Increased activity of lysosomal enzymes in the peritoneal fluid of patients with gynecologic cancers and pelvic inflammatory disease.

PURPOSE: To investigate whether the activity of lysosomal enzymes is increased in the peritoneal fluid of patients with gynecologic cancers compared to activity in the peritoneal fluid from normal subjects and those with pelvic inflammatory disease, and fluid from benign ovarian cysts. PATIENTS AND METHODS: beta-glucuronidase, beta-galactosidase, and alpha-mannosidase activity was measured in the peritoneal fluid from patients with gynecologic cancer, pelvic inflammatory disease, and normal subjects, and fluid from benign ovarian cysts. RESULTS: The mean+/-SD of beta-glucuronidase, beta-galactosidase, and alpha-mannosidase activity in the gynecologic cancers was 120+/-50 nmol, 203+/-86 nmol, and 240+/-119 nmol 4-methylumbelliferone/ml/h, respectively; in the normal control subjects it was 22+/-9 nmol, 46+/-10 nmol, and 80+/-23 nmol, respectively (P=0.00003, 0.0001, and 0.0001, respectively). The activity was increased even in cases without malignant cells in the peritoneal fluid. In pelvic inflammatory disease it was 148+/-82 nmol, 278+/-112 nmol, and 291+/-140 nmol, respectively. The activity in the fluid of the ovarian cysts was similar to that of the normal peritoneal fluid. There was a significant positive correlation between enzyme activity and stage of cancer, that was stronger for beta-glucuronidase (r=0.889, P=0.003). CONCLUSION: The increased lysosomal enzyme activity in gynecologic cancers, without overlapping between patients and normal subjects or benign ovarian cyst fluid, indicates that such measurements might be applied for diagnostic purposes.

Beta-glucuronidase in the diagnosis of bacterial meningitis and response to treatment.

AIM: Beta-glucuronidase activity is increased in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. The aim of this study was to investigate the beta-glucuronidase activity in the cell-free CSF of bacterial meningitis and its course during treatment, and compare it with other CSF parameters. METHODS: The beta-glucuronidase activity, cell number, protein concentration and CSF/blood glucose ratio were measured in 43 consecutive infants and children with bacterial meningitis, and 97 control subjects. Patients had one or two follow-up lumbar punctures. RESULTS: The beta-glucuronidase activity was increased early in bacterial meningitis, even when the other CSF parameters were undisturbed. Before treatment, the median activity in affected children was 136 micromoles 4-methylumbelliferone l(-1) h(-1) (range 44-826) and in controls 14 (7-23). In all patients who improved, the activity was lower in the follow-up CSF samples. Six to 12 h after starting treatment, the median activity was already reduced by 59%. The other CSF parameters showed a variability during the first 24 h of treatment independently of the course of the disease. Multiple comparisons of the CSF parameters in 17 patients who had two follow-up punctures showed that the beta-glucuronidase activity was the best prognostic index. CONCLUSION: Beta-glucuronidase activity in the CSF is a reliable indicator of bacterial meningitis, which can identify the response to treatment early in the course of illness. The enzyme activity is increased early in the disease, even when the other laboratory parameters from the CSF remain normal.

Molecular epidemiology of penicillin-susceptible non-beta-lactam-resistant Streptococcus pneumoniae isolates from Greek children.

A total of 128 Streptococcus pneumoniae isolates that were susceptible to penicillin but resistant to non-beta-lactam agents were isolated from young carriers in Greece and analyzed by antibiotic susceptibility testing, serotyping, restriction fragment end labeling (RFEL), and antibiotic resistance genotyping. The serotypes 6A/B (49%), 14 (14%), 19A/F (11%), 11A (9%), 23A/F (4%), 15B/C (2%), and 21 (2%) were most prevalent in this collection. Of the isolates, 65% were erythromycin resistant, while the remaining isolates were tetracycline and/or trimethoprim-sulfamethoxazole resistant. Fifty-nine distinct RFEL types were identified. Twenty different RFEL clusters, harboring 2 to 19 strains each, accounted for 76% of all strains. Confirmatory multilocus sequence typing analysis of the genetic clusters showed the presence of three international clones (Tennessee(23F)-4, England(14)-9, and Greece(6B)-22) representing 30% of the isolates. The erm(B) gene was present in 70% of the erythromycin-resistant isolates, whereas 18 and 8% contained the mef(A) and mef(E) genes, respectively. The pneumococci representing erm(B), erm(A), and mef genes belonged to distinct genetic clusters. In total, 45% of all isolates were tetracycline resistant. Ninety-six percent of these isolates contained the tet(M) gene. In conclusion, penicillin-susceptible pneumococci resistant to non-beta-lactams are a genetically heterogeneous group displaying a variety of genotypes, resistance markers, and serotypes. This suggests that multiple genetic events lead to non-beta-lactam-resistant pneumococci in Greece. Importantly, most of these genotypes are capable of disseminating within the community.

Maternal smoking during pregnancy improves the anatomy of the hip joint in the female neonate.

OBJECTIVE: Because the greater frequency of developmental dysplasia of the hip in the female could have an endocrine etiology, and because maternal smoking in pregnancy causes fetal endocrine disequilibrium, we investigated the anatomy of the hip in neonates of smoking and non-smoking mothers. METHODS: Clinical and sonographic examination was performed on 2066 hips of 521 male and 512 female neonates. In 48 male and 53 female neonates, the mothers smoked during pregnancy. RESULTS: The mean +/- SD alpha angle in the male neonates of the non-smoking mothers was 62.3 degrees +/- 5.1 degrees and of the smoking mothers 62.1 degrees +/- 4.9 degrees (p = 0.7). In the female neonates of the non-smoking and the smoking mothers, it was 60.7 degrees +/- 5.3 degrees and 61.9 degrees +/- 4.8 degrees, respectively (p = 0.02). The difference between the male and the female neonates of the non-smoking mothers was significant (p < 0.000001), but there was no significant difference between the female neonates of the smoking mothers and the male neonates (p = 0.5). Among the female neonates whose mothers were non-smokers, the number of those with hip type IIa or worse was significantly greater than among the female neonates whose mothers were smokers. The clinical findings were in agreement with the sonographic findings. CONCLUSIONS: Maternal smoking during pregnancy reduces the frequency of sonographic and possibly clinically detected hip dysplasia in female but not in male neonates. Nonetheless, because smoking causes numerous adverse effects on the fetus and child, it is contraindicated during pregnancy.

High prevalence of erythromycin resistance of Streptococcus pyogenes in Greek children.

BACKGROUND: Macrolide resistance among Streptococcus pyogenes strains is increasing in many European countries. Greece was not considered a country with high prevalence of macrolide-resistant S. pyogenes strains, and until now the genetic mechanism of resistance was unknown. METHODS: During the 25-month period from December, 1998, to December, 2000, pharyngeal cultures for S. pyogenes were performed on 743 Greek children with the clinical diagnosis of pharyngitis. The children were 1 to 16 years old (median age, 7 years) and were living in Central and Southern Greece. S. pyogenes isolates were tested for their susceptibility to erythromycin, clarithromycin, azithromycin, clindamycin, penicillin G, amoxicillin/clavulanate and cefprozil. The erythromycin-resistant isolates were further studied for their genetic mechanism of resistance by means of PCR. RESULTS: Of a total of 275 S. pyogenes isolates recovered, 105 (38%) were erythromycin-resistant (MIC > or = 1 microgram/ml) [corrected], with 54, 45 and 1% of them carrying mef(A), erm(A) [subclass erm(TR)] and erm(B) gene, respectively. The prevalence of erythromycin-resistant strains was 29 and 42% during the time periods December, 1998, to December, 1999, and January, 2000, to December, 2000, respectively. All erythromycin-resistant isolates were also resistant to clarithromycin and azithromycin. The isolates carrying the erm(A) gene were inducibly resistant to clindamycin. The 275 S. pyogenes isolates had ceprozil MICs < or = 0.032 microgram/ml. CONCLUSIONS: The current high (38%) prevalence of erythromycin-resistant S. pyogenes in Central and Southern Greece requires continuous surveillance and careful antibiotic policy.

Sterile cerebrospinal fluid pleocytosis in young infants with urinary tract infection.

BACKGROUND: During the first 3 months of life febrile infants are subjected to sepsis workup, which includes evaluation for urinary tract infection (UTI) and meningitis. We investigated the existence of concomitant meningeal inflammation in infants younger than 90 days old affected with UTI. METHODS: We reviewed the medical records of all infants younger than 90 days old, who were hospitalized for UTI from January, 1990, to January, 2001. For the diagnosis of sterile cerebrospinal fluid (CSF) pleocytosis, the child's age, the CSF total white blood cell (WBC) count and the CSF absolute neutrophil count were taken into consideration. CSF pleocytosis was defined as the presence of > or = 35, > or = 21 and > or = 15 WBC/mm3 of CSF during the first, second and third month of life, respectively. The CSF Gram-stained smear, latex agglutination test and bacterial culture were negative. RESULTS: Sterile CSF pleocytosis was found in 15 (12.8%) of 117 infants with UTI who had had a lumbar puncture included in their initial laboratory evaluation. The 15 infants had a median age +/- semiinterquartile range of 40 +/- 25 days (range, 4 to 75 days). In these infants the median CSF WBC count +/- semiinterquartile range was 55 +/- 125/mm3 (range, 21 to 1,270/mm3). CONCLUSIONS: Sterile CSF pleocytosis was found in 12.8% of infants younger than 90 days old with UTI. The pathogenesis of this meningeal inflammation is not fully understood. Although bacterial infection of the subarachnoid space, with low bacterial seeding, cannot be excluded, at least in some cases, it is possible that CSF pleocytosis in some of the infants with UTI is mainly caused by the endotoxin of Gram-negative or other inflammation-inducing molecules of Gram-positive urine pathogens.

Novel application of IGF-I and IGFBP-3 generation tests in the diagnosis of growth hormone axis disturbances in children with beta-thalassaemia.

OBJECTIVE: Children with beta-thalassaemia major (beta-thal) frequently have growth retardation in the presence of low serum IGF-I and a normal GH response to pharmacological stimulation suggesting that they have GH insensitivity (GHIS). This study was carried out to study the cause of their growth retardation. DESIGN: We studied IGF-I and IGFBP-3 generation after exogenous GH administration for four days, in 15 prepubertal controls (C) and 41 prepubertal beta-thal patients divided into three groups according to their growth status: (Group 1) 15 with normal growth (N-thal) (Group 2) 16 with decelerated growth (D-thal) and (Group 3) 10 with short stature (S-thal), in order to determine whether GHIS is the cause of their growth retardation. MEASUREMENTS: IGF-I and IGFBP-3 were measured daily, before and for 4 days after daily administration of 0.1 IU/kg hGH, in 3 groups of prepubertal beta-thal patients and normal controls. RESULTS: N-thal and C had similar basal serum IGF-I (142 +/- 52 and 196 +/- 56 ng/ml, respectively) and IGFBP-3 concentrations (2.07 +/- 0.49 and 2.66 +/- 0.41 mg/l, respectively) as well as a similar percent increase of IGF-I (101 +/- 23% and 104 +/- 37%, respectively) and IGFBP-3 (52 +/- 36%, and 38 +/- 14%, respectively) during the generation tests. S-thal and D-thal had significantly lower basal IGF-I and IGFBP-3 concentrations (85 +/- 42 and 101 +/- 36 ng/ml; and 1.60 +/- 0.49 and 1.79 +/- 0.52 mg/l, respectively) as compared to N-thal and C (P < 0.001 and P < 0.005, respectively), and a significantly higher percent increase of IGF-I and IGFBP-3 during the generation tests (249 +/- 43 and 161 +/- 76%; and 121 +/- 99 and 73 +/- 35%, respectively) as compared to N-thal and C (P < 0.0001 and P < 0.01, respectively). Twenty-five percent of the growth retarded patients had classic GH deficiency (GHD) and percent increases of IGF-I and IGFBP-3 in the generation tests (164 +/- 86% and 80 +/- 49%, respectively) which were similar to those of the remaining growth-retarded children. CONCLUSION: The greater percent increases of IGF-I and IGFBP-3 in the generation tests of the growth retarded beta-thal patients, both with and without GHD, strongly suggest impaired GH secretion rather than GHIS as the cause of their growth retardation. We conclude that the IGF-I and IGFBP-3 generation tests are useful tools for the study not only of GHIS but also of GH secretory disorders in patients with beta-thal and short stature that can easily be performed in an outpatient setting as an initial test to identify the patients that may benefit from GH therapy.

Molecular epidemiology of penicillin-susceptible, multidrug-resistant serotype 6B pneumococci isolated from children in Greece.

Since January 1996, and over a 3-year time span, a significant spread of serotype 6B multidrug-resistant (MDR) pneumococci, susceptible to penicillin and resistant to erythromycin, clindamycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole, was noted in young carriers living in central and southern Greece. Using restriction fragment end labeling and penicillin binding protein (PBP) genotyping, we studied 41 serotype 6B penicillin-susceptible MDR pneumococci isolated during two independent studies in Greece. Forty (98%) of these 41 isolates were strongly related, representing a single lineage (genetic relatedness, > or = 91%). The Greek isolates were closely related (genetic relatedness, approximately 91%) to the penicillin-resistant MDR clone of serotype 6B that spread from Spain to Iceland in the late 1980s. Moreover, the Greek group of isolates was genetically distinct (genetic relatedness, < or = 83%) from other penicillin-susceptible or -resistant serotype 6B strains from various parts of the world. All serotype 6B penicillin-susceptible MDR isolates displayed a penicillin-susceptible PBP 1A-2B-2X genotype. Our findings suggest that the penicillin-susceptible MDR 6B clone that was found in Greece between the years 1996 and 1999 represents the ancestor of the pandemic penicillin-resistant MDR clone 6B.

Identification of an erm(A) erythromycin resistance methylase gene in Streptococcus pneumoniae isolated in Greece.

In a serotype 11A clone of erythromycin-resistant pneumococci isolated from young Greek carriers, we identified the nucleotide sequence of erm(A), a methylase gene previously described as erm(TR) in Streptococcus pyogenes. The erm(A) pneumococci were resistant to 14- and 15-member macrolides, inducibly resistant to clindamycin, and susceptible to streptogramin B. To our knowledge, this is the first identification of resistance to erythromycin in S. pneumoniae attributed solely to the carriage of the erm(A) gene.

Molecular epidemiology of penicillin-nonsusceptible Streptococcus pneumoniae among children in Greece.

A total of 145 penicillin-nonsusceptible Streptococcus pneumoniae strains were isolated from young carriers in Greece and analyzed by antibiotic susceptibility testing, serotyping, restriction fragment end labeling (RFEL), and penicillin-binding protein (PBP) genotyping. The serotypes 23A and 23F (54%), 19A and 19F (25%), 9V (5%), 15A, 15B, and 15C (4%), 6A and 6B (4%), and 21 (4%) were most prevalent in this collection. Fifty-three distinct RFEL types were identified. Sixteen different RFEL clusters, harboring 2 to 32 strains each, accounted for 82% of all strains. Eight of these genetic clusters representing 60% of the strains were previously identified in other countries. A predominant lineage of 66 strains (46%) harboring five RFEL types and the serotypes 19F and 23F was closely related to the pandemic clone Spain(23F)-1 (genetic relatedness of > or =85%). Another lineage, representing 11 strains, showed close genetic relatedness to the pandemic clone France(9V)-3. Another lineage of 8 serotype 21 strains was Greece specific since the RFEL types were not observed in an international collection of 193 genotypes from 16 different countries. Characterization of the PBP genes pbp1a, pbp2b, and pbp2x revealed 20 distinct PBP genotypes of which PBP type 1-1-1, initially observed in the pandemic clones 23F and 9V, was predominantly present in 11 RFEL types in this Greek collection of penicillin-nonsusceptible strains (55%). Sixteen PBP types covering 52 strains (36%) were Greece specific. This study underlines the strong contribution of penicillin-resistant international clones to the prevalence and spread of penicillin-nonsusceptible pneumococci among young children in Greece.

Antimicrobial use and colonization with erythromycin-resistant Streptococcus pneumoniae in Greece during the first 2 years of life.

We evaluated nasopharyngeal colonization with erythromycin-resistant Streptococcus pneumoniae during the first 2 years of life in central and southern Greece. Of 2448 children studied from February 1997 to February 1999, 766 (31%) carried 781 pneumococcal isolates. Ninety-five (3.9%) of the children attended day care centers. Eighteen percent of the pneumococci were resistant to erythromycin (minimal inhibitory concentration 1 to >128 microg/mL), with 67.9% of them carrying the erm(B) gene and 29.2% mef(A) gene products. Four strains possessed neither the erm(B) nor the mef(A) gene. Multidrug resistance occurred in 97% and 40% of isolates carrying the erm(B) and mef(A) gene, respectively. An association was found between the erm(B) gene and serotypes 6B and 23F and between the mef(A) gene and serotypes 14 and 19F. A significant relationship existed between carriage of erythromycin-resistant pneumococci and use of macrolides or beta-lactams in the previous 3 months; the association was strongest when macrolide therapy was administered during the last month (odds ratio, 5.92; P=.0001). The findings indicate the necessity of a judicious use of both macrolides and beta-lactams in young children to reduce the colonization with erythromycin-resistant pneumococci and the subsequent spread of such strains to the community.

Carriage of antibiotic-resistant Streptococcus pneumoniae in Greek infants and toddlers.

The prevalence, resistance patterns and serotypes of antibiotic-resistant Streptococcus pneumoniae strains recovered from Greek carriers under 24 months of age were studied. From February 1997 to April 1998, nasopharyngeal cultures were performed in 1,269 children (ages 2-23 months, median 11 months) living in various areas of central and southern Greece. Resistance (including both intermediate and resistant isolates) to one or more antimicrobial agents was found in 132 of the 421 (31%) Streptococcus pneumoniae isolates, as follows: penicillin, 9% intermediate, 7.6% resistant; cefotaxime, 5.2% intermediate, 0.5% resistant; erythromycin, 0.7% intermediate, 18.1% resistant; clindamycin, 0.2% intermediate, 12.4% resistant; tetracycline, 0.7% intermediate, 16.4% resistant; chloramphenicol, 12.4% resistant; and trimethoprim-sulfamethoxazole, 3.8% intermediate, 14.3% resistant. The MICs of penicillin for 66% of the penicillin-nonsusceptible pneumococci were 1-4 microg/ml. Multidrug resistance was found in 64% of penicillin-nonsusceptible and 37% of penicillin-susceptible strains. Sixty-two percent of the penicillin-susceptible, multidrug-resistant strains belonged to serotype 6B and were resistant to all five non-beta-lactam agents tested. This notable serotype 6B resistance pattern was described for the first time in a previous study performed from December 1995 to February 1996 in the city of Patras, southwestern Greece. Seventy-two percent of antibiotic-resistant isolates belonged to serotypes 6B, 9V, 14, 18C, 19F and 23F. These results document the spread of resistant pneumococcal strains in central and southern Greece, many of which are multidrug resistant.

Vascular retinal abnormalities in neonates of mothers who smoked during pregnancy.

OBJECTIVE: To investigate whether maternal smoking during pregnancy causes retinal abnormalities in the newborn. STUDY DESIGN: One hundred sixty-two neonates of smoking mothers and 162 matched neonates of nonsmoking mothers (112 appropriate for gestational age [AGA], 30 small for gestational age [SGA], 20 large for gestational age [LGA] in each group) were studied. RESULTS: Retinal arterial narrowing and straightening (RANS) was observed in 52 and 10 eyes of the newborns of smoking and nonsmoking mothers, respectively (P <. 000001) in association with elevated blood pressure in the neonates. The frequency of RANS was more than 3-fold greater in the SGA neonates than in the AGA and LGA neonates of the smoking mothers. Retinal venous dilatation and tortuosity (RVDT) was found in 100 and 36 eyes of neonates of smoking and nonsmoking mothers, respectively (P <.000001). The frequency of RVDT in the SGA neonates of the smoking mothers was 2.5-fold and 4.2-fold greater than in the AGA infants and the LGA infants, respectively. Also, intraretinal hemorrhages were found in 61 and 31 eyes of neonates of smoking and nonsmoking mothers, respectively (P =.0007) in association with elevated hematocrit and RVDT, whereas no intraretinal hemorrhages were found when RANS was present. All retinal abnormalities resolved by 6 months in infants of smoking mothers and by 2 months in infants of nonsmoking mothers. CONCLUSIONS: Maternal smoking during pregnancy causes increased frequency of RANS, RVDT, and intraretinal hemorrhages; but these retinal abnormalities resolve by 6 months of age.

Cord blood alpha-fetoprotein concentrations in term newborns of smoking mothers.

UNLABELLED: To investigate the toxic effect of tobacco smoke on the fetus, we measured in cord blood the concentrations of alpha-fetoprotein (AFP), the principal serum protein in early ontogenic development, and erythropoietin (EPO), as an index of chronic fetal hypoxia. A total of 103 consecutively enrolled term newborns of smoking mothers and 103 term infants of nonsmoking parents were studied. The mean +/- SD AFP concentrations in the newborns of the mothers who smoked 1-50, 5-50, and 10-50 cigarettes/day were 86.4 +/- 88.9, 96.3 +/- 91.9 and 118.7 +/- 103.7 ng/ml, respectively. The difference of all three groups from the control neonates (57.7 +/- 37.2) was significant. The EPO concentrations in the newborns of the mothers who smoked 1-50 (53.9 +/- 64.6 mU/ml) and 5-50 (56.3 +/- 68.5) cigarettes/day were significantly greater than in the control neonates (29.5 +/- 16.1). In the newborns of the smoking mothers there was a significant positive correlation between AFP concentrations and number of cigarettes smoked per day, and a negative correlation between AFP and birth weight or length. There was no correlation between AFP and EPO concentrations, as well as between EPO and birth weight, length or number of cigarettes smoked per day. CONCLUSION: The absence of a correlation between erythropoietin and birth weight or length and the negative correlations between alpha-fetoprotein and these anthropometric parameters suggest that the intra-uterine growth retardation caused by maternal smoking is not due to tissue hypoxia, but that both growth retardation and elevated alpha-fetoprotein result from the direct or indirect toxic effect of a factor(s) present in tobacco smoke.

Cord blood leptin concentrations in relation to intrauterine growth.

OBJECTIVE: Leptin, a hormone that signals the amount of energy stores to the brain, has recently been shown to play a role in the regulation of several hypothalamic pituitary axes, including the growth hormone axis. To investigate a potential association between cord blood leptin concentrations and intrauterine growth we measured leptin concentrations in the cord blood of small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) healthy newborns. PATIENTS AND MEASUREMENTS: Cord blood leptin concentrations were evaluated in 25 SGA, 100 AGA, and 45 LGA, neonates. RESULTS: Leptin was detectable in all newborns in concentrations comparable with those found in adults. Moreover, SGA newborns had lower leptin concentrations (3.70 +/- 1.81 micrograms/l) than AGA (5.65 +/- 4.98 micrograms/l) and LGA newborns (11.99 +/- 7.06 micrograms/ l)(P < 0.01). Cord blood leptin concentrations were significantly associated with ponderal index, cord blood insulin concentrations, placental weight and maternal serum leptin concentrations. Importantly, the association between cord blood leptin concentrations and intrauterine growth status persisted after adjusting for adiposity, placental weight, maternal serum leptin concentrations and cord blood insulin concentrations. CONCLUSIONS: Cord blood leptin concentrations are independently associated with intrauterine growth. Future studies are needed to elucidate the underlying mechanism and clarify the role of leptin in regulating growth and controlling appetite in newborns.

Natural antibodies in childhood: development, individual stability, and injury effect indicate a contribution to immune memory.

Natural, often autoreactive antibodies are present in normal sera in large quantity and show alterations in specificity in diverse pathological situations. They have, however, usually not been studied longitudinally. Here we investigated some representative serum reactivities of natural antibodies in 67 normal children and 10 with injury during childhood, followed up for 3 years. Normal children showed an individually characteristic and relatively stable level of most IgM, IgG, and IgA reactivities when measured with ELISA by reference to a standard. Injured children showed some very rapidly enhanced reactivities within 3 days after trauma, which thereafter slowly diminished over years before coming back to a normal level. This period exceeds by far the lifetime of antibodies and plasma cells. We conclude that natural antibodies contribute to the establishment and maintenance of immune memory in a manner that is distinct from classical immune reactions.

Correlation of leucocyte count and erythrocyte sedimentation rate with the day of illness in presumed bacterial pneumonia of childhood.

We investigated the effect of the duration of illness on the white blood cell (WBC) and total neutrophil counts and the erythrocyte sedimentation rate (ESR) in untreated children with clinical and roentgenographic findings compatible with bacterial pneumonia. According to the duration of illness before admission, the patients were divided into: Group I, 48 patients ill for < 24 h; Group II, 39 patients ill for 24-48 h; Group III, 21 patients ill for 48-72 h; and Group IV, eight patients ill for 72-96 h. In children with presumably bacterial pneumonia the number of the WBC was greater during the first 2 days of illness. Thereafter, the leucocyte count declined, reaching the lowest levels on the fourth day. A similar course was followed by the absolute number of total neutrophils. During the second day of illness, 92% and 72% of the patients had leucocyte counts > 10,000 and > 15,000/mm3, respectively, whereas on the fourth day of illness only half of the patients had > 10,000 and one-quarter > 15,000 WBC/mm3. The ESR followed an opposite course to that of the WBC. During the first day of illness it was normal or mildly elevated, increasing steadily thereafter. The validity of the WBC and total neutrophil counts in conjunction with the ESR in the evaluation of bacterial pneumonia is augmented when the day of illness is taken into consideration.

Effect of birth weight and maternal smoking on cord blood leptin concentrations of full-term and preterm newborns.

Prematurity, maternal smoking, and low birth weight each result in neuroendocrine dysfunction and increased perinatal morbidity and mortality. Leptin, an adipocyte-secreted protein, has provided the first physiological link to the regulatory system controlling starvation-induced neuroendocrine changes in rodents. This study investigated whether leptin concentrations were detectable in cord blood of newborns, and assessed the effect of birth weight, prematurity, and maternal smoking on cord blood leptin concentrations. Fifty consecutively enrolled full-term and 12 preterm newborns born to mothers who smoked during pregnancy were compared to 50 full-term and 12 preterm newborns born to parents who were nonsmokers. RIA for leptin was performed using cord blood samples collected immediately after birth. Leptin concentrations were detectable in newborns and correlated positively with obesity (full-term, r = 0.30, P < 0.01; preterm, r = 0.47, P < 0.05). Maternal smoking during pregnancy was associated with decreased leptin concentrations in the cord blood of both full-term and preterm newborns. This effect was independent of obesity (full-term newborns: 5.25 +/- 2.48 vs. 4.21 +/- 2.71 ng/ml, P = 0.01) and was more pronounced in premature newborns (5.67 +/- 3.6 vs. 2.46 +/- 2.03, P = 0.02), and its magnitude in full-term newborns was directly related to the reported number of cigarettes the mothers of the full-term newborns smoked per day (r = -0.438, P < 0.001). Thus, low birth weight and maternal smoking are both associated with decreased leptin concentrations, and these effects are more pronounced in premature newborns. Future studies will be needed to determine whether administration of leptin might reverse the neuroendocrine dysfunction caused by maternal smoking.

Resistance patterns of streptococcus pneumoniae from carriers attending day-care centers in southwestern Greece.

The resistance to beta-lactam and non-beta-lactam antibiotics of 133 nasopharyngeal isolates of Streptococcus pneumoniae recovered from December 1995 to February 1996 from children attending seven day-care centers in southwestern Greece was studied. Reduced susceptibility to one or more anti-microbial agents was found in 70 isolates (53%), as follows: penicillin, 17% intermediate, 12% resistant; cefotaxime, 10.5% intermediate, 1.5% resistant; trimethoprim-sulfamethoxazole, 8% intermediate, 35% resistant; chloramphenicol, 27% resistant; tetracycline, 29% resistant; and erythromycin/clindamycin, 19% resistant. Eighty-seven percent of penicillin-intermediate or -resistant strains belonged to serogroups/serotypes 19, 21, and 23. Fifty-six percent of the antibiotic-resistant pneumococci were multiply resistant, including serogroup 6 strains that were penicillin-susceptible but resistant to all non-beta-lactam drugs tested, as well as serogroup 23 strains resistant to penicillin, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole. The high incidence of antibiotic-resistant pneumococci and the divergent and unique resistance patterns found in this study underline the need for global surveillance of S. pneumoniae to document the evolution and spread of resistant strains and to guide therapy.

Increased activity of lysosomal acid hydrolases in the cell-free cerebrospinal fluid of bacterial meningitis.

Because inflammation could affect lysosomal enzyme trafficking, resulting in increased enzyme release from the cells, tissue necrosis, or altered blood- and the brain-cerebrospinal fluid (CSF) barrier, the activity of four lysosomal enzymes in the cell-free CSF of 34 patients with bacterial meningitis, 20 with aseptic meningitis, and 39 control subjects was measured. Activities are expressed in nanomoles of 4-methylumbelliferone mL/h. The median beta-hexosaminidase A activity in bacterial meningitis was 313, in aseptic meningitis it was 173, and in the control subjects it was 175, the median beta-hexosaminidase B activity was 417, 165, and 120; the median alpha-mannosidase activity was 171, 124, and 113; and the median beta-glucuronidase activity was 133.7, 14.3, and 10.0, respectively. The difference of the activities of the four enzymes measured between the bacteria meningitis and the controls is significant (p < 0.000). Also significant is the difference between bacterial and aseptic meningitis (p = 0.005 to < 0.000), but it is not significant between aseptic and control subjects. Both the sensitivity and specificity of the beta-glucuronidase activity between bacterial meningitis and control subjects were 100%, whereas the corresponding values between bacterial and aseptic meningitis were 100% and 90%, respectively. No significant correlation was observed between the activities of the enzymes measured and the number of the polymorphonuclear leukocytes or other laboratory characteristics of the CSF. The increased lysosomal enzyme activities in the CSF of patients with meningitis may result from diffusion across the blood-CSF or the brain-CSF barrier or from enzyme leakage through the cell membranes.