Congenital cytomegalovirus infection and audiological follow-up: electrophysiological auditory threshold before 3 months of age as a predictor of hearing outcome at 3 years of age.

OBJECTIVE: We aimed to evaluate whether electrophysiological auditory thresholds (EATs) before 3 month of age, as assessed by the auditory brainstem responses (ABR) test and the auditory steady state responses (ASSR) test, can predict hearing outcome at 3 years of age among children born with congenital cytomegalovirus (cCMV) infection. STUDY DESIGN: Audiological assessment was performed before 3 months of age, and every 6 months thereafter until 3 years of age, in a population of 63 children (126 ears). EATs before 3 months of age and at 3 years of age were compared. RESULT: No ear with an EAT of ≤30 dBHL (i.e. normal hearing) before 3 months of age showed worsening EATs at 3 years of age. CONCLUSION: An EAT of ≤30 dBHL obtained by ABR and ASSR tests before 3 months of age is predictive of a normal hearing at 3 years of age in children born with cCMV.

Congenital esophageal stenosis diagnosed in an infant at 9 month of age.

Esophageal stenosis is a relatively uncommon condition in pediatrics and requires an accurate diagnostic approach. Here we report the case of a 9-month old female infant who presented intermittent vomiting, dysphagia and refusal of solid foods starting after weaning. She was treated for gastroesophageal reflux. At first, radiological investigation suggested achalasia, while esophagoscopy revelaed a severe congenital esophageal stenosis at the distal third of the esophagus. She underwent four endoscopic balloon dilatations that then allowed her to swallow solid food with intermittent mild dysphagia. After 17 months of esomeprazole treatment off therapy impedance-pH monitoring was normal. At 29 months of follow-up the child is asymptomatic and eats without problems.Infants with dysphagia and refusal of solid foods may have undiagnosed medical conditions that need treatment. Many disorders can cause esophageal luminal stricture; in the pediatric age the most common are peptic or congenital. Careful assessment with endoscopy is needed to diagnose these conditions early and referral to a pediatric gastroenterologic unit may be necessary.

Advances on human milk hormones and protection against obesity.

Extensive research shows that breast milk could have positive health effects not limited to infancy, but extend into childhood and adulthood. Recently many studies have provided new evidence on the long—term positive effects of breastfeeding, in particular protection against obesity and type 2 diabetes, suggesting that breast milk may have a role in the programming of later metabolic diseases. The mechanism throughout breastfeeding that exerts these effects has been a major focus of interest for researchers and it is still not completely known. There are some hints for biological plausibility of beneficial effects of breastfeeding including macronutrient intake, hormonal and behavioural mechanisms related to breast milk composition. Breast milk biochemical components, such as protein quantity and quality, polyunsaturated fatty acids, oligosaccharides, cytokines and hormones, in particular leptin, adiponectin and resistin together with the breastfeeding practice itself can influence infants feeding behaviour and regulation of growth and appetite control later in life. Further research is needed to confirm the possibility that hormones present in breast milk exert a metabolic and beneficial effects.

High serum leptin levels in infancy can potentially predict obesity in childhood, especially in formula-fed infants.

AIM: To investigate serum leptin levels in breast-fed and formula-fed infants in infancy and their possible relationship to body mass index (BMI) in childhood. METHODS: We enrolled 237 healthy term infants between September 2000 and April 2004 and tested their serum leptin levels, took anthropometric measurements and calculated BMI. A follow-up study was carried out to evaluate the BMI of 89 of these infants in childhood, in relation to their serum leptin levels in infancy, at a median (interquartile range) age of 8.8 years (7.8-10.2). The statistical significance of this multivariate analysis was set at p < 0.05. RESULTS: Breast-fed infants had significantly higher serum leptin levels than formula-fed ones (p < 0.05). Children who were formula-fed in infancy had a significantly higher BMI, at follow-up, than those who were breast-fed (p < 0.001). Furthermore, we identified a leptin cut-off value of 2.7 ng/mL, below which infants had a higher BMI in childhood. CONCLUSION: A higher leptin level in infancy may be inversely associated with BMI in childhood, suggesting that this hormone in infancy is a potential predictor of obesity in later life. Further investigation is required to be conclusive and to confirm our empirical evidence.

Chitosan/pectin polyelectrolyte complexes: selection of suitable preparative conditions for colon-specific delivery of vancomycin.

The influence of polyelectrolyte complexes composed of chitosan and pectin on the release behaviour of vancomycin has been investigated. Polyelectrolyte complexes between chitosan and pectin were prepared in various pH regions and at different molar ratios by mixing solutions of pectin and chitosan with the same ionic strength. The precipitates were collected by spray-drying and tablets were obtained with the different complexes and vancomycin. FT-IR spectra and TGA thermograms were analysed to study the degree of interactive strength between polyions. In vitro swelling, mucoadhesion and release tests were performed in order to investigate the chitosan/pectin complex ability in the delivery of vancomycin in the gastro-intestinal tract. The results confirmed the formation of polyelectrolyte complexes between pectin and chitosan at pH values in the vicinity of the pKa interval of the two polymers. Chitosan/pectin complexes showed a pH-sensitive swelling ability and drug release behaviour suggesting their possible use for colon-specific localization of vancomycin. Among the different complexes, chitosan/pectin complex prepared in molar ratio of 1:9 showed the highest mucoadhesive properties and a pH-dependent swelling sensitivity suitable for colon-delivery. Moreover, the particular composition of these complexes improved vancomycin availability at alkaline pH on the bases of an enzyme-dependent degradation as confirmed from release studies performed in presence of beta-glucosidase.

Assessment of solid-state interactions of naproxen with amorphous cyclodextrin derivatives by DSC.

A microcalorimetric method based on differential scanning calorimetry (DSC) of drug-additive binary systems to assess kneading-induced interactions was applied to naproxen (NAP) in combinations with amorphous hydroxypropyl beta-cyclodextrin (HPbetaCd), beta-cyclodextrin sulfobutyl ether, sodium salt ((SBE)(7m)-betaCd), acetyl beta-cyclodextrin (AcbetaCd) and acetyl gamma-cyclodextrin (AcgammaCd). Modifications of thermal parameters of NAP in DSC curves of physical mixtures indicate heating-induced interactions which resulted in a broadening of the NAP melting endotherm in the combinations with HPbetaCd, AcbetaCd and AcgammaCd. The effect of kneading on the interaction was particularly pronounced for the NAP-HPbetaCd and NAP-(SBE)(7m)-betaCd systems, which show a similar drug-to-carrier interaction ratio (1:2 by weight) as that of the other systems. Drug-to-carrier ratios, calculated considering the amount of NAP which recrystallizes from the melted mixtures equivalent to NAP not bound to the carrier, show a distinctly lower affinity in solid-state of the drug for the anionically charged (SBE)(7m)-betaCd with respect to other neutral carriers. The similar affinity of NAP for AcbetaCd and AcgammaCd demonstrates that the geometry of the cavity, which is a determinant factor for the inclusion complexation in liquid state, does not influence the interaction process in solid-state.

Structure and solid-state chemistry of anhydrous and hydrated crystal forms of the trimethoprim-sulfamethoxypyridazine 1:1 molecular complex.

The crystal structure of the equimolar trimethoprim (TMP) and sulfamethoxypyridazine (SMPD) complex in the anhydrous form (TMP. SMPD) and that of the species with 1.5 molecules of water of crystallization (TMP.SMPD.W) are reported in this article. X-ray powder diffraction patterns (both computer generated and experimental) and thermal analytical data from differential scanning calorimetry (DSC) and thermogravimetry useful for the characterization of TMP.SMPD and TMP.SMPD.W are provided. The stability of TMP.SMPD.W, which retains its crystallographic order under 0% relative humidity (RH) conditions at room temperature (22 degrees C) and 20 mmHg, is accounted for in terms of crystal structure and hydrogen bonding. Transformation of TMP.SMPD to the hydrate complex by exposure to approximately 100% RH, suspension in water, and wet granulation, and dehydration of TMP.SMPD.W by thermal treatment and by desiccation with methanol were investigated and tentatively interpreted in terms of crystal properties. Interactions in the physical mixture of TMP and SMPD by grinding, compression, heating, and contact with water were also studied. Water-mediated formation of TMP.SMPD.W by wetting and metastable eutectic melting-mediated formation of TMP.SMPD by heating was demonstrated. Mechanical activation by milling makes the physical mixture prone to solid-state transformation into dimorphic anhydrous cocrystals by supply of thermal energy during a DSC scan.

Physical characterization of picotamide monohydrate and anhydrous picotamide.

Picotamide is an antiplatelet agent given by mouth as monohydrate (PICOW) (Plactidil) in thrombo-embolic disorders. This study deals with physical characterization of PICOW recrystallized from various solvents and the respective dehydration products using X-ray powder diffractometry (XRD), infrared spectroscopy (IR), and thermal analytical techniques (differential scanning calorimetry, DSC; thermogravimetric analysis, TGA; simultaneous TGA/DSC; hot stage microscopy, HSM). Monophasic and biphasic DSC and TGA profiles of water loss were recorded under open conditions for PICOW samples which showed the same monoclinic crystal structure. Biphasic profiles became monophasic for gently ground samples which were, however, structurally identical to the intact samples. Morphological factors, the various degree of "perfection" of the PICOW crystal lattice, and/or cluster aggregation of PICOW crystals were assumed to be responsible for the differing dehydration patterns. Polymorphism in anhydrous picotamide, i.e., nucleation of crystal forms A, mp 135.5 +/- 0.4 degrees C, and B, mp 152.9 +/- 0.3 degrees C after dehydration of PICOW, was detected by DSC and HSM. The dehydration product of PICOW under isothermal conditions (115 degrees C, 20 mmHg), PICOA, was mainly composed of the lower melting polymorph A (fusion enthalpy 74.4 +/- 2.2 J g(-1)), which gradually reverted to the starting hydrate by storing in an ambient atmosphere. Dissolution tests of PICOW and PICOA in water at 37 degrees C as both powders and compressed disks reflected to some extent the higher solubility of the metastable form (by 24% at 37 degrees C) in terms of both higher dissolution efficiency and percent of active ingredient dissolved (by 28%) and intrinsic dissolution rate (by 32%).

Interaction of naproxen with alpha-cyclodextrin and its noncyclic analog maltohexaose.

PURPOSE: To study the effect of mechanical grinding on crystallinity changes of naproxen (NAP) in mixtures with alpha-cyclodextrin (alphaCd), amorphous alphaCd, and maltohexaose (M6); and the possible formation of a pseudo-inclusion complex between NAP and M6 in aqueous solution. METHODS: NAP-additive physical mixtures at 0.30, 0.18, and 0.10 mass fraction of drug were tested, after increasing grinding times, by differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Interaction in aqueous solution was examined by phase-solubility and fluorescence analyses supported by molecular modelling. RESULTS: In the mixtures with each additive the fusion enthalpy per unit mass of NAP decreased and the half width at half maximum of selected X-ray diffraction peaks of NAP increased with the progress of grinding time following the loss of crystallinity of the samples. The mechanical treatment apparently did not affect the chemical integrity of the drug. Particularly active in the equimolar mixture was the best amorphizing agent, M6. Solution studies and molecular modelling confirmed M6 may have the feature of a supermolecule for NAP, which forms a 1:1 pseudo-inclusion complex that was as stable as the true inclusion complex with alphaCd. CONCLUSIONS: The intrinsically amorphous linear analog of aCd might be a potential amorphism-inducing agent and solubilizer for scarcely water soluble drugs.

Chlamydia trachomatis diagnosis: a correlative study of pap smear and direct immunofluorescence.

From June 1989 to September 1990, 255 women with recurrent vaginitis, were evaluated, at the "Service of Precocious Diagnosis and Therapy of Gynecological Tumor" of the 1st Department of Obstetrics and Gynecology. They were compared with a control group of 255 women selected in the same time. All patients between the ages of 18-40 years, with normal sexual behaviour, had a negative colposcopy for HPV and HSV2 infections. The cervical smear with Papanicolaou technique and direct immunofluorescence (DIF) was performed in all patients. The specimens were examined with a fluorescence microscope (Leitz). Positive determinations were confined by examination a tha magnification of 600 X. Slides were scored as positive if at least 5 distinct apple-green fluorescence-stained elementary body per field was observed. The two groups were entirely comparable in age, parity, method of contraception, and number of sexual contacts over the preceding three months. Our data confirmed a higher incidence of Chlamydial infections in women with recurrent vaginitis (34.1%) than in control group (8.23%). In symptomatic women, more cases of metaplastic cells with cytoplasmic vacuolation, less inflammatory alteration and a lack of specific agents like CA and TV, were found than in the control group. The DIF positivity, in both groups, was connected with a cytological findings of metaplastic cells with cytoplasmic vacuolation in 72.3% and 50% respectively.