Biomedical subjects

B Singh

Publications and source records attributed to B Singh.

At least 253 records · Page 14Linked to original sources

PubMed1999

Effect of lithium augmentation on the trace elemental profile in diabetic rats.

Energy dispersive X-ray fluorescence technique was employed to study the interactions among various elements, viz.: K, Zn, Br, Fe, Cu, Br & Rb in 4 groups of rats viz. control-GI, diabetic-GII (diabetes induced by i.p. administration of alloxan monohydrate at a dose level of 150 mg/kg b.w; single injection), lithium treated-GIII (lithium administered as Li2 Co3 at a dose level of 1.1 g of Li2 Co3/kg animal diet; free access; serum lithium levels--0.5-1.2 mEq/L) and lithium + diabetic rats-GIV. The different treatments continued for a total duration of 1 month. The K contents were found to be significantly lowered in all the treatment groups which was maximum (28%) in lithium treated diabetic rats. Depression in the levels of Rb was noticed in lithium treated and lithium treated diabetic (G-III and G-IV) groups. However, the levels (Rb) remained unaltered in diabetic (G-II) group. Interestingly, a significant decline was observed in Fe levels in G-III following lithium administration but the levels remained unchanged in G-IV with lithium administration to diabetic rats. On the other hand, lithium treatment to normal (G-III) and diabetic (G-IV) rats indicated statistically significant elevation in the levels of Cu and Br. However, diabetic (G-II) rats did not indicate any elevation in the levels of these two elements. Interestingly, the concentrations of Zn were found to be significantly elevated in all the treatment groups, which was maximum (37%) in G-III (lithium) group. A comparison of various elements from lithium treated diabetic group G-IV with the corresponding elements from the diabetic group G-II, implied a significant depression in K and Rb levels and a significant elevation in the levels of Br.

Animals↗

PubMed1999

Evolutionary relationships among photosynthetic prokaryotes (Heliobacterium chlorum, Chloroflexus aurantiacus, cyanobacteria, Chlorobium tepidum and proteobacteria): implications regarding the origin of photosynthesis.

The presence of shared conserved insertions or deletions in proteins (referred to as signature sequences) provides a powerful means to deduce the evolutionary relationships among prokaryotic organisms. This approach was used in the present work to deduce the branching orders of various eubacterial taxa consisting of photosynthetic organisms. For this purpose, portions of the Hsp60 and Hsp70 genes, covering known signature sequence regions, were PCR-amplified and sequenced from Heliobacterium chlorum, Chloroflexus aurantiacus and Chlorobium tepidum. This information was integrated with sequence data for several other proteins from numerous species to deduce the branching orders of different photosynthetic taxa. Based on signature sequences that are present in different proteins, it is possible to infer that the various eubacterial phyla evolved from a common ancestor in the following order: low G+C Gram-positive (H. chlorum) --> high G+C Gram-positive --> Deinococcus-Thermus --> green non-sulphur bacteria (Cf. aurantiacus ) --> cyanobacteria --> spirochaetes --> Chlamydia-Cytophaga-Aquifex-flavobacteria-green sulphur bacteria (Cb. tepidum) --> proteobacteria (alpha, delta and epsilon) and --> proteobacteria (beta and gamma). The members of the Heliobacteriaceae family that contain a Fe-S type of reaction centre (RC-1) and represent the sole photosynthetic phylum from the Gram-positive or monoderm group of prokaryotes are indicated to be the most ancestral of the photosynthetic lineages. Among the Gram-negative bacteria or diderm prokaryotes, green non-sulphur bacteria such as Cf. aurantiacus, which contains a pheophytin-quinone type of reaction centre (RC-2), are indicated to have evolved very early. Thus, the organisms containing either RC-1 or RC-2 existed before the evolution of cyanobacteria, which contain both these reaction centres to carry out oxygenic photosynthesis. The eubacterial divisions consisting of green sulphur bacteria and proteobacteria are indicated to have diverged after cyanobacteria. Some implications of these results concerning the origin of photosynthesis and the earliest prokaryotic fossils are discussed.

Amino Acid Sequence↗

PubMed1999

Mechanisms of induction of renal allograft tolerance in CD45RB-treated mice.

BACKGROUND: Rejection is the most significant problem in the field of transplantation. The current goal of transplant immunology is to develop better immunotherapeutic protocols that are aimed at specifically suppressing alloreactivity and preserving an otherwise intact immune system. We have previously shown that mice will accept renal allografts indefinitely with normal renal function after two injections of a monoclonal antibody to the CD45RB protein. Furthermore, this antibody will reverse acute rejection when therapy is delayed until day 4 and will still induce tolerance. The mechanisms of this therapeutic benefit are not known. METHODS: BALB/C mice were used as recipients of major multiple histocompatibility complex-mismatched kidneys using C57BL/6 as donors. Immunoperoxidase microscopy and Northern blots for cytokine gene expression were used to study the renal allografts. Fluorescence-activated cell sorter (FACS) analyses of peripheral blood lymphocytes were performed. Phosphotyrosine peptide phosphatase assays were performed on splenic lymphocyte membranes. RESULTS: A CD45RB monoclonal antibody (MB23G2) induced tolerance and partially depletes peripheral blood lymphocytes. A therapeutically ineffective CD45RB monoclonal antibody (MB4B4) merely coated the circulating lymphocytes. Furthermore, MB23G2 stimulated more tyrosine phosphatase activity than MB4B4 in mouse T-cell membranes. CONCLUSIONS: The clearance of peripheral blood lymphocyte populations and stimulation of protein tyrosine phosphatase activity may be important in the mechanism of tolerance induction by CD45RB therapy, which may be clinically relevant in the therapy of organ rejection in humans.

Animals↗

PubMed1999

Coexistent Hashimoto's thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome.

BACKGROUND: This study was performed to assess the relationship between Hashimoto's thyroiditis and the development, presentation, management, and outcome of papillary thyroid carcinoma. METHODS: Two complementary analytic methods were used. The clinical study was a retrospective case-control study, including patients seen with papillary thyroid carcinoma presenting during a 12-year period. We also used a systematic literature review to identify suitable reports and meta-analysis to statistically combine published results. RESULTS: The prevalence of Hashimoto's thyroiditis is significantly higher in patients with papillary thyroid cancer (odds ratio, 1.89; 95% CI, 1.02-3.50). These patients typically have a dominant nodule, 44% of which are discovered incidentally on routine examinations. Fine-needle aspiration has a sensitivity of 91% for the identification of papillary cancer. The prognostic variables at the time of a diagnosis of papillary cancer and the approach to management are not altered by the presence of coexistent Hashimoto's thyroiditis. In addition, the rate of surgical complications was not higher in patients with coexistent Hashimoto's disease. Meta-analysis suggested a positive correlation between Hashimoto's disease and disease-free survival (r = 0.09; 95% CI, 0.05-0.12) and overall survival (r = 0.11; 95% CI, 0.07-0.15). CONCLUSIONS: There is an increased prevalence of Hashimoto's thyroiditis in patients with papillary thyroid carcinoma. The presence of coexistent Hashimoto's thyroiditis does not affect the diagnostic evaluation or management of papillary thyroid cancers. The survival of patients who have papillary thyroid cancers may be superior in coexistent Hashimoto's thyroiditis.

Adult↗

PubMed1999

Alterations in head and neck cancer occurring in HIV-infected patients--results of a pilot, longitudinal, prospective study.

To assess the impact of human immunodeficiency virus (HIV) infection on the presentation and course of head and neck squamous cell carcinoma (HNSCC), we performed a pilot, prospective, longitudinal study of all patients with HNSCC presenting to our institutions over a 6-month period (n = 10). A 60% incidence of HIV infection was seen in this study population, with SCC presenting as the initial manifestation of HIV infection in 2 of the 6 patients. In addition. HIV-infected patients were significantly younger than non-infected patients at (p = 0.01). None of the HIV-infected patients had acquired immunodeficiency syndrome (AIDS) at the time of presentation, but 5 of 6 patients had an abnormal CD4 count, compared to none of the non-infected patients (p = 0.05). The absolute CD4 count in HIV-infected patients decreased to less than 100x10(9)/L in the majority of these patients within 3 months of presentation with HNSCC (p = 0.05). Treatment-associated complications were common in HIV-infected patients, occurring in 4 of the 6 cases in contrast to none of the patients without HIV infection (p = 0.046). Outcome was significantly poorer for HIV-Infected patients, with 5 patients succumbing to their disease within one year, in contrast to none of the non-infected patients (p = 0.046). These data, combined with our previous work, justify further investigation of the relationship between HNSCC and HIV infection and the possibility of its inclusion as an AIDS-defining process.

Adult↗

PubMed1999

Unpredictable cyclosporin--fluconazole interaction in renal transplant recipients.

BACKGROUND: Cyclosporin (CsA) is metabolized primarily in the liver by cytochrome P-450 enzymes. Concomitant use of fluconazole can increase CsA concentrations by inhibiting this enzyme system and the effect seems to be dose dependent, with no interaction noted when fluconazole is used in a dose of 100 mg/day. Two previous investigations studying this interaction while using higher doses of fluconazole have provided inconsistent results. Recommendations advising an empirical 50% CsA dosage reduction in these patients have not been tested in a prospective trial. METHODS: We studied six renal transplant recipients on CsA immunosuppression in a prospective, unblinded, crossover trial. Baseline renal functions, CsA area under the curve (AUC), Cmax, Cmin, CsA clearance, and Tmax were compared with those 2, 4 and 7 days after starting fluconazole orally in a dose of 200 mg/day. From day 8 onwards, patients reduced CsA dose by 50% and the above parameters were repeated on day 14. RESULTS: CsA AUC increased from 2887 +/- 1729 ng.h/ml on day 0 to 3842 +/- 1975 ng.h/ml on day 2 (P < 0.05), 4750 +/- 1718 ng.h/ml on day 4 (P< 0.01) and then decreased to 4052 +/- 1687 ng.h/ml on day 7 (P<0.01). Following CsA dose reduction by 50%, the mean AUC decreased significantly to 2330 +/- 1602 ng x h/ml (P<0.01). The Cmax showed a significant increase from 701 +/- 345 ng/ml on day 0 to 941 +/- 326 ng/ml (P < 0.01) on day 4 but decreased from 768 +/- 292 ng/ml on day 7 to 498 +/- 289 ng/ml on day 14, P<0.01. The mean Cmin increased from 207 +/- 138 ng/ml on day 0 to 274 +/- 168 ng/ml on day 4. No significant changes were observed in CsA clearance and Tmax. On repeated-measurement ANOVA, only the AUC and Cmax on day 4 of fluconazole were significantly higher than day 0 (P<0.001). There was a large interindividual variability in the degree of drug interaction between patients. CONCLUSIONS: Fluconazole given orally in a dose of 200 mg/day is associated with significant increase in bioavailability of CsA. The maximum effect occurs on day 4 after starting fluconazole. Although repeated monitoring of CsA Cmin is convenient as opposed to repeated determination of AUC, changes in Cmin may not be sensitive enough to pick up this interaction. The increase in bioavailability of CsA is unpredictable in individual patients and all patients should be monitored with AUC near day 4 of treatment to guide CsA dosage reductions.

Adult↗

PubMed1999

Intestinal parasites in Malaysian children with cancer.

In this prospective study, we examined stool specimens from children with cancer receiving chemotherapy who were admitted for fever to the Universiti Sains Malaysia Hospital in Kota Baru, Kelantan. Stool specimens were examined for ova and cysts of parasites. Over a period of 15 months, there were 129 febrile episodes in 50 children with cancer and, in all, 237 stool specimens were examined. Sixty-six per cent of febrile episodes were associated with neutropenia and 9 per cent were associated with diarrhoea. Stool parasites were found in 42 per cent of children. The most common were helminths, followed by protozoa. Trichuris trichiura was the most common parasite (24 per cent), followed by Ascaris lumbricoides (22 per cent). Hookworm was found in 2 per cent. Giardia lamblia was found in 6 per cent of children, Blastocystis hominis in 4 per cent, and Cryptosporidium parvum in 2 per cent.

Animals↗

PubMed1999

Ischemic and nonischemic heart failure do not require different treatment strategies.

Published clinical practice guidelines from the U.S. Agency for Health Care Policy and Research, the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the Task Force of the Working Group on Heart Failure of the European Society of Cardiology--supported by the results of numerous large-scale randomized controlled trials--define the standard universal pharmacologic approach to all patients with left ventricular systolic dysfunction. According to these guidelines, all heart failure patients regardless of etiology (with rare exceptions such as obstructive valvular heart disease) should be treated with an angiotensin-converting enzyme (ACE) inhibitor as first-line treatment of the heart failure. In fact, the non-edematous patient with only mild exertional dyspnea may be treated with an ACE inhibitor as sole therapy of the left ventricular dysfunction. As patients become edematous or complain of more moderate congestive symptoms, it is then appropriate to add a diuretic along with the ACE inhibitor. Digoxin is reserved for those patients who remain symptomatic on an ACE inhibitor and diuretic. Carvedilol, the only beta-adrenergic receptor blocker approved by the U.S. Food and Drug Administration for the treatment of heart failure, has been shown to reduce morbidity and mortality in patients with New York Heart Association Class II or III symptoms. In the U.S. Carvedilol Heart Failure Trials Program, carvedilol's benefit was seen in patients with either ischemic or nonischemic etiologies of heart failure. Similar findings of benefit in both ischemic and nonischemic heart failure have been observed in the recently reported Second Cardiac Insufficiency Bisoprolol Study (CIBIS II) trial as well as in ACE inhibitor heart failure trials. Studies suggesting differences in outcome based on etiology during pharmacologic treatment of heart failure have been too small (inadequately powered) or have assessed this difference only in post-hoc analyses. Thus, the universal pharmacologic management of heart failure with an ACE inhibitor, diuretic, beta-blocker (e.g. carvedilol), and digoxin may be applied to all patients with ischemic or nonischemic heart failure. This makes sense since the pathophysiology of heart failure following myocardial injury is similar for both forms of the disease.

Cardiac Output, Low↗

PubMed1999

Hemangiopericytoma of the head and neck.

OBJECTIVE/HYPOTHESIS: Hemangiopericytomas are uncommon neoplasms of vascular origin that may arise in the head and neck. Their rare occurrence and variable malignant potential have limited attempts to characterize their clinical behavior. This study reviews the experience in treating hemangiopericytomas of the head and neck at a single institution. STUDY DESIGN: Retrospective. METHODS: The records of 12 patients with hemangiopericytomas of the head and neck presenting between 1979 and 1995 were reviewed. Site of origin included the neck (4), oral cavity (3), parotid (2), orbit (1), maxillary sinus (1) and mandible (1). Five patients had lesions characterized as high or intermediate grade histologically, and six had lesions characterized as low grade. RESULTS: Nine patients were treated with curative intent; three presented either with pulmonary metastasis (2) or unresectable primaries (1) and were treated with radiation therapy and/or palliative Adriamycin-based chemotherapy. Patients treated with curative intent underwent a variety of surgical resections dictated by tumor location and size. Four patients received postoperative radiation therapy to a median dose of 60 Gy, for positive surgical margins (2), high-grade histology (1) or a recurrent lesion (1). Five-year overall survival in patients treated surgically was 87.5%. A single mortality occurred in a patient with a recurrent high-grade lesion who failed at local, regional, and distant sites. Median follow-up of survivors was 73 months. CONCLUSION: The clinical behavior of hemangiopericytomas appears to be related to their histological grade. Aggressive local therapy including surgery and radiation therapy appears to be effective in providing tumor control.

Antineoplastic Agents↗

PubMed1999

Factors associated with complications in microvascular reconstruction of head and neck defects.

The use of microvascular free tissue transfer has allowed the reconstruction of increasingly complex defects in higher risk patients after head and neck cancer resections. However, the combination of these factors also gives rise to a higher risk for the development of complications. This study was performed to establish the pretreatment factors associated with complication development after microvascular free tissue transfer for the reconstruction of defects resulting from head and neck cancer ablations, with particular attention to the role of comorbid conditions. A retrospective cohort study was conducted including 200 consecutive microvascular free tissue transfers performed for the reconstruction of surgical defects in the head and neck region at a single tertiary care institution. Comorbidity severity was assessed using the Charlson comorbidity index, a novel approach to comorbid staging in this setting. The flap survival rate was 98 percent. Complications developed in 56 cases (28 percent), with multiple complications occurring in 21 of these cases (10.5 percent). Univariate analysis revealed that prior radiation treatment (p = 0.03), anesthesia time over 10 hours (0.05), and advanced Charlson comorbidity grade (0.002) were associated with an increased risk for the development of complications. However, only the presence of advanced Charlson grade proved significant after multivariate analysis (odds ratio 3.9; 95 percent CI = 1.5 to 10.1). In addition, increasing Charlson grade (p = 0.003) and age over 70 years (p = 0.04) correlated with increasing complication severity. Systemic complications occurred in 28 patients (14 percent), with advanced Charlson grade being the only significant factor associated with the development of complications after controlling for confounding factors (odds ratio 3.8; 95 percent CI = 1.5 to 9.7). In patients over 70 years of age, increasing operative time also impacted on the development of systemic complications (p = 0.002), especially in patients with advanced Charlson grades (0.01). Recipient site complications occurred in 30 patients (15 percent), with history of prior radiation therapy being the only factor associated with increased risk by multivariate analysis (odds ratio 2.5; 95 percent CI = 1.1 to 5.7). No factors predicted the development of donor-site complications, which occurred in 11 cases (5.5 percent). The median hospital stay for the entire population was 16 days. The development of complications increased the median hospital stay by 7.5 days (p < 0.001). The effect of the development of complication on hospital stay remained significant even after controlling for the effects of confounding variables (relative risk = 9.87; 95 percent CI = 5.9 to 19.9). Microvascular surgery is a highly successful and relatively safe method for the reconstruction of large head and neck defects. The Charlson comorbidity index grading may be useful for identifying patients at increased risk for the development of complications after microvascular reconstruction, allowing for improved perioperative planning. In addition, patients with prior radiation exposure have a significantly higher risk for developing complications at the recipient site. Although advanced age is not associated with an increased risk for complications, older patients may be more sensitive to the effects of prolonged anesthesia and are likely to develop more severe complications.

Animals↗

PubMed1999

Barium swallows after free jejunal transfer: should they be performed routinely?

Fistula formation after free jejunal transfer for pharyngoesophageal reconstruction is a serious complication with potentially critical consequences. Barium swallow is used postoperatively to check for anastomotic competence before feeding but has been unreliable as a predictor of leak at our institution. The objective of this study was to evaluate the role of routine postoperative barium swallow in 41 consecutive jejunal transfers. Thirty-nine patients who underwent 41 consecutive free jejunal transfers had a routine barium swallow performed between postoperative days 12 and 17. Radiologic findings and clinical outcome were evaluated and correlated. All barium swallows were reviewed by a single experienced radiologist in a blinded fashion. One total and one partial flap failure necessitated a second free jejunal transfer. Pharyngocutaneous fistulae developed after nine free jejunal transfers, of which the barium swallow was normal in four (44 percent) and showed a leak in five (56 percent). In the 32 free jejunal transfers with no clinical leaks, 6 (19 percent) had radiologic leakage of contrast. Thus, barium swallow was normal in 30 patients and showed leakage in 11 patients. Normal barium swallow correlated with uncomplicated clinical course in 26 of 30 cases. In the remaining four cases (13 percent), however, a delayed fistula developed, which was secondary to flap necrosis in one case (negative predictive value 87 percent). On the other hand, radiologic leaks corroborated clinical fistula in 5 of 11 cases (45 percent), whereas no fistula developed in 6 cases (positive predictive value 46 percent). Of the five patients with clinical fistulae, four had early leaks (within 1 week), and the barium swallow did not provide additional information. The fifth patient developed a delayed leak 2 weeks after the barium swallow. Review of these barium swallows at the time of this study reversed the initial report of leakage in three patients, improving the predictive value to 63 percent. These patients had an uncomplicated clinical course. The positive predictive value of clinical assessment alone was 63 percent. We conclude that barium studies following free jejunal transfers can be difficult to interpret, but an experienced radiologist can improve their accuracy. A normal barium swallow, however, does not ensure an uneventful clinical course. Similarly, radiologic leaks do not imply a clinical complication of fistula. Clinical judgment should therefore be exercised in initiating oral intake after free jejunal transfer. Barium swallow should be used only as an adjunct to aid in patient management.

Adolescent↗

PubMed1999

Increase in intake with sham feeding experience is concentration dependent.

Most sham feeding studies show that about three sham feeding tests are required for intake to reach maximum. One study, however, using a dilute solution, reported maximum sham intake in the first sham feeding test, suggesting that the progressive rise in sham intake may be concentration dependent. We tested this hypothesis with six groups of rats given five sham feeding tests each with one of six concentrations of sweetened condensed milk (0.5:1, 1:1, 2:1, 4:1, 8:1, 16:1, water-to-milk dilutions). It took three sham tests for intake to reach maximum with the three most concentrated solutions, but only one with the three weakest. Thus the intake of concentrated solutions of milk is limited by two negative feedback signals, one derived from the accumulation of fluid in the gastrointestinal tract, the other from a labile signal that loses its effectiveness with sham feeding experience. In contrast, the intake of weak concentrations is limited only by the nonlabile negative feedback signal because the labile signal is missing.

Animals↗

PubMed1999

Effect of asbestos-related pleural fibrosis on excursion of the lower chest wall and diaphragm.

To examine mechanisms responsible for reduced lung volumes (restriction) in asbestos-related pleural fibrosis (APF), we studied diaphragm function and lower rib-cage excursion in 26 subjects with previous asbestos exposure and no evidence of asbestosis. Using posteroanterior (PA) and lateral chest radiographs taken at residual volume and at 25%, 70%, and 100% vital capacity (VC) during a slow inspiratory maneuver, we measured fractional expansion of the lower rib cage (FErc), fractional shortening of the diaphragm (FSdi), and changes (Delta) in diaphragm dome height (Hdo) and subphrenic volume (Vdi). Vdi was estimated by measuring the major and minor axes of the subphrenic space at 1-cm intervals, assuming an elliptical cross-sectional shape, and correcting for the volume of spinal and paraspinal tissues. Seven subjects had no evidence of APF (control), 12 had pleural plaques (PP), and seven had diffuse pleural thickening with costophrenic obliteration (DPT). Over the range of VC, results (mean +/- SEM, normalized for height) in control subjects were VC = 101.2 +/- 4.0 % predicted and DeltaVdi = 326 +/- 8 ml/m(3), and for the right hemithorax and hemidiaphragm on the PA film, FErc = 0.07 +/- 0.02, FSdi = 0.32 +/- 0.02 and DeltaHdo = 0.8 +/- 0.2 cm/m. Relative to controls: DPT subjects had reduced VC (77.4 +/- 4.9%, p < 0.01), DeltaVdi (256 +/- 2 ml/m(3), p < 0.01), FErc (0.01 +/- 0.02, p < 0.01), FSdi (0.24 +/- 0.01, p < 0.001), and DeltaHdo (-0.9 +/- 0.06 cm/m, p < 0.01); PP subjects had reduced FSdi (0.25 +/- 0.01, p < 0.001) and DeltaVdi (233 +/- 47 ml/m(3), p < 0.01), and no difference in FErc, DeltaHdo, or VC. We conclude that restriction in DPT is due to obliteration of the zone of apposition, and that by limiting separation of the diaphragm from the rib cage during inspiration, this reduces volume contributed by motion of the diaphragm and lower rib cage. Reduction in the latter contribution was the main cause of restriction, because the reduction in volume contributed by the diaphragm was partly compensated by flattening of its dome.

Asbestos↗

PubMed1999

Pressure is proinflammatory in lung venular capillaries.

Endothelial responses may contribute importantly to the pathology of high vascular pressure. In lung venular capillaries, we determined endothelial [Ca(2+)](i) by the fura-2 ratioing method and fusion pore formation by quantifying the fluorescence of FM1-43. Pressure elevation increased endothelial [Ca(2+)](i). Concomitantly evoked exocytotic events were evident in a novel spatial-temporal pattern of fusion pore formation. Fusion pores formed predominantly at vascular branch points and colocalized with the expression of P-selectin. Blockade of mechanogated Ca(2+) channels inhibited these responses, identifying entry of external Ca(2+) as the critical triggering mechanism. These endothelial responses point to a proinflammatory effect of high vascular pressure that may be relevant in the pathogenesis of pressure-induced lung disease.

Animals↗

PubMed1999

Laryngeal pathology in the acquired immunodeficiency syndrome: diagnostic and therapeutic dilemmas.

The acquired immunodeficiency syndrome has produced a growing population of patients who, because of their associated immune system compromise, are prone to opportunistic infections and neoplastic diseases. The larynx, with its relatively inaccessible yet critical anatomic location, is a site in which these processes can produce clinical dilemmas, with respect to diagnosis as well as to therapy. By presenting 4 cases involving unusual laryngeal problems in patients infected with the human immunodeficiency virus (HIV), we emphasize these inherent diagnostic and therapeutic problems. Otolaryngologists must be familiar with the many diagnostic possibilities and therapeutic alternatives when HIV-infected patients present with laryngeal complaints.

AIDS-Related Opportunistic Infections↗

PubMed1999

Antioxidants mimic the ability of chorionic gonadotropin to suppress apoptosis in the rabbit corpus luteum in vitro: a novel role for superoxide dismutase in regulating bax expression.

We have recently reported that members of the bcl-2 gene family are expressed and estradiol regulated in rabbit luteal cells during corpus luteum (CL) regression, and that estradiol and hCG are effective inhibitors of apoptosis in the rabbit CL in vivo and in vitro. As Bcl-2 and related proteins are known to regulate levels of reactive oxygen species or their intermediates in cells as one possible mechanism to control apoptosis, the present studies were designed to examine if oxidative stress plays a role in luteal cell apoptosis during CL regression in the rabbit. In the first set of experiments, healthy CL obtained from day 11 pseudopregnant rabbits were incubated in serum-free medium for 2 h in the absence or presence of superoxide dismutase (SOD; 1.5-150 U/ml), ascorbic acid (1-100 mM), N-acetyl-L-cysteine (25 and 50 mM), or catalase (10-1000 U/ml). Cells within CL incubated in medium alone exhibited extensive apoptosis (examined by analysis of extracted DNA using 3'-end labeling), and this onset of apoptosis was blocked in a dose-dependent fashion by treatment with SOD, ascorbic acid, N-acetyl-L-cysteine, or catalase. In the second set of experiments, expression of bax and bcl-x in CL after in vitro treatment without and with 100 U/ml SOD was examined. Although SOD treatment did not alter the levels of bcl-x messenger RNA (mRNA) over the 2-h incubation period, this antioxidant enzyme significantly reduced the levels of bax mRNA in incubated CL. In the final set of experiments, we observed that expression of mitochondrial- or manganese-containing SOD was significantly increased by treatment of isolated CL with 1 microg/ml hCG in vitro, whereas bax mRNA levels were significantly reduced under the same culture conditions. Collectively, these data indicate that the gonadotropin-mediated inhibition of apoptosis in rabbit luteal cells involves enhanced expression of the oxidative stress response gene, manganese-containing SOD, whose protein product may then function to protect luteal cells directly from the damaging effect of reactive oxygen species and/or indirectly by acutely down-regulating expression of Bax, a prooxidant member of the Bcl-2 protein family.

Animals↗

PubMed1999

Late outcome from percutaneous tracheostomy using the Portex kit.

OBJECTIVE: To assess late outcome following percutaneous tracheostomy using the Portex kit (Hythe, Kent, UK). DESIGN: Prospective observational cohort study. SETTING: Teaching hospital. PATIENTS: Forty-nine consecutive patients who underwent percutaneous tracheostomy in the ICU using the Portex kit and who survived 6 months after the procedure. INTERVENTIONS: Questionnaires regarding six symptoms were sent to all 49 surviving patients; the 39 respondents were invited to attend for review. Thirteen patients underwent pulmonary function testing, of whom 10 also underwent fiberoptic laryngotracheoscopy under local anesthesia. RESULTS: The most common symptom was a minor change in voice. One patient had required treatment for symptomatic tracheal stenosis by the time of review; one was referred for revision of a tethered scar. Pulmonary function testing was easily performed by all patients and revealed no evidence of upper airway obstruction. Tracheoscopy likewise showed no evidence of tracheal stenosis. CONCLUSIONS: One of 49 patients had developed tracheal stenosis. None of the patients attending for detailed review showed any sign of late complications other than one tethered scar.

APACHE↗

PubMed1999

Induction of growth inhibition and apoptosis in pancreatic cancer cells by auristatin-PE and gemcitabine.

Pancreatic adenocarcinoma is the fifth leading cause of cancer related deaths in the United States. Treatment for this disease has largely been unsuccessful, which may partly be due to insufficient data regarding the molecular mechanisms of chemotherapeutic drugs currently being used as single agents or in combined modality regimens. In this study, we investigated the molecular mechanisms by which auristatin-PE, a newly developed experimental agent, and gemcitabine, a commercially available anti-cancer agent, exert their inhibitory effects on pancreatic cancer cell lines containing wild-type p53 (HPAC) and mutant p53 (PANC-1). Our results showed that auristatin-PE and gemcitabine inhibited cell growth and induced cell cycle arrest in G2/M and S phase, respectively. Auristatin-PE also induced apoptosis in both cell lines. Western blot analysis showed that auristatin-PE up-regulated the expression of wt-p53, p21WAF1 and Bax, and down-regulated Bcl-2 and cyclin B in HPAC cells, while only up-regulation of p21WAF1 and Bax was observed in PANC-1 cells. These results suggest that auristatin-PE may induce apoptosis and p21WAF1 expression through p53-dependent or independent pathways, and that up-regulation of p21WAF1 and Bax and down-regulation of Bcl-2 may be the molecular mechanism through which auristatin-PE inhibits cell growth and induces apoptosis. Furthermore, the up-regulation of p21WAF1 and down-regulation of cyclin B may contribute to the G2/M cell cycle arrest. Combination of auristatin-PE and gemcitabine showed significantly greater inhibition of cell growth and up-regulated expression of p21WAF1 and Bax. From these results, we conclude that the selection of therapeutic agents based on their molecular mechanism may improve therapeutic outcome, and that auristatin-PE may be more effective in the treatment of pancreatic cancer when given in combination with gemcitabine, rather than as a single agent.

Adenocarcinoma↗