Chlamydial etiology of acute lower respiratory tract infections in children in the Sudan

The role of Chlamydia pneumoniae in 110 Sudanese children with signs of acute lower respiratory tract infections (ALRI) was investigated. Four (3.6%) had evidence of C. pneumoniae infection, of whom 3 were culture-positive, while 1 had an antibody response suggesting a recent infection. IgG antibodies at a titer of ≥1:32 to C. pneumoniae, Chlamydia psittaci and Chlamydia trachomatis were detected in 27 (24.5%), 27 (24.5%) and 7 (6.4%) of the 110 ALRI cases, respectively. C. pneumoniae, C. trachomatis or C. psittaci were not detected in nasopharyngeal secretions from any of 110 patients when fluorescence-labeled specific monoclonal antibodies were used. In a seroepidemiological survey, 318 healthy Sudanese persons aged between 1 month and 67 years were studied for C. pneumoniae antibodies.     

Cytokeratin phenotyping does not help in distinguishing oesophageal adenocarcinoma from cancer of the gastric cardia

BACKGROUND: It is sometimes difficult to distinguish between cardia cancer and oesophageal cancer. AIMS: To evaluate whether cytokeratin (CK) expression of the tumour can be of value in differentiating between the two tumour types. METHODS: Consecutive patients with a malignant tumour in the oesophagus or stomach were recruited. Biopsy specimens were taken for routine haematoxylin and eosin staining. One tissue block with representative tissue was selected for immunohistochemical staining (CK7 and CK20). RESULTS: Endoscopically located adenocarcinoma of the oesophagus was present in 84 patients (64 men, 20 women; mean age, 68 years; range, 44-91). Cancer located primarily in the gastric cardia was present in 63 patients (42 men, 21 women; mean age, 68 years; range, 42-88). The histological diagnosis was metastasis from a primary tumour outside the oesophagus or stomach in 19 patients. The patients were divided into three groups for the immunohistochemical analysis. Patients in group A had definite oesophageal cancer, group B patients had a definite carcinoma located in the gastric cardia, and group C patients had an obstructing tumour distal in the oesophagus at the level of the diaphragm, which could not be passed with the endoscope. Paraffin wax embedded material was available from 122 patients for immunostaining and CK analysis. There was no significant difference in expression or distribution of CK7 or CK20 in the three groups of patients. CONCLUSION: CK phenotyping cannot distinguish between cancer arising from a Barrett's oesophagus and carcinoma originating in the gastric cardia.     

A long-term study to maximise migraine relief with zolmitriptan

Part 1 of this international study was a randomised, double-blind, placebo-controlled study of 2.5 mg and 5 mg zolmitriptan (Zomig) in the treatment of persistent migraine headache, two hours after an initial dose of 2.5 mg zolmitriptan. Part 2 was a non-comparative evaluation of long-term, unrestricted zolmitriptan use for treatment of initial, persistent and recurrent migraine headaches. In Part 1, following the treatment of moderate or severe persistent headache, two-hour headache response rates with 5 mg zolmitriptan (51.6%, n = 322), 2.5 mg zolmitriptan (49.7%, n = 324) and placebo (51.6%, n = 343) were not significantly different. However, the pain-free response rate following the treatment of persistent migraine headache of any intensity was significantly higher with 5 mg zolmitriptan than with placebo (36.0% vs. 25.5%; p < 0.001). This was predominantly due to effects in the subgroup of patients with mild headache. Thus, migraine relief in patients whose initial headache shows a partial response to 2.5 mg zolmitriptan may be maximised by a second 5 mg dose. In Part 2 (involving 2499 evaluable patients), 65.8% of attacks were treated with a single dose of zolmitriptan (2.5 mg or 5 mg). Of those migraine attacks initially treated with 2.5 mg zolmitriptan, 70.3% required no further dose, similarly 62.7% of migraine attacks treated initially with 5 mg zolmitriptan only required a single dose. Over the whole attack (i.e. initial and any persistent headache), headache response rates to one or two zolmitriptan doses were greater than 88.8%. 'Level of pain' was the primary factor influencing the choice of dose. Zolmitriptan provided consistent migraine headache relief in the majority of patients and was well tolerated.     

Lessons from BWS twins: complex maternal and paternal hypomethylation and a common source of haematopoietic stem cells

The Beckwith–Wiedemann syndrome (BWS) is a growth disorder for which an increased frequency of monozygotic (MZ) twinning has been reported. With few exceptions, these twins are discordant for BWS and for females. Here, we describe the molecular and phenotypic analysis of 12 BWS twins and a triplet; seven twins are MZ, monochorionic and diamniotic, three twins are MZ, dichorionic and diamniotic and three twins are dizygotic. Twelve twins are female. In the majority of the twin pairs (11 of 13), the defect on chromosome 11p15 was hypomethylation of the paternal allele of DMR2. In 5 of 10 twins, there was additional hypomethylation of imprinted loci; in most cases, the loci affected were maternally methylated, but in two cases, hypomethylation of the paternally methylated DLK1 and H19 DMRs was detected, a novel finding in BWS. In buccal swabs of the MZ twins who share a placenta, the defect was present only in the affected twin; comparable hypomethylation in lymphocytes was detected in both the twins. The level of hypomethylation reached levels below 25%. The exchange of blood cells through vascular connections cannot fully explain the degree of hypomethylation found in the blood cell of the non-affected twin. We propose an additional mechanism through which sharing of aberrant methylation patterns in discordant twins, limited to blood cells, might occur. In a BWS-discordant MZ triplet, an intermediate level of demethylation was found in one of the non-affected sibs; this child showed mild signs of BWS. This finding supports the theory that a methylation error proceeds and possibly triggers the twinning process.     

CLINICAL AND MOLECULAR PATHOLOGICAL FEATURES OF SEVERE CHILDHOOD AUTOSOMAL RECESSIVE MUSCULAR DYSTROPHY IN SAUDI ARABIA

The clinical, biochemical and histochemical features of 14 patients (nine females and five males) with severe childhood autosomal recessive muscular dystrophy (SCARMD) seen at a tertiary hospital in Riyadh from 1982 to 1993 arc described. Onset was at 3 (o 9 (median 3) years and four of five children aged >12 years lost ambulation. Five of the eight pairs of parents were closely consanguineous. The mean creatine kinase was 20 times the upper normal limit. Histochemistry of muscle showed dystrophic features in all cases, and dystrophin was positive in all cases examined (N=6). Three patients (two girls and a boy) were deficient in adhalin, the 50-kDa dystorphin-associated glycoprotein. A boy aged 13 years had rapidly progressing disease. Another boy of the same age (from a family characterized by early onset and slower progression) had normal dystrophin and adhalin. The clinical features conformed with previous observations from Sudan. North Africa and Qatar in the Arabian Peninsula. The disease is common in Saudi Arabia and seems to be more prevalent than Duchenne muscular dystrophy.     

Tolerability and efficacy of naratriptan tablets with long-term treatment (6 months)

This open-label study was conducted to examine the long-term tolerability and efficacy of the novel 5HT₁ agonist naratriptan tablets 2.5 mg used to treat all migraine attacks for 6 months. Patients could reduce the dose to 1 mg in the event of intolerable adverse events. The results demonstrate that the majority (median 83%) of attacks treated with naratriptan tablets 2.5 mg were not associated with an adverse event. Among attacks treated with naratriptan tablets 2.5 mg (+optional 2.5 mg for headache recurrence), the most frequently reported adverse event was nausea (4% of attacks after a single naratriptan dose). Both the overall incidence of adverse events and the incidences of specific adverse events were no higher during months 4–6 of treatment compared with months 1–3. Only 5 of 414 patients elected to reduce their naratriptan dose to 1 mg. Headache relief 4 h postdose was reported in a mean of 68% of 6770 moderate or severe migraine attacks treated with naratriptan tablets 2.5 mg. The median number of naratriptan tablets used per attack was 1.0 (mean 1.25); patients treated only a median 7% of attacks (mean 13%) with a 2nd naratriptan tablet for headache recurrence. Patients rated naratriptan tablets as good or excellent in 61% of 7566 treated attacks. In summary, the data from this study demonstrate that naratriptan tablets 2.5 mg were very well tolerated and effective for the acute treatment of migraine for 6 months in a situation closely resembling actual clinical use.     

Exercise and adrenaline increase PGC-1α mRNA expression in rat adipose tissue

The purpose of the present investigation was to explore the effects of exercise and adrenaline on the mRNA expression of PGC-1α, a master regulator of mitochondrial biogenesis, in rat abdominal adipose tissue. We hypothesized that (1) exercise training would increase PGC-1α mRNA expression in association with increases in mitochondrial marker enzymes, (2) adrenaline would increase PGC-1α mRNA expression and (3) the effect of exercise on PGC-1α mRNA expression in white adipose tissue would be attenuated by a β-blocker. Two hours of daily swim training for 4 weeks led to increases in mitochondrial marker proteins and PGC-1α mRNA expression in epididymal and retroperitoneal fat depots. Additionally, a single 2 h bout of exercise led to increases in PGC-1α mRNA expression immediately following exercise cessation. Adrenaline treatment of adipose tissue organ cultures led to dose-dependent increases in PGC-1α mRNA expression. A supra-physiological concentration of adrenaline increased PGC-1α mRNA expression in epididymal but not retroperitoneal adipose tissue. β-Blockade attenuated the effects of an acute bout of exercise on PGC-1α mRNA expression in epididymal but not retroperitoneal fat pads. In summary, this is the first investigation to demonstrate that exercise training, an acute bout of exercise and adrenaline all increase PGC-1α mRNA expression in rat white adipose tissue. Furthermore it would appear that increases in circulating catecholamine levels may be one potential mechanism mediating exercise induced increases in PGC-1α mRNA expression in rat abdominal adipose tissue.