Tetanus of suspected dental causality.

Tetanus infection by Clostridium tetani is a major health problem in many developing countries, including India. Significant morbidity and mortality is attributed to lack of awareness, hygiene and incomplete vaccination. The most common cause of tetanus infection follows cutaneous injury or infection. However, a localized point of entry cannot always be determined. Tetanus has been associated with tooth extraction, root canal therapy, gross caries, periodontal abscess and intraoral soft tissue trauma. The classic symptoms of trismus and risus sardonicus may result in an initial presentation to an oral and maxillofacial surgeon. Due to the rarity of this infection, the dentist or the health care provider may fail to corroborate the findings and be unsuspecting of the diagnosis. Prompt recognition is the key in such a scenario due to the inherent risk of rapid progress of symptoms, progressive deterioration of the health condition and catastrophic complications. A sound knowledge of the effects of tetanospasmin, the disease process, prevention and vaccination against tetanus with its management is essential for health care workers. The authors hereby present a case of tetanus with a suspected dental etiology to make the dental fraternity aware of this lurking malady.

Endogenous sex steroid hormones and glucose in a South-Asian population without diabetes: the Metabolic Syndrome and Atherosclerosis in South-Asians Living in America pilot study.

AIMS: To examine the associations between endogenous sex steroid hormones (oestradiol, testosterone and sex hormone-binding globulin) with diabetes risk in a South-Asian population living in the USA. METHODS: We used data from the Metabolic Syndrome and Atherosclerosis in South-Asians Living in America pilot study. The analytical sample included 60 women and 45 men of Asian Indian origin living in the San Francisco Bay Area, who were free from diabetes and cardiovascular disease and did not use exogenous sex steroids. Sex steroid hormone levels were assessed by validated conventional radioimmunoassays, and visceral and hepatic adiposity were assessed by computed tomography. We used multivariable regression to examine the association between endogenous sex steroid hormone levels (log-transformed) and fasting glucose and 2-h glucose levels in a series of sex-stratified models adjusted for age, waist circumference, visceral and hepatic adiposity, and insulin resistance. RESULTS: In age-adjusted models, lower levels of sex hormone-binding globulin (ß = -0.18, 95% CI -0.30, -0.06) and higher levels of free testosterone (ß = 0.14, 95% CI 0.02, 0.26) were associated with elevated fasting glucose levels in South-Asian women, whereas lower levels of sex hormone-binding globulin (ß = -0.14, 95% CI -0.26, -0.02) and lower levels of total testosterone (ß = -0.12, 95% CI -0.24, 0.00) were associated with elevated fasting glucose levels in South-Asian men. Adjustment for waist circumference, visceral adiposity and insulin resistance attenuated most of these associations, while adjustment for hepatic adiposity strengthened some of the observed associations. Similar results were found for 2-h glucose levels. CONCLUSIONS: Results were consistent with previous research, which suggests that endogenous sex steroid hormones are a risk factor for diabetes across multiple race/ethnic groups. Additional studies are needed to determine whether visceral fat is a mediator or confounder of associations between sex steroid hormone and glucose levels.

Analysis of membrane tank-tread of nonspherical capsules and red blood cells.

We present an analysis of membrane motion of deformable capsules and red blood cells suspended in a linear shear flow and undergoing swinging and tumbling motions using three-dimensional numerical simulations. This study is motivated by the theory of the shape-preserving cells which predicts that the direction of the membrane rotation depends on the cell orientation and reverses at every 45° inclination angle of the cell major axis with respect to the external flow direction. By considering large deformation of capsules and red blood cells, here we investigate how the shape oscillation affects the time dependence and the direction reversal of the membrane rotation. We find that the membrane tank-tread is highly time-dependent in nature and synchronized with the time-dependent deformation. The maximum and minimum of the tank-tread velocity occur at and near the minimum and maximum deformation, respectively. For the swinging capsules and red blood cells, the direction of the membrane rotation is always along the direction of the external fluid rotation; however, a direction reversal occurs during the tumbling motion in which case the membrane rotates in the direction of the external fluid rotation when the major axis is mostly in the extensional quadrant of the shear flow, and in the opposite direction when it is mostly in the compressional quadrant. Unlike the theory which predicts the direction reversal at every 45° inclination angle irrespective of the control parameters, namely, the capillary number, viscosity ratio, and asphericity, we find that the angle at which the direction reversal occurs depends on these parameters. In particular, if the tumbling motion occurs by decreasing the capillary number, the membrane rotation is in the direction of the external flow rotation in the entire extensional quadrant, but in the opposite direction in the compressional quadrant, irrespective of the specific values of the capillary number. If the tumbling motion occurs by increasing the viscosity ratio and asphericity, the angle at which the direction reversal occurs depends on the specific values of these two parameters. The spatial variation of the tank-tread velocity also is analyzed and attributed to the straining motion of the external flow.

Cell death regulation during influenza A virus infection by matrix (M1) protein: a model of viral control over the cellular survival pathway.

During early infection, viruses activate cellular stress-response proteins such as heat-shock proteins (Hsps) to counteract apoptosis, but later on, they modulate these proteins to stimulate apoptosis for efficient viral dissemination. Hsp70 has been attributed to modulate viral entry, transcription, nuclear translocation and virion formation. It also exerts its anti-apoptotic function by binding to apoptosis protease-activating factor 1 (Apaf-1) and disrupting apoptosome formation. Here, we show that influenza A virus can regulate the anti-apoptotic function of Hsp70 through viral protein M1 (matrix 1). M1 itself did not induce apoptosis, but enhanced the effects of apoptotic inducers. M1-small-interfering RNA inhibits virus-induced apoptosis in cells after either virus infection or overexpression of the M1 protein. M1 binds to Hsp70, which results in reduced interaction between Hsp70 and Apaf-1. In a cell-free system, the M1 protein mediates procaspase-9 activation induced by cytochrome c/deoxyadenosine triphosphate. A study involving deletion mutants confirmed the role of the C-terminus substrate-binding domain (EEVD) of Hsp70 and amino acids 128-165 of M1 for this association. The M1 mutants, which did not co-immunoprecipitate with Hsp70, failed to induce apoptosis. Overall, the study confirms the proapoptotic function of the M1 protein during influenza virus infection.

Full genomic analyses of human rotavirus G4P[4], G4P[6], G9P[19] and G10P[6] strains from North-eastern India: evidence for interspecies transmission and complex reassortment events.

In hospitalized patients with acute gastroenteritis in Manipur, India, four rotavirus strains were found to possess VP7 and/or VP4 genes with porcine or bovine characteristics. Considering the animal-like nature of these strains, the remaining eight gene segments were analysed to decipher their exact origin. Analyses of full genome of these strains exhibited their origin from porcine/bovine rotaviruses. This study suggests single or multiple events of reassortment involving multiple gene segments of more than one host type among the strains and emphasizes the significance of complete genetic characterization of unusual strains in regions with high incidence and mortality rates.

An innovative surgical technique for treating penile incarceration injury caused by heavy metallic ring.

Penile incarceration injury by heavy metallic ring is a rare genital injury. A man may place metal object for erotic or autoerotic purposes, for masturbation or increasing erection, and due to psychiatric disturbances are some of the reasons for a penile incarceration injury. The incarcerating injury results in reduced blood flow distal to the injury, leading to edema, ischemia, and sometimes gangrene. These injuries are divided into five grades and their treatment options are divided into four groups. Surgical techniques are reserved for the advanced grades (Grades IV and V). We describe an innovative surgical technique, which can be adopted in Grades II and III injuries.

Phase II evaluation of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in advanced, measurable breast carcinoma.

The purpose of this study was to determine whether methotrexate, vinblastine, doxorubicin, and cisplatin, each individually active in metastatic breast cancer (MBC), could, in combination, produce an overall response rate, median survival, and long-term survival sufficiently promising to merit its consideration for phase III trials in MBC and as induction therapy prior to autologous bone marrow transplant. From July 1986 through February 1990, 30 patients with stage IV, measurable breast carcinoma received M-VAC: methotrexate--30 mg/m2 days 1, 15, 22; vinblastine--3 mg/m2 days 2, 15, 22; doxorubicin--30 mg/m2 day 2; cisplatin--70 mg/m2 day 2. Cycles were repeated at 4-week intervals for up to six courses. Median age was 53 years (range 34-64 years). Prior treatment included adjuvant cyclophosphamide, methotrexate, and 5-Fluorouracil in 12 patients, radiotherapy in 13 patients, and hormonal therapy in 14 patients. Eleven patients were ER (+) at the time of initial diagnosis. Five patients had disease restricted to bone and/or nodes; the other 25 had visceral-dominant sites of metastases, with or without bone involvement, or evidence of rapid, inflammatory chest wall relapse. Twenty-nine of 30 patients were evaluable for toxicity and response; all were evaluable for survival. The major overall response rate was 83%, with a 21% complete remission rate. The chief toxicity was bone marrow suppression, with grade 4 granulocytopenia in 20 patients, grade 3 in 7 patients, and grade 3 and 4 thrombocytopenia in 5 patients. Grade 3 stomatitis occurred in 9 patients. Renal insufficiency was clinically insignificant, and neurotoxicity mild, with 7 patients sustaining grade 1 or 2 paresthesias. Median time to progression was 9 months and median survival 19 months (range, 5-84+ months) with 4 patients still alive at least 45+ months or more from the start of treatment and 2 presently free of progressive disease. Although highly toxic, M-VAC produces a response rate and survival duration in visceral-dominant MBC competitive with, if not superior to, conventional regimens such as CAF (Cytoxan, doxorubicin, 5-fluorouracil); it therefore merits further investigation in conjunction with hematopoietic growth factors and as cytoreductive therapy prior to autologous bone marrow transplantation.

Report of phase II trial of concurrent chemoradiotherapy with radical thoracic irradiation (60 Gy), infusional fluorouracil, bolus cisplatin and etoposide for clinical stage IIIB and bulky IIIA non-small cell lung cancer.

PURPOSE: To assess the response rate, median and long-term survival of patients (pts) with locally advanced, initially inoperable non-small cell lung cancer (NSCLC) treated on a phase II study of radical thoracic radiotherapy (TRT) and concurrent radiosensitizing chemotherapy. METHODS AND MATERIALS: From 3/87 to 7/90, 41 previously untreated patients at Fox Chase Cancer Center with locally advanced non-small cell lung cancer, 24 with bulky clinical Stage IIIA, and 17 with IIIB disease, received concurrent thoracic radiotherapy (60 Gy/2.0 Gy/d in 6 weeks) and 2 cycles of infusional 5FU (640-800 mg/m2/24 hrs x 5 d); cisplatin (20 mg/m2 qd x 5); and etoposide (50 mg/m2 d 1, 2, 5) administered days 1 and 28 of TRT. RESULTS: Forty of 41 were evaluable. Response rate was 90%, with radiographic CR in 20%. Thirteen pts (33%) underwent thoracotomy and complete resection with clinical downstaging in 10, including three pathologic CR's. Overall median survival was 14 months and 2-year survival was 38% with no difference between CS IIIA and IIIB pts (p = 0.2224). At median potential follow-up of 42 months, 8/40 pts. (20%) are alive and progression-free, including 4 of 13 resected pts. The chief toxicity was esophagitis, occurring in 32 pts. (80%), Grade 3-4 in 21 (52%), with 13 (33%) requiring hospitalization and 7 (18%) needing TPN. Grade 3-4 granulocytopenia was noted in 20 pts. (50%) with ten episodes of fever mandating intravenous antibiotics. Cardiac ischemia was documented in 2 (5%). Of 13 thoracotomy pts, six underwent lobectomy without perioperative mortality; 3 of 7 pneumonectomy pts died post-operatively, two from broncopleural fistula, and one from ARDS. CONCLUSION: This aggressive regimen produced a 2-year survival (38%) comparable to the best arm of cancer and leukemia groups B study 8433, which administered radical thoracic radiotherapy after protoadjuvant vinblastine and cisplatin in similar and earlier stage non-small cell lung cancer patients. Toxicity, particularly esophagitis, was severe, but of short duration. An unacceptably high complication rate was seen following pneumonectomy, but not lobectomy.

Intraperitoneal cisplatin and etoposide in peritoneal mesothelioma: favorable outcome with a multimodality approach.

Ten patients with histologically documented peritoneal mesothelioma were treated with intraperitoneal cisplatin 200 mg/m2, sodium thiosulfate rescue and etoposide 65-290 mg/m2 every 4 weeks for a maximum of six cycles. All had epithelial or mixed epithelial-fibrous histology. Toxicity was tolerable, with 50% sustaining grade 3 or 4 granulocytopenia. There was one episode of neutropenic fever. Grade 2 peripheral neuropathy occurred in one patient, grade 1 in five patients. Complete remission occurred in one of five patients with measurable disease. Median survival for patients whose tumors were surgically debulked to < 2 cm residua prior to treatment was 22 months, while it was 5 months for those with measurable, surgically inaccessible disease (P = 0.0731 by Cox regression proportional hazard model). These data suggest that patients who present with resectable disease may benefit from an aggressive adjuvant approach. This possibility warrants prospective testing in a randomized clinical trial.

Compound regressive models for quantitative multivariate phenotypes: application to lipid and lipoprotein data.

In this paper we consider the compound version of the class D regressive models for a p variate phenotypic outcome. The likelihood function is noted and the results are illustrated with the Donner Laboratory data, without the assumption of a major gene for the brevity of presentation.

Effect of quinalphos on testicular steroidogenesis in rats.

The effect of quinalphos (250 micrograms/kg i.p.) an organophosphorus insecticide treatment for 13 and 26-days on the testicular steroidogenic enzymes viz. 3 beta-Hydroxysteroid Dehydrogenase and 17 beta-Hydroxysteroid Dehydrogenase, as well as cholesterol content and histology of the testes of the Wistar strain rats was studied. The time duration of 13 days is approximately equivalent to one cycle of the seminiferous epithelium in Wistar strain rats. Treatment of quinalphos for 13 days failed to produce any effect on the relative weights of the testes and accessory sex glands. However, significant inhibition of 3 beta-HSD activity and increased cholesterol level in testis were observed. The rats treated for 26 days similarly showed a highly significant inhibition of the activity of both 3 beta-HSD and 17 beta-HSD. The relative weights of the testes and accessory sex glands were also significantly reduced. Histological examination of the testis revealed that quinalphos treatment produced detrimental changes in the seminiferous epithelium. Treatment with quinalphos for 13-days produced no toxic effect with the exception of a significant increase in serum alkaline phosphatase. However, after 26-days of treatment toxicity was significantly increased as reflected on serum transaminases, phosphatases and blood urea levels of rat. Present study indicated that quinalphos impairs testicular functions in rats.

Suppression of testicular steroidogenesis in rats by the organochlorine insecticide Aldrin.

Treatment with Aldrin, an organochlorine insecticide, for 13 and 26 days caused suppression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities, along with accumulation of cholesterol in the testicular tissues of adult rats. The same treatment also resulted in a reduction in the nuclear diameter of Leydig cells (LCND) and diameter of seminiferous tubules. A decrease in the weight of testes, seminal vesicles and ventral prostate was also noted. HCG administration in the long-term (26 days) treatment restored the steroidogenic enzymes activity and the nuclear diameter of the Leydig cells. It also reduced the accumulation of tissue cholesterol towards the vehicle-injected controls. The inhibition of steroidogenesis in the testes possibly reflects a decrease in pituitary gonadotrophin release after the treatment with Aldrin.

Release of synaptosomal dopamine formed from tyrosine and L-DOPA.

The present report compares the synaptosomal release of [3H]dopamine, continuously forming from [3H]DOPA, with that of [14C]dopamine, forming from [14C]tyrosine as a marker of dopaminergic nerve endings. For the purpose of the comparison, synaptosomal (P2) preparations from rat caudate nuclei were incubated with L-[3H]DOPA and [14C]tyrosine for 10 min and the particulates were rapidly separated from the medium postincubation. The separated fractions were analyzed for the level of double labelled (14C/3H) dopamine and the synaptosomal content of the labelled substrates. Of the total labelled dopamine formed, the fraction that was present in the medium, following the synaptosomal release, was determined. Tested were the release enhancing effects of various additions which included several known dopaminergic agents, serotonin and 5-hydroxytryptophan. The data show that the addition of dopamine to the incubation mixture to either 0.5 or 1.0 muM concentration markedly enhanced the release of labelled dopamine. Serotonin when added to 5.0 muM concentration also raised the medium content of labelled dopamine but it was ineffective at 1.0 muM. 5-Hydroxytryptophan, 1.0 or 5.0 muM, had no effect. For the comparison of the release enhancing effects of an addition on [14C]dopamine and [3H]dopamine, the corresponding release indices (release index = medium/total ratio of labelled dopamine in the presence of an addition divided by the same ratio in control (no addition) sample) were determined. The data indicate that the index of [14C]dopamine did not differ significantly from that of [3H]dopamine following the addition of either dopamine, serotonin or 5-hydroxytryptophan at any of the concentrations tested. A similar lack of difference between the index of [14C]dopamine and that of [3H]dopamine was observed following the addition of reserpine (1.8 muM), although a considerable enhancement of labelled dopamine release occurred. The addition of either amphetamine (9.1 muM) or amfonelic acid (9.1 muM) also enhanced labelled dopamine release but in their presence the index of [3H]dopamine was significantly higher than that of [14C]dopamine. Amfonelic acid preferentially raised the [3H]dopamine index at the lowest concentration of 0.91 muM that we have tested and also after only 5 min of incubation; coaddition of reserpine increased the [14C]dopamine release, thus abolishing the preferential effect of amfonelic acid on [3H]dopamine release, thus abolishing the preferential effect of amfonelic acid on [3H]dopamine. When the incubation was performed without an addition (control sample), no difference (NS) was observed between the particulate to medium distribution of [14C]dopamine and that of [3H]dopamine after either 5, 10 or 15 min. The results suggest that (a) dopamine synaptosomally formed from L-DOPA may exist in a pool distinct from that dopamine arising from tyrosine hydroxylation and (b) the observed dopamine compartmentation may be due to some mechanism distinct from any possible participation of serotoninergic particles...

Ovarian steroidogenesis in rats following inhibition of DNA synthesis after administration of mitomycin C.

Suppression of delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-OHD) and glucose-6-phosphate dehydrogenase (G-6-PD) activities were observed in the rat ovarian tissues following treatment with Mitomycin C (MC), an antibiotic which depresses DNA synthesis. The same treatment also resulted in accumulation of cholesterol and ascorbic acid in the ovaries and a decrease of uterine weight. The atretic changes in the treated ovaries were judged from the activity of the lysosomal enzyme leucine amino-peptidase (LAP). The results suggest a diminution in ovarian steroid biogenesis following an alteration of DNA synthesis.