bluuebunny/crossref_metadata_2025 huggingface dataset:
Orientation by magnetic field in leaf‐cutter ants, Atta colombica (Hymenoptera: Formicidae)
Authors: Banks Alexander N. , Srygley Robert B.
Published: October 2003

Leaf‐cutter ants (Atta colombica) use trail following to travel between foraging sites and the home nest. However, this combination of pheromone and visual cues is likely to be complemented by a directional reference system such as a compass, used not only when foraging but also during colony formation, where foraging trails degrade or where ants become displaced. One candidate system is the magnetic polarity compass. We tested the orientation of leaf‐cutter ants under a magnetic field of reversed‐polarity, with the prediction that the ants would show 180° deflection compared with control ants in an unchanged geomagnetic field. When the sun's disc was unobstructed by clouds, orientation was the same as that of control ants, implying that magnetic cues were not used to orient. However, when the sky was overcast, ants in the experimental treatment significantly shifted their mean orientation both in comparison with controls and reversed‐polarity ants under the sun. Although a total reversal in orientation was not induced, the results demonstrate that Atta respond to magnetic reversal in the absence of sunlight cues, and suggest a role for magnetic cues in determining direction during orientation.
Changes in Candida albicans colonization and morphology under influence of voriconazole
Authors: Bernhardt Hannelore , Knoke M. , Bernhardt J.
Published: October 2003

The aim was the investigation of fungal colonization and morphological alterations under the influence of voriconazole in an in vitro system. Voriconazole stopped growth and colonization of Candida albicans (wild type SC5314) on cover slips in microtiter plates dependent on drug concentration, the time of Candida growth before the input of voriconazole and oxygen concentration. The direct microscopy by fluorescence staining with the optical brightener Blancophor® showed short bizarrely deformed mycelia looking swollen. The colonization on cover glass was diminished. Microcolonies or starting of biofilm formation as in the control was not observed. The metabolic activity was demonstrated by vital staining with FUN® 1 resulting in red fluorescent structures in the yeast forms and mycelia in the controls. Under voriconazole influence the remaining cells only showed a green or pale yellow fluorescence. Most of the cells lost their metabolic activity.
Guideline vulvovaginal candidosis: Guideline of the German Dermatological Society, the German Speaking Mycological Society and the Working Group for Infections and Infectimmunology of the German Society for Gynecology and Obstetrics
Authors: Mendling W. , Seebacher C.
Published: October 2003

The Guideline vulvovaginal candidosis, as passed by three German medical societies, is presented.
A novel technique to evaluate the adhesion of Candida species to gingival epithelial cells
Authors: Nikawa H. , Egusa H. , Makihira S. , Nishimura M. , Ishida K. , Furukawa M. , Hamada T.
Published: October 2003

We developed an in vitro ATP assay technique to extract cellular and fungal ATP separately, which allowed to evaluate quantitatively the adhesion of the yeasts to monolayers of human gingival epithelial cells. Thirteen isolates of Candida spp. representing three species (i.e. Candida  albicans, C. tropicalis and C. glabrata) were used in the present study. When the adherent capacity of the Candida species was compared, C. albicans exhibited highest capacity of adherence to gingival epithelial cells, followed by C. tropicalis, and C. glabrata was the lowest [analysis of variance (anova), P < 0.01]. The germ tubes of C. albicans exhibited significantly higher adherence capacity than their blastoconidia cells (anova, P < 0.01), which was not observed with a C. albicans isolate, defect of germ tube formation. Our results suggested that the adherence of C. albicans is promoted by germ tube formation and may play an important role in the pathogenesis of the fungus.
Tinea capitis due to Microsporum audouinii in Malta
Authors: Vella Zahra L. , Vella Briffa D.
Published: October 2003

We describe a case of tinea capitis in a 4‐year‐old boy caused by Microsporum audouinii var. langeronii. This is the first recorded case of tinea capitis due to this dermatophyte in the Maltese Islands.
Decreased monocytic phagosomal acidification among chronic paracoccidioidomycosis patients
Authors: Teresa Guereño M. , Rosario Silaf M. , Javier Bava A. , Negroni Ricardo , Diez Roberto A.
Published: October 2003

To determine the ability of monocyte phagosomal acidification in chronic paracoccidioidomycosis, 13 patients were recruited at different times during follow‐up and compared with 18 normal controls. Eight patients were studied at diagnosis, six of them also during treatment and five additional patients after ending treatment. Phagosomal acidification of monocytes, triggered by challenge with opsonized zymosan, was evaluated with acridine orange and expressed as percentage of orange‐stained intracellular particles, as mean ± SE. In comparison with controls, acidification was severely impaired before treatment (33 ± 11% vs. 67 ± 6%) and reached values similar to controls during treatment (73 ± 6%, n = 6). In addition, phagosomal acidification of the patients studied after treatment (63 ± 4%) had no difference when compared with controls. This study demonstrates that phagosomal acidification is perturbed among chronic paracoccidioidomycosis patients and reverses with antifungal treatment.
Oral Manifestations of Paracoccidioidomycosis. Report of 21 Cases from Argentina
Authors: Godoy H. , Reichart P. A.
Published: October 2003

The present study describes 21 Argentinian patients living in the province of Corrientes, who had developed oral manifestations due to Paracoccidioides brasiliensis infection. Of these, 20 patients were men and one a woman. Patients were of an average age of 39 years (range 25 to 72 years). Approximately, 76.2% of the patients were farmers. Gingival lesions were observed in 76%. Also, the tongue (71%) and the lips (62%) were frequently affected. Cytological smears and histopathology showed the characteristic fungal cells with the characteristic granulomatous inflammatory reaction consisting of lymphocytes, epithelioid cells and giant cells of the Langhans type. All patients except one had detectable pulmonary involvement. Therapy consists of long‐term administration of itraconazole. Oral manifestations of paracoccidioidomycosis are characteristic in their clinical presentation. Early diagnosis and adequate therapy may prevent extensive tissue destructions. Long‐term follow‐up is mandatory.
Fatal pulmonary scedosporiosis
Authors: Horré R. , Jovanić B. , Marklein G. , Schumacher G. , Friedrichs N. , Neuhaus T. , de Hoog G. S. , Becker W. H. J. , Choi S. M. , Schaal K. P.
Published: October 2003

We report on a case of scedosporiosis in a 72‐year‐old German woman. Her disease started with a purulent ulceration of unknown course at her left foot. Soon after onset of oral antibacterial therapy she needed in‐hospital treatment because of an acute pneumonia. The infection progressed despite the application of different antibiotics. Microscopic examination of tracheal fluid revealed fungal hyphae and therefore treatment with itraconazole was initiated. However, the patient developed renal failure, required mechanical ventilation and finally died in treatment‐resistant septic shock. Post‐mortem Scedosporium apiospermum was cultured from lung tissue taken during autopsy. This is the fourth case of human infection caused by Scedosporium species diagnosed in our laboratory during the last 4 years.
Adhesion and cell‐surface‐hydrophobicity of sequentially isolated genetic isotypes of Candida albicans in an HIV‐infected Southern Chinese cohort
Authors: Samaranayake Y. H. , Samaranayake L. P. , Yau J. Y. Y. , Ellepola A. N. B. , Anil S. , Yeung K. W. S.
Published: October 2003

Objectives of the study were to investigate the variability in yeast adhesion and cell‐surface‐hydrophobicity (CSH) during human immunodeficiency virus (HIV) disease progression, using a total of 60 sequential Candida albicans isolated from oral rinse samples of seven HIV‐infected individuals with (4) and without (3) clinical symptoms of oropharyngeal candidosis. Significant differences in the adhesion to buccal epithelial cells (BECs) during sequential visits were observed for all genetic isotypes in five of the seven individuals and three isotypes belonging to the sixth individual. A single isotype of patient HK1 and another of HK4 (genotype I) demonstrated significant variations in their CSH during sequential visits whereas no such differences were noted for the remaining genotypes. On Spearman correlation analysis an isotype from HK1 demonstrated a significant increased adherence to BECs and CSH during HIV disease progression whereas no such correlation was noted for the remaining isotypes studied. No significant differences in adherence to BECs or CSH values were observed between the symptomatic oral candidosis and the asymptomatic carrier group. Further, on regression analysis only the single isotype of HK1 demonstrated a significant positive correlation between adherence to BECs and CSH whereas no such correlation was observed when all tested Candida isolates were pooled and evaluated as a single, large group.
Morphological observations on Absidia corymbifera and Absidia blakesleeana strains preserved under mineral oil
Authors: Santos Manoel J. S. , de Oliveira Pedrina C. , Trufem Sandra F. B.
Published: October 2003

Macro‐ and micromorphology of 30 living subcultures of Absidia corymbifera (10 strains plus three strains of Absidia ramosa) and Absidia blakesleeana (two strains) preserved under mineral oil at room temperature for periods ranging from 3 to 44 years in The Fungal Culture Collection of Instituto Oswaldo Cruz (IOC) were observed and described by permanent mycological preparations mounted in a glycerol 10% and/or Amann lactophenol solution. Vegetative and asexual reproductive structures are illustrated by drawings made with the aid of a camera‐lucida. The study showed that the period of maintenance under mineral oil and the stress which took place during the period of storage did not affect the vegetative and asexual reproductive morphology of the Absidia strains and species studied here.
Comparison of morning and evening administration of rabeprazole for gastro‐oesophageal reflux and nocturnal gastric acid breakthrough in patients with reflux disease: a double‐blind, cross‐over study
Authors: Pehlivanov N. D. , Olyaee M. , Sarosiek I. , McCallum R. W.
Published: October 2003

Aim:  To assess the effect of timing of rebeprazole (RB) 20 mg/d administration on oesophageal acid exposure and nocturnal gastric acid breakthrough (NGAB) in patients with GERD.

Methods:  20 GERD patients received two 7‐day treatments of RB in the morning (a.m.) or in the evening (p.m.) hours. The regimens were randomized in a double‐blind fashion and separated by a 7‐day washout period. The tablets were taken 30 min before standardized meals. A combined (oesophageal & gastric) 24‐hour pH monitoring was performed before and on day 7 of each treatment.

Results:  Total oesophageal acid exposure was normalized in 10/14 (71.4%) patients with RB p.m. and in 6/15 (42.8%) with RB a.m. RB p.m. significantly decreased the nocturnal supine oesophageal acid exposure vs. RB a.m., 0.2% vs. 3.4%. The mean NGAB duration was significantly shortened with RB a.m. and p.m. vs. the baseline recording, 4.1±1.8 and 3.4±1.5 hours vs. 7.8±1.7 hours.

Conclusions:  Rabeprazole significantly reduced the NGAB duration and significantly increased the mean nocturnal gastric pH; RB p.m. normalized more effectively the total oesophageal exposure than RB‐a.m.; RB p.m. provided significantly better control of nocturnal supine gastro‐oesophageal reflux than a.m. dosing. These data suggest that administration of a PPI before the evening meal maximizes acid control and would be the preferred dosing schedule in GERD patients, particularly those with nocturnal symptoms.
The basis for the decreased response to proton pump inhibitors in gastro‐oesophageal reflux disease patients without erosive oesophagitis
Authors: Gardner J. D. , Gallo‐Torres H. , Sloan S. , Robinson M. , Miner P. B.
Published: October 2003

Background : The reason why heartburn in gastro‐oesophageal reflux disease subjects without oesophagitis is less responsive to proton pump inhibitors than heartburn in those with erosive oesophagitis is not known.

Methods : Gastric and oesophageal pH were determined in 26 subjects with gastro‐oesophageal reflux disease at baseline and on days 1, 2 and 8 of treatment with 20 mg omeprazole or 20 mg rabeprazole in a randomized, two‐way cross‐over fashion. The presence or absence of erosive oesophagitis at baseline was documented by upper gastrointestinal endoscopy.

Results : At a given value of the integrated gastric acidity during treatment with a proton pump inhibitor, the probability of pathological oesophageal reflux was significantly higher in subjects with no oesophagitis than in those with erosive oesophagitis. This occurred because the post‐prandial gastric acidity in subjects with no oesophagitis showed a decreased response to the antisecretory agent.

Conclusions : Compared with gastro‐oesophageal reflux disease subjects with erosive oesophagitis, those with no oesophagitis are relatively refractory to the pharmacodynamic effects of proton pump inhibitors on the post‐prandial integrated gastric acidity.
Drug interaction between infliximab and azathioprine in patients with Crohn's disease
Authors: Roblin X. , Serre‐Debeauvais F. , Phelip J.‐M. , Bessard G. , Bonaz B.
Published: October 2003

Background : A drug interaction has been observed between infliximab and methotrexate in rheumatoid arthritis.

Aim : To look for an interaction between infliximab and azathioprine in Crohn's disease patients using the active metabolites of azathioprine: 6‐tioguanine nucleotides.

Methods : Patients receiving azathioprine who required infliximab for ileo‐colonic or ano‐perineal Crohn's disease were recruited prospectively. 6‐tioguanine nucleotide levels were evaluated before infusion, within 1–3 weeks after the first infusion and 3 months after the first infusion. The clinical outcome was evaluated by the Harvey–Bradshaw index or the closure of ano‐perineal fistulas.

Results : Thirty‐two patients were included (17 received one infusion and 15 received three infusions). The mean 6‐tioguanine nucleotide level was comparable before and 3 months after the first infusion, but a significant increase was observed within 1–3 weeks after the first infusion (P < 0.001). In parallel, a significant decrease in leucocyte count and increase in mean corpuscular volume were observed; these modifications were normalized 3 months after infusion. An increase in 6‐tioguanine nucleotide level of greater than 400 pmol/8 × 108 erythrocytes was strongly related to good tolerance and a favourable response to infliximab, with a predictive value of 100%.

Conclusions : This prospective study provides evidence for a drug interaction between azathioprine and infliximab.
Oral and intestinal mucositis — causes and possible treatments
Authors: Duncan M. , Grant G.
Published: October 2003

Chemotherapy and radiotherapy, whilst highly effective in the treatment of neoplasia, can also cause damage to healthy tissue. In particular, the alimentary tract may be badly affected. Severe inflammation, lesioning and ulceration can occur. Patients may experience intense pain, nausea and gastro‐enteritis. They are also highly susceptible to infection. The disorder (mucositis) is a dose‐limiting toxicity of therapy and affects around 500 000 patients world‐wide annually.

Oral and intestinal mucositis is multi‐factorial in nature. The disruption or loss of rapidly dividing epithelial progenitor cells is a trigger for the onset of the disorder. However, the actual dysfunction that manifests and its severity and duration are greatly influenced by changes in other cell populations, immune responses and the effects of oral/gut flora. This complexity has hampered the development of effective palliative or preventative measures. Recent studies have concentrated on the use of bioactive/growth factors, hormones or interleukins to modify epithelial metabolism and reduce the susceptibility of the tract to mucositis. Some of these treatments appear to have considerable potential and are at present under clinical evaluation.

This overview deals with the cellular changes and host responses that may lead to the development of mucositis of the oral cavity and gastrointestinal tract, and the potential of existing and novel palliative measures to limit or prevent the disorder.

Presently available treatments do not prevent mucositis, but can limit its severity if used in combination. Poor oral health and existing epithelial damage predispose patients to mucositis. The elimination of dental problems or the minimization of existing damage to the alimentary tract, prior to the commencement of therapy, lowers their susceptibility. Measures that reduce the flora of the tract, before therapy, can also be helpful. Increased production of free radicals and the induction of inflammation are early events in the onset of mucositis. Prophylactic administration of scavengers or anti‐inflammatories can partially counteract or limit some of these therapy‐mediated effects, as can the use of cryotherapy. The regular use of mouthwashes, mouth coatings, antibiotics and analgesics is essential, prior to and during loss and ablation of the epithelial layer. Granulocyte–macrophage colony‐stimulating factor/granulocyte colony‐stimulating factor or the use of laser light therapy may aid restitution and repair. Glutamine supplements may be beneficial in the repair/recovery phase.
Re‐treatment of patients with anti‐HBe‐positive chronic hepatitis B who relapsed after an initial course of lamivudine
Authors: Niro G. A. , Santantonio T. , Fontana R. , Insalata M. , Facciorusso D. , Signorile F. , Perri F. , Guastadisegni A. , Gioffreda D. , Palmieri O. , Pastore G. , Andriulli A.
Published: October 2003

Aim : To evaluate the efficacy of a long‐term course of lamivudine monotherapy in patients with anti‐HBe‐positive chronic hepatitis B who relapsed after the first course of either lamivudine/interferon (n = 16; Group 1) or lamivudine (n = 20; Group 2).

Methods : Biochemical and virological tests were performed every 3 months. At baseline and breakthrough, the region coding for the YMDD amino acid motif was sequenced.

Results : The length of re‐treatment averaged 24 months. The virological response peaked at 6 months (94.4%), and declined to 66.7% and 50% at 12 and 24 months, respectively. The rates of breakthrough were 2.9%, 31.4% and 48.6% at 6, 12 and 24 months, respectively. By the second year, responders amounted to 62.5% and 40% in Groups 1 and 2, respectively (P = 0.10). The 18 responders at month 24 are still on therapy after 25–51 months of treatment: 14 still maintain a response, nine from Group 1 and five from Group 2.

Conclusions : Re‐treatment with lamivudine can control viral replication. This effect is maintained for the initial 12 months in two‐thirds of patients, but afterwards the duration of response lessens due to the development of viral resistance.
Effects of hepatitis A vaccination on atherogenesis in a murine model
Authors: Burnett M. S. , Zhu J. , Miller J. M. , Epstein S. E.
Published: October 2003

Summary. Our laboratory demonstrated that seropositivity to hepatitis A virus (HAV) independently predicts risk for coronary artery disease (CAD). As these findings are based only on the presence of HAV‐specific antibodies, and not infectious virus, this prompted questions regarding possible effects of HAV vaccines on CAD development. If seropositivity to HAV alone, resulting from HAV vaccination, leads to increased atherogenesis, this raises important issues regarding the benefit of protection against HAV infection vs the risk of developing CAD. This study examines the effect of HAV vaccination on atherosclerosis development in a cholesterol‐fed mouse model. Animals either received HAV vaccine, adjuvant, or saline. After 15 weeks, no significant differences were found in lesion area between the groups: HAV vaccine, 13 470 μm2; adjuvant, 16 332 μm2 and saline, 14 356 μm2. Only animals receiving HAV vaccination developed HAV‐specific IgG. Thus, in this mouse model, vaccination against HAV does not contribute to the development of atherosclerosis.
Vogt‐Koyanagi‐Harada disease associated with interferon alpha‐2b/ribavirin combination therapy
Authors: Sylvestre D. L. , Disston A. R. , Bui D. P.
Published: October 2003

Summary. The complex immunological effects of interferon and ribavirin therapy (IFN/R) in hepatitis C virus (HCV) may also exacerbate or trigger the de novo development of autoimmunity. We report the first case of IFN/R therapy associated with Vogt‐Koyanagi‐Harada disease, a T‐cell‐mediated autoimmune response to melanocytes. This condition, which has characteristic ocular, neurological and integumentary findings, elicits a systemic prodrome that may mimic side‐effect profile and delay of IFN or mask its recognition. We discuss this disease in the context of the known immunomodulatory effects of IFN‐alpha and ribavirin and suggest potential mechanistic explanations for the association.
Dynamics of hepatitis C virus quasispecies turnover during interferon‐α treatment
Authors: von Wagner M. , Lee J.‐H. , Rüster B. , Kronenberger B. , Sarrazin C. , Roth W. K. , Zeuzem S.
Published: October 2003

Summary. Interferon‐α (IFN) has been shown to accelerate the evolution of hepatitis C virus (HCV) variants (quasispecies) in nonresponder patients. Different sensitivities of HCV variants to IFN are discussed as a possible mechanism. In the present study, quasispecies were investigated in detail by a newly established and validated direct solid‐phase sequencing of the hypervariable region 1 (HVR1), during the initial 3 months of IFN therapy. According to single strand conformation polymorphism (SSCP) analysis, 14 of 26 (54%) virologic nonresponders with quasispecies evolution were identified. Six representative patients with SSCP changes were selected for frequent HVR1 sequencing. Pre‐existing variants were identified by cloning and sequencing of the pretreatment serum HCV sample. In one patient the major type was substituted by a minor variant within 3 days of treatment while in the majority of patients the pretreatment major type did not decline before days 26–57 of treatment. Total serum HCV RNA levels remained constant in all patients. In conclusion, although quasispecies evolution during IFN therapy is common, it occurs after a wide range of time intervals after initiation of therapy. Thus, nonresponse to IFN cannot exclusively be explained by changes in the quasispecies.
A serological study of intrafamilial spread from patients with sporadic hepatitis E virus infection
Authors: Somani S. K. , Aggarwal R. , Naik S. R. , Srivastava S. , Naik S.
Published: October 2003

Summary. Intrafamilial transmission is rare in epidemic hepatitis E; its frequency in sporadic hepatitis E is not known. We followed up 86 household contacts (age range 4–75 years, mean ± SD 32.4 ± 15.8; 49 males), who were family members of patients with acute sporadic hepatitis E. Of the 86 contacts, 68 (79%) tested negative for IgG anti‐hepatitis E virus antibodies. Four (4.7%) had IgM anti‐hepatitis E virus antibodies at the time of diagnosis of hepatitis E in the index case; two of these contacts possibly had hepatitis E virus infection acquired simultaneously with that in the index case, and two could have had intrafamilial transmission. None developed serological evidence of hepatitis E virus infection over a period of 49 ± 18 days after the diagnosis of index case, although a majority lacked IgG antibodies to hepatitis E virus and were likely to be susceptible. This suggests that person‐to‐person transmission is uncommon in sporadic hepatitis E.
Hepatitis C virus proteins do not directly trigger fibrogenic events in cultured human liver myofibroblasts
Authors: Tan K. , Guibert C. , Neaud V. , Rosenbaum J.
Published: October 2003

Summary. Although liver fibrosis is the major complication of hepatitis C virus (HCV) infection, the mechanisms of fibrogenesis in this setting are not completely understood. The aim of this study was to test the direct effect of HCV proteins on signalling‐ and fibrosis‐related events in cultured human liver myofibroblasts, the effector cells of liver fibrogenesis. Cultured myofibroblasts were exposed to recombinant HCV core, a structural protein, and nonstructural proteins (NS) 3, NS 4 and NS 5. HCV proteins did not significantly increase DNA synthesis in myofibroblasts. We then examined if these proteins affected early signalling events. None of the HCV proteins affected the phosphorylation of the mitogen activated protein kinases/extracellular regulated kinases 1 and 2, or of the phosphatidylinositol 3‐kinase target, Akt. HCV proteins had also no effect on intracellular calcium concentration. In other experiments, fibrogenesis‐related parameters were measured. None of the HCV proteins had any effect on the secretion of type I collagen, tissue inhibitor of matrix metalloproteinases type 1, gelatinase or urokinase. Alpha‐smooth muscle actin expression was also not modified. In summary, our experiments do not support a direct effect of these HCV proteins on fibrogenic cells.
Occult hepatitis C virus infection in type II mixed cryoglobulinaemia
Authors: Casato M. , Lilli D. , Donato G. , Granata M. , Conti V. , Del Giudice G. , Rivanera D. , Scagnolari C. , Antonelli G. , Fiorilli M.
Published: October 2003

Summary. Mixed cryoglobulinaemia, when not secondary to other well‐defined immunological disorders, is commonly associated with hepatitis C virus (HCV) infection. However, a minority of cases lack evidence of HCV infection and are, therefore, defined as ‘true essential’ mixed cryoglobulinaemias. We thoroughly investigated three such patients to determine the aetiology of this disorder.

Antibodies to HCV (anti‐HCV) and HCV RNA, detected by sensitive enzyme‐linked immunosorbent and polymerase chain reaction assays in serum and in concentrated cryoglobulins, were repeatedly negative in the three patients. Despite the lack of evidence for HCV infection, two of them were still treated with interferon α‐2a assuming unrecognized viral infection. Both patients demonstrated excellent clinical and laboratory responses, but cryoglobulinaemia relapsed after the withdrawal of therapy. At the time of relapse, HCV RNA genomic sequences were detected for the first time in the cryoprecipitates of both patients. In the third case, HCV RNA was demonstrated for the first time during a flare of cryoglobulinaemia coincident with varicella infection. In all three patients anti‐HCV antibodies remained negative throughout follow‐up.

We conclude that some apparently ‘essential’ forms of mixed cryoglobulinaemia can be caused by occult HCV infection. Interferon therapy can be taken into consideration in such HCV‐negative cases.
Daily induction combination treatment with alpha 2b interferon and ribavirin or standard combination treatment in naive chronic hepatitis C patients. A multicentre randomized controlled trial *
Authors: Van Vlierberghe H. , Leroux‐Roels G. , Adler M. , Bourgeois N. , Nevens F. , Horsmans Y. , Brouwer J. , Colle I. , Delwaide J. , Brenard R. , Bastens B. , Henrion J. , de Vries R. A. , de Galocsy C. , Michielsen P. , Robaeys G. , Bruckers L.
Published: October 2003

Summary. The standard treatment for patients with chronic hepatitis C is a 6–12‐month combination therapy with interferon alpha and ribavirin. Induction treatment could result in a faster early decline of the hepatitis C virus (HCV) load and a better response rate. Naive chronically infected HCV patients (n = 454) were randomized into two arms to receive either induction treatment with interferon alpha 2b 5 million units (MU) subcutaneously (s.c.) daily during a period of 8 weeks (arm A); or treatment with interferon alpha 2b 5 MU s.c. three times a week (TIW) for a period of 8 weeks (arm B). After week 8, interferon treatment in both arms was 3 MU s.c. TIW for a total period of 12 months. In both arms, ribavirin (1000–1200 mg orally per day) was added at week 4. Induction treatment resulted in a higher virological response at week 8 of treatment (66%vs 47%; P < 0.01). However, response at the end of treatment and at 6 months follow‐up was not different (53%vs 50%, 41%vs 33%). The occurrence of adverse events and the drop‐out rate were similar in both arms. Although an early virological response is observed more frequently in the induction treatment, end of treatment response and sustained responses did not differ.
Genetic mosaic in a marine species flock
Authors: Mccartney Michael A. , Acevedo Jenny , Heredia Christine , Rico Ciro , Quenoville Brice , Bermingham Eldredge , Mcmillan W. Owen
Published: October 2003

We used molecular approaches to study the status of speciation in coral reef fishes known as hamlets (Serranidae: Hypoplectrus). Several hamlet morphospecies coexist on Caribbean reefs, and mate assortatively with respect to their strikingly distinct colour patterns. We provide evidence that, genetically, the hamlets display characteristics common in species flocks on land and in freshwaters. Substitutions within two mitochondrial DNA (mtDNA) protein‐coding genes place hamlets within a monophyletic group relative to members of two related genera (Serranus and Diplectrum), and establish that the hamlet radiation must have been very recent. mtDNA distances separating hamlet morphospecies were slight (0.6 ± 0.04%), yielding a coalescent estimate for the age of the hamlet flock of approximately 430 000 years. Morphospecies did not sort into distinct mtDNA haplotype phylogroups, and alleles at five hypervariable microsatellite loci were shared broadly across species boundaries. None the less, molecular variation was not distributed at random. Analyses of mtDNA haplotype frequencies and nested clades in haplotype networks revealed significant genetic differences between geographical regions and among colour morphospecies. We also observed significant microsatellite differentiation between geographical regions and in Puerto Rico, among colour morphospecies; the latter providing evidence for reproductive isolation between colour morphospecies at this locale. In our Panama collection, however, colour morphospecies were mostly genetically indistinguishable. This mosaic pattern of DNA differentiation implies a complex interaction between population history, mating behaviour and geography and suggests that porous boundaries separate species in this flock of brilliantly coloured coral reef fishes.
Population genetic structure of mahogany (Swietenia macrophylla King, Meliaceae) across the Brazilian Amazon, based on variation at microsatellite loci: implications for conservation
Authors: Lemes Maristerra R. , Gribel Rogério , Proctor John , Grattapaglia Dario
Published: October 2003

Mahogany (Swietenia macrophylla, Meliaceae) is the most valuable and intensively exploited Neotropical tree. No information is available regarding the genetic structure of mahogany in South America, yet the region harbours most of the unlogged populations of this prized hardwood. Here we report on the genetic diversity within and the differentiation among seven natural populations separated by up to 2100 km along the southern arc of the Brazilian Amazon basin. We analysed the variation at eight microsatellite loci for 194 adult individuals. All loci were highly variable, with the number of alleles per locus ranging from 13 to 27 (mean = 18.4). High levels of genetic diversity were found for all populations at the eight loci (mean HE = 0.781, range 0.754–0.812). We found moderate but statistically significant genetic differentiation among populations considering both estimators of FST and RST, θ = 0.097 and ρ = 0.147, respectively. Estimates of θ and ρ were significantly greater than zero for all pairwise population comparisons. Pairwise ρ‐values were positively and significantly correlated with geographical distance under the isolation‐by‐distance model. Furthermore, four of the populations exhibited a significant inbreeding coefficient. The finding of local differentiation among Amazonian mahogany populations underscores the need for in situ conservation of multiple populations of S. macrophylla across its distribution in the Brazilian Amazon. In addition, the occurrence of microgeographical genetic differentiation at a local scale indicates the importance of maintaining populations in their diverse habitats, especially in areas with mosaics of topography and soil.
High caffeine consumption in the third trimester of pregnancy: gender‐specific effects on fetal growth
Authors: Vik Torstein , Bakketeig Leiv S. , Trygg Kerstin Ulla , Lund‐Larsen Kari , Jacobsen Geir
Published: October 2003

It has been suggested that a high caffeine intake in pregnancy may be a risk factor for fetal growth retardation. We have tested this hypothesis in a population‐based case‐control study. Caffeine intake among 111 mothers of small‐for‐gestational‐age (SGA) infants (56 boys, 55 girls) was compared with the intake among 747 mothers of non‐SGA infants (368 boys, 379 girls). Food records for 3 days were collected in the second (week 17–20) and in the third (week 33) trimester, and caffeine intake from coffee, tea, soft drinks and chocolate was calculated and dichotomised as low or high, based upon the median value. Mothers of SGA infants had higher mean intake of caffeine [281 ± 210 (SD) mg/day] in the third trimester than mothers of non‐SGA infants (212 ± 150 mg/day; P < 0.001). The risk of SGA birth was nearly doubled if the mother had a high rather than a low caffeine intake in the third trimester [odds ratio (OR) 1.8; 95% confidence intervals (CI) 1.2, 2.5]. The increased risk was mainly found in boys (OR 2.8; 95% CI 1.5, 5.2), and not in girls (OR 1.2; 95% CI 0.7, 2.1). The increased risk for boys persisted after adjustment for cigarette smoking alone, or for smoking and various other SGA risk factors together. Our results suggest that a high caffeine intake in the third trimester may be a risk factor for fetal growth retardation, in particular if the fetus is a boy.
Rates of twinning before and after fortification of foods in the US with folic acid, Texas, 1996 to 1998
Authors: Waller D. K. , Tita A. T. N. , Annegers J. F.
Published: October 2003

Several investigators have reported a 40% increase in the prevalence of twinning among women who have taken folic acid or multivitamins containing folic acid at the time of conception. Given that infant morbidity and mortality are greatly increased among twins, such a large increase in twinning could have serious implications. We undertook this study to determine if US fortification of enriched cereal‐grain products with folic acid was associated with an unexpected increase in the prevalence of twinning in the state of Texas. We examined 1 003 207 deliveries conceived in Texas, between 1 January 1996 and 31 December 1998. We compared the prevalence of twin deliveries conceived before, during and after fortification with folic acid, mandated to begin on 1 January 1998. Comparing pregnancies conceived in 1997 with those conceived in 1996, we observed a 2.4% yearly increase in twinning, 1.024 [0.98, 1.07]. Comparing pregnancies conceived in 1998 with those conceived in 1997, we observed a 4.6% yearly increase in twinning, 1.046 [1.00, 1.09]. These increases were adjusted for maternal age, race, education, parity and season of conception. The size and pattern of these increases are consistent with the ongoing increase in twinning of 1–4% per year which began in the US prior to fortification.
Support for breastfeeding mothers: a systematic review
Authors: Sikorski Jim , Renfrew Mary J. , Pindoria Sima , Wade Angela
Published: October 2003

Although the benefits of breastfeeding are widely accepted, the effectiveness of different strategies to promote the continuation of breastfeeding once initiated are less clear. The objective of this systematic review was to describe studies comparing standard care with the provision of extra breastfeeding support and to measure its effectiveness. Outcome measures used were rates of cessation of any breastfeeding or exclusive breastfeeding at chosen points in time. Measures of child morbidity and maternal satisfaction were also used when these were reported.

Twenty eligible randomised or quasi‐randomised controlled trials were identified, involving 23 712 mother–infant pairs. Extra support had a beneficial effect on the duration of any breastfeeding (RR [95% confidence intervals] for stopping any breastfeeding before the last study assessment up to 6 months 0.88 [0.81, 0.95]; 15 trials, 21 910 women). The effect was greater for exclusive breastfeeding (RR for stopping exclusive breastfeeding before the last study assessment 0.78 [0.69, 0.89]; 11 trials, 20 788 women).

Although the point estimates of relative risk were very similar, benefit derived from professional support achieved statistical significance for any breastfeeding (RR 0.89 [0.81, 0.97]; 10 trials, 19 696 women) but not for exclusive breastfeeding (RR 0.90 [0.81, 1.01]; six trials, 18 258 women). Lay support was effective in reducing the cessation of exclusive breastfeeding (RR 0.66 [0.49, 0.89]; five trials, 2530 women) while the strength of its effect on any breastfeeding was less clear (RR 0.84 [0.69, 1.02]; five trials, 2224 women). Professional support in the largest trial to assess health outcomes produced a significant reduction in the risk of gastrointestinal infections and atopic eczema. In two trials with children suffering from diarrhoeal illness, extra support was highly effective in increasing short‐term exclusive breastfeeding rates and reducing recurrence of diarrhoea.

This review supports the conclusion that supplementary breastfeeding support should be provided as part of routine health service provision. There is clear evidence for the effectiveness of professional support on the duration of any breastfeeding although the strength of its effect on the rate of exclusive breastfeeding is uncertain. Lay support is effective in promoting exclusive breastfeeding although the strength of its effect on the duration of any breastfeeding is uncertain. Evidence supports the promotion of exclusive breastfeeding as central to the management of diarrhoeal illness in partially breast‐fed infants.
Secular trends of fetal growth in Canada, 1981 to 1997
Authors: Wen Shi Wu , Kramer Michael S. , Platt Robert , Demissie Kitaw , Joseph K. S. , Liu Shiliang , Sauve Reg
Published: October 2003

Preterm birth and low birthweight in Canada have shown paradoxical temporal trends, with an increase in preterm birth and a decrease in low birthweight. Mean birthweight has increased in many industrialised countries, despite a recent rise in preterm birth, suggesting a temporal increase in fetal growth (birthweight for gestational age) in Canada. We thus described temporal trends in the distribution of fetal growth from 1981 to 1997, including means and proportions of infants at both the low and high ends of the fetal growth distribution. We used data for singleton live births from Statistics Canada's Canadian Birth Data Base for the years 1981–97 (excluding Ontario and Newfoundland) and analysed temporal trends in birthweight and birthweight‐for‐gestational‐age z‐score as continuous outcomes and the derived dichotomised  outcomes  [i.e.  low  birthweight  (<2500 g),  very  low  birthweight  (<1500 g), small‐for‐gestational‐age (<10th percentile), very small‐for‐gestational‐age (<3rd percentile), high birthweight (>4000 g), very high birthweight (>4500 g), large‐for‐gestational‐age (>90th percentile), and very large‐for‐gestational‐age (>97th percentile)]. The birthweight‐for‐gestational‐age was based on a newly developed population‐based Canadian reference. The results showed that in the overall sample and in a subsample of term and post‐term births, mean birthweight, mean z‐score, rates of high birthweight, very high birthweight, large‐for‐gestational‐age, and very large‐for‐gestational‐age increased whereas rates of low birthweight, very low birthweight, small‐for‐gestational‐age, and very small‐for‐gestational‐age decreased between 1981–83 and 1995–97. The reverse was observed in preterm births. These temporal changes were larger for more extremely distributed measures of fetal growth. For example, compared with 1981–83, the decrease in 1995–97 for very small‐for‐gestational‐age (<3rd percentile) was 38.9%, whereas the decrease for small‐for‐gestational‐age (<10th percentile) was only 29.7%. Corresponding temporal increases were 21.4% for very large‐for‐gestational‐age (>97th percentile) and 15.2% for large‐for‐gestational‐age (>90th percentile). Among infants with gestational age 34–36 weeks, all measures of fetal growth, including the rates for all dichotomous outcomes, decreased in 1995–97 as compared with 1981–83. We conclude that Canadian infants are getting bigger, but only those born at term. The temporal trends for more extremely distributed fetal growth measures are particularly marked.
Childhood malnutrition and its predictors in rural Malawi
Authors: Maleta Kenneth , Virtanen Suvi M. , Espo Merimaaria , Kulmala Teija , Ashorn Per
Published: October 2003

We prospectively followed up a population‐based cohort of 767 rural Malawian children from birth to 36 months to characterise the timing and predictors of malnutrition. Underweight and wasting incidence peaked between 6 and 18 months of age, whereas stunting incidence was highest during the first 6 months of age. After infancy about 40% of the children were underweight, 70% stunted, and about 4% wasted. Small size during the first 3 months of life predicted the incidence of severe underweight (relative risk [95% confidence interval], 1.8 [0.9, 3.4]), severe stunting ( 2.1 [1.3, 3.4]), and moderate wasting (2.0 [1.1, 3.5]). Children with many illness episodes in infancy had a twofold risk for the development of severe underweight and moderate wasting. Severe underweight was further predicted by residence far away from a health facility and moderate wasting by maternal HIV infection. Our conclusion is that the intrauterine period and first 6 months of life are critical for the development of stunting whereas the subsequent year is more critical for the development of underweight and wasting. Strategies combating intrauterine growth retardation, maternal HIV and infant morbidity are likely to reduce the burden of malnutrition in this population.
The effect of caffeine consumption and nausea on the risk of miscarriage
Authors: Giannelli Massimo , Doyle Pat , Roman Eve , Pelerin Margo , Hermon Carol
Published: October 2003

Evidence for a harmful effect of caffeine intake on risk of miscarriage (spontaneous abortion) is inconsistent and nausea during pregnancy has been claimed to explain any association seen. The objective of this analysis was to determine whether caffeine consumption both before and during pregnancy influenced the risk of miscarriage in a group of pregnant women in the UK. We examined the association with maternal caffeine intake in a case–control study of 474 nulliparous women. Participants were recruited during the years 1987–89 from the Royal Berkshire Hospital in Reading and from a large group practice situated within the hospital's catchment area. Cases were 160 women with a clinically diagnosed miscarriage and controls were 314 pregnant women attending for antenatal care. Information on coffee/tea/cola consumption and potential confounders was collected by interview and caffeine content was assigned to individual drinks according to published data on caffeine content of beverages. Compared with a maternal caffeine intake of < 151 mg/day, we found evidence that caffeine consumption > 300 mg/day doubled the risk of miscarriage. Adjusted odds ratios were 1.94 [95% CI 1.04, 3.63] for 301–500 mg/day and 2.18 [95% CI 1.08, 4.40] for > 500 mg/day. This effect could not be explained by nausea in pregnancy. Nausea appeared to be strongly independently associated with a reduced risk of miscarriage (test for trend P < 0.0001). There was no evidence that prepregnancy caffeine consumption affected the risk. Our results indicate that high caffeine consumption during pregnancy (>300 mg/day), in particular coffee consumption, is an independent risk factor for increased risk and nausea is an independent protective factor for a lower risk of miscarriage.
Is midwife workload associated with quality of process of care (continuous electronic fetal monitoring [CEFM]) and neonatal outcome indicators? A prospective study in consultant‐led labour wards in Scotland
Authors: Tucker J. , Parry G. , Penney G. , Page M. , Hundley V.
Published: October 2003

Evidence for staffing recommendations in labour wards is scant. This study aimed to test association between midwife workload with adjusted process of continuous electronic fetal monitoring (CEFM) and neonatal outcome indicators. This was a prospective workload study in 23 consultant‐led labour wards in Scotland. There were 3489 livebirths during September 2000, and 1561 consecutively delivered women with CEFM case review during the mid‐two weeks. Process measures were: adjusted rates of CEFM, appropriate CEFM, and time to medical response for a serious fetal heart trace abnormality. Neonatal outcome indicators were: Apgar score < 7 at 5 minutes, admission to neonatal unit (NNU) > 48 hours, and neonatal resuscitation. Complete information was available for 99% (2553/2576) of workload time points, 99% (1559) of CEFM process, and 3083 eligible neonates. There were no associations between occupancy or staffing ratios and adjusted CEFM process, Apgar < 7 at 5 minutes (0.98 [0.83, 1.15]) or admission to NNU for > 48 hours (0.97 [0.95, 1.00]). However, there was association between increasing staffing ratios and lower odds of adjusted neonatal resuscitation (excluding bag and mask only) (0.97 [0.94, 0.99]). The direction of effect of increasing workload suggests detriment to outcome indicators, although the size of effect may be small.
Correlated evolution of colour pattern and body size in polymorphic pygmy grasshoppers,Tetrix undulata
Authors: Ahnesjö J. , Forsman A.
Published: October 2003

Theory posits that selection on functionally interrelated characters will promote physical and genetic integration resulting in evolution of favourable trait‐value combinations. The pygmy grasshopperTetrix undulata(Orthoptera: Tetrigidae) displays a genetically encoded polymorphism for colour pattern. Colour morphs differ in several traits, including behaviours, thermal biology and body size. To examine if these size differences may reflect phenotypic plasticity of growth and development in response to temperature we used a split brood‐design and reared hatchlings from mothers belonging to different morphs in different thermal environments (warm or cold) until maturity. We found that time to maturity was longer in the cold compared with the warm treatment. In the warm (but not in the cold) treatment time to maturity also varied among individuals born to mothers belonging to different colour morphs. Although low temperature and long development time are normally accompanied by increased body size in ectotherms, our results revealed no difference in size at maturity between individuals reared in the two temperature treatments. There was also an increase (not a decrease) in adult body size with shortened time to maturity across families within each treatment. Taken together, this suggests that body size is canalized against environmental perturbations, and that early maturation does not necessarily trade off against a size‐mediated decrease in fecundity. Heritability of body size was moderate in magnitude. Moreover, body size at maturity varied among individuals belonging to different morphs and was influenced also by maternal colour morph, suggesting that a genetic correlation exists between colour pattern and body size. These findings suggest that different characters have evolved in concert and that the various colour morphs represent different evolutionary strategies, i.e., alternative peaks in a multi‐modal adaptive landscape.