BACKGROUND: Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis (CF). It is widely accepted that clinical testing using surrogate markers including pulmonary function will be useful in assessing clinical efficacy. One problem with pulmonary surrogate markers of CF disease is the large number of patients and length of time required to demonstrate clinical efficacy. An alternative to pulmonary testing of new CF treatments is use of the maxillary sinuses as a surrogate model of CF lung disease. Using CF sinusitis as a surrogate model for testing clinical efficacy of new treatments is attractive because CF upper respiratory disease is similar to the lower respiratory disease with respect to electrophysiology and microbiology. METHODS: Sinusitis recurrence in untreated sinuses was analyzed during a prospective, randomized, unblinded, dose-escalation, within-subjects, phase I clinical trial of the adeno-associated virus mediated cystic fibrosis transmembrane conductance regulator (AAV-CFTR) gene transfer. RESULTS: Clinical symptoms combined with sinus endoscopy proved useful in the diagnosis of unilateral and bilateral sinusitis recurrence. Sinusitis recurred at a rate of 45% during one month of follow-up. IL-8 concentration rose in sinus fluids from affected sinuses. Bacterial cultures and increased sinus leukocytes corroborated recurrent sinusitis. Sinus CT scans were also useful in diagnosing recurrent sinusitis in this surrogate model of CF infectious exacerbations. CONCLUSIONS: CF sinusitis as a surrogate for lung disease is particularly well-suited for phase II clinical trials of gene transfer agents, with the potential for measuring clinical efficacy in relatively small numbers of patients over relatively short periods of time.

Adult↗

PubMedDate not supplied

Intestinal calcium absorption and vitamin D status in chronic cholestatic liver disease.

Metabolic bone disease is common in patients with cholestatic liver disease. The importance of vitamin D status and calcium malabsorption in the pathogenesis of bone disease in these patients remains undefined. We have measured intestinal calcium absorption in relation to vitamin D status in 14 patients with chronic cholestatic liver disease including 11 with primary biliary cirrhosis. Fractional calcium absorption was determined from radioactive counts in the right forearm after separate oral and intravenous doses of 47CaCl2 in the fasting state. Eight of 14 patients (57%) had a decreased calcium absorption compared to controls. A significant correlation was observed between serum 25-hydroxyvitamin D levels and fractional calcium absorption (r = 0.623, p less than 0.02). Treatment with oral 25-hydroxyvitamin D3 in three patients with low serum 25-hydroxyvitamin D levels resulted in correction of serum 25-hydroxyvitamin D levels and improvement in fractional calcium absorption. No correlation was found between serum 1,25-dihydroxyvitamin D levels and fractional calcium absorption (r = 0.221). Calcium malabsorption was common in this series of patients, and serum 25-hydroxyvitamin D levels were useful in predicting fractional calcium absorption. Treatment with oral 25-hydroxyvitamin D3 was accompanied by improved calcium absorption.

Adult↗

PubMedDate not supplied

Anemia in newborn.

Various blood indices vary in a newborn as compared to older child or adult. It depends on the gestational age, day of life, maternal factors, mode of delivery and site of blood collection. Hemoglobin, HCT & MCV tend to be higher in newborns. They further increase in first 2 days of life. Reticulocytosis and presence of nucleated red cells are normally seen in first week of life. Neonatal anemia is a common problem in NICU. It is usually caused by either hemorrhage or hemolysis and rarely due to decreased production. Hemorrhage can be ante or intra or post natal and it could be external or internal. It could be acute or chronic. Management of acute severe hemorrhage includes packed cell transfusion. Hemolysis is usually due to isoimmune hemolysis, G6PD deficiency or rarely due to the hemoglobinopathy like alpha-thalassemia or due to spherocytosis. Usually patients will have indirect hyperbilirubinemia which needs phototherapy or exchange transfusion. Rarely congenital pure red cell aplasia can present at birth with physical anomalies and anemia. Treatment of neonatal anemia depends on the arteriology.

Adult↗

PubMedDate not supplied

Fluorides in dental health: recent concepts.

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Dental Caries↗

PubMedDate not supplied

Delayed puberty.

Delayed puberty is a frequently encountered problem causing much anxiety to patient and parents alike. Proper understanding of the normal pubertal events and its variation sets off the background to understand disorders leading to delayed puberty. An orderly clinical approach combined with continued observation helps to arrive at a final diagnosis in most of the patients. The treatment modalities available, even if not curative, can achieve the goals of management set off at the end of evaluation of the patient.

Adolescent↗

PubMedDate not supplied

Foetal co-relates and mode of delivery in asphyxia neonatorum.

A prospective study was conducted on consequitively born live births for determining the role of certain foetal factors and mode of delivery on asphyxia neonatorum. The difference in the incidence of neonatal asphxia in 1208 singleton births (8.5%) and in the 66 multiple births (9.7%) was statistically significantly (p less than 0.01). Among the singleton live births a significantly increased incidence of asphyxia was recorded in preterms when compared to term and post term babies collectively (p less than 0.001). Small for date babies were at a greater risk for asphxia neonatorum when compared to babies weighing appropriate for gestational age (p less than 0.001). An inverse relationship was observed between birth weight and asphyxia neonatorum. A significant difference was seen in the occurrence of neonatal asphyxia between babies weighing less than 2000 g. and those weighing more than 2000 g. (p less than 0.001). The incidence was significantly influenced by mode of delivery, being highest in vaginal breech delivery followed in decreasing frequency by forceps and normal vaginal delivery. Among vaginal breech delivered neonates those weighing greater than or equal to 2500 g were at the highest risk. Evidence of foetal distress and meconium stained amniotic fluid had a low predictability of asphyxia being 35.0% and 40.0% respectively though both were statistically significant (p less than 0.001).

Asphyxia Neonatorum↗

PubMedDate not supplied

Tropical splenomegaly syndrome.

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Child↗

PubMedDate not supplied

Orientation, structure, wet-spinning, and molecular basis for supercontraction of spider dragline silk.

This manuscript reviews work from our laboratory that addresses the orientation, secondary structure, wet-spinning, and molecular basis for supercontraction of spider silk. It identifies the poly(alanine) runs as the crystalline regions, establishes the degree of orientation of these regions, and identifies the secondary structural elements of the conserved L-G-X-Q (X = G, S, or N) regions. It also describes methods for spinning very small amounts of protein polymers and it sets forth several molecular-level hypotheses concerning supercontraction.

Amino Acid Sequence↗

PubMedDate not supplied

A novel approach to high-throughput quality control of parallel synthesis libraries.

Combinatorial chemistry is a powerful tool to enhance drug discovery efforts in the pharmaceutical industry. One type of combinatorial chemistry, parallel synthesis, is now widely used to prepare numerous compounds of structural diversity. A novel high-throughput method for quality control of parallel synthesis libraries has been developed. The method uses flow injection MS, for proof of structure and estimation of purity, and a novel direct injection CLND technique for quantitation of amount. Following the synthesis of a small molecule library, compounds analyzed using this technique were characterized by mass spectrometry, and an accurate concentration of the compound was assessed by CLND. Characterization of one compound is completed in 60 s, allowing for up to 1000 compounds to be analyzed in a single day. The data is summarized using pass/fail criteria using internally developed software.

Chemistry, Organic↗

PubMedDate not supplied

Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy.

Frequency-domain photon migration (FDPM) is a non-invasive optical technique that utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure optical properties in thick tissues. Optical properties (absorption, mu(a), and scattering, mu(s)', parameters) derived from FDPM measurements can be used to construct low-resolution (0.5 to 1 cm) functional images of tissue hemoglobin (total, oxy-, and deoxy-forms), oxygen saturation, blood volume fraction, water content, fat content and cellular structure. Unlike conventional NIR transillumination, FDPM enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by FDPM makes it well-suited to characterizing tumors in thick tissues. In order to test the sensitivity of FDPM for cancer diagnosis, we have initiated clinical studies to quantitatively determine normal and malignant breast tissue optical and physiological properties in human subjects. Measurements are performed using a non-invasive, multi-wavelength, diode-laser FDPM device optimized for clinical studies. Results show that ductal carcinomas (invasive and in situ) and benign fibroadenomas exhibit 1.25 to 3-fold higher absorption than normal breast tissue. Within this group, absorption is greatest for measurements obtained from sites of invasive cancer. Optical scattering is approximately 20% greater in pre-menopausal versus post-menopausal subjects due to differences in gland/cell proliferation and collagen/fat content. Spatial variations in tissue scattering reveal the loss of differentiation associated with breast disease progression. Overall, the metabolic demands of hormonal stimulation and tumor growth are detectable using photon migration techniques. Measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development.

Breast Neoplasms↗

PubMedDate not supplied

Improving functions in leprotic hands.

PURPOSE: In the developed countries there is a shift in the rehabilitation strategy from community based services to work site based services for the disabled. Leprosy disabled are more at a disadvantage that many of them have not had the benefit of disability prevention activities and harbour such hand deformities for which the only solution is community based rehabilitation. METHOD/RESULTS: Of the various modalities of rehabilitation the authors consider one for this article suitable for work site based rehabilitation as the Modulan grip-aids. CONCLUSION: Essential components of the material and its uses are described with examples.

Equipment Design↗