Association of P2X7 receptor +1513 (A-->C) polymorphism with tuberculosis in a Punjabi population.

BACKGROUND: Development of tuberculosis (TB) disease is an outcome of complex host-pathogen interactions. The purinergic P2X(7) receptors are adenosine triphosphate gated molecules shown to induce killing of intracellular Mycobacterium tuberculosis, followed by apoptosis of the infected macrophage. A single nucleotide polymorphism in exon 13 of the P2X(7) receptors gene at +1513 position has been shown to abolish the function of this receptor and to be associated with increased susceptibility to TB in some ethnic groups. OBJECTIVE: To explore the association of +1513 (A-->C) polymorphism in TB patients in Punjab, North India. DESIGN: A case-control study was conducted by studying peripheral blood samples from 204 TB patients (181 pulmonary, 23 extra-pulmonary) and 177 controls with no history of TB. P2X(7) +1513 (A-->C) polymorphism was studied using amplification refractory mutation system analysis. RESULT: The distribution of +1513 A/C genotypes in the TB patient and the control groups revealed a statistically significant association with TB (P = 0.002). CONCLUSION: The +1513C allele is a risk factor for the development of TB in the North Indian Punjabi population.

Spatial variability of atrazine and metolachlor dissipation on dryland no-tillage crop fields in Colorado.

An area of interest in precision farming is variable-rate application of herbicides to optimize herbicide use efficiency and minimize negative off-site and non-target effects. Site-specific weed management based on field scale management zones derived from soil characteristics known to affect soil-applied herbicide efficacy could alleviate challenges posed by post-emergence precision weed management. Two commonly used soil-applied herbicides in dryland corn (Zea mays L.) production are atrazine and metolachlor. Accelerated dissipation of atrazine has been discovered recently in irrigated corn fields in eastern Colorado. The objectives of this study were (i) to compare the rates of dissipation of atrazine and metolachlor across different soil zones from three dryland no-tillage fields under laboratory incubation conditions and (ii) to determine if rapid dissipation of atrazine and/or metolachlor occurred in dryland soils. Herbicide dissipation was evaluated at time points between 0 and 35 d after soil treatment using a toluene extraction procedure with GC/MS analysis. Differential rates of atrazine and metolachlor dissipation occurred between two soil zones on two of three fields evaluated. Accelerated atrazine dissipation occurred in soil from all fields of this study, with half-lives ranging from 1.8 to 3.2 d in the laboratory. The rapid atrazine dissipation rates were likely attributed to the history of atrazine use on all fields investigated in this study. Metolachlor dissipation was not considered accelerated and exhibited half-lives ranging from 9.0 to 10.7 d in the laboratory.

Influence of histamine and H1-receptor antagonists on ejaculated human spermatozoa: role of intrasperm Ca2+.

Histamine reduced sperm viability in a dose- and time-dependent manner, accompanied by rise in intrasperm Ca2+. Further, 2',4'-dichlorobenzamil hydrochloride (DBZ), a Na+-Ca2+ exchange inhibitor, known to elevate intrasperm Ca2+, potentiated both, elevation of intrasperm Ca2+ and spermicidal action of histamine. Pretreatment of sperm with very low doses of H1-receptor antagonists (chlorpheniramine, promethazine or diphenhydramine) prevented the histamine-induced elevation of intrasperm Ca2+ as well as its spermicidal action. However, pretreatment with famotidine, a H2-receptor antagonist did not produce such a protective action. The results strongly suggest that histamine elicits its spermicidal action via H1-receptors present on sperm cells.

Repair of a critical size defect in the rat mandible using allogenic type I collagen.

Mandibular fractures, resulting from either trauma or reconstructive surgery, can be challenging craniofacial problems. The morbidity of failed fracture healing is significant and may require bone grafting. Donor site morbidity and finite amounts of autogenous bone are major drawbacks of autogenous bone grafting. Similarly, the use of allografts and xenografts may be associated with an increased risk of rejection, infection, and nonunion. To circumvent the limitations of bone grafting, research efforts have focused on formulating a suitable bone substitute. The purpose of our study was to evaluate the efficacy of type I collagen implants in repairing critical sized mandibular defects in rats. Twelve male Sprague-Dawley rats (200-300g) were divided equally into control and experimental groups. Full thickness, round, four millimeter in diameter defects were created in the ramus of the right mandible of all rats using an electrical burr at low speed. The defects were irrigated of all bone chips, and either filled with a precisely fitted disk of allogenic collagen type I gel (experimental animals) or left empty (control animals). Animals were killed 6 weeks after surgery and healing of the bone defects was assessed in a blinded fashion using radiologic and histologic analysis. Radiologic analysis of the control group revealed a clear circular right mandibular defect in all animals, whereas the collagen disk implant group revealed an indistinct to nonexistent right mandibular defect in all animals. Densitometric analysis revealed a significant difference between these groups (* P = 0.01). Similarly, gross analysis of control mandibles revealed a 4mm round, soft-tissue filled defect, while implanted defects demonstrated gross bone spanning the defect. Finally, histologic analysis of all control mandibles revealed clearly demarcated bony edges at the defect border with connective tissue spanning the defect. In contrast, histological analysis of all implanted mandibles revealed indistinct bony edges at the defect border with a thin layer of osteoblasts and viable bone spanning the defects. We have demonstrated the ability of type I collagen to promote healing of a membranous bony defect that would not otherwise heal at 6 weeks. The suitability of type I collagen as a carrier matrix provides ample opportunity for tissue-engineered approaches to further facilitate bony defect healing. Promoting bone formation through tissue engineering matrices offers great promise for skeletal healing and reconstruction.

Constrained scaling: the effect of learned psychophysical scales on idiosyncratic response bias.

We report seven experiments in which subjects were trained to respond with numbers to the loudness of 1000-Hz pure tones according to power functions with exponents of 0.60, 0.30, and 0.90. Subjects were then presented with stimuli from other continua (65-Hz pure tones or 565-nm lights varying in amplitude) and were asked to judge the subjective magnitude of these stimuli on the same numerical scale. Stimuli from the training continuum were presented, with feedback, on every other trial in order to maintain the trained scale. Except for the 0.90 scale, subjects readily learned the predetermined scales and were able to use them to judge the non-training stimuli with group results consistent with those usually reported. Also, in contrast to the usual magnitude estimation results, these results produced extremely low levels of intersubject variability. We argue that such learned scales can be used as "rulers" for measuring perceived magnitudes, according to a common unit.

Heat-related illnesses.

The majority of clinicians will encounter patients with heat-related illness in one form or the other. Early recognition and management are important to prevent morbidity and mortality. In children and elderly, the clinical signs may be subtle and in such situations a sound knowledge of heat-related illnesses is crucial. Besides diagnosing and treating heat-related illnesses, it is equally important to know how to prevent them as they are easily preventable.

Streptogramins: a new class of antibiotics.

Streptogramin antibiotics represent a unique class of antibacterials in the each member of the class consists of at least 2 structurally unrelated molecules: group a streptogramins (macrolactones) and group B streptogramins (cyclic hexadepsipeptides). Both group A and group B streptogramins inhibit protein synthesis at the ribosomal level, and they act synergistically against many isolates their combination generating bactericidal activities and reducing the possibility of emergencies of resistant strains. The mechanisms of acquired resistance to group B streptogramins remain unaffected by target modifications and active efflux. The pharmacokinetic parameters of group A and group B streptogramins in blood are quite similar. In addition, both the A and B group penetrate and accumulate in macrophages and in the bacterial gegetations of experimental endocarditis. Until recently, the complex and irregular composition of naturally occurring pristinamycin and virginiamycin, as well as the unavailability of soluble forms, have limited the clinical development of streptogramins. The synthesis of water soluble derivatives of pristinamycin IA and IIB has now allowed the development of injectable streptogramins with fixed compositions. This unique class of antibacterials will have a significant clinical impact in a world of increasing multidrug resistance affecting the Gram-positive cocci, especially staphylococci and pneumococci. The absence of cross-resistance to macrolides in many of these isolates and the rapid antibacterial killing against these species bright future for this class of antibiotics.

Opioid receptor mediated anticonvulsant effect of pentazocine.

Intraperitoneal (i.p.) administration of (+/-) pentazocine (10, 30 & 50 mg/kg), a Sigma opioid agonist, resulted in a dose dependent anticonvulsant action against maximal electroshock seizures in mice. This anticonvulsant effect of pentazocine was not antagonized by both the doses of naloxone (1 and 10 mg/kg) suggesting thereby that its anticonvulsant action is probably mediated by Sigma opiate binding sites. Its anticonvulsant effect was potentiated by both the anticonvulsant drugs viz. diazepam and diphenylhydantoin. Morphine, mu opioid agonist, on the other hand, failed to protect the animals against maximal electroshock seizures when it was given in doses of 10-40 mg/kg body wt.

Simvastatin-induced lupus erythematosus.

We report the case of a 79-year-old man who had onset of fatigue, myalgia, and pleuritic chest pain 3 months after initiation of therapy with simvastatin. He had signs of pleuropericarditis due to simvastatin-induced lupus erythematosus. This should alert clinicians to this possible adverse effect of simvastatin and other statins.

Cholecystectomy alleviates acalculous biliary pain in patients with a reduced gallbladder ejection fraction.

BACKGROUND: We sought to determine whether a reduced gallbladder ejection fraction, (GBEF) ascertained by cholecystokinin-cholescintigraphy (CCK-CS), predicts symptomatic improvement after cholecystectomy. METHODS: Medical records of patients who had had CCK-CS as well as negative results of gallbladder ultrasonography were reviewed, and patients were contacted by telephone to determine whether they had benefited from cholecystectomy. RESULTS: There were 35 patients (33 female, 2 male) who had a decreased GBEF. Cholecystectomy was done in 30, of whom 20 (67%) had resolution of pain, 8 (27%) had partial improvement, and 2 (7%) had no change. The 5 who declined cholecystectomy included none (0%) who were pain free, 2 (40%) who had partial improvement, and 3 (60%) who had no change. The clinical outcome of the two groups was significantly different. There were 14 patients (10 female, 4 male) with a normal GBEF. The 2 patients who had cholecystectomy were asymptomatic. Of the 12 patients who did not have cholecystectomy, 9 (75%) were asymptomatic, 1 (8%) had some improvement, and 2 (17%) had no change. CONCLUSIONS: Cholecystectomy is indicated for patients with acalculous biliary pain and reduced GBEF, since symptoms will likely resolve with surgery and will persist without it. Cholecystectomy for patients with a normal GBEF should be considered only after failure of a nonoperative trial, since improvement usually occurs over time.

Efficacy of laser-assisted uvulopalatoplasty.

BACKGROUND AND OBJECTIVE: Laser-assisted uvulopalatoplasty (LAUP) is being used increasingly as a surgical treatment for snoring and obstructive sleep apnea (OSA). There is limited evidence for the success of LAUP in eliminating OSA. This study assesses the efficacy of LAUP in eliminating snoring and OSA and addresses which patients may be the best candidates for LAUP treatment. STUDY DESIGN/MATERIALS AND METHODS: From January 1994 to January 1996, 297 patients were evaluated for snoring, with 190 (64%) exhibiting some degree of OSA documented by a PSG: 41/ 190 (22%) mild OSA; 33/190 (17%) moderate OSA; 85/190 (45%) severe OSA; 31/190 (16%) severity unknown. Ninety patients (90/ 297) have undergone LAUP treatment: 58/90 (64%) with OSA and 32/90 (36%) with snoring only. RESULTS: Our results indicate a significant reduction of snoring in patients without OSA, but diminishing success in patients with increasing degrees of OSA. Additionally, LAUP was not efficacious in treating OSA: pre-op respiratory disturbance index (RDI) of 10.8 vs. post-op RDI of 19.5 for mild OSA (P = 0.14); pre-op RDI of 22.9 vs. post-op RDI of 25.4 for moderate OSA (P = 0.43); pre-op RDI of 56.8 vs. post-op RDI of 46.3 (P < 0.05), which is statistically but not clinically significant (i.e., RDI remained in the severe range). CONCLUSION: We conclude that LAUP is an effective treatment for nonapneic snoring, but does not provide sufficient resolution of OSA, and based on our results, LAUP should be considered as an adjunctive therapy rather than a sole treatment for OSA in most cases.

An occult cervical spine fracture.

A 16-year-old athlete developed neck pain after being dropped on his head with his neck flexed while recreationally wrestling. Initial cervical spine radiographs were negative, but he continued to have neck and arm pain, especially after heading a wet soccer ball. Two months after the initial injury, he had a positive Spurling test; cervical spine CT then revealed a parasagittal linear fracture through the body of C-7. The patient avoided contact and collision activities and had no further physical problems. For patients who suffer cervical spine trauma, adequate visualization of the cervical spine can help prevent catastrophic outcomes.

Modulation of convulsive threshold of pentylene tetrazole by zinc.

In the present study which was aimed to see the effect of zinc on pentylenetetrazole induced convulsive threshold in rats we found that zinc sulfate 100 µg intracerebroventricularly) and pentylenetetrazole (50 mg/kg intraperitoneally) produced dose related seizure activity; however, pretreatment with zinc decreased the threshold, increased the severity, incidence of multiple seizures and total duration of pentylenetetrazole induced seizures. Diazepam (5 mg/kg intraperitoneally) pretreatment increased the threshold and lowered the incidence of convulsions in zinc induced seizures which further confirms that the convulsive effect of zinc is through inhibition of gamma aimino butyric acid.

Children's play provisions: time for change.

PIP: An overview is provided of essential features of play environments for children which enhance their creative development: play space, play environments, equipment for play, safe equipment, creative adult input, and time factors. Safety measures are described along with a list of do's and don'ts. Management of play areas and the training of educators were also discussed. Arguments are given as support for creative play provisions, but the conclusion is that the trend is to restrict children's expression, to limit their freedom, to impose limits to action and thought, to encourage normative behavior, and to inhibit creative thinking. Space requirements are that the area be ample. In rural and tribal areas, space is unlimited; in cities, creative use of space may involve use of terraces, enclosed courtyards, dead end road areas free of traffic, or a large open area away from traffic. In spite of space limitations, children tend to adapt to the space available. For instance, a pipe sticking out of a wall could be a bar to swing on. Effective use of space is dependent on organization and structuring. In rural areas, children learn by their own discoveries, and many are denied the exposure to educators who can organize their play or play objects to foster creativity. Play is divorced from work and learning, when it can also be structured to offer opportunities for development of cognitive skills. Stimulating play environments may include a mound of earth that separates one part of an open space from another; children find looking to see what is on the other side intriguing. Children can run up and down the hill. A sand pit with building and digging instruments can provide hours of fascination. A water hole with stones could provide a place to jump across and foster imaginative games. A tunnel could be carved out of the hill to provide a place of dramatic play. A low tree with a twisted trunk is inviting for climbing, swinging, jumping, or playing hide and seek. Play equipment should be simple, natural, everyday objects, available at low cost and able to withstand rough use. Highly structured equipment tends to be ignored over time. Rope, drums, old tires, wooden planks and poles, metal pipes, sacks, and cardboard boxes are some types of equipment that are described for play use. These discarded objects must be safe and can be enhanced with a fresh coat of nontoxic paint.^ieng

Comparative study of out-reach immunization strategies in rural area.

Efficiency of out-reach immunization strategies operationalised in a rural area of district Ambala (Haryana) was evaluated. Till year 1984-85 immunization delivery was 'sporadic'. Annual cluster immunization campaigns were conducted during 1985-86 and 1986-87. This comprised of delivery of oral polio vaccine (OPV) and/or measles once in a year to all eligible children, other vaccine continued to be delivered by health workers during routine beats. Regular immunization sessions were undertaken in 1987-88 and 1988-89. All the vaccines were delivered on 4 fixed days (one day per week) of each month, covering village at least once a month. Significant increase in immunization coverage was observed after cluster campaigns. OPV increased from 46.5 to 73.6%, DPT from 49.1 to 75.5%, BCG from 48.7 to 72.2%, measles from 8.6 to 45.8% and tetanus toxoid (TT) for pregnant women (PW) from 41.8 to 65.3%. Under regular programme the coverage levels were maintained at OPV 79.4%, DPT 78.2%, BCG 70.6%, measles 48% and TT (PW) 76.2%. Regular out-reach immunization strategy was found to be better than cluster campaigns as it was 'regular' and high coverage level could be maintained.

Nd:YAG laser modulation of synovial tissue metabolism.

In studies designed to establish the safety and efficacy of laser treatment of arthritis, the in vitro effect of Nd:YAG laser radiation on normal, osteoarthritic and rheumatoid synovial tissue and synovial fibroblast metabolism has been addressed. Defined energy levels of normal pulsed radiation (TEMoo mode) consistently up-regulated synovial tissue explant culture hyaluronic acid and protein synthesis. In contrast, high intensity Q-switched delivery down-regulated the response. The application of normal pulsed radiation had a variable effect on synovial fibroblast synthesis but the response of any given cell isolate was consistent. DNA synthesis and cell viability were not affected.