Comparison of the cytotoxic activity of melphalan with L-prolyl-m-L-sarcolysyl-L-p-fluorophenylalanine in human tumour cell lines and primary cultures of tumour cells from patients

By means of sequential videotape recordings, the relevance of the quality of general movements for neurological outcome was determined in a group of 21 appropriate-for-gestational-age preterm infants with transient periventricular echodensities of variable localization and duration and in 6 infants without echodensities. Echodensities, especially in the parieto-occipital area, affected the quality of general movements. Echodensities persisting beyond 14d were associated with abnormal general movements; infants with echodensities up to 14 d had either normal or abnormal general movements. The developmental course of movement quality was correlated to neurological outcome (p < 0.005): normal outcomes were found in 11/12 infants with normal general movements throughout and in 9/11 infants with transient abnormal general movements; all 4 infants with persistent abnormal general movements had impaired outcomes. In infants with transient echodensities, longitudinal assessment of the quality of general movements helps to determine if there is brain dysfunction, either transient or persistent, and identifies infants at risk for impaired neurological outcomes.     

Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome

Sixteen infants with hypoxic-ischaemic encephalopathy (HIE) were studied using serial magnetic resonance imaging (MRI) up to the age of 2 years. The infants had regular neurological and developmental assessments. An nuclear magnetic resonance (NMR) score was devised to quantify the early and late MRI findings and a neurological optimality score was used to quantify abnormal neurological signs at the time of the final examination. The follow up MRI score was compared with the neonatal MRI score and the outcome of the child. There was a strong positive correlation between the neonatal and follow up MRI scores and between MRI scores and optimality score. All infants with a normal outcome had patchy white matter abnormalities. All infants with an abnormal outcome had extensive white matter abnormalities. The outcome was most severe in those infants with additional basal ganglia atrophy with or without cyst formation. Infants with mild HIE who are developmentally normal at the age of 2 years do not have normal MRI scans and may be at risk of minor neurological problems by school age. Bilateral basal ganglia abnormalities are associated with severe developmental delay, but infants with mainly white matter and cortical abnormalities have less severe problems despite extensive tissue loss.     

Comparison between observation of spontaneous movements and neurologic examination in preterm infants

OBJECTIVE: The Prechtl method of qualitative assessment of general movements (GMs) has been shown to be a good predictor of neurologic outcome in fetuses, preterm infants, and term infants. The aim of this study was to compare the results of this new technique with those of traditional neurologic examination and of cranial ultrasonography in preterm infants. METHODS: Serial videotape recordings (with off-line assessment of GMs), ultrasound examination of the brain, and neurologic examinations were performed from birth until about 6 months of corrected age, on a group of 66 preterm infants whose gestational age ranged from 26 to 36 weeks (mean 30.7 weeks). The agreement between the two techniques and their predictive power, with respect to the neurologic outcome at 2 years of corrected age, were evaluated for five different age groups from preterm age to 65 weeks of postmenstrual age. RESULTS: Overall agreement of the neurologic and GM findings was 80.3% and strongly age related (lower during the preterm and term periods and higher thereafter). At all ages the results of GM observation correlated highly with neurologic outcome; they showed higher sensitivity and specificity than the neurologic examination. This held true in particular before term age, when poor neurologic responses might be related to transient complications, and at term age, mainly because of infants with normal neurologic examination results but unfavorable outcome. During the preterm period the ultrasound results showed a better specificity and a lower sensitivity to outcome than GM findings. CONCLUSIONS: The results of this study indicate that quality assessment of GMs should be added to traditional neurologic assessment, neuroimaging, and other tests of preterm infants for diagnostic and prognostic purposes.     

Increase of hematocrit in experimental renal hypertension and its reversal

The electroencephalograms of 82 infants (between 27 and 37 weeks of conceptional age) recorded during the neonatal period were analyzed and compared with the ultimate clinical evolution. Three groups of infants were identified according to their neurological state at 3 years of age or older: group A: normal (34 infants), group B: minor neurological sequellae (13 infants) and group C: major neurological sequellae (17 infants). A fourth group (group D: 18 infants) died during the neonatal period. The E.E.Gs were classified as: normal, questionably abnormal, moderately abnormal or grossly abnormal. The analysis revealed that E.E.Gs classified as grossly abnormal, were found only in groups B, C and D. Serial E.E.Gs were of more value in distinguishing these groups. Only infants in groups C and D (with I exceptional case in group B) had E.E.Gs which remained abnormal for several weeks or which deteriorated during the neonatal period. This study shows the prognostic value of the E.E.G. recorded during the neonatal period, particularly serial recordings obtained during and after a period of clinical deterioration. A detailed statistical analysis of the E.E.Gs is in progress.     

Cardiac performance during insulin clamp: its evaluation by bioimpedance measurement

OBJECTIVE: The objective of this study was to know the most common organisms causing neonatal meningitis in a defined region of southern Madrid, the developmental outcome of these babies and the risk factors associated with the prognosis. PATIENTS AND METHODS: This was an observational study of 56 cases of meningitis diagnosed in our Neonatal Service between 1988 and 1994. In order to study the handicaps of these babies, only those who were born before May 1993 were considered so that they had a corrected age of at least 2 years when the neurological evaluations were done. RESULTS: The most common causative organisms were group B Streptococcus (27%), E. coli (11%) and enteroviruses (9%). In the premature infants the leading organisms were E. coli and Candida albicans. The age at diagnosis was 8 +/- 6 days in the group of preterm infants (p = 0.002). The mortality was associated with the prematurity (risk ratio: 17.8), the isolation of a gram-negative organism in the cerebral fluid (RR: 3.3) and the presence of abnormal findings in cerebral ultrasound studies (RR: 12.7). Sequelae were associated with the presence of abnormal findings in cerebral ultrasound studies (RR: 24.7) or in the neurologic examination (R: 7) and with the presence of previous cerebral lesions (RR: 5.7). CONCLUSIONS: Neonatal ultrasound examination, as well as the gestational age, the causative organisms, the presence of a previous cerebral lesion and the neurological examination, seem to be very important in predicting the prognosis of these babies.     

Prognosis of infants of diabetic mothers in relation to neonatal hypoglycaemia

A prospective follow-up study was conducted to determine whether neonatal hypoglycaemia in infants of diabetic mothers affects subsequent neurological and intellectual performance. 37 such infants (25 hypoglycaemic and 12 non-hypoglycaemic) were examined for physical, neurological and developmental performance at an average age of 4 1/2 years. 11 children were abnormal, with generalised retardation and neurological abnormalities, or delays in particular areas of development; three children were possibly abnormal; and 23 children were normal. Abnormality at follow-up could not be related to neonatal blood glucose level, to the duration of hypoglycaemia or to any other measurement made in the neonatal period, nor to any factor relating to the maternal diabetes. Compared with the normal children, the abnormal group had slightly small head-circumferences at birth relative to their gestational age, but a follow-up there was no difference in head size. At follow-up the children of diabetic mothers tended to be shorter than average. The poor prognosis of the infants in this study was not due to brain damage caused by neonatal hypoglycaemia.     

Pericranial injection of local anesthetics for the management of resistant headaches

This study investigated the effect of early feeding mode on the neurological condition at 42 months. For this purpose, healthy pregnant women were recruited in Groningen and Rotterdam, The Netherlands. Children were healthy and born at term. At 42 months, the children were neurologically examined by means of the Touwen/Hempel technique. In addition to the clinical diagnosis, the neurological findings were interpreted in terms of optimality. Special attention was paid to the quality of movements in terms of fluency. In total, 200 (51%) exclusively breastfed(for > or = 6 weeks) and 194 (49%) formula-fed children were studied. Twelve (3%) 42-month-old children were considered to be neurologically mildly abnormal and 1 child was diagnosed as abnormal. No effect of the type of feeding was found on the clinical diagnosis or the neurological optimality. After adjustments for study centre and social, obstetric, perinatal and neonatal neurological differences, a beneficial effect of breastfeeding on the fluency of movements was found (odds ratio for non-optimal fluency 0.56; 95% confidence interval 0.37-0.85). The prolongation of full breastfeeding beyond 6 weeks did not influence the quality of movements. In conclusion, among Dutch preschool children, there was a small advantageous effect of full breastfeeding during the first 6 weeks of life on the fluency of movements.     

Brainstem dysfunction in the infant apnea syndrome

Thirty-six infants identified as infant apnea syndrome (IAS) and 25 controls with a comparable age distribution were evaluated with Brainstem Auditory Evoked Potential (BAEP) testing. There was a significant predilection for leftsided BAEP abnormalities in IAS patients. Fifteen IAS patients had bilateral abnormalities, and of the 21 IAS patients with unilateral abnormalities, 17 had abnormalities on the left side (p less than 0.01 by McNemar's test). Significant differences (p less than 0.05 by analysis of covariance adjusting for age) between normal controls and IAS infants were found for peak latencies I, III, and V, and amplitude III. Linear regression analyses of the above parameters versus age in months for normal controls were constructed with 68% and 95% prediction interval bands to permit analysis of individual data points. Data points from the IAS infants with bilateral BAEP abnormalities have been plotted on these linear regression curves. No single measurement of latency or amplitude is abnormal in the majority of IAS infants, but many of the individual points fall outside of the 95% prediction curve.     

Extreme hyperbilirubinaemia in Zimbabwean neonates: neurodevelopmental outcome at 4 months

As part of a prospective study of severely jaundiced Zimbabwean infants, the relationship between maximum total serum bilirubin (TSB) concentration in the neonatal period and neurodevelopmental outcome at the corrected age of 4 months was studied. Fifty infants with a TSB of > 400 micromol/l (23.4 mg/dl) were enrolled and screened with a neonatal neurological examination (NNE). The cause of jaundice was low birth weight in 22 (44%), ABO incompatability in 8 (16%), sepsis in 8 (16%) and congenital syphilis (6%) in 3 infants. In 9 infants a cause could not be determined. At 4 months, 2 infants had died and 3 were lost to follow up, leaving 45 infants for the infant motor screen (IMS) at 4 months of age. Mean TSB in the neonatal period was 485 micromol/l (28.2 mg/dl), and 7 infants received an exchange transfusion. Mean TSB of the infants with an exchange transfusion was 637 micromol/l (37.2 mg/dl) (range 429-865 micromol/l (25-50.3 mg/dl)) and of the infants without transfusion 459 micromol/l (26.8 mg/dl) (range 400 740 micromol/l (23.4-43 mg/dl)) (P < 0.0001). The TSB was not associated with birth weight, gestational age, gender or head circumference of the baby. On the IMS, 6 of 45 (13.3%) infants scored abnormal, 6 (13.3%) suspect and 33 (73%) scored normal. Three of the six (50%) remaining infants who received an exchange transfusion scored abnormal on the IMS while only 3 of the 39 (8%) infants without exchange transfusion were abnormal. CONCLUSION: More than 25% of infants with a TSB of > 400 micromol/l (23.4 mg/dl) scored abnormal or suspect at 4 months of age and half of these infants already showed irreversible neurological symptoms. All infants who scored abnormal or suspect on the IMS with bilirubin levels between 400 and 500 micromol/l (23.4 and 29.2 mg/dl) had haemolytic disease or were premature.     

Spontaneous abnormal involuntary movements in first-episode schizophrenia and schizophreniform disorder: baseline rate in a group of patients from an Irish catchment area

OBJECTIVE: This study investigated the rate of spontaneous abnormal involuntary movements in a group of patients presenting with a first episode of schizophrenia or schizophreniform psychosis. METHOD: Seventy-nine patients with a first episode of schizophrenia or schizophreniform psychosis who presented to a catchment area psychiatric service over a 3-year period, and who were neuroleptic-naive or had been medicated for less than 1 month, were examined for the presence of involuntary movements with use of the Abnormal Involuntary Movement Scale. RESULTS: Six patients (7.6%) had spontaneous dyskinesia as defined by the criteria of Schooler and Kane, and nine other patients had mild orofacial involuntary movements. The patients with spontaneous dyskinesia had completed significantly fewer years of education than the patients without dyskinesia. Spontaneous involuntary movements were unrelated to age at presentation for treatment. CONCLUSIONS: Spontaneous abnormal involuntary movements were evident among a proportion of patients with first-episode schizophrenia or schizophreniform psychosis at baseline presentation and were associated with reduced educational attainment. This finding supports previous suggestions that abnormal involuntary movements in schizophrenia may be related to the pathophysiology of the illness and therefore cannot be attributed entirely to the adverse effects of neuroleptic medication.     

Binding of properdin to solid-phase immune complexes: critical role of the classical activation pathway of complement

OBJECTIVE: Our objectives were to assess the clinical and microbiological aspects of septic osteoarthritis in children admitted to our center from 1987 until July 1997 and to determine the sensitivity of ultrasound in this age group. PATIENTS AND METHODS: The medical records of 36 children diagnosed as having septic osteoarthritis of the hip were reviewed retrospectively. The diagnosis had been based on clinical criteria, along with synovectomy and drainage of purulent material from the affected joint. An X-ray and/or ultrasound had been performed when the diagnosis was suspected. RESULTS: Nineteen children were diagnosed during the neonatal period, 8 between the ages of 1 and 12 months and 9 older than one year of age. Mean age at diagnosis was 16.8 +/- 6.2 months (median 29 days, range 6 days to 13 years). The hip was involved in 32 children, the ankle in 3 and the elbow in 1. A microbiological diagnosis was achieved in 22 cases (61%) by culture from blood, CSF, and/or synovial fluid. The most common isolates were Gram positive cocci (S. aureus in 9 cases and coagulase negative Staphylococcus in 3). The diagnostic value of the X-rays was very low (18%). The ultrasound was initially considered abnormal in 64.5% of the patients, with a lower sensitivity in the neonatal period. After a mean follow-up period of 36 months, the outcome was good in 86% of the cases, although three children continue with sequelae. Two preterm infants died due to sepsis associated with the osteoarthritis. CONCLUSIONS: At the time of diagnosis of septic arthritis of the hip, the ultrasound is frequently normal. Due to the poor outcome when there is a delay in surgery, we suggest immediate synovectomy and drainage when there is clinical suspicion of septic arthritis despite an apparently normal ultrasound.     

The organization of leg movements in preterm and full-term infants after term age

In a sample of 13 full-term and 10 preterm infants, the development of kicking movements was studied at 6, 12, and 18 weeks (corrected) age. In healthy full-term infants some characteristics are strikingly stable, such as the duration of the flexion and extension phase and the within-joint organization. These parameters did not differ in preterm compared to full-term infants. For other features, however, developmental changes and differences were observed. Full-term infants tended to decrease their kick frequencies slightly with age. In preterm infants much higher initial kick rates were found, followed by a steep decrease, which resulted in kick frequencies comparable to the full-term levels after the (corrected) age of 12 weeks. There is a tight coupling between the movements in the different joints of the leg in full-term newborns. Preterm infants, in contrast, initially show much lower cross-correlations between hip and ankle and between knee and ankle. This is particularly the case for those preterm infants who were born before 32 weeks gestation. Again, the differences resolved after the age of 12 weeks, which might be related to a transformation in neural functions reported previously around this age. The initial differences in the characteristics of kicking appeared to be more readily explainable by differences in neurological condition than by contrasts in leg volume or postural control.     

The utility of chest radiography in the follow-up of pneumonia

AIM: We conducted this study to determine whether chest radiography was clinically useful in the follow-up of uncomplicated pneumonia affecting children aged between 6 weeks and 15 years. METHOD: We examined the case records of all 78 paediatric admissions for pneumonia to our hospital over one year. Thirteen children were excluded on account of age or other complicating factors. RESULTS: Of the 65 study cases, the mean age was 3.5 years (range 0.4-13 years). On admission 51 (79%) had cough, 53 (82%) fever, 53 (82%) tachypnoea and 50 (77%) had abnormal chest signs. Elevation of C reactive protein was recorded in 43 (66%) cases and leukocytosis in 42 (65%). All children received initial chest radiographs which showed unilobular/lobar changes in 34 (53%), bilobar changes in 19 (29%) and diffuse abnormalities in 7 (11%). Forty-one patients were followed up both clinically and radiologically, usually (31 cases) between four and six weeks after discharge. Thirty-seven children had no abnormal symptoms or signs and had normal chest radiographs. The remaining four had symptoms and signs, their radiographs showed either slight resolution or no change from the admission films. CONCLUSION: In cases of uncomplicated pneumonia, follow-up chest radiography should be deferred until at least four weeks after discharge and is not indicated if symptoms and signs are absent.     

Insulin, glucagon, portal systemic shunting, and hepatic failure in the dog

The cerebrospinal fluid (CSF) composition was studied in 54 premature infants. The pregnancy was normal and the delivery normal and non traumatic in all of them, and the 5 minutes Apgar score ranged from 6 to 9. No abnormalities were found on physical examination including neurological examination. Blood cell countings and blood gasometry were normal. CSF composition was studied as to: total cell count and total protein, glucose, bilirrubin and hemoglobin concentrations. Data found permit to stablish as physiologic the following values: leucocytes, until 16 per cumm; erithrocytes, until 1,280 per cumm; total protein content until 300 mgm/100 ml; bilirrubin until 80 micrometer/1; hemoglobin until 8 micrometer/1; glucose, two thirds of the concentration found in the blood. Protein, bilirrubin and hemoglobin are significantly increased as compared to values found for the CSF of 79 fullterm normal newborn babies evaluated previously. Hemoglobin was not detected in the CSF of any full term newborn baby. The differences found are probably due to a less efficient blood-CSF barrier in premature infants as compared to full-term newborn babies.     

Visual, cognitive, and neurodevelopmental outcome at 51/2 years in children with perinatal haemorrhagic-ischaemic brain lesions

To determine predictive values of early visual and neurocognitive assessment in children with perinatally acquired haemorrhagic or ischaemic brain lesions selected on the basis of ultrasound, 63 children (37 boys, 26 girls), who had been followed and examined until the age of 18 months, were reexamined at 5 1/2 years. Good correlations between visual and neurodevelopmental assessments at 18 months and at 5 1/2 years were found. When ultrasound abnormalities were combined with early visual and neurocognitive assessment data, good predictive values, especially for the group of children who had grade 2 to 4 leukomalacia, were found for visual acuity and neurodevelopment.     

Technetium-99m-HMPAO brain SPECT in Beh?et's disease

Beh?et's disease (BD) is an idiopathic multisystem disorder. Involvement of the central nervous system (CNS) occurs in 4%-48% of cases. The aim of this study was to evaluate 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT findings in BD patients and eventually to detect CNS involvement by depicting cerebral blood flow disturbances. METHODS: Technetium-99m-HMPAO brain SPECT was performed on 33 consecutive BD patients. Qualitative and quantitative evaluation of the cortical uptake was done using an automatic program that generated 32 regions of interest (ROIs). An uptake index for each ROI was obtained. Reference values were obtained from a healthy control group (n = 20). Twenty-five patients also had an MRI study. RESULTS: Twelve of 32 patients (36%) presented with a clinical neurological disorder. SPECT and visual evaluation revealed that 17 patients (51.5%) had abnormalities; 9 of 25 MRI studies (36%) were abnormal. Using the quantitative approach for SPECT, 23 patients (69.7%) had abnormally low values. Six of 12 patients with neurological symptoms had a visually abnormal SPECT scan, whereas quantitative analysis showed abnormalities in 11 patients. Of the 21 patients with no neurological findings, 9 had abnormal SPECT results, and 12 had low uptake indexes. CONCLUSION: HMPAO brain SPECT shows high rates of cerebral blood flow abnormalities in BD patients presenting with neuropsychiatric symptoms, and it also is frequently abnormal in asymptomatic BD patients who have no abnormalities on MR scans. Compared with visual analysis, quantitative analysis detects an even higher rate of SPECT changes in BD patients.     

Blood pressure survey in a population of newborn infants

Systolic blood pressure in the arm was measured in infants at the ages of 4 to 6 days and 5 to 7 weeks by the Doppler ultrasound technique. At the age of 4 to 6 days the mean blood pressure (+/- SE of mean) in 469 sleeping infants was 70-7 +/- 0-3 mm Hg, rising at 5 to 7 weeks to 89-7 +/- 0-9 mm Hg (in 144 infants). In 252 infants awake at 5 to 7 weeks blood pressure was 96-8 +/- 0-6 mm Hg. In 391 infants in whom measurements were made on both occasions blood pressure at 4 to 6 days was significantly related to blood pressure at 5 to 7 weeks. Thus those infants with relatively high blood pressures at 4 to 6 days showed a weak tendency to have relatively high blood pressures at 5 to 7 weeks. In this trend continues with age it would suggest that the tendency to develop hypertension may already be demonstrable at the age of 4 to 6 days.     

A prospective analysis of office-based breast ultrasound

OBJECTIVE: To determine the usefulness of office-based breast ultrasound. DESIGN: Prospective, nonrandomized study. SETTING: Academic-affiliated community teaching hospital. PATIENTS: Among 653 consecutive patients seen in our office during a 30-month period, we performed 660 ultrasound examinations. The presenting complaint included a palpable mass in 53%, abnormal mammogram in 39%, and nipple discharge or retraction in 3%. INTERVENTION: Ultrasound examination was performed using a handheld 7.5-MHz linear array transducer. Findings and pertinent clinicopathologic data were recorded prospectively in our Breast Ultrasound Registry. MAIN OUTCOME MEASURE: Contribution of breast ultrasound to diagnosis and treatment. RESULTS: The sonogram was normal in 201 cases (30%), showed duct ectasia in 20 cases (3%), a simple cyst or seroma in 101 cases (15%), and a focal complex or solid abnormality in 338 cases (51%). Among the last group, 114 (97%) of 118 lesions thought to be benign on ultrasonography proved to be benign, whereas 13 (12%) of 111 indeterminate and 72 (75%) of 96 sonographically suspicious lesions proved to be cancer (including 13 cases with normal mammograms). Ultrasonographic features of malignancy included an anteroposterior-to-lateral dimension ratio of 1 or greater, heterogeneous hypoechoicity, irregular shadowing, and fuzzy and/or jagged margins. Ultrasound-guided needle biopsy accurately diagnosed 46 benign nonpalpable lesions and 20 malignant nonpalpable lesions. CONCLUSIONS: These data suggest that ultrasonography is a useful adjunct to clinical and mammographic evaluation of breast disease. Breast ultrasound identifies cysts, aids in differentiating benign from malignant lesions, and facilitates office needle biopsy of nonpalpable abnormalities, permitting timely and cost-effective patient care.     

Synthesis and evaluation of 5-aminosalicyl-glycine as a potential colon-specific prodrug of 5-aminosalicylic acid

OBJECTIVE: To estimate more precisely the risk of fetal loss and congenital abnormalities after maternal parvovirus B19 infection, and to assess the long term outcome for surviving infants. DESIGN: Prospective cohort study of pregnant women with confirmed B19 infection with follow up of the surviving infants. The rate of fetal loss in the study cohort was compared with that in pregnant women with varicella. SETTING: Cases reported by laboratories in England and Wales between 1985-1988 and 1992-1995. SAMPLE: Four hundred and twenty-seven pregnant women with B19 infection and 367 surviving infants of whom 129 were followed up at 7-10 years of age. METHODS: Questionnaires to obstetricians and general practitioners on outcome of pregnancy and health of surviving infants. Maternal infection confirmed by B19-specific IgM assay and/or IgG seroconversion. RESULTS: The excess rate of fetal loss in women with B19 infection was confined to the first 20 weeks of gestation and averaged 9%. Seven cases of fetal hydrops followed maternal infections between 9 and 20 weeks of gestation (observed risk 2.9%, 95% CI 1.2-5.9). No abnormalities attributable to B19 infection were found at birth in surviving infants (observed risk 0%, upper 95% CI 0.86%). No late effects were found at 7-10 years. CONCLUSIONS: Around 1 in 10 women infected before 20 weeks of gestation will suffer a fetal loss due to B19. The risk of an adverse outcome of pregnancy after this stage is remote. Infected women can be reassured that the maximum possible risk of a congenital abnormality due to B19 is under 1% and that long term development will be normal.     

Growth graphs for the clinical assessment of infants of varying gestational age

Two graphs are presented showing means and 1 and 2 SD for growth in weight, length, and head circumference: (1) a fetal-infant graph with lines of growth from 26 weeks of gestational age until one year of age after "term' has been reached: and (2) a similarly constructed graph for children ages one through ten years. The standards of growth were obtained from published data in which the subjects received optimal health care. The graphs allow comparisons of infants of varying gestational age with standards for that age. Normal and abnormal deviations in growth are easily identified. Some examples of common variations in physical growth are described.