bluuebunny/crossref_metadata_2025 huggingface dataset:
Transmissibility of Trypanosoma brucei during its development in cattle
Authors: Van den Bossche P. , Ky‐Zerbo A. , Brandt J. , Marcotty T. , Geerts S. , De Deken R.
Published: August 2005

Recent outbreaks of Trypanosoma brucei rhodesiense sleeping sickness in Soroti District of eastern Uganda have demonstrated the important role cattle can play as reservoirs of this parasite. To clarify the epidemiological importance of the cattle reservoir, experiments were conducted to determine the ease with which T. brucei is transmitted during the course of its development in Friesian cattle. The development of T. brucei in cattle is characterized by an acute phase with high levels of parasitaemia and a decline in PCV. The acute phase is followed by a chronic phase during which the PCV remains low but stable and the parasitaemia is low. Parasites are often difficult to detect using parasitological diagnostic tools during this chronic phase. Challenge of chronically infected cattle with T. congolense results in a sudden increase in the T. brucei parasitaemia. Despite significant differences in parasitaemia, the proportion of tsetse flies that developed metacyclic infections after a first bloodmeal on the infected cattle did not differ significantly between the acute and chronic phases or the phase of mixed T. b. brucei/T. congolense infection. This suggests that, throughout the observation period, the parasitaemia was above the threshold above which infection rates of tsetse are independent of the parasitaemia. The repercussions of the research findings for the understanding of the epidemiology, spread and the control of T. b. rhodesiense sleeping sickness are discussed.
Susceptibility of Grammomys surdaster thicket rats to Trypanosoma brucei gambiense infection
Authors: Büscher Philippe , Shamamba Stomy Kahremere Bin , Ngoyi Dieudonne Mumba , Pyana Pati , Baelmans Rudy , Magnus Eddy , Overmeir Chantal Van
Published: August 2005

Human African Trypanosomiasis is caused by Trypanosoma brucei gambiense and T. b. rhodesiense. Historically, a treatment relapse rate of about 5% is observed in patients treated with melarsoprol, an arsenical derivative used for treatment of both gambiense and rhodesiense second stage sleeping sickness. More recently, relapse rates up to 30% are noted in gambiense sleeping sickness foci in Angola, Sudan and Uganda. Therefore, WHO established a Network on Treatment Failure and Drug Resistance in Sleeping Sickness. One of its objectives is to improve isolation of T. b. gambiense from relapsing cases for research on drug resistance mechanisms. Trypanosoma b. gambiense isolation techniques suffer from low success rates and long periods needed to adapt the parasite to its new host. Usually, rodents are inoculated with patient's blood or cerebrospinal fluid and sub‐passaged until the strain becomes sufficiently adapted to yield high parasitaemia within few days after inoculation. Until now, the best recipient for T. b. gambiense is Mastomys natalensis, with a success rate of about 50%. In this study, Grammomys surdaster (former Thamnomys surdaster) was investigated as a potential recipient for isolation of T. b. gambiense. Comparative experimental infections of Swiss mice, Wistar rats and G. surdaster thicket rats with T. b. gambiense clearly show that this trypanosome grows faster in G. surdaster. Inoculation of the same rodent species with patient's blood and cerebrospinal fluid in Kinshasa (R.D. Congo) confirms the observation that the thicket rats are more susceptible to T. b. gambiense infection than typical laboratory rodents.
Antenatal syphilis screening in sub‐Saharan Africa: lessons learned from Tanzania
Authors: Watson‐Jones Deborah , Oliff Monique , Terris‐Prestholt Fern , Changalucha John , Gumodoka Balthazar , Mayaud Philippe , Semakafu Ave Maria , Kumaranayake Lilani , Gavyole Awene , Mabey David , Hayes Richard
Published: August 2005

Objectives  To synthesise data from four recent studies in Tanzania examining maternal syphilis screening and its operational implementation in routine antenatal clinics (ANC), drawing lessons for strengthened antenatal services for the prevention of mother‐to‐child transmission (PMTCT) of HIV.

Methods  The impact of untreated maternal syphilis was examined in a retrospective cohort of 380 Tanzanian women. Effectiveness and cost‐effectiveness of screening and single dose benzathine penicillin treatment were prospectively examined in 1688 pregnant women. Observation, interviews and facility audits were carried out in health facilities within nine districts to determine the operational reality of syphilis screening.

Results  Overall, 49% of women with untreated high titre syphilis experienced an adverse pregnancy outcome compared with 11% of uninfected women. Stillbirth and low birthweight rates among those treated for high‐ or low‐titre syphilis were reduced to rates similar to those for uninfected women. The economic cost was $1.44 per woman screened and $10.56 per disability‐adjusted life year saved. In the operational study, only 43% of 2256 ANC attenders observed were screened and only 61% of seroreactive women and 37% of their partners were treated. Adequate training, continuity of supplies, supervision and quality control are critical elements for strengthened antenatal services, but are frequently overlooked.

Conclusions  Maternal syphilis has a severe impact on pregnancy outcome. Same‐day screening and treatment strategies are clinically effective and highly cost‐effective, but there are significant challenges to implementing syphilis screening programmes in sub‐Saharan Africa. Current PMTCT interventions present an opportunity to reinforce and improve syphilis screening. Increasing PMTCT coverage will involve similar operational challenges to those faced by syphilis screening programmes.
Epidemiological assessment of mucocutaneous infections in patients with recurrent infection syndrome
Authors: Orrego Julio C. , Montoya Carlos J. , Gómez Rubén D. , Franco José L. , Patiño Pablo J. , Vargas María E. , García de O Diana , Wolff Juan C.
Published: August 2005

Background  Recurrent infection syndrome (RIS) results from repeated interactions between hosts and environmental infectious agents and is considered normal (NRIS) because of its benign evolution and positive effects in the development of normal immune responses. Abnormal RIS (ARIS) is characterized by the unusually high frequency of severe infections, either as a result of anatomical or functional abnormalities or due to primary or secondary immunodeficiencies (PIDs and SIDs, respectively). Recurrent mucocutaneous infections (MCIs) can be manifestations of RIS or ARIS and could be more frequent in primary immunodeficiencies. Similarly, etiologic agents might vary from what is observed in the general population.

Methods  We carried out a descriptive study to determine the prevalence of aerobic bacterial and fungal mucocutaneous infections in 452 patients with recurrent infections, using clinical records to establish immunological status associated with the presence and characteristics of the infections. Microbiological analyses from mucocutaneous lesions were used to confirm the etiology.

Results  We found mucocutaneous infections in 50 patients for a total of 62 episodes (bacterial or fungal infections in 38 vs. 12 patients, respectively). Mucocutaneous infections were more frequent (21.8% vs. 9.1%; OR = 2.8) and recurrent (8.7% vs. 0.2%; P= 0.000) in primary immunodeficient patients. Furthermore, those with defects in phagocytic cells presented more mucocutaneous infections (56.2%) than patients with other primary immunodeficiencies (11.3%; OR = 10.1).

Conclusions  Bacterial and fungal mucocutaneous infections are more frequent and severe in primary immunodeficient patients, particularly those with defective phagocytosis. Early and adequate assessment of the nature of mucocutaneous infections in ARIS should impact the ability of physicians to treat promptly, avoid complications and reduce the costs of medical assistance.
Narrow‐band UVB311 nm vs. broad‐band UVB therapy in combination with topical calcipotriol vs. placebo in vitiligo
Authors: Hartmann Anke , Lurz Christa , Hamm Henning , Bröcker Eva‐B. , Hofmann Uta B.
Published: August 2005

Background  Recently, it has been shown that UVB phototherapy may be more effective than UVA in the treatment of vitiligo. Currently, however, no studies have compared the efficacy of UVB311 nm and broad‐band UVB therapy. Calcipotriol has recently been reported to be effective adjunctive treatment for vitiligo, enhancing the efficacy of 8‐methoxypsoralen plus UVA (PUVA) therapy.

Methods  Ten patients were enrolled in the study; nine completed the 12 months of therapy. The upper part of the body was treated twice weekly with UVB311 nm and the lower part with broad‐band UVB. Calcipotriol was applied onto the vitiligo lesions of the right side of the body and placebo on the left side. Repigmentation was documented by photography, planimetry, and Vitiligo Disease Activity (VIDA) score. The quality of life was measured by the Dermatology Life Quality Index (DLQI).

Results  After 7–16 weeks, six of the nine patients showed initial repigmentation on the side treated with UVB311 nm. After 6 months of treatment, none of the patients showed repigmentation on the areas treated with broad‐band UVB, which prompted us to apply UVB311 nm all over the body. At the end of 12 months, two patients showed > 75% repigmentation, two showed 51–75%, two showed 26–50%, and three showed 0–25%. In all patients with progressive vitiligo (seven of the nine patients), disease activity was stopped. Remarkably, vitiligo lesions treated with calcipotriol initially showed delayed repigmentation compared with control areas; however, there was no therapeutic difference between calcipotriol and placebo, both in combination with UVB311 nm, by the end of the study. The DLQI score improved significantly by an average of 28%.

Conclusion  UVB311 nm therapy was effective in the treatment of vitiligo, whereas broad‐band UVB had no effect. Combination with calcipotriol ointment was not superior to UVB311 nm monotherapy. The quality of life significantly improved with narrow‐band UVB311 nm phototherapy.
The relationship between lichen planus and hepatitis C in dermatology outpatients in Kerman, Iran
Authors: Rahnama Zahra , Esfandiarpour Iraj , Farajzadeh Saideh
Published: August 2005

Background  Lichen planus (LP) is classified as a papulosquamous disease. It has been associated with liver disease, particularly hepatitis C virus (HCV) infection, in several studies. Most of these reports, especially the larger series, were conducted in Europe and Japan.

Objective  We conducted a case–control study in Kerman, Iran to explore the association between LP and HCV.

Methods  The study included 66 patients with LP (as cases; mean age = 39.7 ± 15.8 years; 31 female, 35 male) and 140 volunteer blood donors (as controls; mean age = 29.5 ± 8.4 years; 43 females, 97 males). An enzyme‐linked immunosorbent assay (ELISA) was used to determine the presence of anti‐HCV antibodies in all subjects in both groups. To confirm positive diagnoses, a second generation recombinant immunoblot assay (RIBA II) test was performed.

Results  Lichen planus lesions were most frequently located on the trunk and extremities, and the most common clinical type was generalized LP (48.5%). One of the patients with LP (1.5%) and three of the controls (2.1%) were HCV‐Ab positive. No significant difference was observed in HCV‐Ab positive between the two groups (OR = 0.7; 95% CI = 0.1–6.9).

Conclusion  The findings indicate that an investigation for HCV infection should not necessarily be performed in all patients with LP. It is recommended that further studies should focus on larger groups in other regions of Iran to determine whether testing for HCV infection is necessary in patients with LP.
Classic Kaposi's sarcoma in Sardinia: HLA positive and negative associations
Authors: Masala Maria Vittoria , Carcassi Carlo , Cottoni Francesca , Mulargia Marina , Contu Licinio , Cerimele Decio
Published: August 2005

Background  The incidence of classic Kaposi's sarcoma (CKS) in northern Sardinia is one of the highest in the world.

Methods  Sixty‐two patients with CKS were typed for class I and class II antigens. All patients had been born and were living in northern Sardinia.

Results  In the Sardinian patients, we observed a positive CKS association with Cw7, DRB1*1104, DRB1*1302, DQA1*0302, and DQB1*0604, and a negative CKS association with A30, B58, Cw5, DRB1*1601, and DQB1*0502.

Conclusions  The strong positive CKS association with DRB1*1104 and DQB1*0604 and negative association with B58 are particularly significant and further support the notion of a genetic predisposition to CKS.
Finger pebbles in a diabetic patient: Huntley's papules
Authors: Guarneri Claudio , Guarneri Fabrizio , Borgia Francesco , Vaccaro Mario
Published: August 2005

A 60‐year‐old obese man was referred to our department from the internal medicine unit. He had a 20‐year history of poorly controlled diabetes (no other cases in the family), and was admitted to hospital because of respiratory and consequent heart failure.

Skin examination showed diffuse xerosis and a rough, sandpaper‐like appearance of the skin of the finger, of approximately 15 years’ duration, consisting of multiple, minute, hyperkeratotic papules grouped in a miniature “cobblestone” pattern on the dorsum of the distal phalanges (Fig. 1), more dense over the knuckles and the interphalangeal joints. No pruritus was present.

Pebbly pattern of the skin on the dorsum of the second digit

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He was a pensioner, who had been physically inactive for months previously, and this condition had occurred progressively in the absence of any known trauma. No other cutaneous manifestations were evident.

Histologic examination was performed using hematoxylin and eosin staining of a biopsy specimen taken from the left second finger; it displayed a hyperorthokeratotic epidermis with enlarged dermal papillae, thickened and vertically oriented collagen bundles, few elastic fibers, and a mild perivascular inflammatory infiltrate (Fig. 2).

Histologic view of a biopsy specimen of the skin of the finger: the epidermis is hyperkeratotic, the dermal papillae are enlarged and there are thickened vertical collagen bundles, elastic fibers, and a mild perivascular inflammatory infiltrate (hematoxylin and eosin stain; original magnification, ×100)

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Treatment of cutaneous leishmaniasis with cryosurgery
Authors: Panagiotopoulos Antonios , Stavropoulos Panagiotis G. , Hasapi Vassiliki , Papakonstantinou Anastasia‐Metaxia , Petridis Athanassios , Katsambas Andreas
Published: August 2005

Background  The management of cutaneous leishmaniasis with topical methods, if effective, can spare patients from long and costly inpatient treatments.

Methods  Seventeen patients with cutaneous leishmaniasis were treated with cryosurgery using liquid nitrogen as the cryogen. Two cycles of 10–30 s freezing time were used and repeated at 3‐week intervals.

Results  All patients responded well to therapy with excellent cosmetic results and no relapse in any case. Side‐effects were rare.

Conclusions  Cutaneous leishmaniasis can be successfully treated with a simple protocol of cryosurgery with minor side‐effects.
Novel thioester reagents afford efficient and specific S‐acylation of unprotected peptides under mild conditions in aqueous solution
Authors: Sang S. Leung Wai , Silvius J.R.
Published: August 2005

Abstract:  S‐acylated peptides have many potential uses for elucidating the biophysical, structural and other properties of the numerous S‐acylated proteins of mammalian cells. However, with the currently available reagents, preparation of specifically S‐acylated derivatives of peptides is generally laborious or simply unfeasible. We here show that novel, easily preparable aryl and alkyl thioester derivatives of palmitic acid can mediate S‐acylation of peptides corresponding to physiologically S‐acylated sequences from the proteins p56lck and H‐ras and the Po glycoprotein of peripheral myelin, with high selectivity for cysteine over other amino acid functional groups (including hydroxyl and both α‐ and ɛ‐amino residues), and with much greater efficiency than is obtained using acyl‐coenzyme A derivatives. Efficient and selective S‐acylation can be accomplished under very mild conditions in aqueous systems containing lipid vesicles or detergent micelles, or in homogenous aqueous/acetonitrile mixtures. Using these novel thioesterifying reagents, we confirm previous suggestions that the N‐terminal cysteine residue of Hedgehog proteins can exhibit rapid, uncatalyzed S‐to‐N acyl transfer following S‐acylation to produce the N‐palmitoylated amino terminus found in the mature protein. By contrast, we demonstrate that spontaneous S‐to‐N acyl transfer from the cysteine to the terminal glycine residue in the amino‐terminal peptide of Gαs is far less rapid and is likely too slow to explain the physiological N‐palmitoylation of the amino terminus of this protein.
Characterization of naturally occurring peptides in the skin secretion of Rana pipiens frog reveal pipinin‐1 as the novel insulin‐releasing agent
Authors: Marenah L. , Flatt P. R. , Orr D. F. , Shaw C. , Abdel‐Wahab Y .H. A.
Published: August 2005

Abstract:  Naturally occurring insulinotropic peptides were isolated from the skin secretions of Rana pipiens frogs. Crude secretions (50 mg; 5–10 frogs) obtained by mild electrical stimulation of the dorsal skin surface were purified by reversed‐phase high‐performance liquid chromatography (HPLC) yielding 80 fractions. In acute incubations with glucose‐responsive BRIN‐BD11 cells, fractions 40–47 (band 1) and fractions 60–65 (band 2) showed significant 1.7–6.7‐fold increases in insulin‐releasing activity (P < 0.001) compared with 5.6 mm glucose alone. Pooled fractions in bands 1 and 2 were rechromatographed yielding a total of seven peaks capable of subsequent 1.2–1.8‐fold stimulation of insulin release. Final purification by HPLC to single homogenous peaks revealed one prominent peptide (peak 4.1) with insulin‐releasing activity which lacked effects on cell viability. Electrospray mass spectrometric analysis of this peptide indicated molecular mass of 2562.6 Da. Determination of the primary amino acid sequence of this peptide revealed a 24‐amino acid sequence: FLPIIAGVAAKVFPKIFCAISKKC. Database search showed a 100% homology to histamine‐releasing pipinin‐1. In conclusion, this study revealed the skin secretions of Rana pipiens to be a rich source of insulin‐releasing peptides. The discovery of insulinotropic activity for pipinin‐1, initially characterized as an antimicrobial is interesting and merits further investigation.
Synthesis and evaluation of peptidic metal chelators for neuroprotection in neurodegenerative diseases
Authors: Zheng H. , Youdim M. B. H. , Weiner L. M. , Fridkin M.
Published: August 2005

Abstract:  A series of novel derivatives of neuropeptides with a metal‐chelating moiety was synthesized and examined for various properties related to iron (Fe) chelation and neuroprotective action. All derivatives chelated Fe to form stable Fe complexes in water. Some strongly inhibited Fe‐induced lipid peroxidation with an IC50 value of about 12 μm. In PC12 cell culture, several compounds, at concentrations as low as 1 μm, attenuated serum‐free stimulated cell death and improved cell survival by 20–35%. At this concentration, these analogs also protected against 6‐hydroxydopamine (6‐OHDA)‐induced cell death, increasing cell viability by 20–30%. Electron paramagnetic resonance (EPR) studies indicated that besides being good Fe chelators, these analogs act as radical scavengers to directly scavenge hydroxyl radicals. Together, the data indicate that some of the analogs could be further developed as possible neuroprotective agents for treatment of neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's diseases, Friedreich's atxia, amyotrophic, and lateral sclerosis where Fe misregulation has been reported.
Angioedema from angiotensin‐converting enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrate
Authors: Nielsen E. W. , Gramstad S.
Published: August 2005

Background:  Up to seven in every 1000 patients experience angioedema from angiotensin‐converting enzyme (ACE) inhibitors, even after many years of use. In 2003, every 20th Norwegian used an ACE inhibitor.

Case report:  A 61‐year‐old woman with chronic obstructive pulmonary disease and a past acute myocardial infarction had used 7.5 mg of ramipril daily for the past 7 years. She also used acetylsalicylic acid, simvastatin, theophylline and salmeterol. One night she woke up with edema of the tongue. On hospital arrival, 250 mg of hydrocortisone and 5 mg of dexchlorpheniramine were given intravenously (i.v.) and 0.3 mg of epinephrine was given subcutaneously (s.c.). The edema of the tongue progressed over the next 8 h and made the tongue protrude. Fiberscopy revealed glassy edema of the arytenoids. Inspiratory stridor was heard and the patient could not speak. She became increasingly uneasy and restless. Berinert® complement 1 (C1) inhibitor concentrate (1500 units) was administered i.v. Over the following 20 min, stridor gradually subsided, the patient calmed and she was able to talk.

Discussion:  ACE inhibitor‐provoked angioedema shares many clinical features with hereditary angioedema (HAE), including a limited effect of steroids, antihistamines and epinephrine. HAE, caused by excess bradykinin formation as a result of C1 inhibitor deficiency, usually has its laryngeal edema effectively reversed by C1 inhibitor in less than 0.5 h. Although patients experiencing ACE inhibitor‐provoked angioedema have normal C1 inhibitor values, as in our patient, excess bradykinin is probably important as ACE breaks down bradykinin. It is unknown why ACE inhibitor‐provoked angioedema appears in some and sometimes after many years of use.

Conclusion:  We believe that C1 inhibitor was effective in reversing the ACE inhibitor‐induced angioedema in our patient.
High success rate and low incidence of headache and neurological symptoms with two spinal needle designs in children*
Authors: Kokki H. , Turunen M. , Heikkinen M. , Reinikainen M. , Laisalmi M.
Published: August 2005

Background:  In children, only a few trials have evaluated the use of spinal needles with special tip designs. In this study, we compared the success rate and incidence of post‐dural puncture complaints of two small‐gauge spinal needle designs used in children undergoing spinal anaesthesia (SA).

Methods:  Three hundred and three children aged 9 months to 17 years presenting for subumbilical surgery were randomly assigned to have a 26G Atraucan (n = 156) or 27G Whitacre (n = 147) spinal needle for SA. The number of attempts to obtain successful cerebrospinal fluid (CSF) return and the success rate of SA were recorded. The first week of recovery was recorded by a diary.

Results:  Both groups had a similar one‐attempt success rate: 80% in the Atraucan group and 81% in the Whitacre group. Failure to obtain CSF occurred in one patient in the Atraucan group and in two patients in the Whitacre group. Paraesthesia was observed more commonly in the Whitacre group (10%) than in the Atraucan group (2%) (P = 0.004). The success rate of SA was 96%, with no differences between the two needles; one child was given general anaesthesia and 11 children (3%) a single dose of supplemental analgesia for the skin incision. Forty‐one children (15%) developed a headache, 13 of which were classified as post‐dural puncture headache (PDPH), seven cases (5%) in the Atraucan group and six (4%) in the Whitacre group; none of the children required a blood patch. Fifteen children (10%) in the Atraucan group and nine (7%) in the Whitacre group developed low back pain. Two children (1%) in the Atraucan group and four (3%) in the Whitacre group developed transient neurological symptoms (TNSs).

Conclusion:  Both needles were associated with a high success rate and a low incidence of complaints.
Factors explaining the intention to give blood among the general population
Authors: Godin G. , Sheeran P. , Conner M. , Germain M. , Blondeau D. , Gagné C. , Beaulieu D. , Naccache H.
Published: August 2005

Background and Objectives  The aim of this study was to identify factors explaining the intention to donate blood.

Materials and Methods  A random sample of 4000 respondents drawn from the general population received a questionnaire by mail. This questionnaire assessed variables as defined by the most prominent social cognitive theories.

Results  Overall, the respondents expressed a neutral mean level of intention to give blood in the next 6 months (2·84 on a five‐point scale); 56·2% had never given blood in the past. The variables explaining 74% of the variance of intention were: perceived behavioural control (β = 0·39; P < 0·001); factors facilitating taking action (β = 0·25; P < 0·001); anticipated regret (β = 0·16; P < 0·001); moral norm (β = 0·11; P < 0·001); attitude (β = 0·08; P < 0·01); level of education (β = −0·03; P < 0·05); and past experience in giving blood (β = 0·09; P < 0·001). Nonetheless, the predictive power of perceived behavioural control and moral norm was higher among the ever donors (both at P < 0·01) compared to the never donors, whereas the reverse was observed for attitude (P < 0·05).

Conclusions  People's intentions are mainly determined by perceived barriers and obstacles regarding blood donations. This suggests that promotional strategies should focus on the elimination of barriers to action as well as the development of a higher perception of control. Also, messages should be adapted to the targeted population, based on their previous blood donation behaviour (i.e. never donors vs. ever donors).
Dissociation in the effect of nedocromil on mannitol‐induced cough or bronchoconstriction in asthmatic subjects*
Authors: KOSKELA Heikki O. , MARTENS Ruth , BRANNAN John D. , ANDERSON Sandra D. , LEUPPI Joerg , CHAN Hak‐Kim
Published: August 2005

Objective:  Inhaled mannitol induces both bronchoconstriction and cough. Nedocromil sodium greatly attenuates mannitol‐induced bronchoconstriction. Knowledge about the effect of nedocromil on mannitol‐provoked cough might, therefore, clarify the mechanisms of this response.

Methodology:  Inhalation challenges with mannitol powder were performed after inhalation of 8 mg of nedocromil or its placebo in 24 subjects with asthma. The study was double‐blind, randomised, and placebo‐controlled. The mannitol‐provoked coughs were manually recorded and the mannitol‐induced bronchoconstriction was measured with a spirometer.

Results:  The cumulative dose of mannitol that provoked at least two coughs tended to be higher on the nedocromil day than on the placebo day (34 (22–53) mg vs 26 (18–37) mg, P = 0.051). The cumulative number of coughs per dose of mannitol was slightly, but significantly, lower on the nedocromil than on the placebo day (4.2 (2.8–6.3) coughs/100 mg vs 6.1 (4.0–9.4) coughs/100 mg, P = 0.037). However, when analysed on a constant‐dose basis, nedocromil provided no protection for coughing (−1% protection), whereas the protection for bronchoconstriction was clear (55% protection).

Conclusions:  Nedocromil strongly attenuates mannitol‐induced bronchoconstriction but has a negligible effect on mannitol‐provoked cough. Therefore, these responses seem to have different pathways in asthma. Recording of both provoked coughs and induced bronchoconstriction during mannitol challenge may provide supplementary information about a patient's disease.
A pilot study of aerosolized N‐acetylcysteine for idiopathic pulmonary fibrosis
Authors: TOMIOKA Hiromi , KUWATA Youichirou , IMANAKA Kazufumi , HASHIMOTO Kimio , OHNISHI Hisashi , TADA Kimihide , SAKAMOTO Hiroko , IWASAKI Hironobu
Published: August 2005

Objective:  Idiopathic pulmonary fibrosis poses a significant therapeutic challenge because of its progressive course. Since oxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis, an open, randomized trial of long‐term inhalation therapy with the antioxidant, N‐acetylcysteine was conducted.

Methodology:  A total of 30 patients with idiopathic pulmonary fibrosis were randomly assigned to one of the following inhalation therapies: N‐acetylcysteine (352 mg per day) or bromhexine hydrochloride (4 mg per day) as the control. Efficacy was assessed by analysing changes occurring from baseline to 12 months in pulmonary function, the 6‐min walking test, high‐resolution CT, health‐related quality of life, and serum KL‐6‐values.

Results:  Four patients (n = 2 in each group) died within 12 months due to progression of idiopathic pulmonary fibrosis. A total of 22 patients (control, n = 12; N‐acetylcysteine, n = 10) completed the study. At 12 months there were significant differences between the N‐acetylcysteine and control groups in terms of mean changes in lowest SaO2 during the 6‐min walking test (−0.3 ± 2.1% vs −6.8 ± 1.8%, P < 0.05), serum KL‐6 (−482 ± 220 U/mL vs 176 ± 204 U/mL, P < 0.05), and the ground‐glass score on high‐resolution CT (−1.3 ± 1.6 vs 6.7 ± 1.5, P < 0.01). No significant differences were observed in pulmonary function, 6‐min walking distance or quality of life.

Conclusions:  These data suggest that although long‐term aerosolized N‐acetylcysteine administration did not influence pulmonary function or quality of life, it may delay disease progression as evidenced by exercise desaturation, high‐resolution CT, and serum KL‐6.
Effects of ambient particulate matter on peak expiratory flow rates and respiratory symptoms of asthmatics during Asian dust periods in Korea
Authors: PARK Jeong Woong , LIM Young Hee , KYUNG Sun Young , AN Chang Hyeok , LEE Sang Pyo , JEONG Seong Hwan , JU Young‐Su
Published: August 2005

Objective:  Dust generating events frequently produce ambient dust particles that are less than 10 µm in diameter, and these have been linked to adverse effects in the general population. However, the evidence linking these particles to adverse effects on the airways of asthmatic individuals is limited. The objective of this study was to investigate the possible adverse effects of Asian dust events on the respiratory functions and symptoms of subjects with bronchial asthma.

Methodology:  From March to June 2002, individuals were enrolled who had been diagnosed as having asthma by bronchial challenge or by their bronchodilator response. The patients were divided into three groups according to asthma severity: mild, moderate and severe. Patients with other major disease states were excluded. Patients completed twice‐daily diaries monitoring PEF, respiratory symptoms, and daily activities. The daily and hourly mean levels of particulate matter <10 µm in diameter (PM10), as well as nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and carbon monoxide (CO) were measured at 10 monitoring sites in Incheon, Korea.

Results:  Dust events occurred 14 times during the study period. On dusty days there were increased levels of PM10, decreased levels of NO2 and SO2, and no change in the CO levels, compared to the levels on control days. An increase in PM10 concentration was associated with increases in PEF variability of >20% (P < 0.05), more night‐time symptoms (P < 0.05), and a decrease in the mean PEF (P < 0.05), calculated by longitudinal data analysis. In contrast, there was no association between the PM10 levels and bronchodilator inhaler use or daytime respiratory symptoms. Using a general additive Poisson regression model, a borderline association was noted between PM10 and respiratory symptoms, with a relative risk of 1.05 (95% confidence interval (CI), 0.99–1.17). There was no association between the PM10 concentrations and PEF measurements, with PEF variability of >20% between the morning and evening values and a relative risk of 1.05 (95% CI, 0.89–1.24) in all subjects.

Conclusions:  This study provides evidence that Asian dust events are impacting on the respiratory symptoms of subjects with bronchial asthma, and ambient air pollution, particularly elevated PM10, might be one of the aggravating factors.
Endobronchial metastases: a clinicopathological analysis
Authors: DURSUN Adile Berna , DEMIRAG Funda , BAYIZ Hulya , SERTKAYA Durdu
Published: August 2005

Objective:  It is important to distinguish endobronchial metastases (EBM) from both primary lung cancers and benign lesions, as treatment will differ. The clinicopathological characteristics of EBM cases were documented to see whether any distinguishing features exist.

Methodology:  Histological cases diagnosed as EBM in the pathology laboratory of a tertiary hospital were re‐evaluated. Symptoms, primary tumour sites, recurrence interval, radiological and bronchoscopic features, and histopathological properties were assessed.

Results:  There were 18 cases (eight female, 10 male) with EBM. All were diagnosed by bronchoscopic bronchial biopsy. The primary tumour sites were: colorectal (4), breast (3), renal (3), lymphoma (3), rhabdomyosarcoma (2), bladder (1), thyroid (1) and malignant melanoma (1). The mean time from the diagnosis of the primary tumour to their presentation was 3.89 ± 1.09 (range, 0–19) years. In five patients, EBM was diagnosed synchronously with their extra pulmonary primary tumour. Two had other metastatic sites. Haemoptysis and cough were the more common symptoms. Interestingly, three patients were asymptomatic. There was no predilection for a particular airway segment to be involved but a predilection for the upper lobe existed. Endoscopic appearance was polypoid in 10 cases and mucosal infiltration in the remainder. Histopathological examination revealed epithelial tissue at the surface of the tumour in nine cases and four of these were metaplastic. In all but one there was inflammation, mainly lymphocytic. Necrosis was present in 10 cases and bleeding was seen in four. There were no statistically significant differences between the level of lymphocytic inflammation and other clinicopathological parameters.

Conclusion:  EBM is a rare condition that can be synchronous or occur late. Surprisingly, it can be asymptomatic. It is usually found in the upper lobes. Lymphocytic inflammation is a common histopathological finding. There is need for further studies to clarify the clinical importance of EBM.
Inhaled corticosteroid for persistent cough following upper respiratory tract infection
Authors: PORNSURIYASAK Prapaporn , CHAROENPAN Poonkasem , VONGVIVAT Kulanee , THAKKINSTIAN Ammarin
Published: August 2005

Objective:  The aim of this study was to determine the clinical effect of inhaled corticosteroid treatment for persistent cough, post upper respiratory tract infection (URTI) in previously healthy individuals, and on bronchial hyperresponsiveness (BHR).

Methodology:  This was a prospective, randomized, double‐blinded, placebo‐controlled study conducted at a university hospital. A total of 30 non‐asthmatic, non‐smoking patients who were >15 years old and who had persistent post‐URTI cough for >3 weeks were assessed by a physical examination, CXR and spirometry, and were allocated to receive inhaled budesonide (400 µg/puff, twice daily) or placebo for 4 weeks. If a patient suffered from sinusitis, it was a requirement that it had been well treated. A symptom score (frequency of cough, frequency of coughing bouts, symptoms associated with cough, night‐time cough, frequency of taking medications to relieve cough, and number of medications) was recorded at entry, and after 2 and 4 weeks of treatment. A methacholine challenge test was performed at entry and after 4 weeks of treatment.

Results:  The mean symptom scores for the treatment group (9.4) and the placebo group (9.8) at baseline were not significantly different (P = 0.79), and no differences were found between the groups after week 2 and week 4 of treatment (3.93 and 4.27 vs 2.26 and 2.66, P = 0.29). The mean change in symptom scores from baseline to week 2 and to week 4 of treatment were also not different between groups (5.93 and 5.6 vs 7.00 and 7.58, P = 0.23). No difference between groups was found in the mean changes in FEV1, FVC, and FEF25–75% after 4 weeks of treatment. A positive bronchial provocation test occurred in three patients (10%) but these were borderline.

Conclusion:  Inhaled corticosteroid is ineffective in treating persistent post‐URTI cough in previously healthy individuals.
A case of non‐specific interstitial pneumonia effectively treated with a combination of prednisolone and colchicine, in which granulation tissue was extensive
Authors: ISHIZUKA Tamotsu , HISADA Takeshi , MONDEN Tsuyoshi , TSUNEKAWA Katsuhiko , IIZUKA Kenichi , TSUKAGOSHI Hideo , DOBASHI Kunio , MORI Masatomo
Published: August 2005

Abstract:  A 56‐year‐old woman was admitted for interstitial pneumonia, and subsequently diagnosed with idiopathic non‐specific interstitial pneumonia with a bronchiolitis obliterans organizing pneumonia pattern, on the basis of clinical and surgical lung biopsy findings. Histological findings revealed diffuse thickness of alveolar walls accompanied by lymphocyte infiltration and fibrosis in the lobules. In addition to those findings, granulation tissue was extensive. Although initial symptom and CT improvement occurred following high‐dose prednisolone therapy, the CT did not show further improvement and her serum KL‐6 level began increasing again as prednisolone was reduced. With the addition of colchicine therapy, clinical and CT findings improved remarkably and a further reduction of the prednisolone dose was achieved. This case suggests that the combination of colchicine and corticosteroids may be an effective therapy for non‐specific interstitial pneumonia.
Rigid and semirigid pleuroscopy: The future is bright
Authors: LEE Pyng , COLT Henri G.
Published: August 2005

Abstract:  Pleuroscopy provides the pulmonologist with a unique opportunity to visualize the contents of the pleural space, perform biopsy of the parietal pleura under direct visual guidance, allow optimal chest tube placement and perform pleurodesis to prevent recurrent pleural effusion or pneumothorax in selected patients. We discuss the techniques, indications, contraindications and complications of pleuroscopy using rigid and semirigid instruments. In addition, the potential value and expanding role of pleuroscopy with semirigid instrumentation is debated.
Mucociliary clearance in patients with chronic asthma: Effects of β2 agonists
Authors: DAVISKAS Evangelia , ANDERSON Sandra D. , SHAW Janet , EBERL Stefan , SEALE J. Paul , YANG Ian A. , YOUNG Iven H.
Published: August 2005

Objective:  Chronic asthma is characterized by airway inflammation, mucus hypersecretion and impaired mucociliary clearance (MCC). We investigated baseline MCC and the acute effect of terbutaline in chronic asthmatics with sputum production while on long‐term treatment with salmeterol in combination with inhaled corticosteroids (ICS).

Methodology:  MCC was measured at baseline and in response to 1 mg terbutaline (or placebo) on three visits over 80 min in 16 asthmatics (52 ± 13 years of age). Subjects who had greater than 10% absolute increase in MCC above baseline and placebo, after terbutaline, were categorized in group A and subjects who had less than 10% in group B.

Results:  In group A subjects (n = 6), MCC increased from 23.7 ± 4.0% at baseline to 43.7 ± 4.9% with terbutaline (P < 0.0001) and to 34.4 ± 5.7% with placebo (P < 0.01). In group B subjects (n = 10), MCC remained similar: 11.3 ± 3.2% at initial baseline, 12.0 ± 3.2% with terbutaline and 7.3 ± 3.0% with placebo (P > 0.05). Group B subjects withdrew from all β2 agonists for a week and MCC was remeasured. After withdrawal, baseline MCC (7.0 ± 1.8%) was similar to the initial baseline value (P > 0.1) and MCC with terbutaline (15.8 ± 4.9%) was greater than baseline (P < 0.005) but remained abnormal in most subjects. Baseline percentage predicted FEV1 and FEF25−75% were 77.3 ± 7.2 and 41.7 ± 5.6 in group A and 59.9 ± 8.1 and 29.5 ± 8.4 in group B subjects, respectively.

Conclusion:  MCC was impaired in most of these asthmatics with persistent airway obstruction and sputum production, despite regular treatment with ICS and salmeterol. In addition, there was little or no stimulation of MCC acutely after terbutaline in most of these asthmatics.
A prospective, multicentre clinical trial comparing cisplatin plus gemcitabine with cisplatin plus etoposide in patients with locally advanced and metastatic non‐small cell lung cancer
Authors: GOKSEL Tuncay , HATIPOGLU Osman Nuri , OZTURK Can , GORGUNER Metin , KIYIK Murat , YILMAZ Ugur , GUZELANT Asuman , TASBAKAN Sezai , TABAKOGLU Erhan , FIRAT Hikmet , TUTAR Umit , CIKRIKICIOGLU Sadettin , AKKOCLU Atila , SOYER Serdar , CAKIR Ebru , ITIL Oya , SANAL Salahattin
Published: August 2005

Objective:  Cisplatin‐gemcitabine (PG) and cisplatin‐etoposide (PE) combinations are active regimens for non‐small cell lung cancer (NSCLC). The present study aimed to compare PG with PE in the treatment of patients with stage IIIB and IV NSCLC.

Methodology:  We conducted a prospective, multicentre trial. A total of 166 patients were enrolled into the study and received either gemcitabine (1000 mg/m2) on days 1, 8 and 15 plus cisplatin (80 mg/m2) on day 2 every 4 weeks, or etoposide (100 mg/m2) on days 1, 2 and 3 plus cisplatin (80 mg/m2) on day 1 every 3 weeks.

Results:  The overall response rate was superior in the PG group (54.8%vs 39.0%, P = 0.045). There was no significant difference in survival between the two groups, with respective median and 1‐year survival of 38 weeks and 33.3% for the PG group, and 34 weeks and 23.2% for the PE group. There was also no statistical difference for time to progression between the two groups. Neutropenia and thrombocytopenia were seen more frequently in the PG group (grade 3 neutropenia, 33.3%vs 15.9%, P = 0.012; grade 3 thrombocytopenia, 27.4%vs 3.7%, P < 0.001 and grade 4 thrombocytopenia, 10.7%vs 1.2%, P = 0.018).

Conclusion:  PG is an active chemotherapy regimen and has a better response rate than PE in advanced NSCLC, although there was no difference in time to progression and overall survival. A higher incidence of haematological toxicity was seen with PG than with PE.
Contribution of aspirin‐intolerant asthma to near fatal asthma based on a questionnaire survey in Niigata Prefecture, Japan
Authors: YOSHIMINE Fumitoshi , HASEGAWA Takashi , SUZUKI Eiichi , TERADA Masaki , KOYA Toshiyuki , KONDOH Ariyoshi , ARAKAWA Masaaki , YOSHIZAWA Hirohisa , GEJYO Fumitake
Published: August 2005

Objective:  Prevention of deaths due to asthma is one of the most important issues in asthma management. However, there are few epidemiological studies of asthma deaths in Japan.

Methodology:  Over an 8‐week period in Niigata Prefecture, Japan, a questionnaire on asthma control and emergency episodes was administered to adult asthmatic patients. A questionnaire was also given to the patients’ physicians to obtain further clinical information. Patients who became unconscious during episodes of asthma, or who required intubation and ventilation, were allocated to a near‐fatal asthma group (NFA). Patients who did not fulfill these criteria were allocated to the non‐NFA group. The NFA group was divided into two subgroups, based on the date of their last NFA episode (old NFA ≥ 5 years and recent NFA < 4 years).

Results:  Characteristic features of the NFA group included severe disease (23.1%vs 7.6%) with more aggressive patient management, including inhaled corticosteroid use (84.3%vs 72.0%). Multiple regression analysis confirmed that aspirin‐intolerant asthma (AIA) was strongly associated with NFA. There was no difference in the incidence of AIA between the recent and old NFA patients. This suggests the incidence of AIA in NFA did not improve over time.

Conclusions:  A history of AIA may be a useful indicator of potential NFA and allow preventative methods to be introduced. It is therefore important to obtain a history of AIA and to be aware of the risk of NSAID administration to these patients.
Case‐control study of medical history and idiopathic pulmonary fibrosis in Japan
Authors: MIYAKE Yoshihiro , SASAKI Satoshi , YOKOYAMA Tetsuji , CHIDA Kingo , AZUMA Arata , SUDA Takafumi , KUDOH Shoji , SAKAMOTO Naomasa , OKAMOTO Kazushi , KOBASHI Gen , WASHIO Masakazu , INABA Yutaka , TANAKA Heizo ,   THE JAPAN IDIOPATHIC PULMONARY FIBROSIS STUDY GROUP
Published: August 2005

Objectives:  A few epidemiological studies have indicated that a patient's past medical history may contribute to the risk of developing idiopathic pulmonary fibrosis (IPF). A relationship between a history of selected disorders and the risk of IPF was assessed in a multicentre hospital‐based case‐control study in Japan.

Methodology:  Included in the study were 104 patients of IPF, aged 40 years or over, who had been diagnosed within the previous 2 years, in accordance with the most recent criteria. Control subjects, aged 40 years or over, consisted of 56 hospitalized patients diagnosed as having acute bacterial pneumonia and four outpatients with the common cold. Adjustment was made for age, gender, region, pack‐years of smoking, employment status, occupational exposure and BMI.

Results:  Medical histories of hypertension, hyperlipidaemia, coronary heart disease, diabetes mellitus, hepatitis C virus infection, tuberculosis, asthma, atopic dermatitis and allergic rhinitis were not statistically significantly associated with the risk of IPF, although cases were more likely to have suffered from allergic rhinitis and less likely to have been asthmatics than control subjects. Having a child with a history of allergic rhinitis, but not of asthma or atopic dermatitis, was significantly related to an increased risk of IPF.

Conclusions:  These findings suggest that a genetic predisposition to allergic rhinitis may be associated with an increased risk of IPF.
Percentage reduction of pleural effusion as a simple predictor of pleural scarring in tuberculous pleuritis
Authors: WONG Chi‐Fong , LEUNG Simon Kwok‐Fai , YEW Wing‐Wai
Published: August 2005

Objective:  The aim of the present study was to evaluate the utility of serum and pleural fluid biomarkers for predicting residual pleural scarring (RPS) in tuberculous pleuritis.

Methodology:  A retrospective study of patients with pleural tuberculosis was performed. Demographic data, clinical parameters, haematological indices, serum and pleural fluid biochemistry and pleural effusion area were assessed for correlation with the extent of RPS.

Results:  RPS was found in 41.4% of the 70 cases evaluated, with significant pleural scarring being present in 7.1%. It was more common in males (odds ratio 5.55). Among the variables studied, only the percentage reduction of the effusion after 2 weeks of treatment was found to independently predict the extent of RPS (r = −0.502, P < 0.001).

Conclusion:  RPS was more common in males and the percentage reduction in pleural effusion on CXR after 2 weeks of treatment was found to be a useful predictor of RPS.
Sarcoidosis caused by interferon therapy
Authors: ÇELIK Göhkan , SEN Elif , ULGER A. Fusun , KUMBASAR Ozlem Ozdemir , BOZKAYA Hakan , ALPER Doganay , KARAYALCIN Selim
Published: August 2005

Abstract:  Interferon alpha (IFN‐α) is an immunomodulator that is used as an antiviral agent in active chronic viral hepatitis C. IFN therapy can cause an induction or exacerbation of sarcoidosis. Although several reports in the gastroenterology literature have suggested an association between IFN therapy and sarcoidosis, this association has rarely been described elsewhere. A 47‐year‐old woman developed sarcoidosis after cessation of treatment with IFN and ribavirin for chronic hepatitis C. Her sarcoidosis showed liver, pulmonary and skin involvement. She continues to be monitored regularly in the Department of Pulmonary Diseases without steroid therapy. Her sarcoidosis improved spontaneously. We conclude that patients should be monitored for sarcoidosis during and after IFN therapy.