The association of adult Onchocerca volvulus with lymphatic vessels.

Immunocytochemical examination of onchocercal nodule tissues containing adult Onchocerca volvulus using immuno-markers for blood and lymphatic vessels (vWF, D2-40, podoplanin, Prox-1, and Lyve1) shows a distinct pattern of distribution of these vessels within nodules. Blood vessels were commonly seen associated with organized lymphoid cellular aggregates in the both the outer and inner areas of the nodules. In contrast, the majority of the lymphatic vessel positivity was seen in the central zone in close apposition to the adult parasites, and the remainder usually associated with microfilariae in the outer areas of the nodule. These findings suggest an intimate relationship between adult O. volvulus and lymphatic vessels, including the likely proliferation of lymphatic endothelial cells (lymphangectasia) akin to that seen with other filariae. These findings indicate that adult O. volvulus may migrate via the lymphatic system, and that clinical manifestations of this disease that involve tissue edema may be the result of the location of these worms in the lymphatic system.

Endotoxin contamination in the dental surgery.

Dental waterlines contain large numbers of Gram-negative bacteria. Endotoxin, a component of such organisms, has significant health implications. Paired samples of dental unit water and the aerosols generated during dental procedures were collected, and assayed for bacteria and endotoxin levels, using heterotrophic plate counts and the Limulus amoebocyte lysate test. Consistent with published studies, the extent of bacterial contamination in the dental waters sampled for this investigation surpassed the levels associated with potable water, with counts in excess of 2.0x10(6) c.f.u. ml(-1) in some samples. Correspondingly high concentrations of endotoxin [up to 15 000 endotoxin units (EU) ml(-1)] were present in the water. A statistically significant Spearman correlation coefficient of rho=0.94 between endotoxin (EU ml(-1)) and bacterial load (c.f.u. ml(-1)) was demonstrated. All of the aerosol samples contained detectable endotoxin. Further studies of the consequences of dental endotoxin exposure, and evaluation of means to prevent exposure, are warranted.

Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers.

The present study examined whether rofecoxib (VIOXX), a new specific inhibitor of cyclooxygenase-2 (COX-2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serum-generated thromboxane B2 (TXB2) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double-blind, randomized, placebo-controlled, parallel study of two treatment groups (n = 12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open-label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet-derived serum TXB2 (COX-1 assay) was measured in blood clotted for 1 hour at 37 degrees C. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 microgram/mL collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen-induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low-dose aspirin (inhibition of platelet aggregation and TXB2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low-dose aspirin.

Efficacy and tolerability of the specific cyclooxygenase-2 inhibitor DFP compared with naproxen sodium in patients with postoperative dental pain.

DFP [3-(2-propyloxy)-(4-methyl-sulfonylphenyl)-(5,5-dimethyl)-fu ranone] is a highly specific cyclooxygenase-2 inhibitor (>2500-fold selective in transfected Chinese hamster ovary cell assays) that has demonstrated efficacy in preclinical models of pain and inflammation. The present single-dose, randomized, double-masked, double-dummy, placebo-controlled, parallel-group study was undertaken to compare DFP 5, 25, and 50 mg with naproxen sodium 550 mg and with placebo in 196 patients (mean age, 25.8 years; 187 [95.4%] males) who experienced moderate-to-severe pain after surgical removal of > or =2 third molars. Overall analgesic effect, duration of effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. Both DFP 25 and 50 mg, as well as the active comparator, naproxen sodium 550 mg, were significantly more effective than placebo. The onset of analgesic effect in the DFP 25-mg, DFP 50-mg, and naproxen sodium 550-mg groups did not differ significantly. DFP was generally well tolerated in single doses up to 50 mg. DFP 50 mg was efficacious in the treatment of postoperative dental pain and was indistinguishable from the active comparator, naproxen sodium 550 mg.

Bombesin-like neuropeptides in nematodes.

This paper reports evidence of members of the bombesin-like peptide family in a number of nematodes, including Caenorhabditis, Panagrellus, Dirofilaria, Onchocerca, Brugia, Haemonchus, Ostertagia, Toxocara, and Ascaris. One of these (Ostertagia) secretes the bombesin-like material into its environment. Specific binding of gastrin-releasing peptide to the hypodermis consistent with the presence of receptors was demonstrated. These data suggest that this class of peptides may play an important role in nematode hypodermal physiology.

Legionella contamination of dental-unit waters.

Volume 61, no. 4, p. 1211, column 2, line 40: this sentence should read as follows. "The viable-culture methods for Legionella sp. detection, however, often fail, and the Centers for Disease Control and Prevention has turned, when necessary, to PCR for epidemiological investigations of Legionnaires' disease and Pontiac fever (19)." Line 46: "(6)" should read "(11)." [This corrects the article on p. 1208 in vol. 61.].

Legionella contamination of dental-unit waters.

Water samples collected from 28 dental facilities in six U.S. states were examined for the presence of Legionella pneumophila and other Legionella spp. by the PCR-gene probe, fluorescent-antibody microscopic, and viable-plate-count detection methods. The PCR and fluorescent-antibody detection methods, which detect both viable and viable nonculturable Legionella spp., gave higher counts and rates of detection than the plate count method. By the PCR-gene probe detection method, Legionella spp. were detected in 68% of the dental-unit water samples and L. pneumophila was detected in 8%. Concentrations of Legionella spp. in dental-unit water reached 1,000 organisms per ml or more in 36% of the samples, and 19% of the samples were in the category of 10,000/ml or above. L. pneumophila, when present in dental-unit water, never reached concentrations of 1,000/ml or more. Microscopic examination with fluorescent-antibody staining indicated that the contamination was in the dental-unit water lines rather than in the handpieces. Legionella spp. were present in 61% of potable water samples collected for comparative analysis from domestic and institutional faucets and drinking fountains; this percentage was not significantly different from the rate of detection of Legionella spp. in dental-unit water. However, in only 4% of the potable water samples did Legionella spp. reach concentrations of 1,000 organisms per ml, and none was in the 10,000 organisms-per-ml category, and so health-threatening levels of Legionella spp. in potable water were significantly lower than in dental-unit water. L. pneumophila was found in 2% of the potable water samples, but only at the lowest detectable level.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbial contamination of dental unit waterlines: short- and long-term effects of flushing.

The extensive microbial contamination of DUW in this study is consistent with that described in previous reports. Comparisons with other common public potable water sources emphasize the relatively high concentrations of microorganisms in DUW, and the low numbers of bacteria in most domestic water samples. Microscopic evidence of amebas and worms in DUW reinforces the need for further qualitative and quantitative studies of these contaminants of dental tubing biofilm. In most cases, flushing for two minutes reduced microbial concentrations in DUW. However, in a few cases, concentrations rose; in others, the reductions were negligible. Moreover, after 30 minutes of stasis, or use of the waterline in a routine dental procedure, microbial counts were frequently restored to preflush levels or higher. The longer-term ineffectiveness 30 minutes after flushing is understandable when the hydrodynamics of laminar flow of water in narrow-bore tubing are considered. Biofilm on the tubing wall remains intact during flushes and quickly generates more bacteria during stasis. Increased bacterial concentrations after flushing probably result from sloughing of biofilm from the tubing wall because of stretching and movement of the line during routine use. These two phenomena undermine the benefits of routine water flushes. It is a common belief that bacterial levels build to extremes during overnight or weekend stasis; we observed more variation in contamination levels during the workday than between overnight stasis and typical workday samples. The presence of hemolytic staphylococci and streptococci in water samples from lines that were supplied only from sterile water reservoirs adds to the growing evidence that part of the microbial flora in DUWLs may be derived from patients' mouths. Additional prophylactic measures to limit bacterial contamination in DUW should be implemented according to standard principles used in other medical fluid delivery devices.

Microbial contamination of dental unit waterlines: prevalence, intensity and microbiological characteristics.

Microbiological studies on dental unit water samples from 150 operatories revealed widespread and unacceptably high levels of contamination. Biofilm formation along the walls of the fine-bore waterlines is primarily responsible. These findings are reviewed and their relevance to contemporary infection control concerns discussed.

Coronary hypertension and diastolic compliance in isolated rabbit hearts.

Acute pulmonary edema during hypertensive crisis has been attributed to acute left ventricular systolic failure secondary to increased afterload. We tested the hypothesis that the increase in coronary artery perfusion pressure associated with systemic hypertension could also contribute to increased left ventricular filling pressures by acutely increasing coronary intravascular volume and decreasing left ventricular diastolic compliance. Isolated isovolumic (balloon in left ventricle) normal rabbit hearts (n = 13) with pericardium removed and right ventricle vented were blood perfused at an initial coronary artery perfusion pressure of 100 mm Hg; left ventricular balloon volume was adjusted to produce an initial left ventricular end-diastolic pressure of 15 +/- 1 mm Hg; left ventricular systolic pressure was 102 +/- 3 mm Hg. When coronary perfusion pressure was increased to 130 +/- 1 mm Hg to simulate a hypertensive crisis, coronary flow increased from 2.0 +/- 0.2 to 3.0 +/- 0.2 ml/min/g left ventricle (p less than 0.001), left ventricular systolic pressure increased to 116 +/- 4 mm Hg, and isovolumic left ventricular end-diastolic pressure increased to 21 +/- 1 mm Hg (p less than 0.001), which indicated a decrease in left ventricular diastolic compliance. When coronary perfusion pressure was decreased to a physiological level of 70 mm Hg, coronary flow rate decreased to 1.4 +/- 0.1 ml/min/g left ventricle (p less than 0.001), left ventricular systolic pressure fell to 82 +/- 4 mm Hg, and left ventricular end-diastolic pressure fell to 14 +/- 1 mm Hg (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Weight gain in patients receiving adjuvant chemotherapy for carcinoma of the breast.

Twenty-nine patients treated with adjuvant chemotherapy for carcinoma of the breast were evaluated for frequency and amount of weight gained during treatment. No difference with respect to age, menopausal status, estrogen receptor status, nodal status, biochemical parameters, or treatment regimen (CMF versus CMFVP) were seen. The gain in weight seen in some 50% of the patients treated seems to be a function of a decrease in activity level during treatment.

Streptozotocin therapy in 22 cancer patients.

Twenty-two cancer patients were treated with streptozotocin (SZN) in six weekly intravenous doses of 1.0-1.5 g/m2. The results of the initial courses of therapy include 3 complete and 2 partial responses, 11 patients with no change, 4 with progression, and 2 deaths due to tumor progression. Three additional deaths also due to tumor progression occurred in previously responding patients. All responses were in patients with pancreatic tumor. Toxicity consisted of transient proteinuria in 11/15 patients, transient azotemia in 11/18 patients, marked reduction of creatinine clearance in 1 patient, burning pain at site of injection, nausea, and vomiting in 20/22 patients, change of FBS from pretherapy to post-therapy of at least 10 mg/100 ml in 11/17 patients, significantly decreased platelet count in 1/22 patients, decreased Hgb in 2/22 patients, and duodenal ulcer in 2/22 patients. A reduced dosage schedule and combination with other drugs known to be effective in pancreatic tumors deserves further investigations.