The UK accelerated immunisation programme and sudden unexpected death in infancy: case-control study.

OBJECTIVES: To investigate whether the accelerated immunisation programme in the United Kingdom is associated, after adjustment for potential confounding, with the sudden infant death syndrome. DESIGN: Population based case-control study, February 1993 to March 1996. Parental interviews were conducted for each death and for four controls matched for age, locality, and time of sleep. Immunisation status was taken from records held by the parents. SETTING: Five regions in England with a combined population of over 17 million. SUBJECTS: Immunisation details were available for 93% (303/325) of infants whose deaths were attributed to the sudden infant death syndrome (SIDS); 90% (65/72) of infants with explained sudden deaths; and 95% (1515/1588) of controls. RESULTS: After all potential confounding factors were controlled for, immunisation uptake was strongly associated with a lower risk of SIDS (odds ratio 0.45 (95% confidence interval 0.24 to 0.85)). This difference became non-significant (0.67 (0.31 to 1.43)) after further adjustment for other factors specific to the infant's sleeping environment. Similar proportions of SIDS deaths and reference sleeps (corresponding to the time of day during which the index baby had died) among the controls occurred within 48 hours of the last vaccination (5% (7/149) v 5% (41/822)) and within two weeks (21% (31/149) v 27% (224/822)). No longer term temporal association with immunisation was found (P=0.78). Of the SIDS infants who died within two weeks of vaccination, 16% (5/31) had signs and symptoms of illness that suggested that medical contact was required, compared with 26% (16/61) of the non-immunised SIDS infants of similar age. The findings for the infants who died suddenly and unexpectedly but of explained causes mirrored those for SIDS infants. CONCLUSIONS: Immunisation does not lead to sudden unexpected death in infancy, and the direction of the relation is towards protection rather than risk.

Weight gain and sudden infant death syndrome: changes in weight z scores may identify infants at increased risk.

AIMS: To investigate patterns of infant growth that may influence the risk of sudden infant death syndrome (SIDS). DESIGN: Three year population based case control study with parental interviews for each death and four age matched controls. Growth was measured from prospective weight observations using the British 1990 Growth Reference. SETTING: Five regions in England (population greater than 17 million, more than 470 000 live births over three years). SUBJECTS: 247 SIDS cases and 1110 controls. RESULTS: The growth rate from birth to the final weight observation was significantly poorer among the SIDS infants despite controlling for potential confounders (SIDS mean change in weight z score (deltazw) = -0.38 (SD 1.40) v controls = +0.22 (SD 1.10), multivariate: p < 0.0001). Weight gain was poorer among SIDS infants with a normal birth weight (above the 16th centile: odds ratio (OR) = 1.75, 95% confidence interval (CI) 1. 48-2.07, p < 0.0001) than for those with lower birth weight (OR = 1. 09, 95% CI 0.61-1.95, p = 0.76). There was no evidence of increased growth retardation before death. CONCLUSIONS: Poor postnatal weight gain was independently associated with an increased risk of SIDS and could be identified at the routine six week assessment.

Surgery for a fractured femur and elective ICU admission at 113 yr of age.

Disability and medical dependence increase with age and as the percentage of the population over 80 yr old increases, demands on our healthcare budget will likewise grow. Clinical decision making should always balance the physiological state of the patient against the likely prognosis of the pathological state. Age may influence this decision-making process in an indirect way, as a perceived measure of physiological status, but whether age alone may be used as criteria for the type or degree of clinical intervention is a contentious point. In light of these issues, we present a woman of 113 yr, admitted to hospital with a fractured shaft of femur. The patient underwent surgery and was electively admitted to the intensive care unit for postoperative treatment. She survived surgery and several complications and was subsequently returned to the community where she celebrated her 114th birthday.

A clinical comparison of SIDS and explained sudden infant deaths: how healthy and how normal? CESDI SUDI Research Group. Confidential Inquiry into Stillbirths and Deaths in Infancy study.

OBJECTIVES: To compare the clinical characteristics associated with sudden infant death syndrome (SIDS) and explained sudden unexpected deaths in infancy (SUDI). DESIGN: Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING: Five regions in England (population, > 17 million; live births, > 470,000). SUBJECTS: SIDS: 325 infants; explained SUDI: 72 infants; controls: 1,588 infants. RESULTS: In the univariate analysis, all the clinical features and health markers at birth, after discharge from hospital, during life, and shortly before death, significant among the infants with SIDS were in the same direction among the infants who died of explained SUDI. In the multivariate analysis, at least one apparent life threatening event had been experienced by more of the infants who died than in controls (SIDS: 12% v 3% controls; odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.02 to 6.41; explained SUDI: 15% v 4% controls; OR = 16.81; 95% CI, 2.52 to 112.30). Using a retrospective illness scoring system based on "Baby Check", both index groups showed significant markers of illness in the last 24 hours (SIDS: 22% v 8% controls; OR = 4.17; 95% CI, 1.88 to 9.24; explained SUDI: 49% v 8% controls; OR = 31.20; 95% CI, 6.93 to 140.5). CONCLUSIONS: The clinical characteristics of SIDS and explained SUDI are similar. Baby Check might help identify seriously ill babies at risk of sudden death, particularly in high risk infants.

Babies sleeping with parents: case-control study of factors influencing the risk of the sudden infant death syndrome. CESDI SUDI research group.

OBJECTIVE: To investigate the risks of the sudden infant death syndrome and factors that may contribute to unsafe sleeping environments. DESIGN: Three year, population based case-control study. Parental interviews were conducted for each sudden infant death and for four controls matched for age, locality, and time of sleep. SETTING: Five regions in England with a total population of over 17 million people. SUBJECTS: 325 babies who died and 1300 control infants. RESULTS: In the multivariate analysis infants who shared their parents' bed and were then put back in their own cot had no increased risk (odds ratio 0.67; 95% confidence interval 0.22 to 2.00). There was an increased risk for infants who shared the bed for the whole sleep or were taken to and found in the parental bed (9.78; 4.02 to 23.83), infants who slept in a separate room from their parents (10.49; 4.26 to 25.81), and infants who shared a sofa (48.99; 5.04 to 475.60). The risk associated with being found in the parental bed was not significant for older infants (>14 weeks) or for infants of parents who did not smoke and became non-significant after adjustment for recent maternal alcohol consumption (>2 units), use of duvets (>4 togs), parental tiredness (infant slept 2 people per room of the house). CONCLUSIONS: There are certain circumstances when bed sharing should be avoided, particularly for infants under four months old. Parents sleeping on a sofa with infants should always be avoided. There is no evidence that bed sharing is hazardous for infants of parents who do not smoke.

Use of student-centred, computer-mediated communication to enhance the medical school curriculum.

OBJECTIVES: While it is clear that computers will play an important role in the study and practice of medicine their introduction into the curriculum remains controversial. Computer purchase has been made compulsory for incoming students. DESIGN: Members of the incoming class were allowed to purchase any computer and modem capable of using the communication program chosen by the school. No formal computer training was given. Students were encouraged to call for assistance or bring in their computers for configuration. The primary object of the system was for communication between the students and between students and faculty. SETTING: The School of Medicine of the University of New Mexico. SUBJECTS: First-year medical students. RESULTS: The vast majority of students set up their computers and connected to the system with little assistance. At the end of the first week of studies all the students were connected. Most of the students used the system on a daily basis. The greatest interest was in discussions concerning examinations with 93% of students reading these postings. The least-used aspect of the system was the exchange of learning issues from small group case discussions. Students also downloaded the curricular material provided but were discriminating in accessing this content. CONCLUSIONS: The student use of the computer as a communication tool has been a success. Students used the system in a variety of ways and by so doing also learned the basics of computer use and maintenance. The area of faculty training is often ignored but is considered crucial to the success of such a project.

Epidemiology of SIDS and explained sudden infant deaths. CESDI SUDI Research Group.

OBJECTIVES: To establish whether epidemiologic characteristics for sudden infant death syndrome (SIDS) have changed since the decrease in death rate after the "Back to Sleep" campaign in 1991, and to compare these characteristics with sudden and unexpected deaths in infancy (SUDI) from explained causes. DESIGN: Three-year, population-based, case-control study. Parental interviews were conducted soon after the death and for 4 controls matched for age and date of interview. All sudden unexpected deaths were included in the study and the cause of death was established by a multidisciplinary panel of the relevant health care professionals taking into account past medical and social history of the mother and infant, the circumstances of death, and a full pediatric postmortem examination. Contributory factors and the final classification of death were made using the Avon clinicopathologic system. SETTING: Five regions in England, with a total population of >17 million people, took part in the study. The number of live births within these regions during the particular time each region was involved in the study was 473 000. STUDY PARTICIPANTS: Three hundred twenty-five SIDS infants (91.3% of those available), 72 explained SUDI infants (86.7% of those available), and 1588 matched control infants (100% of total for cases included). RESULTS: Many of the epidemiologic features that characterize SIDS infants and families have remained the same, despite the recent decrease in SIDS incidence in the United Kingdom. These include the same characteristic age distribution, few deaths in the first few weeks of life or after 6 months, with a peak between 4 and 16 weeks, a higher incidence in males, lower birth weight, shorter gestation, and more neonatal problems at delivery. As in previous studies there was a strong correlation with young maternal age and higher parity and the risk increased for infants of single mothers and for multiple births. A small but significant proportion of index mothers had also experienced a previous stillbirth or infant death. The majority of the SIDS deaths (83%) occurred during the night sleep and there was no particular day of the week on which a significantly higher proportion of deaths occurred. Major epidemiologic features to change since the decrease in SIDS rate include a reduction in the previous high winter peaks of death and a shift of SIDS families to the more deprived social grouping. Just more than one quarter of the SIDS deaths (27%) occurred in the 3 winter months (December through February) in the 3 years of this study. In half of the SIDS families (49%), the lone parent or both parents were unemployed compared with less than a fifth of control families (18%). This difference was not explained by an excess of single mothers in the index group. Many of the significant factors relating to the SIDS infants and families that distinguish them from the normal population did not distinguish between SIDS and explained SUDI. In the univariate analysis many of the epidemiologic characteristics significant among the SIDS group were also identified and in the same direction among the infants dying as SUDI attributable to known causes. The explained deaths were similarly characterized by the same infant, maternal, and social factors, 48% of these families received no waged income. Using logistic regression to make a direct comparison between the two index groups there were only three significant differences between the two groups of deaths: 1) a different age distribution, the age distribution of the explained deaths peaked in the first 2 months and was more uniform thereafter; 2) more congenital anomalies were noted at birth (odds ratio [OR] = 3.14; 95% confidence intervals [CI]: 1.52-6. (ABSTRACT TRUNCATED)

Pacifier use and sudden infant death syndrome: results from the CESDI/SUDI case control study. CESDI SUDI Research Team.

OBJECTIVES: To investigate the relation between pacifier use and sudden infant death syndrome (SIDS). DESIGN: Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING: Five regions in England (population > 17 million). SUBJECTS: 325 infants who had died from SIDS and 1300 control infants. RESULTS: Significantly fewer SIDS infants (40%) than controls (51%) used a pacifier for the last/reference sleep (univariate odds ratio (OR), 0.62; 95% confidence interval (CI), 0.46 to 0.83) and the difference increased when controlled for other factors (multivariate OR, 0.41; 95% CI, 0. 22 to 0.77). However, the proportion of infants who had ever used a pacifier for day (66% SIDS v 66% controls) or night sleeps (61% SIDS v 61% controls) was identical. The association of a risk for SIDS infants who routinely used a pacifier but did not do so for the last sleep became non-significant when controlled for socioeconomic status (bivariate OR, 1.39 (0.93 to 2.07)). CONCLUSIONS: Further epidemiological evidence and physiological studies are needed before pacifier use can be recommended as a measure to reduce the risk of SIDS.

Neonatal insulin secretion: implications for the programming of metabolic homeostasis.

Patterns of metabolic adaptation are described in the neonate, which generate two fundamental concepts. First, that early nutritional experiences may have long-term effects on the control of metabolic homeostasis, and second, that insulin has a fundamental role in this process. The endocrine pancreas in the neonate is unable to regulate insulin secretion in relation to blood glucose concentration with the same level of tight control seen in the older child and adult. Moreover, the pattern of metabolic adaptation in the fullterm infant in the first postnatal week is different to that of the preterm baby and the infant born small-for-gestational-age (SGA), with both preterm and SGA infants being unable to generate counter-regulatory ketogenesis as blood glucose concentrations fall. The inability to initiate ketogenesis and switch off insulin secretion after birth persists for several weeks in preterm infants. Methods of feeding term and preterm infants have profound effects on the neonatal endocrine milieu and it is suggested that patterns of insulin secretion provoked in the newborn period may 'programme' the subsequent development of metabolic control. The recently described molecular mechanisms that underlie the pathogenesis of abnormal insulin secretion in the syndrome of persistent hyperinsulinaemic hypoglycemia of infancy (or pancreatic nesidioblastosis) may offer insights into how such programming may occur.

In vivo hemolytic activity of group B streptococcus is dependent on erythrocyte-bacteria contact and independent of a carrier molecule.

Experiments were performed to determine the interaction between the hemolysin of group B streptococcus (GBS) and sheep erythrocytes. Growing GBS were shown to possess a potent hemolysin at a very early stage of the growth cycle. After separation of the cells from the growth medium, all the hemolytic activity remained with the bacterial cells, and no activity could be detected in the growth medium. When fetal calf serum was added to the media, some "soluble" activity was detected. This activity, however was completely removed by ultracentrifugation, the hemolytic activity being found solely in the pellet. After the hemolysin had formed, no new protein synthesis was needed to cause hemolysis because the addition of chloramphenicol to cells caused no difference in their hemolytic potential. For proof that no short-lived, soluble factors are produced by the bacteria, bacteria and sheep erythrocytes were incubated in contiguous media, separated by a 0.22-microns membrane. No hemolytic activity was detected on the erythrocyte side of the membrane, although high amounts of hemolysin could be extracted from the bacteria. Only when a detergent was added to the growth medium was hemolysis detected from the erythrocytes, showing that extracted hemolysin could indeed pass through the membrane. These results suggest that the hemolysin is attached to the surface of the cell and that contact is needed between the bacteria and erythrocyte to cause lysis. Where soluble activity was detected, it was connected to bacterial fragments.

Increased recovery of group B Streptococcus by the inclusion of rectal culturing and enrichment.

Detection of intrapartum carriage of group B streptococcus (GBS) and subsequent antibiotic prophylaxis may prevent GBS infections in neonates. Because the gastrointestinal tract is the primary source of this organism, detection of carrier status requires both rectal and vaginal swabs. Vaginal swabs from 651 obstetric outpatients were plated onto 5% sheep blood agar. A second vaginal and a rectal swab were collected and incubated overnight in an enrichment medium of Todd-Hewitt broth containing antibiotics. By at least one method, 110 (16.9%) patients were positive for GBS. Only 31.8% of these positive patients were detected by direct culture of vaginal swabs. The use of vaginal swabs directly plated onto blood agar identified only three carriers not detected by another method. Inoculation of an enrichment broth with the vaginal swab and subsequent subculture detected 70.9% of the total. The use of both vaginal and rectal swabs with enrichment detected 97.3% of total GBS carriers. A subset of enrichment broths inoculated with vaginal and rectal specimens from 279 patients was tested for GBS by direct latex agglutination (Streptex; Murex Diagnostics, Inc., Norcross, GA, USA). Of the 90 broths that grew GBS on subculture, only 59 (65.6%) were positive by the direct agglutination method. The use of this method, although reducing processing time by 1 day, gave false-negative results for one-third of the GBS-positive broths. An accurate detection of the GBS carrier state can only be achieved by a combination of vaginal and rectal swabs incubated in enrichment broth and subcultured on blood agar.

Mivacurium in short to intermediate surgical procedures.

Mivacurium, a new benzylisoquinoline muscle relaxant, appears to be close to the ideal for short to intermediate surgical procedures. Ideal properties of such an agent are discussed, in addition to indications for muscle relaxation in such procedures. Two studies are presented, showing the onset and offset times of mivacurium and its cardiovascular stability in both young and elderly patients. It is concluded that it is a well-tolerated and appropriate agent for use in short to intermediate surgical procedures in those patients with normal plasma cholinesterase function, despite a slight prolongation of action in the elderly.

Antifungal effects of Allium sativum (garlic) extract against the Aspergillus species involved in otomycosis.

Otomycosis due to saprophytic keratolytic fungi represents a small percentage of clinical external otitis. Although there are certain antibacterial and antifungal agents available, they usually are very caustic, potentially ototoxic and cannot be used if the ear drum is perforated. Garlic is utilized as a folk medicine in many countries for its antimicrobial and other beneficial properties. In response to a lack of otic preparations, the authors studied the efficacy of garlic extracts against the fungi belonging to the genus Aspergillus which are the most common cause of this infection. Aqueous garlic extract (AGE) and concentrated garlic oil (CGO) along with various commercial garlic supplements and pharmaceutical prescriptions were used in an in-vitro study. AGE and especially CGO were found to have antifungal activity. These agents showed similar or better inhibitory effects than the pharmaceutical preparations and demonstrated similar minimum inhibitory concentrations.

The effects of growth in human serum on an acapsular group B Streptococcus mutant.

A Group B Streptococcus Type III (GBS) mutant which, when grown in Todd Hewitt broth (THB), does not produce any detectable capsule, produced a clearly visible polysaccharide capsule when grown in human serum. We isolated cytoplasmic membranes from GBS and separated the component membrane proteins by polyacrylamide gel electrophoresis. A significant change in membrane composition was found during growth in human serum. Several unique proteins were produced on serum growth and there was both up- and down-regulation of other proteins. We measured the intracellular levels of sialic acid for a variety of GBS serotype III isolates. Interestingly, while there was little difference between the intracellular sialic levels of most isolates, the sialic acid level of COH31-15 grown in THB was over 100% higher than that of any other isolate. When grown in serum this pool was reduced to a level similar to that in other strains. The concentration of bacterial cell sialic acid was directly correlated with the sialic acid content of the serum. Exogenous sialic acid content, in concert with other serum factors, plays a role in determining the capsular size in GBS.

Comparison of desflurane and fentanyl-based anaesthetic techniques for coronary artery bypass surgery.

We have compared, in 51 ASA II and III patients undergoing coronary artery bypass surgery, an inhaled anaesthetic technique based on desflurane, supplemented with low-dose (10 micrograms kg-1) fentanyl, with an i.v. technique using high-dose (50 micrograms kg-1) fentanyl with midazolam for induction. Satisfactory records were available for analysis in 50 patients. There were no differences between groups in operating time, cardiopulmonary bypass time, aortic cross-clamp time or duration of stay in the intensive care unit after surgery. Desflurane maintained mean systemic arterial pressure at the awake level during incision and sternotomy (end-tidal concentrations 3.7% and 4.6%, respectively) but decreased it significantly at all other times. With fentanyl, mean systemic arterial pressure was unchanged from awake values during induction and laryngoscopy but increased significantly at incision and sternotomy by 8% and 12.8%, respectively, to exceed the desflurane group at sternotomy by 20 mm Hg (P < 0.001). With desflurane, heart rate remained at 60-67 beat min-1 at all times before cardiopulmonary bypass. This was always lower than the fentanyl group by 5-15 beat min-1 and the difference was significant at induction, during skin preparation and before aortic cannulation. In comparison with the desflurane group, cardiac index was significantly greater in the fentanyl group at induction, laryngoscopy and during skin preparation, but was significantly less before aortic cannulation. The need for vasodilator intervention was significantly more common in the fentanyl group before, during and after cardiopulmonary bypass and for beta adrenoceptor block before cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth of group B streptococci in human serum leads to increased cell surface sialic acid and decreased activation of the alternative complement pathway.

Group B streptococcus type III is a major cause of neonatal death. The terminal sialic acid moiety of the group B streptococcus type specific capsule has been shown to be an important virulence factor. We demonstrate here that bacteria grown in human serum have increased cell surface sialic acid content compared with cells grown in common laboratory media. This sialic acid was removed by incubation with neuraminidase, showing that it was on the bacterial surface. Serum-dependent sialylation was dependent on metabolic activity, as the addition of chloramphenicol reduced the amount of added sialic acid by more than 90%. Probing the cell surface with an antibody specific for group B streptococcus type III capsular sialic acid showed an increase in antibody binding after growth in human serum. This effect could be lowered by incubating serum-grown cells in neuraminidase prior to antibody exposure. A group B streptococcus mutant that when grown in laboratory media lacks cell surface sialic acid showed significant cell surface sialic acid when grown in human serum. This increase was associated with a significantly decreased ability to bind C3 and hence activate the alternative complement pathway.

Group B streptococcal disease in the perinatal period.

Group B streptococcus is the major cause of neonatal sepsis in the United States. It is estimated that 2,000 infants die annually of syndromes related to group B streptococcus infection. In the early-onset syndrome, transmission is from mother to child, either in utero or during birth. Pneumonia is the most common presentation in infants who develop symptoms during the first seven days of life. The principal manifestation of late-onset infection is meningitis, which occurs in 85 percent of this group. Although group B streptococcus infection is normally remediable with penicillin therapy, rapid diagnosis and treatment are necessary to prevent the serious consequences of the disease. A vaccine is under development, although the cost-effectiveness of a widespread immunization program for a disease with such a low frequency is still unknown. The potentially serious outcomes of this infection, however, make it a major problem for physicians involved in neonatal care.