bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Inflammatory Bowel Disease: Different Treatment Response to Specific or All Medications?
Authors: Markowitz James
Published: September 2009

Background: The literature suggests that medications prescribed for the treatment of inflammatory bowel disease may be more efficacious in children than adults. Care must be exercised in comparing these data, however, as significant differences in disease duration and concomitant therapy are present among studies. Methods: Review of key clinical trials, meta-analyses and observational registries for which there are treatment response data from both pediatric and adult Crohn’s disease (CD) populations. Results: Acute response to corticosteroids is similar in children (84–89%) and adults (80–84%), but prolonged response may be better in children (50–61 vs. 32–44%). Differences in duration of CD among the various studies’ subjects and the proportion of subjects receiving concomitant immunomodulators probably explain much of these differences. CD remission rates with thiopurines appear higher in children at both 6 months (85 vs. 31%) and 15–18 months (81 vs. 42%), but the reported outcomes are likely influenced by very short duration of CD in the pediatric populations studied. Similarly, remission of CD 1 year following initiation of infliximab also appears higher in children (56%) than adults (28%), but again differences in study populations’ durations of CD and use of concomitant immunomodulators likely are responsible for the observed differences. Conclusion: Differences between pediatric and adult responses to a variety of IBD treatments appear to be due more to study design than the age of the subjects evaluated. As published pediatric trials have generally evaluated subjects with potent treatments at or shortly after diagnosis, the consistently higher rates of responses seen in children lend weight to the argument that some form of ‘top-down’ therapy offers the best option to maximize remission rates in all patients with IBD.
How Do We Manage Vaccinations in Patients with Inflammatory Bowel Disease?
Authors: Esteve Comas Maria , Loras Alastruey Carme , Fernandez-Bañares Fernando
Published: September 2009

The mortality in inflammatory bowel disease (IBD) has been reported similar or slightly increased as compared to that of the general population. However, deaths related to infectious and parasitic diseases have been repeatedly reported in clinical trials, open series and registries. The IBD patients are exposed to the same infections affecting the community, added to opportunistic infectious related to the immunosuppression. Some of these infectious diseases may be prevented by the appropriate use of a vaccination program. Thus, vaccination status should be assessed at IBD diagnosis, and from time to time, and vaccination should be updated to every patient as soon as possible, since deaths due to preventable diseases should never occur. Present recommendations include vaccination for influenza (annually), for pneumococcal disease with the 23-valent strain (every 5 years), for hepatitis B virus (in patients with no detectable hepatitis B surface antibodies), combined vaccination against tetanus, diphtheria and inactivated poliomyelitis (every 10 years). The role of human papillomavirus vaccine preventing cervical dysplasia and neoplasia in IBD women taking immunosuppressive are at present unknown. In patients lacking varicella immunization, specific vaccination should be considered. Nevertheless, it should be taken into account that varicella vaccine contains live attenuated virus that cannot be administered in patients taking immunosuppressive. The same consideration should be kept in mind for patients travelling to endemic areas for yellow fever. Finally, IBD patients on immunosuppressive may have an altered response to vaccine immunization. Decreased response has been reported for hepatitis B and pneumoccocal vaccination. In those cases, testing for serological responses to vaccine should be performed and booster doses may be required.
Transition from Pediatric to Adult Health Care in Inflammatory Bowel Disease
Authors: Escher Johanna C.
Published: September 2009

Inflammatory bowel disease (IBD) is a lifelong disease that has great psychosocial impact on the adolescent patient and his/her family. Starting around age 12–14 years, many changes take place related to school, work, and sexual development. At some point, usually around the age of 16–18 years, these patients need to move from the pediatric clinic to the adult caregivers. A stepwise program for transition of care, aimed at coaching the adolescent patient into self-management will benefit patients, parents, and the ‘adult gastroenterologist’ who will take over the care from the pediatric gastroenterologist. Differences in pediatric and adult health care, transition goals, tips and tools for successful transition will be discussed.
Fistula Treatment: The Unresolved Challenge
Authors: Michetti Pierre
Published: September 2009

Fistulas are common complications in Crohn’s disease, as their cumulative prevalence reaches up to two thirds of the patients in the long term. Fistulas worsen the overall patient prognosis, with permanent sphincter and perineal tissue destruction as well as professional and personal disabilities. The importance of healing these fistulas has been less well appreciated than mucosal healing for luminal disease. Management should not be left to any specialty alone, but requires an optimal combination of surgery, infection control, and immunosuppression. Outcome of therapy beyond fistula drainage is unclear and the means of assessing healing over a long time period is poorly characterized. Recent studies suggested that a substantial proportion of patients can achieve fistula healing with surgical and medical therapies. However, studies that measure the benefit of integrated approaches, of early intervention and of precise healing assessment are still missing. Such information is particularly needed in this subset of sick patients that undergo substantial physical and emotional distress because of pain, discharge, incontinence, perineal and genital disfigurement. The advent of adequate pelvic imaging, improved surgical outcomes, and potent biological therapies make it timely to develop best-management strategies and appropriateness of care criteria.
Growth Monitoring to Detect Children with Cystic Fibrosis
Authors: van Dommelen Paula , Grote Floor K. , Oostdijk Wilma , de Muinck Keizer-Schrama Sabine M.P.F. , Bouquet Jan , Hendriks Johannes J.E. , Kouwenberg Jan , Verkerk Paul H. , van Buuren Stef , Wit Jan M.
Published: September 2009

Background/Aims: Cystic fibrosis (CF) in infancy and childhood is often associated with failure to thrive (FTT). This would suggest that in countries without a newborn screening program for CF, FTT could be used as a clinical screening tool. The aim of this study is to assess the diagnostic performance of FTT for identifying children with CF. Methods: Longitudinal length and weight measurements up to 2.5 years of age were used from CF patients (n = 123) and a reference group (n = 2,151) in The Netherlands. Growth measurements after diagnosis were excluded. We developed five potential screening rules based upon length, weight and body mass index (BMI) standardized by age and gender (SDS). Outcome measures were sensitivity, specificity and positive predictive value (PPV). Results: BMI SDS had the highest sensitivity at low false-positive rates. An efficient scenario is a BMI SDS below –2.5 SD in combination with a decrease in BMI SDS of at least 0.5 SD. This scenario had a sensitivity of 32%, a specificity of 98.3% and a PPV of 0.75%. Conclusion: In the absence of a newborn screening program, young children with FTT for BMI are candidates to consider testing for CF.
Plant Growth Regulator (4-Chlorophenoxy Acetic Acid) Increases Apoptosis in Gonads of Rats without Changing Hormonal Levels
Authors: Yeşilkaya Ediz , Bideci Aysun , Özer Çiğdem , Elmas Çiğdem , Çamurdan Orhun , Giray Seren Gulsen , Boyraz Mehmet , Vurucu Sebahattin , Cinaz Peyami
Published: September 2009

Background/Aims: Plant growth regulators are considered to leave minimal amounts of remnants and therefore cause no significant side effects in humans. In this study, we aimed to investigate the hormonal and histopathological effects of 4-chlorophenoxy acetic acid (4-CPA), a commonly used plant growth regulator, on the gonadal functions of rats. Methods: The study was implemented on 64 Wistar albino rats (20 days old). Forty-eight rats received 4-CPA every day until 50 days of age. The rats were randomized into 4 groups (a control group and three 4-CPA groups with doses of 25, 50 and 100 mg/kg/day); each group was further divided into males and females, making a total of 8 groups. The levels of FSH, LH, testosterone, estradiol, leptin, inhibin-B and neuropeptide-Y were measured. Histopathological examination of the testes and ductus deferens in male rats, and ovaries and uterus of female rats (caspase-3 and -9 immunoreactivity) was performed. Results:Although hormone levels were similar between the groups, rats that received 4-CPA showed significantly higher degrees of apoptosis compared to the control group (p < 0.001) and increased doses of 4-CPA were directly correlated with the amount of apoptosis (p < 0.001). Conclusion: 4-CPA induced apoptosis in the gonads of rats without concurrent changes in plasma hormone levels.
Early Puberty in Internationally Adopted Girls: Hormonal and Clinical Markers of Puberty in 276 Girls Examined Biannually over Two Years
Authors: Teilmann Grete , Petersen Jørgen H. , Gormsen Magdalena , Damgaard Karen , Skakkebæk Niels E. , Jensen Tina Kold
Published: September 2009

Background and Aims: Retrospectivestudies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Hypothetically, this could be due to selection bias. The aim of this study was to determine age at reaching pubertal milestones in healthy internationally adopted girls in a prospective, clinical study. Methods: A longitudinal cohort study including 276 randomly recruited internationally adopted girls. At baseline, age ranged from 4 to 13 years. Participants were followed with biannual examinations over a period of 2 years. Examinations included height, weight, Tanner staging, blood sampling and bone age assessment. Age distribution at entering pubertal stages B2–B5 (breast development), PH1–PH5 (pubic hair development) and menarche was estimated by probit analysis. Data were compared to a reference population of Danish-born girls, studied cross-sectionally. Results: Mean age at B2+ was 9.5 years (95% prediction interval 7.1–12.0 years) and mean age at menarche was 12.1 (10.2–14.0) years in adopted girls, which was significantly lower compared to the reference group (p < 0.0003). 16% of adopted girls entered stage B2 before 8 years of age. The puberty-related rise in LH, FSH and estradiol was detected at earlier ages in adopted girls compared to the reference group. Conclusion: Internationally adopted girls have a significantly higher risk of precocious pubertal maturation compared to Danish-born girls.
Classical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency in Croatia between 1995 and 2006
Authors: Dumic Katja , Krnic Nevena , Skrabic Veselin , Stipancic Gordana , Cvijovic Katarina , Kusec Vesna , Stingl Katarina
Published: September 2009

Aims: To evaluate the incidence, gender, symptoms and age at diagnosis of patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in Croatia. Methods: Data were collected retrospectively for all classical CAH patients born or electively aborted following prenatal diagnosis between January 1, 1995 and December 31, 2006 and were compared with the data of a previously conducted study evaluating CAH patients discovered between 1964 and 1984. Results: During a 12-year period 34 classical CAH patients were born. There were 20 salt-wasting (SW; 12 female/8 male) and 14 simple-virilizing (SV; 7 female/7 male) patients. If 3 female, electively aborted fetuses were added, there would be a total of 37 CAH patients. With 532,942 live births and 34 CAH patients born over this period, the incidence of classical CAH was estimated at 1:15,574 or 1:14,403 if the 3 electively aborted fetuses were included. The lower incidence of SW boys compared to SW girls (8:12) and similar number of SW and SV boys (8:7) indicate that a substantial proportion of SW boys die unrecognized. Owing to better healthcare, the diagnosis was established significantly earlier in SW and SV girls compared to the period of 1964–1984 (p < 0.003). During 1995–2006, none of the patients died following the diagnosis of CAH and there was no erroneous sex assignment. Conclusion: Despite improvements in healthcare, the diagnosis of CAH in Croatia is still delayed and some of the patients go unrecognized or die. Therefore, the results of our study support the need to introduce newborn screening.
Relationship of the Borderline Symptom List to DSM-IV Borderline Personality Disorder Criteria Assessed by Semi-Structured Interview
Authors: Glenn Catherine R. , Weinberg Anna , Klonsky E. David
Published: September 2009

Background: Borderline personality disorder (BPD) is a debilitating mental illness that affects approximately 6% of the general population and 10–20% of psychiatric patients. The Borderline Symptom List (BSL) is a self-report questionnaire designed to comprehensively assess BPD symptomatology. Sampling and Methods: The present study examined the convergence of the BSL with DSM-IV BPD assessed by semi-structured interview. To ensure variability in BPD symptoms, participants were recruited from a large college sample if they generated either high or low scores on a BPD symptom screening questionnaire. The final sample included 59 participants who completed the BSL, the BPD questions from the Structured Interview for DSM-IV Personality (SIDP-IV), and self-report measures of depression and anxiety. Results: Ten participants (17%) met the full BPD criteria and 29 (49%) met 2 or more criteria. Results indicate strong convergence between the BSL and BPD assessed by semi-structured interview, even when controlling for measures of depression and anxiety. The shortened version of the BSL, the BSL-23, also correlated robustly with BPD assessed by semi-structured interview. Conclusions: Findings support the validity of the BSL (and BSL-23) as a self-report measure of BPD symptomatology. Future research should replicate results in other samples, including those drawn from psychiatric populations.
Use of Procalcitonin-Guided Decision-Making to Shorten Antibiotic Therapy in Suspected Neonatal Early-Onset Sepsis: Prospective Randomized Intervention Trial
Authors: Stocker Martin , Fontana Matteo , el Helou Salhab , Wegscheider Karl , Berger Thomas M.
Published: September 2009

Background: Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific. Early antibiotic therapy is crucial for treatment success. Objective: To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis. Methods: This single-center, prospective, randomized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children’s Hospital of Lucerne, Switzerland, between June 1, 2005 and December 31, 2006. All term and near-term infants (gestational age ≧34 weeks) with suspected early-onset sepsis were randomly assigned either to standard treatment based on conventional laboratory parameters (standard group) or to PCT-guided treatment (PCT group). Minimum duration of antibiotic therapy was 48–72 h in the standard group, whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values. Results: 121 newborns were randomly assigned either to the standard group (n = 61) or the PCT group (n = 60). The two groups were similar for baseline demographics, risk factors for early-onset sepsis, likelihood of infection as assessed by the attending physician and early conventional laboratory findings. There was a significant difference in the proportion of newborns treated with antibiotics ≧72 h between the standard group (82%) and the PCT group (55%) (absolute risk reduction 27%; odds ratio 0.27 (95% CI 0.12–0.62), p = 0.002). On average, PCT-guided decision-making resulted in a shortening of 22.4 h of antibiotic therapy. Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events. Conclusion:Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis. Before this PCT-guided strategy can be recommended, its safety has to be confirmed in a larger cohort of neonates.
Reproducibility of Cutaneous Microvascular Function Assessment Using Laser Doppler Flowmetry and Acetylcholine Iontophoresis
Authors: Brocx K.A. , Drummond P.D.
Published: September 2009

Aim: To investigate the reproducibility of direct and axon-reflex vasodilator responses to increasing doses of acetylcholine administered transcutaneously by iontophoresis. Methods: Increasing doses of acetylcholine ions were introduced into the skin of the volar forearm with weak electric currents. The elicited vasodilatation was measured with laser Doppler flowmetry at the direct site of acetylcholine administration and approximately 5 mm from this site (within the distribution of axon-reflex vasodilatation). To investigate the reproducibility of these measures, iontophoresis was carried out twice at one site after a 50 min interval and once at another site on the forearm of 16 healthy females. Raw scores and data expressed as percentages of baseline, maximum, and response to heating were analysed to determine the most reliable form. Results: The dose-response curve was significantly greater at the upper site on the forearm than at the lower site for direct vasodilator responses, but did not differ between the upper and lower forearm for axon-reflex responses. The various forms of data expression yielded weak to moderate correlations for vasodilatation between sites, and moderate to strong correlations when the iontophoresis was repeated at the same site. Direct responses were most reproducible when expressed in proportion to levels recorded after 5–6 min of local 42°C heating (percentage of shared variance was 54.6% within sites and 61.0% between sites). Conclusion: Cutaneous vasodilatation to acetylcholine iontophoresis is reproducible over time at a single site but varies across sites. This will allow future research to assess microvascular function before and after a laboratory manipulation in a single session.
New and Experimental Skin-Directed Therapies for Cutaneous Lymphomas
Authors: Farkas Arpad , Kemeny Lajos , French Lars E. , Dummer Reinhard
Published: September 2009

Primary cutaneous lymphomas (CLs) originate in the skin and should be differentiated from secondary skin infiltrates, which are manifestations of lymphomas of nodal or extranodal origin. These rare diseases include various lymphoproliferative disorders: cutaneous T-cell lymphomas, cutaneous B-cell lymphomas and some rare subtypes. As definitive cure is often not possible, it is important to control the disease and alleviate symptoms. Patients with early-stage disease limited to the skin usually require skin-directed therapies using topical agents including corticosteroids, chemotherapeutic drugs, bexarotene gel, electron beam therapy and phototherapy. Each of these are effective; however, all have some disadvantages and are associated with significant adverse events. In the field of skin-directed therapies there are interesting developments using antineoplastic compounds, the retinoid tazarotene, imiquimod, gene therapy products (adenovirus vector expressing γ-interferon), the monoclonal anti-CD20 antibody rituximab, photodynamic therapy and 308-nm excimer laser to mention a few. This review highlights some of the promising new and experimental local therapies for primary CLs and focuses on their efficacy and side effects.
Differential Contractile Impairment of Fast- and Slow-Twitch Skeletal Muscles in a Rat Model of Doxorubicin-Induced Congestive Heart Failure
Authors: Ertunc Mert , Sara Yildirim , Onur Rustu
Published: September 2009

Congestive heart failure (CHF) is associated with exercise intolerance that cannot be entirely explained by hypoperfusion of the skeletal muscles. We studied the contractile properties of fast-twitch (extensor digitorum longus; EDL) and slow-twitch (soleus; SOL) skeletal muscles in doxorubicin-induced CHF in rats, and evaluated the defective steps of excitation-contraction coupling. Both types of muscles-obtained from CHF rats displayed significant reduction in twitch and tetanic contractions. Twitch half-relaxation times of CHF SOL muscles were prolonged while there was no significant difference in EDL muscles. High K+ application induced lower contracture amplitudes in CHF muscles. Caffeine-induced contractures were significantly diminished in CHF SOL. Verapamil application depressed tetanic contractions in all preparations while depression was more pronounced in CHF SOL. Immunohistochemistry revealed reduced expression of sarcoplasmic reticulum Ca2+-ATPase-1 and -2 in CHF EDL and in CHF SOL, respectively. Sarcolemmal excitability and spontaneous neurotransmitter release were unaffected since resting membrane potential, action potential and miniature end-plate potentials were unaltered in CHF muscles. We conclude that CHF induces contractile impairment that occurs predominantly in rat slow-twitch skeletal muscles. Our results suggest that this muscle-type-specific effect of CHF is related to the defective intracellular Ca2+ release and uptake mechanisms and reduced sarcolemmal-dihydropyridine-sensitive Ca2+ channel activity.
The Effects of Inhaled KP-496, a Novel Dual Antagonist for Cysteinyl Leukotriene Receptor and Thromboxane A2 Receptor, on Allergic Asthmatic Responses in Guinea Pigs
Authors: Suda Masahiro , Okuda Toshiaki , Ishimura Masakazu , Kurokawa Shigeo , Tokuoka Shota , Nakamura Tsutomu , Takahashi Yoshimasa , Tanaka Hiroyuki , Nagai Hiroichi
Published: September 2009

Aims: The aim of this study was to evaluate the effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor 1 and thromboxane A2 receptor, on the allergic asthmatic responses in guinea pigs. Methods: Actively sensitized animals were repeatedly exposed to antigen, and KP-496 (0.01 and 0.1%) was inhaled for 5 min before every antigen exposure. After evaluating the effects of KP-496 on asthmatic responses, such as immediate and late asthmatic response (IAR and LAR) and airway hyperresponsiveness (AHR), histopathological analyses of the lungs of asthmatic animals were made. Results: KP-496 significantly inhibited both antigen-induced LAR and AHR to acetylcholine, and slightly inhibited antigen-induced IAR. Furthermore, histopathological analyses of the lungs of the asthmatic animals demonstrated the following: (1) KP-496 suppressed infiltration of eosinophils around airway smooth muscle, (2) KP-496 suppressed airway epithelial hypertrophy, and (3) KP-496 suppressed increased mucus production in the airway. Conclusion: In addition to suppression of LAR and AHR, our findings demonstrated that KP-496 inhibits features of airway inflammation. Since these broad ameliorative effects of KP-496 on asthmatic pathology are thought to result from the inhibition of multiple chemical mediators, KP-496 will be a potent agent in the treatment of bronchial asthma.
The Aldose Reductase Inhibitor Fidarestat Suppresses Ischemia-Reperfusion-Induced Inflammatory Response in Rat Retina
Authors: Agardh Carl-David , Agardh Elisabet , Obrosova Irina G. , Smith Maj-Lis
Published: September 2009

Recent studies suggest that increased aldose reductase (AR) activity plays an important role in ischemia-reperfusion injury in the retina. The mechanisms are not completely understood, but may be linked to inflammation. In the present study, we investigated whether the AR inhibitor fidarestat suppressed the retinal inflammatory response induced by ischemia-reperfusion in a rat model. The inflammatory response was manifested by increased gene expression of tumor necrosis factor-α and intercellular adhesion molecule-1 (ICAM-1) as well as elevated protein levels of soluble ICAM-1. This response was partially suppressed by the AR inhibitor fidarestat. The findings may reveal beneficial effects of AR inhibition on retinal inflammation associated with ischemia-reperfusion and are in agreement with recent developments in pharmacological research suggesting that pathological conditions other than diabetes may benefit from AR inhibitors.
Evaluation of Cerebrospinal Fluid Tau/Beta-Amyloid(42) Ratio as Diagnostic Markers for Alzheimer Disease
Authors: Smach Mohamed Ali , Charfeddine Bassem , Ben Othman Leila , Lammouchi Turkia , Dridi Hedi , Nafati Souhir , Ltaief Afef , Bennamou Soufien , Limem Khalifa
Published: September 2009

Background: Alzheimer’s disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. Cerebrospinal fluid (CSF) concentrations of amyloid β (Aβ1-42) peptides and total tau proteins (T-tau) may serve as biomarkers for AD. Aim: The objective of this study was to investigate the usefulness of CSF Aβ1-42 and T-tau analyses in the diagnosis of AD with Tunisians. Methods: We focused on three groups originating from Central Tunisian that matched in age (range 48–85): healthy controls (n = 53), AD patients (n = 93) and non-Alzheimer (nAD) dementia (n = 35) patients. Aβ1-42 and T-tau levels were measured in CSF by sandwich enzyme-linked immunosorbent assay. Results: The ratio of T-tau/Aβ1-42 at baseline yielded a sensitivity of 85.3% for detection of AD and the specificity was 84.8% to differentiate controls and nAD dementia. Conclusion: Our findings confirm the use of T-tau/Aβ1-42 ratio in the discrimination of AD patients from all other patients.
Nonmigrating Rhythmic Activity in the Stomach and Duodenum of Neonates
Authors: Tomomasa T. , Itoh Z. , Koizumi T. , Kuroume T.
Published: September 2009

We studied gastrointestinal motility in 20 infants, using a modified manometric method for neonates, and compared it to that in adults. Changes in the intragastric and intraduodenal pressures were recorded for 3 h after the ingestion of milk. Bands of contractions with the same rhythmicity as phase III activity in adults were frequently recorded. Some of them migrated caudally and were speculated to be the equivalent of phase III activity of the interdigestive migrating complex (IMC) in adults. However, others did not migrate and showed some differences from phase III activity of adults and infants in the time of occurrence, duration and amplitude. The characteristic of gastroduodenal motility in infants was the frequent occurrence of these bands of nonmigrating rhythmic concentrations. Our findings indicated the following problems: (1) there are some differences in gastrointestinal motility between infants and adults and further investigations are required for the evaluation of the physiology or pathophysiology of this phenomenon; (2) in infants, many bands of rhythmic contractions of the alimentary tracts can exist without migration. This indicates the possibility that the occurrence of rhythmic contractions and their migration are regulated by different mechanisms.
Small Intestine Transit Time and Lactose Absorption during Phototherapy
Authors: Sivan Yakov , Dinari Gabriel , Goodman Ciporit , Merlob Paul , Nitzan Menachem
Published: September 2009

Diarrhea is often seen during phototherapy in jaundiced infants. Lactose malabsorption and reduced gut transit time (GTT) are some of the proposed explanations. However, the etiology of the diarrhea is still controversial. We investigated GTT and lactose absorption during phototherapy using the H2 breath test. Breath H2 was measured every 10 min for 150 min after feeding of jaundiced infants with and without phototherapy, and in controls. There were 12 newborns in each group. The time of increase of H2 excretion over 10 ppm was taken as the transit time. Lactose malabsorption was estimated by integrating the area under the excess H2 curve. No difference was found in GTT, lactose absorption, peak breath H2 and the time of the peak between phototherapy-treated infants and jaundiced and nonjaundiced infants. The results did not support the presence of lactose malabsorption during phototherapy and the decreased total GTT reported in the literature was not due to shortened small intestinal transit time.
Sequestration of 3H-Vitamin D3 by the Fetal and Neonatal Rat Liver
Authors: Martial Johanne , Plourde Victor , Gascon-Barré Marielle
Published: September 2009

19- to 21-day-old fetuses as well as 3-, 7-, 14-, and 22-day-old pups were used to evaluate the sequestration of a tracer dose of 3H-D3 by the fetal and neonatal rat liver. In fetuses, 3H-D3 was injected directly into the umbilical vein; in neonates, 3H-D3 was injected into the portal vein. In both cases, 14C-sucrose was used as extracellular marker. 3H-D3 sequestration was evaluated at 11.3 ± 1.1% (X ± SEM) in fetuses, 3.3 ± 0.6, 4.9 ± 0.6, 6.3 ± 0.5 and 42.0 ± 1.9% of the dose administered in 3-, 7-, 14-, and 22-day-old rats, respectively. These results clearly show that, in the rat, the fetal liver can take up 3H-D3. Moreover, when compared to the values obtained in the late fetal period, 3H-D3 uptake decreased significantly during the first 2 weeks post partum (p < 0.0001) and then dramatically increased (6-fold, p < 0.0001) between days 14 and 22 post partum, when it reached an uptake capacity similar to that previously observed in adult rats.
Starvation-Induced Organ Hypoplasia in Prenatal and Postnatal Guinea Pigs
Authors: Lechner Andrew J.
Published: September 2009

The severity and permanence of growth retardation was measured in guinea pigs starved for 3 weeks with a 50% ration in late gestation (prenatal), at birth (neonatal), or at weaning. Acute and chronic effects were assessed as body mass, skeletal length, hematology, and the weight, DNA and protein contents of the hearts, the lungs, and the livers of the starved and refed animals. Organ hypoplasia was most pronounced in the prenatally starved group, and was associated with numerous stillbirths. Among survivors, catch-up growth was eventually complete. Prenatal starvation of this species provides a reproducible model of human intrauterine growth retardation, particularly of the pulmonary system.
Changes in Plasma Arginine Vasopressin during Transition from Fetus to Newborn following Minimal Trauma Delivery of Lambs and Goats
Authors: Leffler Charles W. , Crofton Joan , Brooks David P. , Share Leonard , Hessler Jack R. , Green Robert S.
Published: September 2009

Vasopressin in umbilical arterial and venous blood is high at delivery and may be important in the maintenance of arterial pressure and absorption of lung liquid. We used chronically instrumented near-term fetal lambs and goats to investigate the changes in plasma vasopressin that occur during perinatal cardiovascular transition following cesarean section without labor. Plasma arginine vasopressin was more than 5 times greater 15 min following birth than immediately prior to clamping the umbilicus, and it fell progressively over the ensuing 2–5 h to levels not significantly different from before birth. Fifteen min after delivery, neither arterial pressure, blood gases, nor pH appeared to account for the increase.
Relationship between Resting Glucose Consumption and Insulin Secretion in the Ovine Fetus
Authors: Philipps Anthony F. , Porte Patricia W. , Raye John R.
Published: September 2009

In the chronically catheterized fetal sheep, umbilical glucose uptake has previously been found to be related to maternal glucose concentration over a wide range of values. The relative contribution of fetal insulin secretion to resting umbilical glucose uptake has not previously been assessed. Simultaneous measurements of umbilical glucose uptake and an estimate of fetal insulin secretory rate were performed in 21 fetal lambs in late gestation over 1-hour sampling periods. Because of the relatively narrow range of maternal blood glucose concentrations, no relationship was apparent between maternal glucose concentration and umbilical glucose uptake. However, a significant relationship was present between the area beneath the insulin concentration curve, a rough estimate of insulin secretory rate, and umbilical glucose uptake. The data suggest that fetal insulin secretory rate may be an important regulator of fetal glucose uptake under physiologic circumstances.
Effects of Fasting on Glucose Turnover Rate and Metabolite Levels in Conscious Pregnant Guinea Pigs
Authors: Gilbert Marc , Sparks John W. , Girard J. , Battaglia Frederick C.
Published: September 2009

The effect of fasting during pregnancy is of particular interest in the guinea pig because of the large fetal mass carried to term. The present studies examined the effect of acute and chronic starvation on maternal glucose turnover in the guinea pig. In the first experiment, 7 near-term pregnant guinea pigs were fasted for 6 h. The maternal glucose concentration and glucose production decreased rapidly, falling to about 65–70% of fed levels at 4 h of starvation. Mothers demonstrated a 2.6-fold elevation in ketoacids after 2, 4 and 6 h of starvation. In a second experiment, 5 non-pregnant and 11 near-term pregnant animals were studied in the control period and after 24 h of fasting. The maternal glucose concentration in the control state was independent of fetal mass. The maternal glucose turnover rate in the fed state correlated linearly with fetal mass. After 24 h of fasting, the glucose concentration and glucose turnover rate both decreased, with the magnitude of each decrease proportional to fetal mass. We conclude that, in the pregnant guinea pig, the fetal mass impacts significantly on maternal glucose metabolism in the fed and fasting states.
Autoregulation of Cerebral Blood Flow in the Newborn Beagle Puppy
Authors: Pasternak Joseph F. , Groothuis Dennis R.
Published: September 2009

Regional cerebral blood flow (RCBF) was measured in 17 newborn beagle puppies under conditions of moderate hypotension, normotension, and moderate hypertension. RCBF demonstrated autoregulation over the blood pressure range 35–70 mm Hg. When arterial pressure exceeded 75 mm Hg, RCBF increased significantly for all grey matter structures, 2 of 4 white matter structures, and 2 of 3 germinal matrix structures. The magnitude of the hypertension-induced increase in RCBF was highest for thalamic and mesencephalic nuclei, intermediate in cerebral cortex and other subcortical nuclei, and lowest in white matter. The hypertension-induced increase in CBF was low (similar to white matter) in some areas of germinal matrix but higher (similar to midline cerebral cortex) to rostral germinal matrix. The differences in RCBF during hypertension between rostral germinal matrix and cerebral white matter may partially explain the vulnerability of the germinal matrix to hemorrhage.
Placental Handling of Zinc in the Guinea Pig
Authors: Simmer Karen , Dwight J.St.J. , Brown I.M.H. , Thompson R.P.H. , Young Maureen
Published: September 2009

The distribution of zinc between the mother and the fetoplacental unit, and its placental transfer, were studied using stable and isotopic zinc in unanaesthetized pregnant guinea pigs and an in situ perfusion preparation. The concentration of stable zinc in fetal plasma and skeletal muscle was higher than that in the maternal tissues: 2.0 compared with 1.4 μg/ml and 84 with 49 ng/mg dry weight, respectively. The placenta and maternal and fetal liver had similar zinc concentrations: 90, 75 and 88 ng/mg dry weight, respectively. The ability of the placenta to concentrate 65Zn, measured 1 h after a single intravenous injection into the unanaesthetized mother, was comparable with that of the maternal liver. Maternal-fetal mass transfer of zinc was directly related to maternal plasma zinc concentrations from 0.7 to 24.1 μg/ml (b = 2 ng·min––1·g––1·μg––1, r = 0.92). At physiological plasma levels, the calculated transfer would supply the fetus with 0.12 mg zinc/day, similar to the accretion rate over the last trimester. Placental transfer of zinc was not influenced by the concentration of zinc in the placental perfusate. Extraction of zinc from the perfusate was also slow, and partly by absorption. Matemofetal transfer of zinc was directly related to both uterine and umbilical blood flows. The high concentration of zinc in the syncytium, relative to both maternal and fetal plasma levels, suggests active uptake at the maternal surface, combined with a slow release into the fetus, down a concentration gradient.
Effects of Intrauterine Nutritional Supplementation on Fetal Growth Retardation
Authors: Charlton Valerie , Johengen Michael
Published: September 2009

The effects of fetal nutritional supplementation on experimentally induced growth retardation were investigated in third-trimester sheep. The control group, C, was fed ad libitum (n = 8). Group R received a protein- and calorie-restricted diet over the last 3 weeks of gestation (n = 8). Group RS was given the same restricted diet as group R, and fetal, intragastric supplements of amino acids and glucose (n = 7). Over the experimental period, maternal weight increased 4.1 ± 0.6 kg in C but was stable in R and RS (p < 0.01). R and RS ewes and fetuses showed biochemical evidence of malnutrition but the changes were less severe in the RS group (p < 0.05). Nutrient levels did not change in group C ewes and fetuses. At delivery, R lambs were smaller in weight and length than RS or C (p < 0.05); gestational ages were the same. Weights were: R, 2,702 ± 182 g; RS, 3,235 ± 121 g; and C, 3,290 ± 297 g. R also had lower fetal to maternal weight ratios and higher brain to body weight ratios than RS or C (p ≤ 0.05). Placental size was reduced 28% in R compared to C (p < 0.05) and was intermediate in RS. The disparity in fetal size was explained by differences in nutrient acquisition between groups. Over the experimental period, caloric intake rose 24% in C fetuses; near delivery, they had the highest umbilical uptakes of carbohydrate and α-amino nitrogen. After maternal diet was limited, R and RS fetuses had dramatic decreases in umbilical uptake of α-amino nitrogen and static umbilical uptakes of carbohydrate. Caloric intake fell 42% in R. RS fetuses, however, were receiving sufficient gastric supplementation so that umbilical + gastrointestinal carbohydrate uptake equalled that of controls, and entry of α-amino nitrogen and calories was intermediate, between those of R and C. Fetal oxygen consumption reflected the differences in nutrient uptake, being greatest in C, lowest in R and intermediate in RS. Fetal supplementation lessened the drain on maternal nutrients and promoted more normal fetal growth and metabolism.
Clearance of Compounds of Different Molecular Size in the Human Placenta in vitro
Authors: Challier J.C. , Guerre-Millo M. , Nandakumaran M. , Gerbaut L. , d’Athis Ph.
Published: September 2009

The placental clearance of selected water-soluble molecules and antipyrine was evaluated using a dual perfusion of human placental lobules in vitro. When graded according to decreasing clearance, the sequence of the molecules was as follows: water = antipyrine > urea > p-aminohippuric acid > inulin > dextran 20 > dextran 70. A close correlation was obtained between the clearance and the free diffusion coefficient of these molecules. However, no restricted diffusion was observed in the molecular range studied. These results suggest an equivalent pore size larger than 90 Å for the human placental membrane in vitro.
Development of Sexual Dimorphism in Human Urogenital Sinus Complex
Authors: Kellokumpu-Lehtinen P.
Published: September 2009

The histological differentiation of the human fetal prostatic urethra and the corresponding part of human fetal female urethra was studied during the 10th through 14th weeks of ovulation age.The development of all the prostatic glands started as epithelial outgrowths from the urethral wall of the urogenital sinus during the time covered in this study. These outgrowths grew rapidly in number and size, especially the posterior ones, and no outgrowths were seen from the paramesonephric and mesonephric ducts. However, the more columnar epithelial cells on the colliculus seminalis, from which the middle and posterior lobes developed, may be of different embryonic origin, e.g. mesonephric, paramesonephric and urethral, or may react differently to hormonal factors. The possible differences in the origin and in the morphological differentiation of the epithelial cells may give clues to the differences in localization of neoplastic changes in adult prostate. The gland formation was preceded by mesenchymal changes which progressed during acinic morphogenesis. Mesenchymal cells differentiated into fibroblasts forming a lamina propria the primitive acini. The mesenchymal differentiation in the corresponding part of the female urethra was not equally prominent. However, the increase in urethral epithelial cells density and cell size was more prominent in the females. These morphological differences might be regulated by sex steroids and further strengthen the current view of the role of the mesenchyme in the prostatic morphogenesis.
Carbonic Anhydrase in the Metanephrogenic Zone of the Human Fetal Kidney
Authors: Larsson Lars , Lönnerholm Gudmar
Published: September 2009

The distribution of carbonic anhydrase in the metanephrogenic zone of the human fetal kidney was studied by the histochemical method of Hansson. In stage I nephrons (= renal vesicles) no or very little enzyme activity was found. Adjacent cortical collecting tubules, however, showed enzyme activity at the luminal cell surface. In stage II nephrons (= S-shaped tubules) the tubular cells displayed cytoplasmic carbonic anhydrase activity, while the glomeruli were inactive. Thus, the development of the nephron from stage I to stage II was accompanied by an increase in tubular cell carbonic anhydrase activity with partially another distribution than in the adult kidney. This may indicate an additional function of this enzyme in the developing nephron other than in the process of urinary acidification, e.g. to promote normal growth and differentiation of the tubular cells.
Decreased Uterine Blood Flow in the Diabetic Pregnant Rat Does Not Modify the Augmented Glucose Transfer to the Fetus
Authors: Palacín M. , Lasunción M.A. , Martín A. , Herrera E.
Published: September 2009

To determine whether changes in uterine blood flow affect placental glucose transfer in the diabetic pregnant rat, on the 7th day of gestation rats were intravenously treated with either streptozotocin (45 mg/kg) (diabetics) or buffer (controls). On the 20th day of gestation, fetal body weight and uterine blood flow appeared reduced whereas fetal/maternal plasma glucose was enhanced and lactate ratios were unchanged in diabetics versus controls. After 20 min of (U-14C)-D-glucose infusion through the maternal left uterine artery, plasma values of fetuses from left and right uterine horns were higher for 14C-glucose and lower for 14C-lactate in diabetics versus controls, and placental glucose transfer was greatly augmented in diabetics whether or not uterine blood flow was included in its calculation. Whereas a linear correlation existed between placental glucose transfer and maternal plasma glucose concentration, transferred glucose conversion into lactate remained stable even when the maternal glucose level was high. It was concluded that enhanced placental glucose transfer in the pregnant diabetic rat is not modified by reduced uterine blood flow. The limited capacity of the fetus to handle the great incoming flux of glucose through the placenta of a severely diabetic mother produces permanent hyperglycemia which may impair fetal growth.
Effect of Glucose and Insulin Administration on Hepatic Adenylate Energy Charge and the Cytosolic Redox State in the Neonates of Normal and Insulin-Treated Diabetic Rats
Authors: Cuezva J.M. , Patel M.S.
Published: September 2009

At birth and during the first 3 postnatal hours, the concentrations of hepatic ATP and the adenylate energy charge were significantly higher in neonates of insulin-treated diabetic rats compared to age-matched neonates of normal rats. However, a significant reduction in these parameters was observed after 3 postnatal hours in neonates of insulin-treated diabetic rats compared to normal rats. Administration of glucose to newborns of insulin-treated diabetic rats at birth did not prevent the lowering of hepatic ATP concentrations and the adenylate energy charge in 6-hour-old neonates. In contrast, the administration of glucose or insulin to the newborns of normal rats at birth caused a reduction in the concentration of hepatic ATP and the adenylate energy charge only at 1 h after birth. The postnatal increase in the hepatic cytosolic redox state (NAD+/NADH) in the neonates of insulin-treated diabetic rats was similar to that observed in the neonates of normal rats during the first 3 postnatal hours; however, a significant reduction in this parameter was observed only in the neonates of insulin-treated diabetic rats after the third postnatal hour. Administration of glucose to the neonates of insulin-treated diabetic rats did not prevent the decline in the cytosolic redox state in these neonates at the sixth postnatal hour.
Influence of Hormones and Undernutrition on Brain Development in Newborn Rats
Authors: Pascual-Leone A.M. , Escrivá F. , Alvarez C. , Goya L. , Rodriguez C.
Published: September 2009

High L-thyroxine (T4) and cortisol doses given to rats during the first 8 days of life and on the first day only respectively, produce decrease of body and brain weight and perturbances to brain energy substrates, i.e. glucose and ketone bodies. The same alterations are found in the undernourished rats from the prenatal period. The pituitary GH and TSH is decreased in the T4- and cortisol-injected animals. The plasma ACTH is decreased in the treated cortisol animals at 8, 12 and 22 days of life. The pituitary TSH content is reduced with respect to controls in the undernourished animals from 14 to 70 days of life. From the exposed experiments we suggest an alteration in the hypothalamic-pituitary complex in T4- and cortisol-treated rats, and describe the similarities between the three experimental models.
The Role of Lactate as an Energy Substrate for the Brain during the Early Neonatal Period
Authors: Medina J.M.
Published: September 2009

The role played by lactate as an energy substrate for the newborn rat during the early neonatal period was studied. Plasma lactate is mostly removed within the first 2 h after delivery, i.e. during the presuckling period. Lactate removal was enhanced by hyperoxia but strongly inhibited by hypoxia, showing a direct correlation with blood oxygen concentrations. Lactate was not converted into glucose during the presuckling period, gluconeogenesis being insignificant in these circumstances; instead it was rapidly oxidized through the tricarboxylic acid cycle. Likewise, lactate was significantly oxidized by brain slices from newborns at birth. At physiological concentrations, lactate oxidation by brain slices was 10- and 3-fold higher than that of glucose and 3-hydroxybutyrate, respectively. In the same circumstances, lipogenesis de novo from lactate was 2- and 5-fold higher than from glucose and 3-hydroxybutyrate, respectively. The results suggest that lactate is the main metabolic fuel for the brain during the early neonatal period.