Ralph D. Feigin

Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging.

A method of clinical staging for infants with necrotizing enterocolitis (NEC) is proposed. On the basis of assigned stage at the time of diagnosis, 48 infants were treated with graded intervention. For Stage I infants, vigorous diagnostic and supportive measures are appropriate. Stage II infants are treated medically, including parenteral and gavage aminoglycoside antibiotic, and Stage III patients require operation. All Stage I patients survived, and 32 of 38 Stage II and III patients (85%) survived the acute episode of NEC. Bacteriologic evaluation of the gastrointestinal microflora in these neonates has revealed a wide range of enteric organisms including anaerobes. Enteric organisms were cultured from the blood of four infants dying of NEC. Sequential cultures of enteric organisms reveal an alteration of flora during gavage antibiotic therapy. These studies support the use of combination antimicrobial therapy in the treatment of infants with NEC.

Prospective Evaluation of Hearing Impairment as a Sequela of Acute Bacterial Meningitis

As part of a prospective study of acute bacterial meningitis in children, we studied for five years the hearing of 185 infants and children who had acute bacterial meningitis when they were more than one month of age. Nineteen (10.3 per cent) of the patients had persistent bilateral or unilateral sensorineural hearing loss. The incidence of hearing loss as determined by electric-response audiometry and conventional tests was 31 per cent with Streptococcus pneumoniae, 10.5 per cent with Neisseria meningitidis, and 6 per cent with Hemophilus influenzae infections. Transient conductive hearing impairment was found in 16 per cent of the sample, but in no case was there apparent improvement in a sensorineural deficit over time. The site of disease resulting in impaired hearing cannot be stated with certainty, but involvement of the inner ear or auditory nerve was suspected. The number of days of illness (symptoms) before hospitalization and institution of antibacterial treatment was not correlated with the development of sensorineural deafness.

Seizures and Other Neurologic Sequelae of Bacterial Meningitis in Children

BACKGROUND Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy. METHODS We followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter. RESULTS One month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001). CONCLUSIONS After bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy.

Nitroblue tetrazolium dye test as an aid in thedifferential diagnosis of febrile disorders

Nitroblue tetrazolium (NBT) dye tests were performed upon blood obtained at time of admission or during the course of hospitalization from 247 febrile patients and 20 afebrile individuals. Detailed clinical and laboratory diagnostic evaluation permitted subsequent placement of 181 of the febrile patients into 8 specific groups. Knowledge of only percentage and absolute number of NBT-positive cells permitted reclassification into 4 groups as follows: (1) normal subjects, (2) individuals with viral infection, noninfectious fevers, or partially treated bacterial infection, (3) untreated bacterial infection, and (4) bacterial infection unresponsive to therapy provided. There was generally no correlation between percentage of NBT-positive cells and either white blood cell counts or body temperature recorded at the time blood for the NBT test was obtained. Discriminant analysis was used to prepare a nomogram which permits classification of patients prospectively into one of the 4 groups, if the percentage and absolute number of NBT-positive cells are known.

Group B beta hemolytic streptococcal meningitis in infants

The medical records of 44 infants under three months of age, admitted to the hospital from January, 1965, to February, 1972, with a diagnosis of meningitis, were reviewed. Eleven of these infants had meningitis due to group B beta hemolytic streptococci (GB-BHS); each of them weighed more than 2,500 Gm. at birth. Females outnumbered males 9:2. The mortality rate was 18 per cent. Group B streptococci were the most common cause of meningitis due to gram-positive organisms during the first three months of life and ranked second only to E. coli as a cause of neonatal meningitis. None of the perinatal factors which predisposes to or which has been associated previously with neonatal meningitis was found to correlate specifically with GB-BHS meningitis. Jaundice, diarrhea, and other nonspecific signs of neonatal sepsis were rarely associated with GB-BHS disease. All GB-BHS isolates were sensitive to ampicillin, penicillin, and methicillin. The significant role of this organism in infected neonates underscores the need to elucidate the risk of neonatal infection with GB-BHS in infants born to women who are vaginal carriers of this organism.

Prospective evaluation of treatment of Hemophilus influenzae meningitis

Fifty children with Hemophilus influenzae meningitis have been enrolled in a prospective study. Patients were randomly assigned chloramphenicol or ampicillin treatment; there were no significant differences between groups in other respects. Countercurrent immunoelectrophoresis proved to be a valuable tool for rapid diagnosis of the causative agent even in pretreated patients. Increasing quantities of capsular polyribosephosphate antigen detected in the initial cerebrospinal fluid correlated significantly (r=0.62419; p less than 0.01) with early and late sequelae of meningitis. None of the patients died. Severe and persistent neurologic or intellectual deficits were noted in four (8%) of the children, and an additional 14 (28%) had IQ scores between 70 and 90. The presence of bactericidal antibody in serum was not protective. Anti-PRP antibody generally was not present in acute serum specimens and irrespective of the quantity of antigenic stimulus provided by the disease was nondetectable in 21 of 24 children less than 17 months of age following recovery.

Circadian Periodicity of Blood Amino-acids in Adult Men

THE term circadian was introduced by Halberg1 to describe a recurring sequence of events with a cycle of approximately 24 h, and the present knowledge of human circadian rhythms has been reviewed recently by Mills2. The circadian periodicity of a large number of constituents of blood, plasma, and urine has been described. Although a diurnal periodicity of whole blood amino-acids in man, in which concentrations at 2000 h were consistently greater than those at 0800 h on the same day, has been noted in this laboratory3, there were insufficient sampling times to establish a circadian pattern. A circadian periodicity of serum amino-acids in growing chickens4 and whole blood tryptophan in mice5 has been reported. We report here a circadian periodicity of whole blood and serum amino-acids in healthy adults.

Bacterial meningitis: newer concepts of pathophysiology and neurologic sequelae.

Bacterial meningitis remains a very significant problem, having increased in frequency during the past several decades. This discussion highlights current concepts of pathophysiology, diagnosis, and treatment. In addition, specific attention is drawn to various sequelae of meningitis, and to certain clinical and laboratory findings which may be of value in predicting which sequelae will occur.

Leukocyte function in normal and infected neonates

WBC function was assed in 114 healthy term infants, 34 healthy premature infants, 54 neonates with suspected sepsis, and 13 neonates with documented sepsis. Measurements of unstimulated and stimulated NBT dye reduction and resting and stimulated HMPS activity were obtained. Unstimulated NBT values were significantly (p

Factors affecting circadian periodicity of blood amino acids in man

Abstract Total whole blood amino acids in normal men and all major individual blood amino acids (with the single exception of citrulline) were found to display a circadian periodicity characterized by peak values between 1200 and 2000 hours and lowest values between 0400 and 0800. Possible underlying factors responsible for this rhythm were investigated. Increases and decreases in the total protein content of an isocaloric diet did not affect amino acid periodicity. In addition, the ingestion of a large protein load at 0800 hours, a time of rising whole blood amino acid concentration, resulted in a small but significant additional increase, whereas an identical protein load eaten at 2000 hours did not interfere with the decrease in amino acid concentration normally seen between 2000 and 0400 hours. An acute period of physical exercise did not affect blood amino acid concentrations. A 12-hour shift in the sleep-wakefulness cycle in normal adult males resulted in a rapid reversal of the normal circadian periodicity of blood amino acids, such that peak values were observed at 0400 hours, rather than at 1200 to 2000 hours as seen in subjects on a normal routine. The rhythmicity of blood amino acids could be dissociated from those of body temperature, urine volume and sodium and potassium excretion. These latter observations suggested that blood amino acid periodicity may be influenced significantly by exogenous synchronizers, although it is likely that the basic rhythms are generated by unknown endogenous signals.