Longer term follow up of aerobic capacity in children affected by severe acute respiratory syndrome (SARS).

BACKGROUND: A study was undertaken to investigate the aerobic capacity and pulmonary function of children 6 and 15 months after the diagnosis of severe acute respiratory syndrome (SARS). METHODS: Thirty four patients of mean age 14.7 years completed both pulmonary function and maximal aerobic capacity tests at 6 months. All had normal clinical examination and were asymptomatic. Their exercise responses were compared with a group of healthy controls. Complete data were collected on 27 of the original 34 cases at 15 months. RESULTS: Compared with normal controls, the patient group had significantly lower absolute and mass related peak oxygen consumption (peak V o(2) (p<0.01)), higher ventilatory equivalent for oxygen (p<0.01), lower oxygen pulse (p<0.01), and a lower oxygen uptake efficiency slope (p<0.01) at 6 months. This impairment was unexpected and out of proportion with the degree of lung function abnormality. Residual high resolution computed tomography of thorax (HRCT) abnormalities were present in 14 patients. Those with abnormal HRCT findings had significantly lower mass related peak V o(2) than subjects with normal radiology (p<0.01). Absolute and mass related peak V o(2) in the patient group remained impaired at 15 months despite normalisation of lung function in all patients. CONCLUSIONS: The mechanism for the reduced aerobic capacity in children following SARS is not fully understood, but it is probably a consequence of impaired perfusion to the lungs at peak exercise and deconditioning.

Systematic review: treatment of chronic hepatitis B virus infection by pegylated interferon.

BACKGROUND: Pegylated interferon-alpha has been shown to be more efficacious than conventional interferon in treating chronic hepatitis C. The use of peginterferon in chronic hepatitis B virus infection with positive hepatitis B e antigen has also been tested in a number of trials since 2003. AIM: To systematically summarize and compare the results of these studies. METHODS: Four studies were identified from PubMed, Medline and reference lists. Data from the trials were extracted and analysed. Where appropriate, combined odds ratio of different trials was calculated. Safety data including serious adverse events and emergence of drug-resistant mutants were recorded. RESULTS: Three of the four trials contained predominantly Asian patients. Peginterferon is found to be superior to lamivudine monotherapy and induced sustained biochemical and virological responses in about one-thirds of patients after 12 months of therapy. Coadministration of lamivudine did not result in improvement in viral suppression. Peginterferon appears to reduce the emergence of YMDD mutation in the combination treatment groups. It was well tolerated with serious adverse events reported in <10% of patients in most trials. CONCLUSIONS: Peginterferon-alpha treatment of at least 6 months should be considered as one of the first-line therapeutic options for hepatitis B virus infection.

Variegated micelle surfaces: correlating the microstructure of mixed surfactant micelles with bulk solution properties.

Electron paramagnetic resonance, viscosity, and small-angle neutron scattering (SANS) measurements have been used to study the interaction of mixed anionic/nonionic surfactant micelles with the polyampholytic protein gelatin. Sodium dodecyl sulfate (SDS) and the nonionic surfactant dodecylmalono-bis-N-methylglucamide (C12BNMG) were chosen as "interacting" and "noninteracting" surfactants, respectively; SDS micelles bind strongly to gelatin but C12BNMG micelles do not. Further, the two surfactants interact synergistically in the absence of the gelatin. The effects of total surfactant concentration and surfactant mole fraction have been investigated. Previous work (Griffiths et al. Langmuir 2000, 16 (26), 9983-9990) has shown that above a critical solution mole fraction, mixed micelles bind to gelatin. This critical mole fraction corresponds to a micelle surface that has no displaceable water (Griffiths et al. J. Phys. Chem. B 2001, 105 (31), 7465). On binding of the mixed micelle, the bulk solution viscosity increases, with the viscosity-surfactant concentration behavior being strongly dependent on the solution surfactant mole fraction. The viscosity at a stoichiometry of approximately one micelle per gelatin molecule observed in SDS-rich mixtures scales with the surface area of the micelle occupied by the interacting surfactant, SDS. Below the critical solution mole fraction, there is no significant increase in viscosity with increasing surfactant concentration. Further, the SANS behavior of the gelatin/mixed surfactant systems below the critical micelle mole fraction can be described as a simple summation of those arising from the separate gelatin and binary mixed surfactant micelles. By contrast, for systems above the critical micelle mole fraction, the SANS data cannot be described by such a simple approach. No signature from any unperturbed gelatin could be detected in the gelatin/mixed surfactant system. The gelatin scattering is very similar in form to the surfactant scattering, confirming the widely accepted picture that the polymer "wraps" around the micelle surface. The gelatin scattering in the presence of deuterated surfactants is insensitive to the micelle composition provided the composition is above the critical value, suggesting that the viscosity enhancement observed arises from the number and strength of the micelle-polymer contact points rather than the gelatin conformation per se.

Interaction between a partially fluorinated alkyl sulfate and gelatin in aqueous solution.

The interaction of a partially fluorinated alkyl sulfate, sodium 1H,1H,2H,2H-perfluorooctyl sulfate (C6F13CH2CH2OSO3Na), with the polyampholyte gelatin has been examined in aqueous solution using surface tension and small-angle neutron scattering (SANS). The 19F chemical shift of each fluorine environment in the surfactant is unaltered by the addition of gelatin, indicating that there is no contact between the gelatin and the fluorocarbon core of the micelle. The chemical shift of the two methylene groups closest to the headgroup is altered when gelatin is present, disclosing the location of the polymer. The critical micelle concentration (cmc) of the surfactant, cmc = 17+/-1 mM, corresponds to an effective alkyl chain (CnH2n+1) length of n = 11. In the presence of gelatin, the cmc is substantially reduced as expected, cmc(1) = 4+/-1 mM, which is also consistent with an effective alkyl chain length of n = 11. In the presence of the fluorosurfactant, the monotonic decay of the SANS from the gelatin-only system is replaced by a substantial peak at an intermediate Q value mirroring the micellar interaction. At low ionic strengths, the gelatin/micelle complex can be described by an ellipsoid. At higher ionic strengths, the electrostatic interaction between the micelles is screened and the peak in the gelatin scattering disappears. The correlation length describing the network structure decreases with increasing SDS concentration as the bound micelles promote a collapse of the network.

Treatment of acute lymphoblastic leukemia in Hong Kong children: HKALL 93 study.

A population-based multicentre study for childhood acute lymphoblastic leukemia (ALL) was conducted in Hong Kong from 1993 to 1997. One hundred and forty-five newly diagnosed ALL patients were treated by the HKALL 93 protocol. Patients were stratified into three risk groups according to age, presenting white cell count, immunophenotyping and cytogenetic study. The patients received the same induction and early and late intensification at week 5 and week 20. Fifty-eight standard risk (SR) patients received regular intrathecal methotrexate as CNS preventive therapy, while 49 intermediate risk (IR) patients received high dose intravenous methotrexate and regular intrathecal methotrexate. Thirty-eight high risk (HR) patients were treated with prophylactic cranial irradiation and an additional intensification block at week 35. The induction remission rate was 97.2% with 2% induction death. Two patients died during first complete remission. Relapse occurred in 20.7, 42.9 and 42.1% of SR, IR and HR patients respectively. By multivariate logistic regression, age> or =10 years and white cell count> or =100 x 10(9)/l were the two significant variables accounting for mortality. The 5-year overall and event-free survival of the whole group was 81.3 and 62.6% respectively. According to risk groups, the event-free survival was 79, 49 and 61% for SR, IR and HR patients respectively, while the overall survival was 96, 73 and 68% for SR, IR and HR patients respectively. In conclusion, the treatment protocol had low treatment-related mortality but was associated with a rather high relapse rate, especially in IR patients. Salvage therapy achieved sustained second remission in some patients. More intensive treatment especially a late intensification is required to improve the outcome.

Liver disease in transfusion dependent thalassaemia major.

AIMS: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers. METHOD: Liver biopsy was performed to assess the histological changes and liver iron content (LIC). RESULTS: One hundred patients were evaluated (median age 11.7 years, range 1.5-27). A total of 81 liver biopsies were performed in 73 patients; 43 samples were analysed for LIC. Grade 3-4 haemosiderosis and hepatic fibrosis was found in 44% and 30% of patients respectively; both were significantly associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15 mg/g dry weight) was present in 16.3% of patients. CONCLUSION: Severe haemosiderosis and hepatic fibrosis were common in patients with thalassaemia major despite the use of chelation therapy. Liver biopsy provided information on fibrosis and LIC which could not be accurately predicted from peripheral blood markers.

Haematopoietic stem cell transplantation for thalassaemia major in Hong Kong: prognostic factors and outcome.

From August 1992 to August 1999, 44 patients received allogeneic haematopoietic stem cell transplantation in a single institution. The donors were HLA-identical siblings except for one who was a phenotypically matched father. Thirty-eight patients received bone marrow stem cells and the others received peripheral blood stem cells or umbilical cord blood (UCB). The mean age at transplant was 10.7+/-5.1 years, ranging from 1.8 to 21 years. Patients received busulphan (16 mg/kg) and cyclophosphamide (150 to 200 mg/kg) as conditioning, and antithymocyte globulin was given to 42 patients to prevent graft rejection. All had engraftment except a patient who received a UCB transplant. Four patients died from early treatment-related mortality, and one died from interstitial pneumonitis 3 months after transplant. Two patients developed secondary graft rejection and both received a second transplant. Thirty-eight patients survived and all except one were transfusion independent. The 5-year overall and event-free survival rates were 86% and 82%, respectively. By multivariate stepwise Cox proportional hazard analyses, severe veno-occlusive disease (VOD) of liver and Pesaro class 3 features were the significant factors associated with survival. Patients aged more than 11 years were more inclined to develop VOD. In conclusion, haematopoietic stem cell transplantation should be performed early if an HLA identical sibling is available.

Polarized cell growth in higher plants.

Pollen tubes and root hairs are highly elongated, cylindrically shaped cells whose polarized growth permits them to explore the environment for the benefit of the entire plant. Root hairs create an enormous surface area for the uptake of water and nutrients, whereas pollen tubes deliver the sperm cells to the ovule for fertilization. These cells grow exclusively at the apex and at prodigious rates (in excess of 200 nm/s for pollen tubes). Underlying this rapid growth are polarized ion gradients and fluxes, turnover of cytoskeletal elements (actin microfilaments), and exocytosis and endocytosis of membrane vesicles. Intracellular gradients of calcium and protons are spatially localized at the growing apex; inward fluxes of these ions are apically directed. These gradients and fluxes oscillate with the same frequency as the oscillations in growth rate but not with the same phase. Actin microfilaments, which together with myosin generate reverse fountain streaming, undergo rapid turnover in the apical domain, possibly being regulated by key actin-binding proteins, e.g., profilin, villin, and ADF/cofilin, in concert with the ion gradients. Exocytosis of vesicles at the apex, also dependent on the ion gradients, provides precursor material for the continuously expanding cell wall of the growing cell. Elucidation of the interactions and of the dynamics of these different components is providing unique insight into the mechanisms of polarized growth.

Hydroxyproline-rich glycoproteins in plant reproductive tissues: structure, functions and regulation.

The plant reproductive process of pollination involves a series of interactions between the male gametophyte (the pollen grain or pollen tube) and extracellular matrix (ECM) molecules secreted by different cell types along the pollen tube growth pathway in the female organ, the pistil. These interactions are believed to signal and regulate the pollen tube growth process to effect successful delivery of the sperm cells to the ovules where fertilization takes place. Hydroxyproline-rich glycoproteins secreted by plant cells are believed to play a broad range of functions, ranging from providing structural integrity to mediating cell-cell interactions and communication. The pistil and pollen tube ECM is enriched in these highly glycosylated proteins. Our discussions here will focus on a number of these proteins for which most information has been available, from Nicotiana tabacum, its self-incompatible relative N. alata, and Zea mays. In addition, the regulation of the synthesis and glyco-modification of one of these proteins, TTS (transmitting tissue-specific) protein from N. tabacum will be discussed in the light of how differential glycosylation may be used to regulate molecular interactions within the ECM.

The effect of vertebral rotation of the lumbar spine on dual energy X-ray absorptiometry measurements: observational study.

OBJECTIVE: To estimate how axial rotation of lumbar vertebrae quantitatively affects bone mineral density, as measured by dual energy X-ray absorptiometry in the anteroposterior plane. DESIGN: Observational study. SETTING: University teaching hospital, Hong Kong. PATIENTS: Cadaver lumbar vertebrae (L2 to L4) were removed from four adults. MAIN OUTCOME MEASURES: Using dual energy X-ray absorptiometry, the bone mineral content, bone area, and bone mineral density were measured in the neutral position and with vertebral axial rotation in increments of 7.5 degrees, up to a maximum of 45 degrees. RESULTS: Correlation analysis showed a significant positive correlation between the degree of rotation and measured bone area, a significant negative correlation between degree of rotation and bone mineral density measurements, but no significant correlation between degree of rotation and measured bone mineral content. The measured bone area increased approximately 24% and the bone mineral density decreased approximately 19% when the vertebrae were rotated by 45 degrees. CONCLUSIONS: These results suggest that for patients with rotational deformity of the spine, such as scoliosis, measurements of lumbar spine bone mineral content by dual energy X-ray absorptiometry is not affected, while bone mineral density measurements are not reliable.

A pollen tube growth-promoting arabinogalactan protein from nicotiana alata is similar to the tobacco TTS protein.

Upon germination on the stigma, pollen tubes elongate in the stylar transmitting tract, aided by female factors, with speed and directionality not mimicked in in vitro pollen tube growth cultures. We have shown that a stylar transmitting tissue arabinogalactan protein (AGP) from Nicotiana tabacum (tobacco), TTS protein, stimulates pollen tube growth in vivo and in vitro and attracts pollen tubes grown in a semi-in vivo culture system. It has been reported that the self-incompatible Nicotiana alata produced a stylar glycoprotein, GaRSGP, which had a backbone polypeptide that shared 97% identity with those of TTS proteins but some of its properties were different from those described for TTS proteins. We report here the characterization of a family of stylar transmitting tissue glycoproteins from N. alata that is virtually identical to tobacco TTS proteins and which we refer to as NaTTS proteins. Like their tobacco counterparts, NaTTS proteins are recognized by the traditional AGP-diagnostic reagent beta-glucosyl Yariv reagent, and they are also recognized by JIM13, a monoclonal antibody against AGP. NaTTS proteins also stimulate pollen tube elongation in vitro and attract pollen tubes in a semi-in vivo pollen tube culture system. Biochemical and immunological characterization of NaTTS proteins revealed that they have extraordinary variability in the extent of sugar modifications of their polypeptide backbones. The extent of sugar modifications on NaTTS proteins significantly affects their biochemical properties, influences how they interact with the transmitting tissue extracellular matrix, and affects their solubility from this matrix. Our results suggest that the strategy used to purify GaRSGP only recovered a less glycosylated, more tightly extracellular matrix-bound sub-population of the entire spectrum of N. alata TTS proteins.

Metastatic adenocarcinoma of the uterine cervix to the thyroid gland.

Clinically diagnosed metastasis to the thyroid gland is rare. The authors present the first reported case of metastasis to the thyroid gland from a primary adenocarcinoma of the uterine cervix.

Hydroxyurea-induced fever in cervical carcinoma: case report and review of the literature.

This is a case presentation of a rarely seen hydroxyurea-induced fever in a patient with cervical adenocarcinoma receiving oral hydroxyurea given concurrently with external beam radiotherapy to the pelvis. In the fourth week of treatment, the patient developed recurrent febrile episodes, with no obvious etiology. Eventually, hydroxyurea was discontinued with no further recurrence of fever. A review of the medical literature on fever induced by hydroxyurea suggests a mechanism of delayed hypersensitivity. Since hydroxyurea is an often-used chemotherapeutic drug for various malignancies, clinical oncologists need to be aware of this unusual side effect. The diagnosis is by clinical exclusion and by the recurrent pattern of fever on rechallenge of the drug.

Outcomes and prognostic factors of Chinese children with acute lymphoblastic leukemia in Hong Kong: preliminary results.

BACKGROUND: The Chinese population is the biggest ethnic group in the world. However, there are few reports on the treatment outcome of childhood acute lymphoblastic leukaemia (ALL) among the Chinese population. PROCEDURE: Sixty-five children with ALL were treated with a modified protocol of the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia protocol X(MRC UKALL X) at the Prince of Wales Hospital, Hong Kong. Most patients were ethnic Chinese. They were divided into groups A and B, depending on whether their presenting leucocyte count being was less or greater than 50 x 10(9)/l, respectively. Group A patients of received induction, early intensification (week 5), cranial irradiation, and maintenance for 3 years. Group B patients received an additional late intensification (week 20). RESULTS: The median follow-up duration was 6.8 years(range: 3.4-10.1 years). The event-free and overall survival rates of all patients at 7 years were 66% (confidence interval [CI] 53-76) and 75% (CI 63-84), respectively. The event-free survival rates of groups A and B at 7 years were 67% (CI 52-79) and 60% (CI 32-80), respectively (P= 0.39). The overall survival rates of groups A and B at 7 years were 80% (CI 66-89) and 60% (CI 32-80), respectively (P = 0.07). With this treatment protocol, the factors which adversely affected the outcome were age (<2 years and >10 years) and T-cell subtype. Sex, white blood count at diagnosis, and FAB subtypes were not statistically significant prognostic factors. CONCLUSIONS: The treatment outcomes were comparable with those reported from the MRC UKALL X trials.

Determinants of axial and peripheral bone mass in Chinese adolescents.

OBJECTIVE: To determine the relation of puberty, physical activity, physical fitness, and calcium intake with bone mineral content (BMC) of the distal radius, and on bone mineral density (BMD) of the L2 to L4 vertebrae in a group of healthy Chinese adolescents. DESIGN: Cross sectional survey. SUBJECTS: A group of 179 healthy Chinese adolescents (92 boys and 87 girls) aged 12 to 13 years enrolled in the first year of the Tii Junior High School in Shatin, Hong Kong. Ninety four of the pupils enrolled were in the physical education major class (PE), and the other 85 were in the art major class (ARTS). MAIN OUTCOME MEASURES: Correlation of BMC of the distal radius and BMD of the L2 to L4 vertebrae with level of physical activity, physical fitness (isometric and isokinetic), muscle strength of the upper and lower limb, and calcium intake. RESULTS: BMC of the distal radius and BMD of the L2 to L4 vertebrae were significantly positively correlated. Univariate and regression analysis showed that age, pubertal staging, physical fitness, and muscle strength were significantly associated with bone mass in a positive way. Calcium intake and type of sport practised did not exert a significant influence on BMC of the distal radius and BMD of the L2 to L4 vertebrae in boys. The results for the BMD of the L2 to L4 vertebrae were similar in girls and boys; however, in girls, the BMC of the distal radius had a negative correlation with calcium intake. Physical fitness was a significant positive predictor of BMD of the L2 to L4 vertebrae. CONCLUSIONS: Among Chinese adolescents bone mass was positively influenced by certain measures of physical fitness as well as by age, weight, and pubertal stage.

A new look at the sequential development of elbow-ossification centers in children.

The pattern and sequence of ossification of the six secondary ossification centers around the elbow in the child were mainly derived from studies done >30 years ago. This series reexamined the sequence and pattern based on a cross-sectional study of the elbow radiographs of 1,577 Chinese children with elbow injuries; age range, from newborn to 17 years. The ratio of girls to boys was 1:2. Each child had a radiograph of the normal and the injured elbow giving a total of 3,154 radiographs. A percentile chart of ossification was constructed for each of the ossification centers in both sexes for easy reference. No differences in the timing and ossification pattern were found between the right and left elbow or between the normal and injured elbow in this study. The sequence of ossification in both boys and girls was found to be the same (i.e., the capitulum first, followed by the radial head, medial epicondyle, olecranon, trochlea, and last, the lateral epicondyle). The ages at which 50% of the girls were found to have positive radiologic ossification for each of these centers were ages 1, 5, 5, 9, 9, and 10 years, respectively. In boys, with the exception of the capitulum, an average delay of 2 years was found in each of the ossification centers, although the sequence remained similar.

Evaluation of modern pathologic nomenclature, tumor imaging and treatment of pituitary adenomas in a recent surgical series.

This study reviews retrospectively 49 patients with pituitary adenomas, using a modern, immunohistochemically and ultrastructurally-based nomenclature. It also compares tumor imaging by CT and MRI scans, and analyzes the results of recent neurosurgical and radiotherapeutic treatments. Based on the findings of the study, several recommendations on clinical management of pituitary macroadenoma are made.

Secular trend in the sexual maturation of southern Chinese girls.

In 1993, a cross-sectional study of sexual maturation of normal Chinese schoolgirls was performed in Hong Kong. The aim of the study was to obtain an up-to-date reference for normal pubertal development in Chinese girls. Breast development was assessed in 3749 girls aged 7-19 y, and pubic hair rating was assessed in 3745 girls. Menstrual status was recorded in 6467 girls over 6 y of age. The median age of onset of puberty as indicated by breast stage II or above was 9.78 (95% CI 9.70-9.85) y. The median age of onset of pubic hair development was 11.64 (95% CI 11.56-11.72) y. The median age of menarche was 12.38 (95% CI 11.98-12.78) years. Percentile values for the age at which each puberty staging appeared were constructed and incorporated into the height-for-age charts. When comparison is made with similar studies done in 1962 and 1979, a significant downward secular trend in sexual maturation is observed (p < 0.01). Except for breast development the downward secular trend in sexual maturation appears to be diminishing and may be coming to a halt in the Chinese girls in Hong Kong. Their median ages of sexual maturation are now among one of the earliest medians recorded in the world population studied.