Leptomeningeal carcinomatosis: easy to miss.

Leptomeningeal carcinomatosis is a devastating condition with very poor prognosis. With advances in cancer treatment leading to improved survival in solid tumours, the incidence of ante-mortem diagnosis of leptomeningeal carcinomatosis is likely to rise. Without a high index of suspicion and appropriate imaging the diagnosis can be missed. We report two cases of leptomeningeal carcinomatosis secondary to metastatic breast disease with varied clinical presentation where the diagnosis was initially missed.

Vulnerability of Bacillus spores and of related genera to physical impaction injury with particular reference to spread-plating.

AIMS: To examine whether bacterial spores are vulnerable to impaction injury during standard spread-plating or to other modes of physical impaction. METHODS AND RESULTS: Employing heat-challenged spores of Bacillus pumilus, Bacillus subtilis, Bacillus thuringiensis, Lysinibacillus, Paenibacillus and Brevibacillus spp. from day-4 to day-10 nutrient agar (NA) plates in 50% ethanol, plating the spore suspension to the extent of just drying the agar surface on fresh NA (50-60 s; SP-B) was tested in comparison with the spreader-independent approach of spotting-and-tilt-spreading (SATS), or a brief plating (<10 s; SP-A). Spore CFU was significantly reduced with SP-B in different organisms (23-40%) over SATS independent of the spore size. Comparing 4-, 7- and 10-day-old B. pumilus spores, the former two displayed significant CFU reduction in SP-B indicating a spore age-related effect. Continuous plating for 2-5 min showed a reduction in spore CFU in all organisms depending on plating duration. CFU reduction effect with SP-B was less manifest on refrigerated plates where no friction was experienced but acute on prewarmed and surface-dried plates. Spreader movement over agar surface subsequent to the exhaustion of free moisture proved highly detrimental to spores. A simulated plating study by plating the spores over a plastic film till drying showed a significant reduction in spore CFU. DAPI staining and glass bead-vortexing studies confirmed spore disruption through physical impaction. CONCLUSIONS: Bacterial spores are vulnerable to injury during spread-plating or with other forms of physical impaction with variable effects on different genotypes independent of the spore size but altered by spore age. SIGNIFICANCE AND IMPACT OF THE STUDY: Implications during spore CFU estimations employing spread-plating and during spore surveillance, and the recommendation of SATS as an easier and safer alternative for spore CFU enumeration.

Physical impaction injury effects on bacterial cells during spread plating influenced by cell characteristics of the organisms.

AIMS: To understand the factors that contribute to the variations in colony-forming units (CFU) in different bacteria during spread plating. METHODS AND RESULTS: Employing a mix culture of vegetative cells of ten organisms varying in cell characteristics (Gram reaction, cell shape and cell size), spread plating to the extent of just drying the agar surface (50-60 s) was tested in comparison with the alternate spotting-and-tilt-spreading (SATS) approach where 100 µl inoculum was distributed by mere tilting of plate after spotting as 20-25 microdrops. The former imparted a significant reduction in CFU by 20% over the spreader-independent SATS approach. Extending the testing to single organisms, Gram-negative proteobacteria with relatively larger cells (Escherichia, Enterobacter, Agrobacterium, Ralstonia, Pantoea, Pseudomonas and Sphingomonas spp.) showed significant CFU reduction with spread plating except for slow-growing Methylobacterium sp., while those with small rods (Xenophilus sp.) and cocci (Acinetobacter sp.) were less affected. Among Gram-positive nonspore formers, Staphylococcus epidermidis showed significant CFU reduction while Staphylococcus haemolyticus and actinobacteria (Microbacterium, Cellulosimicrobium and Brachybacterium spp.) with small rods/cocci were unaffected. Vegetative cells of Bacillus pumilus and B. subtilis were generally unaffected while others with larger rods (B. thuringiensis, Brevibacillus, Lysinibacillus and Paenibacillus spp.) were significantly affected. A simulated plating study coupled with live-dead bacterial staining endorsed the chances of cell disruption with spreader impaction in afflicted organisms. CONCLUSIONS: Significant reduction in CFU could occur during spread plating due to physical impaction injury to bacterial cells depending on the spreader usage and the variable effects on different organisms are determined by Gram reaction, cell size and cell shape. The inoculum spreader could impart physical disruption of vegetative cells against a hard surface. SIGNIFICANCE AND IMPACT OF STUDY: Possibility of CFU reduction in sensitive organisms and the skewed selection of hardier organisms during spread plating, and the recommendation of SATS as an easier and safer alternative for CFU enumerations.

Structural insights into the extra cellular segment of integrinß5 and molecular interaction studies.

Primary tumor cells often spread to other organs by metastasis. Despite of it, primary tumor cells break their surrounding extra cellular matrix (ECM) proteins and reach the destination organ by the process of intravasation and extravasation. Metastasized tumor cells induce the process of angiogenesis, this highly regulated process involves several ECM proteins. However, integrins are primarily involved in the blood vessel growth and repair. Therefore, integrins are promising angiogenesis targets. Integrins are receptors on cell surface, involved in signal transduction and attachments in extra cellular matrix (ECM). IntegrinαVß3 and αVß5 are implicated in tumor angiogenesis, metastasis, inflammation and bone resorption. The crystal structure of integrinαvß5 is not available in protein structural databases, therefore; molecular model of integrinß5 structure was prepared and stereo chemical model quality was checked. Integrin ß5 active sites were identified based on insilico analysis tools. Further, molecular level interactions between integrinß5 and ECM proteins were predicted. In the present study ECM proteins such as focal adhesion kinase 1 (FAK1), annexin A5 and P21 activated kinase 4 (PAK4) were considered for protein-protein docking, to understand inter molecular interactions. The predicted model is conceived to be stereo chemically good and can be used for molecular interaction studies of angiogenic inhibitors.

Nonrecovery of varying proportions of viable bacteria during spread plating governed by the extent of spreader usage and proposal for an alternate spotting-spreading approach to maximize the CFU.

AIMS: To elucidate the cause of high variations and inconsistencies in bacterial CFU observed within and between different experiments while assessing viable bacterial counts through spread plating (SP). METHODS AND RESULTS: Following the inconsistent results, CFU estimations were undertaken through conventional SP using the spreader, or a modified approach that did not use spreader employing four organisms. The latter approach involving spotting-and-tilt-spreading of inoculum on agar surface [spotting spreading (SS)] yielded higher CFU by 11-120% over the weighted average depending on the organism and diluent. The adverse effect owing to the spreader was the most obvious in Escherichia coli followed by Staphylococcus epidermidis, Enterobacter cloacae and Bacillus pumilus. Plate attributes that determined the surface moisture levels of agar medium and the spreading practice adopted by the personnel formed two other major influencing factors. Plating for shorter periods (<60 s) using fresh 15/20 ml plates caused loss of 3-12% CFU owing to inoculum adhesion to spreader irrespective of glass or polypropylene make. On the other hand, prolonging the plating brought down the CFU significantly. Spreader movement on agar surface subsequent to the exhaustion of free moisture, which was marked by the experiencing of some friction to smooth spreader movement, was detrimental to vegetative cells, while Bacillus spores were less affected. CONCLUSIONS: The study brings out that the way SP is carried out exerts significant effects on CFU influenced by plate conditions. Prolonged use of spreader on dry agar surface could be highly detrimental to bacterial cells. A mild use of spreader accounting for spreader-adhering inoculum or the practice of SS not involving the spreader is recommended. SIGNIFICANCE AND IMPACT OF THE STUDY: This study unravels the effects owing to the spreader on bacterial cells and the CFU and recommends an alternate approach of SS to minimize CFU inconsistencies and to maximize the viable bacterial counts.

An experimental and clinical evaluation of anti-asthmatic potentialities of Devadaru compound (DC).

Devadaru compound was shown to be beneficial in Tamak Swasa (bronchial asthma). Clinical findings revealed higher percentage of relief in cardinal and general symptoms with decrement in the pulse rate and in the respiration rate. A significant linear increase in PEFR value was observed before and after treatment and an increase in FEV1 values measured in Group I subjects. There was relief of all symptoms in a significant number of patients. Occurrence of relief was observed only among patients who suffer less than 10 years duration with Tamak Swasa and among those the frequency of attacks of Tamak Swasa was at fortnightly or monthly intervals. Antispasmodic activity of Devadaru Compound (DC) on acetylcholine (Ach) induced contractions using rat ileum preparation was studied. The results demonstrated that DC inhibits Ach-induced contractions significantly and bears a dose-response relationship. This suggests that DC has got anti-spasmodic activity and corroborates the clinical findings. The clinical findings and experimental studies show that DC is of significant use in the treatment of Tamak Swasa (Bronchial Asthma) and superior to the standard and placebo therapy.

Annotation and BAC/PAC localization of nonredundant ESTs from drought-stressed seedlings of an indica rice.

To decipher the genes associated with drought stress response and to identify novel genes in rice, we utilized 1540 high-quality expressed sequence tags (ESTs) for functional annotation and mapping to rice genomic sequences. These ESTs were generated earlier by 3'-end single-pass sequencing of 2000 cDNA clones from normalized cDNA libraries constructed form drought-stressed seedlings of an indica rice. A rice UniGene set of 1025 transcripts was constructed from this collection through the BLASTN algorithm. Putative functions of 559 nonredundant ESTs were identified by BLAST similarity search against public databases. Putative functions were assigned at a stringency E value of 10(-6) in BLASTN and BLASTX algorithms. To understand the gene structure and function further, we have utilized the publicly available finished and unfinished rice BAC/PAC (BAC, bacterial artificial chromosome; PAC, P1 artificial chromosome) sequences for similarity search using the BLASTN algorithm. Further, 603 nonredundant ESTs have been mapped to BAC/PAC clones. BAC clones were assigned by a homology of above 95% identity along 90% of EST sequence length in the aligned region. In all, 700 ESTs showed rice EST hits in GenBank. Of the 325 novel ESTs, 128 were localized to BAC clones. In addition, 127 ESTs with identified putative functions but with no homology in IRGSP (International Rice Genome Sequencing Program) BAC/PAC sequences were mapped to the Chinese WGS (whole genome shotgun contigs) draft sequence of the rice genome. Functional annotation uncovered about a hundred candidate ESTs associated with abiotic stress in rice and Arabidopsis that were previously reported based on microarray analysis and other studies. This study is a major effort in identifying genes associated with drought stress response and will serve as a resource to rice geneticists and molecular biologists.

Novel genes are enriched in normalized cDNA libraries from drought-stressed seedlings of rice (Oryza sativa L. subsp. indica cv. Nagina 22).

We have utilized an efficient method to enrich cDNA libraries for novel genes and genes responsive to drought stress in rice (Oryza sativa L. subsp. indica). We separately constructed standard and normalized cDNA libraries from leaf tissue of rice seedlings grown under controlled drought stress. Sequencing from the 3' end was performed on 1000 clones from the normalized leaf cDNA library and 200 clones from the standard leaf cDNA library. For the first 200 clones, the clone redundancy in the non-normalized library was about 10%, compared with 3.5% in the normalized cDNA library. Comparison of these cDNAs with the sequences in public databases revealed that 28.2% of the expressed sequence tags (ESTs) from the normalized library were novel. Clones from the standard and normalized leaf libraries and a root library uncovered numerous cDNAs that are highly homologous to known drought-responsive genes including those that encode metallothioneins, late embroyonic abundant (LEA) proteins, heat-shock proteins, cytochrome P450 enzymes, catalases, peroxidases, kinases, phosphatases, and transcription factors.

Crack detection by measurement of mechanical impedance of a rotor-bearing system.

Measurements were done to determine the influence of a transverse crack on the mobility of a rotor-bearing system. The results show that the mobility changes substantially due to the presence of crack and follows definite trends with the crack depth and direction of force application. The significant changes in mobility were observed at the natural frequency and at the running frequency of the rotor system. Good agreement between the experimental results and numerical simulations has been observed. The measurement of mobility has been suggested for crack detection and condition monitoring of rotor-bearing systems.

Quadriplegia in a case of known rheumatoid arthritis.

Rheumatoid arthritis often involves the axial skeleton. Rheumatoid nodule, often a manifestation of rheumatoid arthritis may be present in 20-30% of patients of rheumatoid arthritis. A 69-year-old male was presented with weakness of all the four limbs. He had history of rheumatoid arthritis for last 10 years. On examination, a soft cystic non-compressible lump was found over sacrum. Histopathological examination of the lump showed some changes which were consistent with the changes occur in rheumatoid nodule. The patient was treated conservatively and keeping well after 3 months of follow-up.

Visual experience and deprivation bidirectionally modify the composition and function of NMDA receptors in visual cortex.

The receptive fields of visual cortical neurons are bidirectionally modified by sensory deprivation and experience, but the synaptic basis for these changes is unknown. Here we demonstrate bidirectional, experience-dependent regulation of the composition and function of synaptic NMDA receptors (NMDARs) in visual cortex layer 2/3 pyramidal cells of young rats. Visual experience decreases the proportion of NR2B-only receptors, shortens the duration of NMDAR-mediated synaptic currents, and reduces summation of synaptic NMDAR currents during bursts of high-frequency stimulation. Visual deprivation exerts an opposite effect. Although the effects of experience and deprivation are reversible, the rates of synaptic modification vary. Experience can induce a detectable change in synaptic transmission within hours, while deprivation-induced changes take days. We suggest that experience-dependent changes in NMDAR composition and function regulate the development of receptive field organization in visual cortex.

Detection and monitoring of cracks using mechanical impedance of rotor-bearing system.

The dynamic behavior of structures, in particular, that of a rotor, containing cracks is a subject of considerable current interest. In the present study, the influence of a transverse surface crack, both open and breathing conditions, on the mechanical impedance of the rotor-bearing system, has been investigated by FEM analysis for flexural vibrations. The results show that the mechanical impedance changes substantially due to the presence of crack and follow definite trends with the crack parameters (depth and location) and force location. The normalized mechanical impedance of rotor system is more sensitive to the breathing crack when compared to the open crack. The sudden changes in mechanical impedance have been observed at the multiples of the running frequency for the breathing crack. The measurement of mechanical impedance has been suggested for crack detection and condition monitoring of rotor-bearing systems.

The population problem and family planning effort.

PIP: A discussion of any aspect of family planning must include an evaluation of the current demographic situation and the prospects for the future. With the rate of population growth in developing countries between 2-5% per annum and the drastic reduction in mortality accepted as a positive goal under any circumstances, it becomes evident that the only way to contain the population growth is by fertility control. It was the recognition of this need to contain the population by controlling their fertility which brought about India's adoption of family planning as an officially sponsored program as early as 1951. The goals and efforts have increased in each Five Year Plan. The initial emphasis on the "clinical approach" which expected the people to visit the clinics and avail themselves of the family planning services changed to the "extension approach" in 1963 which brought the advice and services to the people. The program now aims at promoting voluntary acceptance by individuals of 1 or more methods of contraception through a process of education and motivation. Regarding the national perspective, a comprehensive Bill liberalizing abortion has already been passed by the Parliament, and efforts are being made to raise the legal age of marriage from 16 to 18 for women. Concerning performance, 9.11 million sterilizations and 3.94 million IUD insertions have been performed since August 1971. A rise in the use of conventional contraceptives has also been noted. The current pressing problem is one of motivating and educating the millions of illiterate rural people towards family planning. Even if this were possible, the subsequent problem of providing them with the family planning services is formidable. Other problems are the continuation of social and psychological barriers which block the efforts of those promoting family planning, and the fact that 2 often conflicting facets of the family planning effort, the national good and the interest of the individual, need to be reconciled. Emphasis must be given to educating and motivating young couples toward birth spacing well before they marry. Voluntary organizations can help in motivating the public, and this help is needed for success depends on how best and how soon the individual can be motivated towards the common goal.^ieng