatal period, one (0.4%) died in the first year, four (1.7%) were untraced, 13 (5.5%) had major handicap, 29 (12.3%) had minor handicap, and 72 (30.5%) were considered to be normal. In terms of survival, handicap, and intellectual with that of infants born over the same period (1963-71) in areas where intensive methods of perinatal care were used. These results imply that postnatal survival and potential of infants of very low birth weight are by no means prejudiced when only experienced nursing care is available.     

Melatonin in relation to the antioxidative defense and immune systems: possible implications for cell and organ transplantation

Inguinal hernia (IH) is relatively common in premature newborn infants, and the timing of surgical correction is controversial. We studied 40 premature infants who developed an IH and who were initially treated in a neonatal intensive care unit. Birth weight (BW) ranged from 492 to 2,401 g; 21 infants had a BW less than 1,000 g. The weight of the infants at operation ranged from 1,000 to 4,400 g. Twenty-one patients underwent herniotomy within 2 weeks after the diagnosis (short waiting group), in which 1 case of incarceration occurred; 19 waited longer than 2 weeks between diagnosis and surgery (long waiting group). Two cases of strangulation occurred in this latter group, and in 1 of those testicular necrosis occurred. Operation time was analysed in boys with bilateral herniotomy (n = 25): the short waiting group (n = 12) showed a significantly reduced operation time compared to the long waiting group (n = 13). Patients weighing less than 1,000 g at birth (n = 21) had a longer average waiting period for surgery. In the group of male patients with bilateral herniotomy, average operation time was longer in the group weighing less than 1,000 g at birth (n = 13) than in the group over 1,000 g (n = 12). Body weight at surgery did not affect operation time. It is concluded that early hernia repair should be considered in premature infants to avoid operative difficulties and gonadal ischaemia caused by incarceration.     

Arterial oxygen saturation in Tibetan and Han infants born in Lhasa, Tibet

BACKGROUND: Reduced oxygen availability at high altitude is associated with increased neonatal and infant mortality. We hypothesized that native Tibetan infants, whose ancestors have inhabited the Himalayan Plateau for approximately 25,000 years, are better able to maintain adequate oxygenation at high altitude than Han infants, whose ancestors moved to Tibet from lowland areas of China after the Chinese military entered Tibet in 1951. METHODS: We compared arterial oxygen saturation, signs of hypoxemia, and other indexes of neonatal wellbeing at birth and during the first four months of life in 15 Tibetan infants and 15 Han infants at 3658 m above sea level in Lhasa, Tibet. The Han mothers had migrated from lowland China about two years previously. A pulse oximeter was placed on each infant's foot to provide measurements of arterial oxygen saturation distal to the ductus arteriosus. RESULTS: The two groups had similar gestational ages (about 38.9 weeks) and Apgar scores. The Han infants had lower birth weights (2773 +/- 92 g) than the Tibetan infants (3067 +/- 107 g), higher concentrations of cord-blood hemoglobin (18.6 +/- 0.8 g per deciliter, vs. 16.7 +/- 0.4 in the Tibetans), and higher hematocrit values (58.5 +/- 2.4 percent, vs. 51.4 +/- 1.2 percent in the Tibetans). In both groups, arterial oxygen saturation was highest in the first two days after birth and was lower when the infants were asleep than when they were awake. Oxygen saturation values were lower in the Han than in the Tibetan infants at all times and under all conditions during all activities. The values declined in the Han infants from 92 +/- 3 percent while they were awake and 90 +/- 5 percent during quiet sleep at birth to 85 +/- 4 percent while awake and 76 +/- 5 percent during quiet sleep at four months of age. In the Tibetan infants, oxygen saturation values averaged 94 +/- 2 percent while they were awake and 94 +/- 3 percent during quiet sleep at birth and 88 +/- 2 percent while awake and 86 +/- 5 percent during quiet sleep at four months. Han infants had clinical signs of hypoxemia--such as cyanosis during sleep and while feeding--more frequently than Tibetans. CONCLUSIONS: In Lhasa, Tibet, we found that Tibetan newborns had higher arterial oxygen saturation at birth and during the first four months of life than Han newborns. Genetic adaptations may permit adequate oxygenation and confer resistance to the syndrome of pulmonary hypertension and right-heart failure (subacute infantile mountain sickness).     

Acinetobacter species as a cause of catheter-related infections

In recent years, Acinetobacter species have emerged as clinically important pathogens. Though these organisms are widely prevalent in nature, most human infections are hospital-acquired. Acinetobacter baumannii is the predominant species. Nosocomial Acinetobacter baumannii infections such as respiratory tract infections, urinary tract infections, meningitis following neurosurgical procedures, and bacteremia mainly affect patients with severe underlying disease in the ICU and often, in the setting of nosocomial outbreak. The occurrence of multiresistant strains often limits therapeutic options. A substantial part of Acinetobacter baumannii bacteremia cases represent catheter-related infections that usually carry a favorable prognosis. Acinetobacter species other than Acinetobacter baumannii are less frequently reported as a cause of infection in humans. Bacteremia due to these organisms is mostly sporadic and almost exclusively related to intravascular devices. The underlying diseases are often less severe than those of patients affected by Acinetobacter baumannii infections. The clinical course is usually benign and the infection responds readily to catheter removal irrespective of the appropriateness of antimicrobial therapy.     

Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: midazolam neonatal pharmacokinetics

BACKGROUND: Midazolam is used widely as a sedative to facilitate mechanical ventilation. This prospective study investigated the population pharmacokinetics of midazolam in very premature infants. METHODS: Midazolam (100 microg/kg) was administered as a rapid intravenous bolus dose every 4-6 h to 60 very premature neonates with a mean (range) gestational age of 27 weeks (24-31 weeks), a birth weight of 965 g (523-1,470 g), and an age of 4.5 days (2-15 days). A median (range) of four (one to four) blood samples, 0.2 ml each, were drawn at random times after the first dose or during continuous treatment, and concentrations of midazolam in serum were assayed by high-performance liquid chromatography. A population analysis was conducted using a two-compartment pharmacokinetic model using the NONMEM program. RESULTS: Average parameter values (interpatient percent coefficient of variation) for infants with birth weights 1,000 g or less were total systemic clearance (Cl(T)) = 0.783 ml/min (83%), intercompartmental clearance (Cl(Q)) = 6.53 ml/min (116%), volume of distribution of the central compartment (V1) = 473 ml (70%), and volume of distribution of the peripheral compartment (V2) = 513 ml (146%). For infants with birth weights more than 1,000 g they were as follows: Cl(T) = 1.24 ml/min (78%), Cl(Q) = 9.82 ml/min (98%), V1 = 823 ml (43%), and V2 = 1,040 ml (193%). The intrapatient variability (percent coefficient of variation) in the data was 4.5% at the mean concentration midazolam in serum of 121 ng/mL CONCLUSIONS: Serum concentration-time data were used in modeling the population pharmacokinetics of midazolam in very premature, ventilated neonates. Clearance of midazolam was markedly decreased compared with previous data from term infants and older patients. Infants weighing less than 1,000 g at birth had significantly lower clearance than those weighing more than 1,000 g.     

Delivery of extremely large infants

The purpose of this retrospective study was to find out if more effort should be applied to the diagnosis of extremely large infants, with a birth weight of 5,000 grams or more, and if elective caesarean section can be recommended. In the Department of Obstetrics, Herning Central Hospital, Denmark, 67 mothers delivered an infant with a birth weight of 5000 g or more over a ten year period. This index group was compared with a matched group with infants of normal weight. The result showed significantly more caesarean sections in the index group (24% versus 5%, p = 0.002). Shoulder dystocia and Duchenne-Erb's palsy were more frequent as well. Sixteen percent in the index group were admitted to the paediatric department, but the Apgar scores were not significantly lower. Except for one, all the infants showed complete recovery. In conclusion, elective caesarean section can not be generally recommended for an estimated birthweight exceeding 5,000 g, if a trained obstetrician is present at delivery.     

In which neonates does early recombinant human erythropoietin treatment prevent anemia of prematurity? Results of a randomized, controlled study

To assess whether erythropoietin (EPO) treatment is safe and reduces the need for transfusion, we randomized 44 preterm infants to an EPO group and a comparable control (CON) group. EPO 150 U/kg was given s.c. twice weekly for 6 wk from the 1st wk of life. Hematologic parameters, transfusion requirements, and growth were followed during therapy and for 6 mo thereafter. To better assess in which neonates EPO treatment was effective, we classified retrospectively the EPO and CON groups into uncomplicated neonates (EPO A: n = 9, birth weight = 1247 +/- 126 g, gestational age = 29.8 +/- 1.5 wk; CON A: n = 7, birth weight = 1217 +/- 145 g, gestational age = 29.9 +/- 1.5 wk) and neonates requiring artificial ventilation (EPO B: n = 16, birth weight = 1169 +/- 249 g, gestational age = 28.1 +/- 2 wk; CON B: n = 12, birth weight = 1173 +/- 215 g, gestational age = 28.3 +/- 2 wk). There were significant differences in reticulocytes between both uncomplicated and ventilated neonates in the EPO group compared with respective control groups. However, the need for transfusion was significantly less in the uncomplicated EPO group (EPO A: 0.44 +/- 0.73 versus CON A: 1.28 +/- 0.75, p < 0.05) but not in the neonates on ventilation (EPO B: 8.25 +/- 5 versus CON B: 7.75 +/- 3.7). In conclusion, early EPO administration reduces the need for transfusion in uncomplicated premature neonates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical findings of cefoxitin in the treatment of serious infections and the prevention of postoperative infections (author''s transl)

This clinical trial was designed to evaluate the efficacy, safety and patient tolerance of cefoxitin in 23 patients who were admitted to the hospital from March 1980 to November 1980. The daily dose of cefoxitin for 21 adult patients (ages ranged from 26 to 74 years old) were 6 g for the treatment of infections, and 2 to 6 g for the prevention of infections by either direct or intermittent intravenous infusions. Two children were given 100 mg/kg of cefoxitin either by direct or intermittent intravenous infusions 2 to 3 times a day in divided doses. Summary of findings: I. Treatment of intracranial infections 1. A 60-year-old man with a brain abscess was admitted to the hospital after the unsuccessful treatment with a cephalothin for 9 days. After, the initiation of therapy with cefoxitin, given 6 g a day for 3 days, the abscess was surgically removed. On the second day of treatment with cefoxitin following the operation, his highest temperature was 37.0 degrees C and was normal on the third day of treatment. He was discharged after 12 days after the surgical procedure. 2. A 56-year-old woman with cerebrospinal rhinorrhea and meningitis after the transsphenoidal removal of pituitary microadenoma responded satisfactorily to therapy with cefoxitin, given 6 g a day for 14 days after the unsuccessful treatment with a cephalothin. II. The prevention of infections following surgical operation of the central nervous system 1. Seventeen patients undergoing surgical procedures were treated with cefoxitin for the prevention of postoperative infections. None of the 17 patients developed postoperative infections. 2. A 53-year-old man undergoing repair of cerebrospinal rhinorrhea in the possibly contaminated area was successfully treated with cefoxitin, given intravenous 2 g every 8 hours for 10 days without meningitis having developed. III. The treatment and prevention of complications 1. A 74-year-old comatose male with a brain stem concussion, who was expectorating insufficiently and had difficulty swallowing and developed into pneumonia as a complication. He was successfully treated with cefoxitin, given intravenous 6 g a day for 2 weeks. 2. A 26-year-old male with a brain stem concussion complicated by pneumonia and a urinary tract infection was successfully treated with the same dose regimen of cefoxitin as the previous patient. 3. The prevention of complications A 58-year-old male with pontine glioma undergoing a tracheotomy was administered cefoxitin for the prevention of pulmonary complication. He died of pontine glioma after the three-month treatment. IV. Side effects Results of skin sensitivity tests given prior to the administration of cefoxitin were negative in all of the 23 patients. Neither anaphylaxis nor other allergic reactions or thrombophlebitis occurred with the intravenous administration of cefoxitin. No abnormalities in blood, hepatic function or renal function were observed. Anorexia occurred in 1 patient who was given cefoxitin, 6 g a day.     

BCG vaccination in low birth weight newborns: analysis of lymphocyte proliferation, IL-2 generation and intradermal reaction to PPD

OBJECTIVE: To study vaccinal scar formation and post-vaccinal immune response in newborns with birth weight ranging from 2000 to 2499 g vaccinated in the first week of life with intradermal bacille Calmette-Guérin (BCG) (Moreau-Rio de Janeiro strain). METHOD: Specific immune response to PPD was assessed in 30 low birth weight newborns (mean birth weight = 2311.7 +/- 122.1 g; mean gestational age = 38.1 +/- 1.8 weeks) in comparison to 56 control infants (mean birth weight = 3198.9 +/- 267.2 g; mean gestational age = 38.5 +/- 1.2 weeks. RESULTS: Low birth weight infants have an efficient immune response to vaccinal stimulus when compared to control infants as judged by specific in vitro lymphocyte proliferation (mean SI = 9.7 +/- 12.9 vs SI = 8.8 +/- 10.0, P = 0.72) and IL-2 production (mean SI = 3.1 +/- 3.4 vs SI = 2.6 +/- 2.0, P = 0.38). Intradermal reaction to PPD was also comparable in both groups (mean induration diameter = 9.5 +/- 5.1 mm vs 9.6 +/- 5.0 mm, P = 0.94). CONCLUSION: These data suggest that low birth weight newborns show a good immune response to BCG, thus reinforcing the inclusion of such infants in regular vaccination programs with intradermal BCG.     

An immunogenicity and efficacy study of purified chick embryo cell culture rabies vaccine manufactured in Japan

Purified chick embryo cell rabies vaccine manufactured by the Chemo-Sero-Therapeutic Institute(Kaketsuken) at Kumamoto, Japan (Kaketsuken) was submitted to an immunogenicity and efficacy study. 52 severely rabies exposed patients were treated with the conventional five doses intramuscular WHO approved ('Essen') postexposure schedule. This included the administration of 40 IU kg-1 of equine rabies immune globulin on Day 0. A control group of equally severely exposed subjects were treated with human diploid cell rabies vaccine manufactured by the Swiss Serum and Vaccine Institute as well as human rabies immune globulin. There were no deaths in either group in the more than 2 years follow-up period. Subjects treated with the chick embryo vaccine showed greater suppression of the neutralizing antibody response by the equine rabies immune globulin than those given the human diploid cell vaccine and human rabies immune globulin. A group of 20 less severely rabies exposed patients who received only the chick embryo vaccine without immune globulin all had antibody titers greater than the WHO minimal acceptable level on Day 14, 30, 90 and 180. Fourteen subjects among the severely exposed vaccine and immune globulin study group were given vaccine boosters on Day 180 because of low antibody titers. It is concluded that chick embryo rabies vaccine manufactured by Kaketsuken is an immunogenic and effective rabies vaccine, but that the potency of future batches must be increased to provide a greater safety margin.     

Composition of peripheral blood progenitor cell components collected from healthy donors

OBJECTIVES: The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (< 1500 g) are the result of decreased protein binding of thyroid hormones and to elucidate the mechanism(s) responsible and possible significance thereof. DESIGN: Cross-sectional comparison of thyroid related measurements in cord blood specimens from VLBW infants and from full term infants. Longitudinal comparison in cord and 2- and 4-week blood specimens from VLBW infants. PATIENTS: Cord blood specimens were analysed from 47 VLBW and 45 full term infants weighing > or = 2500 g. Repeat analyses in venous bloods from 32 of the VLBW infants were analysed at 2 weeks of age and again at 4 weeks in 23. The first cohort of patients was studied in 1994 and comprised 28 VLBW and 24 full term infants (Cohort A). The studies were repeated in 1995-96 in 19 VLBW infants and 21 full term infants (Cohort B). MEASUREMENTS: T4, free T4 (FT4), T3, thyroxine binding globulin (TBG), and TSH were measured in cord blood and 2- and 4-week venous specimens from VLBW infants and in cord blood specimens of full term infants. Molar ratios of T4/TBG were calculated. RESULTS: (1) Cord blood TBG, T4 and T3 concentrations of VLBW infants were each 60% of those of term infants. TBG concentrations were 397 +/- 111 vs 680 +/- 172 nmol/l (P < 0.0005). T4 concentrations were 76 +/- 22 vs 139 +/- 26 nmol/l (P < 0.0005). FT4 concentrations were in the normal adult range in both neonatal groups. T4/TBG ratios did not differ between the neonatal groups but were significantly less than that of adults (P < 0.001). (2) TSH concentrations in VLBW infants at 2 and 4 weeks were less than 50% of cord blood values. At 2 weeks, TBG concentrations of VLBW infants were unchanged from cord blood concentrations but mean T4 concentration fell by 18% and T4/TBG ratios by 21% (P < 0.005). Mean FT4 rose by 78% (P < 0.02). The changes in mean T4 and FT4 were due largely to FT4 concentrations of 37-113 pmol/l and T4 concentrations of 13-48 nmol/l in 5 infants. These infants also had lower T4/TBG ratios and were smaller and more ill than the remainder of the cohort. The changes disappeared by 4 weeks in 3 of the 4 infants tested. CONCLUSIONS: Cord T4/TBG ratios are the same in very low birth weight and term infants and are significantly lower than in adult blood. These are more than compensated for in term infants by a 236% increase in thyroxine binding globulin concentrations. The lower thyroxine binding globulin concentrations in very low birth weight infants explain their much lower T4 concentrations. Cord FT4 concentrations of full term and very low birth weight infants are in the normal adult range. T4 concentrations are further depressed and free T4 concentrations elevated in the most ill very low birth weight infants at 2 weeks of age in a manner analogous to that of the 'sick euthyroid syndrome'.