New method for determining faecal fat excretion in infancy

Collecting complete, timed stool samples for the estimation of faecal fat from infants wearing nappies is difficult. A gravimetric method has been adapted by applying a chloroform/methanol homophasic solvent system to extract lipids from whole soiled nappies. In a study of 22 collections in six infants, no stools were lost and the recovery of lipids was 96%, with results similar to a reference titrimetric method. In addition to total fat, individual lipids were measured using gas-liquid chromatography. The method simplifies stool collection and analysis, is aesthetically more acceptable, and leads to reduced microbial hazards. It also allows the detailed study of excreted lipid species enabling the coefficient of absorption of dietary lipids of various chain lengths to be determined individually.     

Initiation of high dose gonadotrophin-releasing hormone antagonist treatment during the late follicular phase in the macaque abolishes luteal function irrespective of effects upon the luteinizing hormone surge

The determination of the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists in blocking the luteinizing hormone (LH) surge and luteal function is important for our understanding of the control of the menstrual cycle and for clinical application. GnRH antagonists have failed to block the LH surge reliably in the non-human primate. The aim of the study was to utilize high dose GnRH antagonist treatment administered during the late follicular phase of the menstrual cycle to block the pre-ovulatory LH surge. It was postulated that the LH surge would be prevented in all animals, but if this failed subsequent luteal function would be blocked by continued suppression of LH, since the early corpus luteum is susceptible to inhibition by GnRH antagonist treatment. A group of 16 adult female stumptailed macaques (Macaca arctoides) with regular menstrual cycles were selected. The GnRH antagonist [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-(Hci)6, Lys(iPr)8,D- Ala10]GnRH (Antarelix) (concentration 10 mg/ml) was administered as three daily s.c. injections, at a dose of 1 mg/kg on days 11, 12 and 13 of the follicular phase of the menstrual cycle. Of nine macaques in which it was judged that the treatment was commenced within 1 day of the expected LH surge (serum oestradiol >400 pmol/l), six demonstrated a decline in serum oestradiol concentrations, a total block of the LH/follicle stimulating hormone (FSH) surge and inhibition of ovulation as judged by an absence of a rise in progesterone concentrations. In the three other animals in this category, a partial LH surge occurred, but this failed to result in a functional corpus luteum. In a further three animals treatment was initiated on the day of the LH surge, and again there was absence of a subsequently functional corpus luteum. These results show that GnRH is involved at the time of the mid-cycle LH/FSH surge in the non-human primate. Initiation of high dose GnRH antagonist treatment during the periovulatory period abolishes luteal function irrespective of its effects upon the LH surge because of its long-term action and resultant withdrawal of luteal support.      

Hearing improvement in patients with Fabry disease treated with agalsidase alfa

Aim : To describe the nature and prevalence of hearing loss in Fabry disease, and its response to enzyme replacement therapy (ERT) with agalsidase alfa. Methods : Fifteen male patients with Fabry disease were enrolled in a randomized, double-blind study and received placebo ( n = 8) or ERT ( n = 7) with agalsidase alfa for 6 months. This was followed by an open-label extension of 36 months thus far. Alongside this trial, an additional eight men and two women have so far received open-label ERT for between 6 and 30 months. Pure-tone audiometry, impedance audio-metry and otoacoustic emission testing were performed at 0 (baseline), 6, 18, 30 and 42 months. Results : Nine patients (36%) had bilateral and ten (40%) had unilateral high-frequency sensorineural hearing loss (SNHL). Three (12%) had unilateral middle ear effusions with conductive losses persisting beyond 6 months. Only five patients (20%) had normal hearing. The high-frequency SNHL deteriorated over the first 6 months in both placebo and active treatment groups by a median 6.3 dB ( p < 0.0001, Wilcoxon matched-pairs). This hearing loss subsequently improved above baseline by 1.5 dB at 18 months (p = 0.07), by 5.0 dB at 30 months ( p = 0.006) and by 4.0 dB at 42 months ( p = 0.01).
Conclusion : Significant hearing loss, usually high-frequency SNHL, is a common manifestation of Fabry disease in adults. α-Galactosidase A replacement therapy with agalsidase alfa appears to reverse the hearing deterioration in these patients. This improvement, however, is gradual, suggesting the need for long-term ERT.     

The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas

Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the aetiology of Hodgkin's disease. To determine the role of EBV in childhood Hodgkin's disease in different geographical areas, immunohistochemical staining and in situ hybridisation were used to analyse latent membrane protein 1 (LMP 1) and small nuclear non-transcribed RNAs (EBER-1) respectively. Testing for EBV within the Reed-Sternberg and Hodgkin's cells was carried out in childhood Hodgkin's disease from 10 different countries. The proportion of LMP 1 positive cases varied significantly, being 50% of cases from the United Kingdom (38/75), South Africa (9/18), Egypt (7/14), and Jordan (8/16), 60% from the United Arab Emirates (6/10), 70% from Australia (11/16), 81% from Costa Rica (34/42), 88% from Iran (7/8), 90% from Greece (20/22), and 100% of the 56 cases from Kenya. A sensitive polymerase chain reaction based EBV strain typing technique was established using archival tissues. EBV strain type 1 was shown to be predominant in childhood Hodgkin's disease from the United Kingdom, South Africa, Australia, and Greece. Type 2 was predominant in Egypt. EBV strain types 1 and 2 were both detected in some cases of childhood Hodgkin's disease in the United Kingdom, Costa Rica, and Kenya. The high incidence of EBV and the presence especially in developing countries of dual infection with both strain types 1 and 2 may reflect socioeconomic conditions leading to malnutrition induced immunological impairment. The possibility of HIV infection also needs to be explored.     

Creation of oral care flavours to deliver breath-freshening benefits

Objective:  Oral care products deliver breath freshening primarily via mechano-chemical cleaning or by antimicrobial active systems. Dental flavours provide taste benefits, and freshen breath mainly by sensorial masking. We aimed to determine whether flavours could deliver breath freshening in products by inhibiting bacterial volatile sulphide compound (VSC) production.
Subjects and methods:  Flavour materials were screened for inhibition of hydrogen sulphide formation by Klebsiella pneumoniae in vitro , grouped by efficacy, and data provided to flavourists. Flavours were formulated to maximize the content of VSC-effective ingredients and re-screened to confirm performance. Extensive, iterative testing of flavours identified reliable creative rules to deliver efficient inhibition of H₂S generation. Breath-freshening flavours in whole products were then tested in-house in a 'breath freshness panel'.
Main outcome measures:  Malodour of panellists (not preselected for malodour score) was scored before and after product use, on the 'Rosenberg' 0–5 scale, together with residual flavour score, by extensively trained judges. Products were tested in double-blind, crossover studies, and results analysed using ANOVA.
Results and conclusions:  Products flavoured using these rules delivered significantly greater breath freshening at 2 h than control products, and equivalent benefits to products containing 0.1% (w/w) triclosan or 0.2% (w/w) zinc sulphate.     

Orthodontic treatment for prominent upper front teeth in children

Background: Prominent upper front teeth are an important and potentially harmful type of orthodontic problem. This condition develops when the child’s permanent teeth erupt and children are often referred to an orthodontist for treatment with dental braces to reduce the prominence of the teeth. If a child is referred at a young age, the orthodontist is faced with the dilemma of whether to treat the patient early or to wait until the child is older and provide treatment in early adolescence. When treatment is provided during adolescence the orthodontist may provide treatment with various orthodontic braces, but there is currently little evidence of the relative effectiveness of the different braces that can be used. Objectives: To assess the effectiveness of orthodontic treatment for prominent upper front teeth, when this treatment is provided when the child is 7 to 9 years old or when they are in early adolescence or with different dental braces or both. Search strategy: The Cochrane Oral Health Group’s Trials Register, CENTRAL, MEDLINE and EMBASE were searched. The handsearching of the key international orthodontic journals was updated to December 2006. There were no restrictions in respect to language or status of publication. Date of most recent searches: February 2007. Selection criteria: Trials were selected if they met the following criteria:

• ? design – randomized and controlled clinical trials;
• ? participants – children or adolescents (age < 16 years) or both receiving orthodontic treatment to correct prominent upper front teeth;
• ? interventions – active: any orthodontic brace or head‐brace, control: no or delayed treatment or another active intervention;
• ? primary outcomes – prominence of the upper front teeth, relationship between upper and lower jaws;
• ? secondary outcomes: self esteem, any injury to the upper front teeth, jaw joint problems, patient satisfaction, number of attendances required to complete treatment.

Data collection and analysis: Information regarding methods, participants, interventions, outcome measures and results were extracted independently and in duplicate by two review authors. The Cochrane Oral Health Group’s statistical guidelines were followed and mean differences were calculated using random‐effects models. Potential sources of heterogeneity were examined. Main results: The search strategy identified 185 titles and abstracts. From this we obtained 105 full reports for the review. Eight trials, based on data from 592 patients who presented with Class II Division 1 malocclusion, were included in the review. Early treatment comparisons: Three trials, involving 432 participants, compared early treatment with a functional appliance with no treatment. There was a significant difference in final overjet of the treatment group compared with the control group of ?4.04 mm (95% CI ?7.47 to ?0.6, chi squared 117.02, 2 df, P < 0.00001, I2 = 98.3%). There was a significant difference in ANB (?1.35 mm; 95% CI ?2.57 to ?0.14, chi squared 9.17, 2 df, P = 0.01, I2 = 78.2%) and change in ANB (?0.55; 95% CI ?0.92 to ?0.18, chi squared 5.71, 1 df, P = 0.06, I2 = 65.0%) between the treatment and control groups. The comparison of the effect of treatment with headgear versus untreated control revealed that there was a small but significant effect of headgear treatment on overjet of ?1.07 (95% CI ?1.63 to ?0.51, chi squared 0.05, 1 df, P = 0.82, I2 = 0%). Similarly, headgear resulted in a significant reduction in final ANB of ?0.72 (95% CI ?1.18 to ?0.27, chi squared 0.34, 1 df, P = 0.56, I2 = 0%). No significant differences, with respect to final overjet, ANB, or ANB change, were found between the effects of early treatment with headgear and the functional appliances. Adolescent treatment (Phase II): At the end of all treatment we found that there were no significant differences in overjet, final ANB or PAR score between the children who had a course of early treatment, with headgear or a functional appliance, and those who had not received early treatment. Similarly, there were no significant differences in overjet, final ANB or PAR score between children who had received a course of early treatment with headgear or a functional appliance. One trial found a significant reduction in overjet (?5.22 mm; 95% CI ?6.51 to ?3.93) and ANB (?2.27 degrees; 95% CI ?3.22 to ?1.31, chi squared 1.9, 1 df, P = 0.17, I2 = 47.3%) for adolescents receiving one‐phase treatment with a functional appliance versus an untreated control. A statistically significant reduction of ANB (?0.68 degrees; 95% CI ?1.32 to ?0.04, chi squared 0.56, 1 df, P = 0.46, I2 = 0%) with the Twin Block appliance when compared to other functional appliances. However, there was no significant effect of the type of appliance on the final overjet. Authors’ conclusions: The evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth is no more effective than providing one course of orthodontic treatment when the child is in early adolescence.     

Not All Küttner Tumors Are IgG4-Related Disease (IgG4-RD)

Küttner tumor is an uncommon cause of salivary gland enlargement that most frequently affects the submandibular gland. More recently it has been considered a manifestation of IgG4-related disease (IgG4-RD) and synonymous with chronic sclerosing sialadenitis (CSS). We present a series of cases to emphasize this clinical entity as a disease pattern and presentation that is separate from IgG4-RD. Retrospective case series of 3 patients with unilateral salivary gland enlargement, or “Küttner tumor,” histologically classified as “chronic sclerosing sialadenitis,” The clinical history, radiology reports, laboratory studies, and pathology slides were reviewed for each case. Radiology showed discrete unilateral mass-like lesions in all three cases. Immunohistochemistry showed reduced tissue IgG4-positive plasma cells in two cases and increased numbers in one case, but insufficient to diagnose IgG4-RD. Storiform fibrosis was not seen in all cases and did not coincide with increased IgG4-positive plasma cells. A systemic workup, including serum IgG4 levels in two cases, was normal. A brief review of the literature on the spectrum of salivary gland involvement by IgG4-RD is presented. Küttner tumor is not necessarily the same as chronic sclerosing sialadenitis and is not always associated with IgG4-related disease. This report includes the second documented case of Küttner tumor of the sublingual gland.