Inbreeding and the incidence of childhood genetic disorders in Karnataka, South India.

Consanguineous marriages are strongly favoured among the populations of South India. In a study conducted on 407 infants and children, a total of 35 genetic diseases was diagnosed in 63 persons: 44 with single gene defects, 12 with polygenic disorders, and seven with Down's syndrome. The coefficient of inbreeding of the total study group, F = 0.0414, was significantly higher than that previously calculated for the general population, F = 0.0271, and autosomal recessive disorders formed the largest single disease category diagnosed. The results suggest that long term inbreeding may not have resulted in appreciable elimination of recessive lethals and sub-lethals from the gene pool.     

Mycobacterial cervical lymphadenitis in childhood

A study of 190 children of chronic cervical lymphadenitis showed tuberculous etiology on histopathological examination in 92 (48.4%) and bacteriological evidence of mycobacterial infection (smear and/or culture) in 42 (22.1%). Of these 42, twelve (28.6%) showed histopathological diagnosis of non-specific lymphadenitis. Positive culture for mycobacteria was obtained in 40, of which 30 (75%) were typical M. tuberculosis and 10 (25%) were atypical mycobacteria. The most predominant species of typical mycobacteria was M. scrofulaceum (60%) followed by M. avium intracellulare (40%). There was no remarkable difference in the histopathological pattern of those in which M. tuberculosis was grown and those in which bacterial growth was that of atypical mycobacteria. The diagnosis of chronic cervical lymphadenitis should therefore be taken a step beyond histopathology, up to complete bacteriological examination, especially to confirm the cases of mycobacterial lymphadenitis caused by atypical mycobacteria.     

Immunoglobulin G, A, and M Responses in Serum and Circulating Immune Complexes Elicited by the 16-Kilodalton Antigen of Mycobacterium tuberculosis

The 16-kDa cytosolic antigen of M. tuberculosis was purified to homogeneity by molecular sieving chromatography, and the diagnostic potential of the antigen was evaluated in various categories of patients by enzyme-linked immunosorbent assay (ELISA). The immunoglobulin G (IgG), IgA, and IgM antibody levels to 16-kDa antigen were estimated in the two polar groups, namely, smear- and culture-positive pulmonary tuberculosis (S⁺C⁺) patients and healthy subjects (HS). Sensitivities of 62, 52 and 11% with specificities of 100, 97, and 95% were obtained for the three isotypes, respectively. The total number of positives by a combination of the three isotypes was analyzed in the polar groups, and the sensitivity improved to 83% with a specificity of 93%. Even when a combination of IgG and IgA alone was considered, the sensitivity was 82% with a specificity of 97%. Polyethylene glycol precipitation of the circulating immune complex (CIC) in sera was carried out. The CIC-bound antibodies to 16-kDa antigen were assessed by ELISA in the S⁺C⁺, S⁻C⁺, and S⁻C⁻ categories of patients. Measuring the IgG-IgA-IgM combination positivities of the CIC-bound antibodies gave sensitivities of 97.5, 100, and 45.3%, respectively. The specificity of the assay with these combinations was maintained at 95.4%.     

Immediate breast reconstruction-impact on radiation management

Breast reconstruction is an option for women undergoing modified radical mastectomy due to a diagnosis of breast cancer. In certain patients, breast reconstruction is performed by insertion of a temporary tissue expander prior to the placement of permanent breast implants. Some of these patients, following mastectomy, may require chest wall irradiation to prevent loco regional relapse. The compatibility of radiation and tissue expanders placed in the chest wall is of major concern to the radiation oncologist. Clinically undetectable changes can occur in the tissue expander during the course of radiation therapy. This can lead to radiation treatment set-up changes, variation in tissue expansion resulting in unwanted cosmesis, and deviation from the prescribed radiation dose leading to over and/or under dosing of tumor burden. At Howard University hospital, a CT scan was utilized to evaluate the status of the temporary tissue expander during radiation treatment to enable us to prevent radiation treatment related complications resulting from dosimetric discrepancies. CT images of the tissue expander were obtained through the course of treatment. To avoid a 'geographic miss' the amount of fluid injected into the tissue expander was kept constant following patient's satisfaction with the size of the breast mound. The CT scans allowed better visualization of the prosthesis and its relation to the surrounding tumor bed. This technique ensured that anatomical changes occurring during radiation treatment, if any, were minimized. Repeated dosimetry evaluations showed no changes to the prescribed dose distribution. A CT of the reconstructed breast provides an important quality control. Further studies with greater number of patients are required for confirming this impact on radiation treatment.     

Design, fabrication, and characterization of a tissue-equivalent phantom for optical elastography

We suitably adapt the design of a tissue-equivalent phantom used for photoacoustic imaging to construct phantoms for optical elastography. The elastography phantom we consider should have optical properties such as scattering coefficient, scattering anisotropy factor, and refractive index; mechanical properties such as storage and loss modulus; and acoustic properties such as ultrasound velocity, attenuation coefficient, and acoustic impedance to match healthy and diseased tissues. The phantom is made of poly (vinyl alcohol) (PVA) and its mechanical, optical, and acoustic properties are tailored by physical cross-linking effected through subjecting a suitable mix of PVA stock and water to a number of freeze-thaw cycles and by varying the degree of hydrolysis in the PVA stock. The optical, mechanical, and acoustic properties of the samples prepared are measured by employing different techniques. The measured variations in the values of optical scattering coefficient, scattering anisotropy factor, and refractive index and storage modulus are found to be comparable to those in normal and diseased breast tissues. The acoustic properties such as sound speed, acoustic attenuation coefficient, and density are found to be close to the average values reported in the literature for normal breast tissue.     

Dystrophin gene deletions in South Indian Duchenne muscular dystrophy patients

66 unrelated patients from Southern India with Duchenne Muscular Dystrophy (DMD) were studied for intragenic deletion in 18 exons and Pm region of the DMD gene using multiplex PCR. Of these 41 (62.1%) showed intragenic deletions. 78% of the deletions were located at the distal hotspot region (44-55 exons) and 22% of the deletions were located at the proximal region (exon 2-19). Exon 50 is most frequently deleted. Deletions in isolated cases were significantly more compared to familial cases. The lower incidence reported from South India compared to North India, is suggestive of variations in the Southern and Northern population.     

The Digital Imaging Workstation

Picture archiving and communication systems (PACS) are expected to convert film-based radiology into a computer-based digital environment, with associated cost savings and improved physician communication. The digital workstation will be used by physicians to display these soft-copy images; however, difficult technical challenges must be met for the workstation to compete successfully with the familiar viewbox. Issues relating to image perception and the impact on physicians practice must be carefully considered. The spatial and contrast resolutions required vary according to imaging modality, type of procedure, and class of user. Rule-based software allows simple physician interaction and speeds image display. A consensus appears to be emerging concerning the requirements for the PACS workstation. Standards such as the American College of Radiology/National Electrical Manufacturers Association Digital Imaging and Communication Standard are facilitating commercial applications. Yet much careful study is needed before PACS workstations will be fully integrated into radiology departments. Abbreviations: CRT = cathode ray tube, H&D = Hurter and Drifield, PACS = picture archiving and communication system, ROC = receiver operating characteristic, S/N = signal-to-noise ratio. Partially supported by grant HL-33332 from the National Heart, Lung, and Blood institute, U.S. Public Health Service. Address reprint requests to R.L.A. Copyright © 1990 by the Radiological Society of North America. Radiology 176:303-315, 1990. Reprinted with permission.     

Adenosine deaminase in cord blood as an immunoenzyme marker in low birth weight neonates

Adenosine Deaminase (ADA) levels were estimated in cord blood of 30 neonates born with birth weight less than or equal to 2.5 kg and 30 neonates born with birth weight greater than 2.5 kg. The mean ADA levels in low birth weight (LBW) group was found to be 6.94 U/L and in normal birth weight group the mean ADA levels were 14.37 U/L which was statistically significant. Therefore ADA may be useful in assessing CMI status in low birth weight infants.     

Survival prediction of glioblastoma patients—are we there yet? A systematic review of prognostic modeling for glioblastoma and its clinical potential

Glioblastoma is associated with a poor prognosis. Even though survival statistics are well-described at the population level, it remains challenging to predict the prognosis of an individual patient despite the increasing number of prognostic models. The aim of this study is to systematically review the literature on prognostic modeling in glioblastoma patients. A systematic literature search was performed to identify all relevant studies that developed a prognostic model for predicting overall survival in glioblastoma patients following the PRISMA guidelines. Participants, type of input, algorithm type, validation, and testing procedures were reviewed per prognostic model. Among 595 citations, 27 studies were included for qualitative review. The included studies developed and evaluated a total of 59 models, of which only seven were externally validated in a different patient cohort. The predictive performance among these studies varied widely according to the AUC (0.58–0.98), accuracy (0.69–0.98), and C-index (0.66–0.70). Three studies deployed their model as an online prediction tool, all of which were based on a statistical algorithm. The increasing performance of survival prediction models will aid personalized clinical decision-making in glioblastoma patients. The scientific realm is gravitating towards the use of machine learning models developed on high-dimensional data, often with promising results. However, none of these models has been implemented into clinical care. To facilitate the clinical implementation of high-performing survival prediction models, future efforts should focus on harmonizing data acquisition methods, improving model interpretability, and externally validating these models in multicentered, prospective fashion.