Cancer and other causes of childhood mortality in Bombay, India

Mortality from cancer and other diseases from 1964 to 1984 and their contributions in 1984 to premature mortality in Bombay, India, were studied. Cancer was the ninth and tenth cause of death in boys and girls younger than 15 years of age, respectively, in 1984. Prematurity and infectious diseases contributed most to years of potential life lost by children younger than 5 years of age in 1984; cancer, heart disease, and accidents-injury became important in children older than 5 years. When currently high mortality rates in infants and children younger than 5 years of age are reduced, cancer may become a greater childhood health problem. Approximately 5% of male and 3% of female patients with cancer in six hospital and three population-based cancer registries in India were children younger than 15 years of age. Cancer mortality declined from the rate during 1964 to 1972 to the rate during 1973 to 1984 by about 40% in children younger than 5 years old and in girls of 10 to 14 years of age and by 7.5% and 14% in the 5 to 9-year-old boys and girls, respectively. It increased by 12% in the 10 to 14-year-old boys. Early diagnosis and treatment of cancer in children older than 5 years of age may yield increased productive person-years of life.     

Influence of the Active Pharmaceutical Ingredient Concentration on the Physical State of Mannitol—Implications in Freeze-Drying

Purpose The aim of this study was to investigate the effect of the concentration of the active pharmaceutical ingredient on the physical state of mannitol in frozen aqueous systems. Methods A human monoclonal antibody was used as the model protein. Mannitol and sucrose were used as the bulking agent and the lyoprotectant, respectively. The thermal behavior of frozen mannitol–sucrose solutions during and after annealing, in the absence and presence of the protein, were characterized by low-temperature powder X-ray diffractometry and differential scanning calorimetry. The influence of the protein on the crystallization behavior of mannitol was also evaluated. Results The excipient concentration had a pronounced effect on the glass transition temperature of maximally freeze-concentrated amorphous phase (T_g′). At fixed excipient compositions, the protein had no effect on the T_g′ if the protein concentration was ≤20 mg/ml. However, at higher protein concentrations, there was a marked increase in T_g′ as a function of protein concentration. The inhibitory effect of the protein on mannitol crystallization was concentration dependent and was directly evident from X-ray diffractometry experiments. Annealing facilitated both mannitol nucleation and crystal growth even in the presence of the protein. Conclusions The ratio of mannitol to sucrose and the protein concentration have an impact on the T_g′ and may therefore influence the primary drying temperature. The protein inhibits both the nucleation and growth of mannitol crystals and this effect seems to be concentration dependent. The presence of the protein and the protein concentration dictate the processing conditions, i.e., annealing time, annealing temperature, and primary drying temperature.     

Dominance of CD86, transforming growth factor- beta 1, and interleukin-10 in Mycobacterium tuberculosis secretory antigen-activated dendritic cells regulates T helper 1 responses to mycobacterial antigens

We report that stimulation of Mycobacterium tuberculosis (M. tuberculosis) secretory antigen (MTSA)-differentiated dendritic cells (DCs) and MTSA-matured DCs with M. tuberculosis cell extract (CE) down-regulated proinflammatory responses to CE-primed T (CE-T) cells by increasing surface expression of CD86 after CE stimulation. CE stimulation also decreased interleukin (IL)-12p40 and interferon (IFN)- gamma levels and increased IL-10 and transforming growth factor- beta 1 (TGF- beta 1) levels from these DCs. Blocking either CD86, IL-10, or TGF- beta with monoclonal antibodies before CE stimulation restored the attenuated T helper 1 (Th1) responses of CE-T cells. Conversely, treatment of these DCs with IL-12p70 and/or IFN- gamma completely restored Th1 responses from CE-T cells. These results indicate that M. tuberculosis secretory antigens down-regulate proinflammatory Th1 responses to mycobacteria by differentially modulating the cytokine profiles and surface densities of costimulatory molecules on DCs. Of importance, this down-regulation is independent of the maturation status of MTSA-activated DCs and can be rescued after treatment of DCs with IFN- gamma or IL-12.     

Efficacy of botulinum toxin in chronic anal fissure

Background Chronic anal fissures (CAF) are caused by anal sphincter hypertonia leading to an ischaemic ulcer. By inducing temporary sphincter relaxation, botulinum toxin (Botox) injection has been shown to heal CAF in approximately 73–96% of cases in clinical trials. Aim This study looks at the efficacy of Botox clinical practice. Methods The medical charts were reviewed of all patients with CAF treated with Botox (30iu injected into the sphincter complex in three 10iu aliquots) in the Ulster Hospital, Dundonald, Northern Ireland between March 1999 and November 2001. Results Fifty-one charts were identified. Four patients failed to attend for review and were excluded from the study. Of the remaining 47 patients, 37 (78.7%) were healed following Botox injection. 10 out of 37 (27.0%) developed a recurrent CAF after a median time of 16.0 months (IQR 3.8–20 months). Eight of these patients opted for repeat Botox injection, which was successful in 7 (87.5%) cases. No adverse effects were reported. Conclusion Botox injection for the treatment of CAF is as effective in clinical practice as reported in clinical trials from specialist centres.     

Diagnostic and treatment challenges of neuronopathic Gaucher disease: Two caseswith an intermediate phenotype

Gaucher disease (GD) is a lysosomal storage disorder with a broad, overlapping clinical spectrum. The presented two case reports highlight the clinical evaluation required in neuronopathic GD to assist with medical management and genetic counselling.     

Association between ductal fluid proteomic expression profiles and the presence of lymph node metastases in women with breast cancer

BACKGROUND: Proteomic analysis of nipple aspiration fluid (NAF) is a noninvasive method for studying the local biologic microenvironment of the breast ducts where carcinoma originates. METHODS: NAF samples from each breast of 23 women with stage I or II unilateral invasive breast carcinoma were collected, and protein expression was analyzed comprehensively by using protein arrays and time-of-flight mass spectrometry. Blinded hierarchical clustering analysis was performed to identify potential associations between protein expression patterns and clinicopathologic factors. RESULTS: After analysis of all spectra, 463 distinct peaks in the mass range of 7 to 30 kD were identified in NAF samples. Blinded hierarchical clustering analysis of protein expression patterns demonstrated a conservation of these patterns between the breasts of individual patients (P=.0003 x 10(-12)). Hierarchical clustering revealed an association between protein expression patterns, and the presence and absolute number of axillary lymph nodes containing metastases (P=.038). CONCLUSIONS: Protein expression patterns are highly conserved between cancerous and noncancerous breasts in women with unilateral invasive breast cancer; unique expression patterns may be associated with extent of disease. High-throughput proteomic methods may reveal biologically relevant proteins involved in carcinogenesis and progression of disease.     

Multidetector-row computed tomography angiography for planning intra-arterial chemotherapy pump placement in patients with colorectal metastases to the liver

PURPOSE: The purpose of this study was to evaluate the use of multidetector computed tomography (MDCT) in the preoperative arterial evaluation of patients scheduled to undergo intra-arterial chemotherapy pump placement. METHODS: Computed tomography scans of 30 patients with hepatic malignancies who were imaged with multiphase MDCT angiography for intra-arterial chemotherapy pump placement were retrospectively analyzed. Dual-phase helical CT was performed, and the arterial phase images were processed to depict the arterial anatomy and to identify pertinent anomalies. All findings were compared and correlated with surgical findings or catheter angiography if surgery was contraindicated. RESULTS: Arterial anomalies identified on CT angiography in 20 of 30 patients included a replaced right hepatic artery (RHA; n = 6) or left hepatic artery (LHA; n = 8), a replaced common hepatic artery (n = 1), an accessory RHA (n = 2) or LHA (n = 6), a replaced gastroduodenal artery (GDA; n = 2), an extrahepatic connection between the accessory RHA and the replaced RHA (n = 1), and a common origin composed of the GDA and RHA and LHA (n = 2). There were no additional arteries or anomalies identified by catheter angiography, when available, or during surgery. Only 1 variant, an accessory hepatic artery, was not located during surgery. In 2 patients, the surgical team decided that pump placement was not feasible because of overly complex anatomy as determined by CT angiography. Computed tomography angiography showed an overall sensitivity of 100% and specificity of 97%. CONCLUSIONS: Multidetector computed tomography angiography is accurate for the preoperative evaluation of normal and aberrant hepatic vasculature in patients under consideration for intra-arterial chemotherapy pump placement. Axial images alone permit recognition of vascular anomalies, including complex anatomy. Nevertheless, 3-dimensional rendering is useful to evaluate complex vascular anatomy and does not require catheter angiographic confirmation. In addition to aiding in selecting patients ideal for pump placement, MDCT permits noninvasive planning of their surgical approach.