Volume 120 Number 4, Part 1
considered in children with these clinical manifestations who have no response to 48 to 72 hours of a d e q u a t e antibiotic t h e r a p y and who have cultures negative for bacterial pathogens.
REFERENCES 1. Rowley AH, Gonzalez-Crussi F, Shulman ST. Kawasaki syndrome. Rev Infect Dis 1988;10:1-15. 2. Levy M, Koren G. Atypical Kawasaki disease: analysis of clinical presentation and diagnostic clues. Pediatr Infect Dis J 1990;9:122-6. 3. Ruef C. Mucoeutaneous lymph node syndrome (Kawasaki syndrome) mimicking a suppurative parapharyngeal space infection. Helv Paediatr Acta 1988;43:307-12.
Clinical and laboratory observations
567
4. Murrant N J, Cook JA, Murch SH. Acute ENT admission in Kawasaki disease. J Laryngol Otol 1990;104:581-4. 5. Brion L, C0urtoy M, Bachelart D, et al. Mucocutane0us lymph node syndrome with necrotic pharyngitis. Eur J Pediatr 1980; 135:111-6. 6. Korkis JA, Stillwater LB. An unusual otolaryngological problem: mucocutaneous lymph node syndrome (Kawasaki's syndrome) case report. J Otolaryngol 1985;14:257-60. 7. Kotloff KL, Wald ER. Uvulitis in children. Pediatr Infect Dis J 1983;2:392-3. 8. Lacroix J, Ahronheim G, Arcand P, et al. Group A streptococcal supraglottitis. J PEDIATR 1986;109:20-4. 9. Grattan-Smith T, Forer M, Kilham H, Gillis J. Viral supraglottitis. J PEDIATR 1987;110:434-5. 10. Case records of the Massachusetts General Hospital (case 431990). N Engl J Med 1990;323:1189-99.
Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2 M i c h a e l S. Silverman, MD, FRCPC, John G. G a r t n e r , MD, FRCPC, William C. Halliday, MD, FRCPC, S t e v e Kohn, MD, a n d J o a n n e Embree, MD, FRCPC From the Departments of Pediatrics and Pathology, Universityof Manitoba, Winnipeg, Manitoba, Canada, and the Department of Pediatrics, Universityof California Medical School, San Francisco
We describe an infant with three unusual features of perinatally acquired herpes simplex virus type 2 encephalitis: onset of Hlness at 34 days of age, absolute cerebrospinal fluid neutrophilia, and systemic viral dissemination after central nervous system disease. To provide early, effective antiviral therapy, clinicians should be aware of atypical presentations of serious herpes simplex virus infections. (J PEDIATR1992;120:567-9) Infection with herpes simplex virus type 2 can result in illness with atypical features. W e describe the course of encephalitis in an i n f a n t probably infected perinatally with H S V - 2 . Delayed onset, C S F neutrophilia, a n d systemic dissemination of the virus after central nervous system involvement were unusual features of this case of encephalitis.
Supported in part by a gran~ from the Canadian Foundation for AIDS Research. Submitted for publication Aug. 5, 1991; accepted Oct. 31, 1991. Reprint requests: Joanne Embree, MD, FRCPC, Department of Medical Microbiology, University of Manitoba, 530-730 William Ave, Winnipeg, Manitoba R3E 0W3, Canada. 9/22/34709
CASE REPORT Clinical summary. After an uncomplicated 33-week gestation, a 2340 gm female infant was born by vaginal delivery. Maternal HSV infection was not suspected. The infant was initially treated for respiratory distress syndrome and hyperbilirubinemia. She was discharged to her home at 24 days of age and remained well until 34 days of age, when irritability and fever developed. A lumbar puncture revealed 250 x 106 leukocytes/L, protein level of 1.87 gm/L, and glucose level of 2.56 ~mol/L (blood glucose level was 5.0 #mol/L); results of CSF bacterial and viral cultures, CSF bacterial antigen detection, and blood and urine cultures were negative for pathogens. The patient received ampicillin and gentamicin intravenously for 2 days. Three days later, seizures began that responded partially to phenobarbital. The next day meningismus, slightly decreased right hand grasp strength, and decreased right facial and arm tone developed. A second CSF examination disclosed a leukocyte count of 139 x 106 cells/L, with 100% neu-
568
Clinical and laboratory observations
The Journal of Pediatrics April 1992
trophils and an erythrocyte level of 8 x 10 6 cells/L, glucose level of 2.0 tzmol/L (36 rag/all) (blood glucose level of 4.1 tlmol/L), and protein level of 3.08 gm/L. Gram-staining, bacterial culture, and antigen-detection tests revealed no pathogens. An enhanced computed tomographic scan of the patient's brain and a chest x-ray study showed no abnormalities. Ampicillin and eefotaxime were given. Phenytoin, phenobarbital, and lorazepam therapy produced some seizure control. During the next 3 days the patient had mild hepatomegaly, decreased consciousness, myoclonic jerks of the arms, and facial twitching. Results of liver function tests were norI
ADCC CSF HSV
Antibody-dependent cellular cytotoxicity Cerebrospinal fluid Herpes simplex virus
I
mal. An electroencephalogram showed suppressed background activity, with bitemporal independent spikes and one left frontotemporal seizure. Treatment with acyclovir, 10 mg/kg every 8 hours, administered intravenously, was started despite negative results of HSV titers. On day 13 the patient's seizure frequency increased, her fontanelles became tense, and disseminated intravascular coagulation developed. A chest radiograph revealed multifocal pulmonary infiltrates. A computed tomographic scan of the patient's head showed diffuse supratentorial hypodense regions, with sparing of the basal ganglia and an increase periventricular subependymal attenuation. Both aspartate aminotransferase and alanine aminotransferase values became elevated (2490 and 490 izg/L, respectively). Hyperkalemia and hyponatremia then developed. Therapy was discontinued because of the profound clinical deterioration in the patient's condition. The infant died at 50 days of age. Postmortem findings. Abnormalities were seen in brain, liver, adrenal glands, and lungs. The cerebral hemispheres showed extensive cortical and subcortical necrosis, with an associated inflammatory cell infiltrate consisting mainly of macrophages. Reactive astrocytes and foci of calcification were present. Wallerian degeneration and loci of necrosis were seen in the brain stem. The liver showed centrilobular hemorrhagic necrosis and portal mononuclear cell infiltrates. No intranuclear inclusions were visible in hepatocytes. The adrenals showed foci of necrosis in the medulla and the deepest layers of the cortex. Examination of lung sections revealed foci of interstitial pneumonitis. The presence of HSV-2 was detected by the immunoperoxidase method using a biotinylated monoclonal antibody to H SV-2 (014D; Biomeda, Foster City, Calif.). Control sections were reacted with biotinylated monoclonal antibody to HSV-1 (Biomeda). Cells staining in reaction to HSV-2 but not HSV- 1 were seen in the brain, the adrenal medulla, the zona reticularis of the adrenal cortex, the lung, and the liver. For examination by immunoelectron microscopy, sections were etched, washed, and then reacted with anti-HSV-2 antibody. Control sections were incubated with anti-HSV-1 antibody. Protein A gold was used as a second-step reagent. 1 Typical intranuclear herpes-type viral particles that reacted with HSV-2 but not HSV-1 were identified. Antlbody-dependent cellular cytotoxicity. Assays for ADCC were performed as described previously2 on samples of serum that had been collected and frozen at - 7 0 ~ C on day 7 of the patient's illness. The patient's serum samples mediated mononuclear cell
ADCC At 1:1000 but did not mediate polymorphonuclear cell ADCC at the highest concentration tested (1:100). Control serum samples demonstrated mononuclear cell ADCC at 1:10,000 and polymorphonuclear cell ADCC at 1:100. DISCUSSION Despite the delayed onset of illness, HSV-2 was probably acquired by this infant during the intrapartum period. 3 Postnatal transmission is unlikely because the virus was H S V - 2 and the patient had not had contact with anyone known to be infected. In the National Institute of Allergy and Infectious Diseases study, 4 the mean age at first symptoms of patients with neonatal H S V encephalitis was 17.4 _+ .8 days; disseminated infection and infection localized to skin, eye, or mouth occurred slightly later. 5 W e are aware of only three reports describing the appearance of perinatal H S V after 34 days of age. 68 A notable feature of our patient's illness was her absolute C S F neutrophilia on day 4. Usually conversion from a predominantly neutrophilic to mononuclear pleocytosis occurs 8 to 24 hours after onset in viral infections of the central nervous system. We are not aware of any previous reports of persistent C S F neutrophilia in association with H S V encephalitis. The concomitant serial seizures are unlikely to have been the cause, because status epilepticus does not usually produce C S F neutrophilia. If pleocytosis does occur, the cell count is usually less than 30. 9 However, macrophages did predominate in the central nervous system at autopsy; conversion from neutrophilic to mononuclear cell C S F pleocytosis eventually did occur. The progression from clinically localized infection to disseminated disease is rare but has been reported.a, lo Aside from the National Institute of Allergy and Infectious Diseases study, 4, 10 to our knowledge there have been no other reports of central nervous system disease evolving to disseminated disease in a neonate who had no involvement of skin, eye, or mouth. The pathophysiology of such infections and their progression is not clearly understood. Our patient had several indicators of a poor prognosis, including prematurity, low levels of antibody mediating mononuclear A D C C , 2 a decreased level of consciousness when therapy was initiated, and long duration of disease before acyclovir therapy was started. Improved chance of recovery from H S V illness depends not only on better antiviral drugs but also on early diagnosis and prompt initiation of therapy. 4 Unfortunately, clinical diagnosis remains difficult because "exceptional" cases are frequent. Use of rapid, specific diagnostic techniques, such as the polymerase-chain reaction, ll should make reliance on nonspecific, exception-prone clinical and laboratory criteria obsolete. We thank Dr. Morven Edwards for her helpful comments and Mr. Malkit Diocee for his technical expertise.
Volume 120 Number 4. Part 1 REFERENCES 1. Bendayan M. Zollinger M. Ultrastructura110calization of antigenic sites on osmium-fixed tissues applying a protein A gold technique. J Histochem Cytochem 1983;31:101-9. 2. Kohl S. West MS. Prober CG. Sullender WM. Loo LS. Arvin AM. Neonatal antibody-dependent cellular cytotoxic antibody levels are associated with the clinical presentation of neonatal herpes simplex virus infection. J Infect Dis 1989;160:770-6. 3. Brown ZA. Benedetti J. Ashley R. et al. Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. N Engl J Med 1991;324:1247-52. 4. Whitley R. Arvin A. Prober C. et al. Predictors of morbidity and mortality in neonates with herpes simplex virus infections: the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med 1991;324: 450-4. 5. Whitley RS. Herpes simplex virus infections. In: Remington JS. Klein JO. eds. Infectious diseases of the fetus and newborn infant. Philadelphia: WB Saunders. 1990:282-305.
Clinical and laboratory observations
569
6. Thomas EA. Scheifele DW. Maclean BS. Herpes simplex type II aseptic meningitis in a two-month-old infant. Pediatr Infect Dis J 1989;8:184-6. 7. Gutman LT. Wilfert CM. Eppes S. Herpes simplex encephalitis in children: analysis of cerebral spinal fluid and progressive neurodevelopmental deterioration. J Infect Dis 1986;154: 415-21. 8. Sullender WM. Miller JL. Yasukawa LL. et al. Humoral and cell-mediated immunity in neonates with herpes simplex virus infection. J Infect Dis 1987;155:28-37. 9. Fishman RA. CSF in disease of the nervous system. Philadelphia: WB Saunders, 1980:323. 10. Whitley R, Arvin A, Prober C, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex infection: Infectious Diseases Collaborative Study Group. N . Engl J Med 1991;324:444-9. 11. Aurelius E, Johansson B, Skoldenberg B, et al. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet 1991 ;337: 189-92.
Decrease in gastric emptying time and episodes of regurgitation in children with spastic quadriplegia fed a whey-based formula Martin D. Fried, MD. Vikram Khoshoo, MD. PhD. Donna J. Seeker, RPDt. David L. Gilday, MD. FRCPC. Judith M. Ash, MD. FRCPC. and Paul B. Peneharz, MB.ChB. PhD. FRCPC From the Divisions of Clinical Nutrition. Nutrition and Food Services. and Nuclear Medicine. Research Institute. Hospital for Sick Children. and the Departments of Pediatrics and Nutritional Sciences. University of Toronto. Toronto. Ontario. Canada
The gastric emptying times associated with three whey-based formulas were Significantly shorter than that associated with a casein-based formula In nine gastrostomy-fed patients with spastic quadriplegia (p
considered in children with these clinical manifestations who have no response to 48 to 72 hours of a d e q u a t e antibiotic t h e r a p y and who have cultures negative for bacterial pathogens.
REFERENCES 1. Rowley AH, Gonzalez-Crussi F, Shulman ST. Kawasaki syndrome. Rev Infect Dis 1988;10:1-15. 2. Levy M, Koren G. Atypical Kawasaki disease: analysis of clinical presentation and diagnostic clues. Pediatr Infect Dis J 1990;9:122-6. 3. Ruef C. Mucoeutaneous lymph node syndrome (Kawasaki syndrome) mimicking a suppurative parapharyngeal space infection. Helv Paediatr Acta 1988;43:307-12.
Clinical and laboratory observations
567
4. Murrant N J, Cook JA, Murch SH. Acute ENT admission in Kawasaki disease. J Laryngol Otol 1990;104:581-4. 5. Brion L, C0urtoy M, Bachelart D, et al. Mucocutane0us lymph node syndrome with necrotic pharyngitis. Eur J Pediatr 1980; 135:111-6. 6. Korkis JA, Stillwater LB. An unusual otolaryngological problem: mucocutaneous lymph node syndrome (Kawasaki's syndrome) case report. J Otolaryngol 1985;14:257-60. 7. Kotloff KL, Wald ER. Uvulitis in children. Pediatr Infect Dis J 1983;2:392-3. 8. Lacroix J, Ahronheim G, Arcand P, et al. Group A streptococcal supraglottitis. J PEDIATR 1986;109:20-4. 9. Grattan-Smith T, Forer M, Kilham H, Gillis J. Viral supraglottitis. J PEDIATR 1987;110:434-5. 10. Case records of the Massachusetts General Hospital (case 431990). N Engl J Med 1990;323:1189-99.
Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2 M i c h a e l S. Silverman, MD, FRCPC, John G. G a r t n e r , MD, FRCPC, William C. Halliday, MD, FRCPC, S t e v e Kohn, MD, a n d J o a n n e Embree, MD, FRCPC From the Departments of Pediatrics and Pathology, Universityof Manitoba, Winnipeg, Manitoba, Canada, and the Department of Pediatrics, Universityof California Medical School, San Francisco
We describe an infant with three unusual features of perinatally acquired herpes simplex virus type 2 encephalitis: onset of Hlness at 34 days of age, absolute cerebrospinal fluid neutrophilia, and systemic viral dissemination after central nervous system disease. To provide early, effective antiviral therapy, clinicians should be aware of atypical presentations of serious herpes simplex virus infections. (J PEDIATR1992;120:567-9) Infection with herpes simplex virus type 2 can result in illness with atypical features. W e describe the course of encephalitis in an i n f a n t probably infected perinatally with H S V - 2 . Delayed onset, C S F neutrophilia, a n d systemic dissemination of the virus after central nervous system involvement were unusual features of this case of encephalitis.
Supported in part by a gran~ from the Canadian Foundation for AIDS Research. Submitted for publication Aug. 5, 1991; accepted Oct. 31, 1991. Reprint requests: Joanne Embree, MD, FRCPC, Department of Medical Microbiology, University of Manitoba, 530-730 William Ave, Winnipeg, Manitoba R3E 0W3, Canada. 9/22/34709
CASE REPORT Clinical summary. After an uncomplicated 33-week gestation, a 2340 gm female infant was born by vaginal delivery. Maternal HSV infection was not suspected. The infant was initially treated for respiratory distress syndrome and hyperbilirubinemia. She was discharged to her home at 24 days of age and remained well until 34 days of age, when irritability and fever developed. A lumbar puncture revealed 250 x 106 leukocytes/L, protein level of 1.87 gm/L, and glucose level of 2.56 ~mol/L (blood glucose level was 5.0 #mol/L); results of CSF bacterial and viral cultures, CSF bacterial antigen detection, and blood and urine cultures were negative for pathogens. The patient received ampicillin and gentamicin intravenously for 2 days. Three days later, seizures began that responded partially to phenobarbital. The next day meningismus, slightly decreased right hand grasp strength, and decreased right facial and arm tone developed. A second CSF examination disclosed a leukocyte count of 139 x 106 cells/L, with 100% neu-
568
Clinical and laboratory observations
The Journal of Pediatrics April 1992
trophils and an erythrocyte level of 8 x 10 6 cells/L, glucose level of 2.0 tzmol/L (36 rag/all) (blood glucose level of 4.1 tlmol/L), and protein level of 3.08 gm/L. Gram-staining, bacterial culture, and antigen-detection tests revealed no pathogens. An enhanced computed tomographic scan of the patient's brain and a chest x-ray study showed no abnormalities. Ampicillin and eefotaxime were given. Phenytoin, phenobarbital, and lorazepam therapy produced some seizure control. During the next 3 days the patient had mild hepatomegaly, decreased consciousness, myoclonic jerks of the arms, and facial twitching. Results of liver function tests were norI
ADCC CSF HSV
Antibody-dependent cellular cytotoxicity Cerebrospinal fluid Herpes simplex virus
I
mal. An electroencephalogram showed suppressed background activity, with bitemporal independent spikes and one left frontotemporal seizure. Treatment with acyclovir, 10 mg/kg every 8 hours, administered intravenously, was started despite negative results of HSV titers. On day 13 the patient's seizure frequency increased, her fontanelles became tense, and disseminated intravascular coagulation developed. A chest radiograph revealed multifocal pulmonary infiltrates. A computed tomographic scan of the patient's head showed diffuse supratentorial hypodense regions, with sparing of the basal ganglia and an increase periventricular subependymal attenuation. Both aspartate aminotransferase and alanine aminotransferase values became elevated (2490 and 490 izg/L, respectively). Hyperkalemia and hyponatremia then developed. Therapy was discontinued because of the profound clinical deterioration in the patient's condition. The infant died at 50 days of age. Postmortem findings. Abnormalities were seen in brain, liver, adrenal glands, and lungs. The cerebral hemispheres showed extensive cortical and subcortical necrosis, with an associated inflammatory cell infiltrate consisting mainly of macrophages. Reactive astrocytes and foci of calcification were present. Wallerian degeneration and loci of necrosis were seen in the brain stem. The liver showed centrilobular hemorrhagic necrosis and portal mononuclear cell infiltrates. No intranuclear inclusions were visible in hepatocytes. The adrenals showed foci of necrosis in the medulla and the deepest layers of the cortex. Examination of lung sections revealed foci of interstitial pneumonitis. The presence of HSV-2 was detected by the immunoperoxidase method using a biotinylated monoclonal antibody to H SV-2 (014D; Biomeda, Foster City, Calif.). Control sections were reacted with biotinylated monoclonal antibody to HSV-1 (Biomeda). Cells staining in reaction to HSV-2 but not HSV- 1 were seen in the brain, the adrenal medulla, the zona reticularis of the adrenal cortex, the lung, and the liver. For examination by immunoelectron microscopy, sections were etched, washed, and then reacted with anti-HSV-2 antibody. Control sections were incubated with anti-HSV-1 antibody. Protein A gold was used as a second-step reagent. 1 Typical intranuclear herpes-type viral particles that reacted with HSV-2 but not HSV-1 were identified. Antlbody-dependent cellular cytotoxicity. Assays for ADCC were performed as described previously2 on samples of serum that had been collected and frozen at - 7 0 ~ C on day 7 of the patient's illness. The patient's serum samples mediated mononuclear cell
ADCC At 1:1000 but did not mediate polymorphonuclear cell ADCC at the highest concentration tested (1:100). Control serum samples demonstrated mononuclear cell ADCC at 1:10,000 and polymorphonuclear cell ADCC at 1:100. DISCUSSION Despite the delayed onset of illness, HSV-2 was probably acquired by this infant during the intrapartum period. 3 Postnatal transmission is unlikely because the virus was H S V - 2 and the patient had not had contact with anyone known to be infected. In the National Institute of Allergy and Infectious Diseases study, 4 the mean age at first symptoms of patients with neonatal H S V encephalitis was 17.4 _+ .8 days; disseminated infection and infection localized to skin, eye, or mouth occurred slightly later. 5 W e are aware of only three reports describing the appearance of perinatal H S V after 34 days of age. 68 A notable feature of our patient's illness was her absolute C S F neutrophilia on day 4. Usually conversion from a predominantly neutrophilic to mononuclear pleocytosis occurs 8 to 24 hours after onset in viral infections of the central nervous system. We are not aware of any previous reports of persistent C S F neutrophilia in association with H S V encephalitis. The concomitant serial seizures are unlikely to have been the cause, because status epilepticus does not usually produce C S F neutrophilia. If pleocytosis does occur, the cell count is usually less than 30. 9 However, macrophages did predominate in the central nervous system at autopsy; conversion from neutrophilic to mononuclear cell C S F pleocytosis eventually did occur. The progression from clinically localized infection to disseminated disease is rare but has been reported.a, lo Aside from the National Institute of Allergy and Infectious Diseases study, 4, 10 to our knowledge there have been no other reports of central nervous system disease evolving to disseminated disease in a neonate who had no involvement of skin, eye, or mouth. The pathophysiology of such infections and their progression is not clearly understood. Our patient had several indicators of a poor prognosis, including prematurity, low levels of antibody mediating mononuclear A D C C , 2 a decreased level of consciousness when therapy was initiated, and long duration of disease before acyclovir therapy was started. Improved chance of recovery from H S V illness depends not only on better antiviral drugs but also on early diagnosis and prompt initiation of therapy. 4 Unfortunately, clinical diagnosis remains difficult because "exceptional" cases are frequent. Use of rapid, specific diagnostic techniques, such as the polymerase-chain reaction, ll should make reliance on nonspecific, exception-prone clinical and laboratory criteria obsolete. We thank Dr. Morven Edwards for her helpful comments and Mr. Malkit Diocee for his technical expertise.
Volume 120 Number 4. Part 1 REFERENCES 1. Bendayan M. Zollinger M. Ultrastructura110calization of antigenic sites on osmium-fixed tissues applying a protein A gold technique. J Histochem Cytochem 1983;31:101-9. 2. Kohl S. West MS. Prober CG. Sullender WM. Loo LS. Arvin AM. Neonatal antibody-dependent cellular cytotoxic antibody levels are associated with the clinical presentation of neonatal herpes simplex virus infection. J Infect Dis 1989;160:770-6. 3. Brown ZA. Benedetti J. Ashley R. et al. Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. N Engl J Med 1991;324:1247-52. 4. Whitley R. Arvin A. Prober C. et al. Predictors of morbidity and mortality in neonates with herpes simplex virus infections: the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med 1991;324: 450-4. 5. Whitley RS. Herpes simplex virus infections. In: Remington JS. Klein JO. eds. Infectious diseases of the fetus and newborn infant. Philadelphia: WB Saunders. 1990:282-305.
Clinical and laboratory observations
569
6. Thomas EA. Scheifele DW. Maclean BS. Herpes simplex type II aseptic meningitis in a two-month-old infant. Pediatr Infect Dis J 1989;8:184-6. 7. Gutman LT. Wilfert CM. Eppes S. Herpes simplex encephalitis in children: analysis of cerebral spinal fluid and progressive neurodevelopmental deterioration. J Infect Dis 1986;154: 415-21. 8. Sullender WM. Miller JL. Yasukawa LL. et al. Humoral and cell-mediated immunity in neonates with herpes simplex virus infection. J Infect Dis 1987;155:28-37. 9. Fishman RA. CSF in disease of the nervous system. Philadelphia: WB Saunders, 1980:323. 10. Whitley R, Arvin A, Prober C, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex infection: Infectious Diseases Collaborative Study Group. N . Engl J Med 1991;324:444-9. 11. Aurelius E, Johansson B, Skoldenberg B, et al. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet 1991 ;337: 189-92.
Decrease in gastric emptying time and episodes of regurgitation in children with spastic quadriplegia fed a whey-based formula Martin D. Fried, MD. Vikram Khoshoo, MD. PhD. Donna J. Seeker, RPDt. David L. Gilday, MD. FRCPC. Judith M. Ash, MD. FRCPC. and Paul B. Peneharz, MB.ChB. PhD. FRCPC From the Divisions of Clinical Nutrition. Nutrition and Food Services. and Nuclear Medicine. Research Institute. Hospital for Sick Children. and the Departments of Pediatrics and Nutritional Sciences. University of Toronto. Toronto. Ontario. Canada
The gastric emptying times associated with three whey-based formulas were Significantly shorter than that associated with a casein-based formula In nine gastrostomy-fed patients with spastic quadriplegia (p
