Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis.

OBJECTIVE: Chronic inflammation in rheumatoid arthritis (RA) is associated with vascular endothelial dysfunction. The aim of this study was to determine the effect of spironolactone on endothelial function in anti-tumour necrosis factor (TNF)-naive RA patients. METHODS: Twenty-four anti-TNF-naive RA patients (mean age 49 +/- 1.8 years; disease duration 8.5 +/- 5.8 years) with high disease activity [Disease Activity Score including a 28-joint count (DAS28 > 5.1)] despite treatment with stable doses of conventional disease-modifying anti-rheumatic drugs (DMARDs) were investigated. Inflammatory disease activity [DAS28 and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)], serum markers of endothelial dysfunction, serum nitrite concentration, and endothelium-dependent and -independent vasodilation of the brachial artery were measured before and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day. RESULTS: After treatment with spironolactone, flow-mediated vasodilation (FMD) improved from 3.18 +/- 0.46% to 3.95 +/- 0.49% (p < 0.001) whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter (18.4 +/- 1.15% vs. 18.3 +/- 1.13%, p = 0.046, and 3.5 +/- 0.1 vs. 3.52 +/- 0.1 mm, p = 0.952, respectively); serum nitrite concentration was reduced significantly from 6.9 +/- 0.34 to 6.8 +/- 0.33 micromol/L (p < 0.001), ESR from 59.90 +/- 4.86 to 51.22+/-4.26 mm in the first hour (p < 0.001), and CRP level from 15.2+/-3.8 to 9.4+/-2.6 mg/dL (p = 0.019). DAS28 and HAQ-DI scores were significantly reduced, from 6.9+/-0.25 to 4.1+/-0.31 (p < 0.05) and from 1.47+/-0.09 to 0.69+/-0.1 (p < 0.05), respectively. CONCLUSIONS: The study suggests that, in RA, endothelial dysfunction is part of the disease process and treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in RA.

Expression of mRNA for gastrin-releasing peptide receptor by human bronchial epithelial cells. Association with prolonged tobacco exposure and responsiveness to bombesin-like peptides.

Bombesin-like peptides (BLPs) are important regulators of lung development and may also act as autocrine growth factors in lung tumors. We have previously demonstrated expression of mRNA for the three BLP receptor subtypes (neuromedin B [NMB]) receptor, gastrin-releasing peptide [GRP] receptor, and bombesin receptor subtype 3 [BRS-3]) in human non-small cell lung carcinoma (NSCLC) cell lines and bronchial biopsies using the reverse transcription-polymerase chain reaction (RT-PCR; DeMichele, et al. Am. J. Respir. Cell Mol. Biol. 1994; 11:66-74). We have also previously found that growth responses to BLPs could be elicited in some, but not all, cultures of human bronchial epithelial (HBE) cells (Siegfried, et al. Anat. Rec. 1993; 236:241-247). In this report, we utilized RT-PCR to demonstrate mRNA expression of BLP receptor subtypes in cultured HBE cells and also assessed the response of these cultures to BLPs in proliferation assays. The pattern of mRNA expression was correlated with proliferative response, and the results were also analyzed in relation to smoking history and pulmonary function of the subjects studied. Our results suggest that expression of mRNA for the GRP receptor is associated with a long smoking history (> 25 pack-years [PY], p = 0.02). This association was related to past tobacco exposure, regardless of whether the subjects were still active smokers at the time of tissue procurement. Responsiveness to GRP and NMB in proliferation assays was also found only in those HBE cultures with expression of mRNA for at least one of the known receptors for BLPs, and there was a significant association between expression of mRNA for the GRP receptor and proliferative response to both GRP and NMB (p = 0.048). HBE cultures from subjects with a greater than 25 PY smoking history were also more likely to respond to BLPs in the proliferation assays than cells from subjects with less than a 25 PY history (10 of 16 versus 1 of 7, p = 0.06). Cultures of HBE cells from four of the five subjects with severe obstructive lung disease gave a positive response to GRP and NMB in proliferation assays, compared to five of fifteen without severe obstructive lung disease, but this difference was not significant (p = 0.13). These results suggest there is an increased likelihood of expression of the GRP receptor mRNA in the respiratory epithelium of some individuals with a history of prolonged tobacco exposure, and that expression of the GRP receptor mRNA is accompanied by responsiveness to the mitogenic effects of BLPs. These effects appear to persist after smoking cessation.

Congenital bladder perforation and urinary ascites caused by posterior urethral valves: a case report.

Neonatal urinary ascites caused by bladder perforation is rare, with fewer than 20 cases reported in earlier literature. Congenital bladder perforation can be associated with bladder outlet obstruction such as posterior urethral valves, urethral atresia, presacral mass, and neurogenic dysfunction of the bladder. The bladder perforation in these cases is most commonly intraperitoneal, which leads to congenital urinary ascites. However, intrauterine perforation of the bladder in a newborn infant with posterior urethral valves is extremely rare, as is evident from the three cases in previous literature. The present case report describes an unusual case of congenital bladder perforation and urinary ascites caused by posterior urethral valves.

Detection and correction of hypoxemia associated with air travel.

Hypoxemia occurs during air travel because the pressure in aircraft cabins is not maintained equal to barometric pressure at sea level. Identification of patients who will develop significant arterial hypoxemia is most conveniently achieved by exposing these individuals to inspired oxygen tensions similar to those experienced during air travel. We utilized commercial Venturi devices with nitrogen as a source gas to lower inspired oxygen tensions (114 and 99 mm Hg) to simulate exposure to altitude (6,700 and 10,000 feet) that occurs with air travel. Oxygen was administered by nasal cannulas to correct the induced hypoxemia. Eleven normal subjects had baseline oxygen saturations of 97.3% as determined by ear oximetry. Exposure to reduced oxygen tensions for 20 min using 35 and 40% Venturi devices caused minimal O2 desaturation (94.8 and 93.8%, respectively). Mean baseline arterial oxygen saturation was 93.2% in 11 patients with chronic obstructive lung disease. Oxygen saturation fell to 89.5 and 87.5%, respectively, with exposure to the two levels of reduced oxygen tensions. Hypoxemia was corrected with administration of O2 by nasal cannulas at rates of 1.2 and 1.5 L/min, respectively. We conclude that individual patients can be evaluated conveniently for possible development of hypoxemia associated with air travel using available Venturi devices. This approach also permits determination of the oxygen therapy needed to correct hypoxemia.

Neonatal pneumoperitoneum of uncertain etiology.

This article describes a case of pneumoperitoneum in a newborn who had no evidence of an associated pulmonary air leak.

Gas chromatographic determination of 2,5-hexanedione in urine as an indicator of exposure to n-hexane.

A sensitive and specific method for determination of 2,5-hexanedione in urine is described. Treatment of the urine specimen directly with n-butylamine yields n-butyl 2,5-dimethyl pyrrole. The latter is extracted into diisopropylether and analyzed by gas chromatography (GC) with flame ionization detection (FID), thermionic specific detection (TSD) (N mode), or mass spectrometric detection (MS). The minimum detectable quantities are 1 mg/L urine when employing FID with a coefficient of variation of less than 6%. Recovery of 2,5-hexanedione added to the urine at the level of 10 mg/L was 78.9%.

Determination of 2-methylaziridine in workplace atmospheres.

A sampling and analytical procedure was developed for the monitoring of airborne 2-methylaziridine (MA). The analyte is collected by drawing air through a solution of 2,4,6-trinitrobenzenesulphonic acid (TNBS). In situ derivatisation of MA with TNBS during sample collection provides stability to the highly reactive analyte and makes it amenable to a sensitive high-performance liquid chromatographic determination with ultraviolet detection. The purified synthetic derivative of MA with TNBS is more suitable as a calibration standard than commercially available MA.

Improvement of neutrophil migration by systemic vitamin C in neonates.

The effect of oral vitamin C on chemotactic and random migration of neutrophils in 20 neonates (10 normal and 10 with suspected sepsis) was evaluated. Chemotaxis and random migration were studied between 24 and 48 hours of life, before and 24 hours after the administration of 400 mg (divided in four doses) of vitamin C. Chemotactic migration improved by 65% and random migration by 57% following vitamin C administration. The significant improvement in chemotaxis (P less than .01) and random migration may justify the inclusion of vitamin C as an adjunct to the therapy of neonatal sepsis.

Ischemic injury to newborn rabbit ileum: protective role of human superoxide dismutase.

The effectiveness of human superoxide dismutase (hSOD) in the prevention of reperfusion injury was evaluated in a rabbit ileal loop model. Weanling white New Zealand rabbits, 6 weeks of age and weighing 500 to 1,000 g, were used. Intraluminal administration of SOD (5 mg/kg) was studied in 12 animals with each animal serving as its own control. In an additional 12 animals, parenteral SOD in a dose of 5 mg/kg in seven animals and 10 mg/kg in five animals was evaluated, while five additional control animals received parenteral saline. The effect of reperfusion injury was evaluated in each bowel loop by interruption of blood supply for five minutes, followed by reperfusion. Blood was drawn at 0, 16, 20, 24 hours in the parenteral group for measurement of hSOD levels by radioimmunoassay. The loops were studied pathologically for extent of mucosal damage. In the intraluminal group, nine of 12 loops without SOD v three of 12 loops with SOD showed necrosis when rendered ischemic (P = .0196). In the parenteral group 22 of 24 loops were normal when pretreated with SOD and subjected to ischemia v five of ten when no SOD was given (P = .0139). In the parenteral group, mean baseline level of hSOD was 0.42 +/- 0.26 micrograms/mL. Levels peaked at 16 hours (3.64 +/- 1.75 micrograms/mL) and progressively decreased at 20 hours (2.85 +/- 1.34 micrograms/mL) and 24 hours (1.82 +/- 1.15 micrograms/mL). This preliminary animal study suggests that hSOD may be an effective method for the prevention of postischemic bowel injury, adding to the literature on the protective effects of SOD in various models of intestinal ischemia.

Clinical consequences of a human non-fluorescent Y chromosome (Ynf).

A new case of ambiguous genitalia and immature tissue in the left gonad is presented. Cytogenetic findings with various techniques demonstrated that the distal two-thirds of the long arm of the Y chromosome is deleted. Q-banding showed a non-fluorescent Y; three positive bands were however noted when the DA/DAPI technique was applied. After a review of the literature, it was concluded that the non-fluorescent Y chromosome (Ynf) when inherited from generation to generation is a heteromorphism in normal males. However, in our case, where the proband's Y is lacking the fluorescent segment, a simple deletion does not appear to adequately explain the DA/DAPI positive bands. Possibly, a deletion followed by a structural rearrangement of the non-fluorescent segment had occurred de novo. The highly Y-specific DNA sequences present in the fluorescent segment are absent in these patients. The abnormal development in these cases is due to the presence of the 45,X cell line. The gene responsible for spermatogenesis has been localized to the non-fluorescent region in the long arm of the Y chromosome. Furthermore, it is concluded that two types of non-fluorescent Y chromosomes can be found in the population; one is a normal inherent heteromorphic variant, while the other appears to be an abnormality, especially in cases with azoospermia. Such distinctions should clearly be established prior to genetic counseling for patients with so called Ynf or del (Yd).

Trisomy 22: report of a patient diagnosed as a neonate.

The present case report describes the occurrence of Trisomy 22 in a neonate. This chromosomal disorder has rarely been diagnosed in the neonatal period. A review of the literature is presented to elucidate the fact that only further diagnosis of new cases of Trisomy 22 in neonates will allow a clearer delineation of this chromosomal abnormality in the neonatal period.

Environmental lead exposure of an urban Indian population.

Environmental lead exposure of the Greater Bombay population has been estimated by measuring lead concentrations in air particulates, water, food and cigarette smoke. Atmospheric lead concentrations in different zones of the city varied between 82 and 605 ng m-3. The dietary intake of lead is estimated to be 245 micrograms day-1 and is calculated from the lead content in different food groups and the amount of that group consumed by an average resident of the city. The uptake by a non-smoker living in the city area is estimated to be 33 micrograms of lead per day, 75% of which comes from food, 15% from air and 10% from water. For a suburban resident 85% of the lead intake comes from food. The blood lead measurements and the contribution of atmospheric lead to the blood lead level are discussed.

Pharmacokinetics of cefoperazone in full-term and premature neonates.

The pharmacokinetics of cefoperazone were evaluated in 28 newborn infants who were being treated for sepsis. A dose of 50 mg/kg was administered intravenously on days 0 to 2 in all, with a second dose administered on days 5 to 7 in 14 infants. Cerebrospinal fluid penetration was also studied in seven neonates. The mean peak concentration of cefoperazone in the serum of premature infants less than 33 weeks of gestational age, 159 (standard deviation, +/- 22) micrograms/ml, was higher than concentrations in premature infants 33 to 36 weeks of age and full-term infants (110 +/- 41 and 109 +/- 29 micrograms/ml, respectively). The mean concentrations 24 h after dosage were similar in all three groups, 13 to 17 micrograms/ml. The mean serum half-lives were similar in the three subgroups and ranged from 7 to 9 h. After the dose at 5 to 7 days, mean blood levels in the subgroups at 0.5 h were 149, 112, and 112 micrograms/ml; 24-h levels ranged from 9 to 12 micrograms/ml. The mean serum half-lives ranged from 5 to 7 h. Cerebrospinal fluid levels in patients with meningitis ranged from 2.8 to 9.5 micrograms/ml and in patients without meningitis from 1 to 7 micrograms/ml. Peak blood levels were 15 to 1,000 times higher than the 90% minimal inhibitory concentration of common pathogens found in newborns. These observations support the potential efficacy of cefoperazone in treatment of infections, including meningitis, in newborn infants.

Studies on oxidation of benzo [a] pyrene by sunlight and ozone.

The destruction of the carcinogen benzo[alpha]pyrene (BaP) by light is well known; laboratory workers are routinely advised to cover fluorescent lamps with yellow filters while treating samples containing BaP. However until recently the mechanism of oxidation by sunlight and ozone had not been studied in detail. Concentrations of benzo[a]pyrene in urban air are in the range of 5-10 micrograms/1000 m3. Oxidant concentrations (predominantly in the form of ozone) are reported to be in the range of 0.01 ppm (22 micrograms per m3). Thus a sampling system with a filter paper would filter about 22,000 micrograms of ozone passing through and collect about 5 micrograms of BaP for analysis. The effect of interactions of such large ozone concentrations with BaP deposited on the filter paper is reported; data for the oxidation rates for benzo[a]pyrene coated on quartz surface and exposed to ozone or sunlight are presented. The oxidation products were analysed by thin-layer chromatography and high-pressure liquid chromatography. From about eight products detected in these experiments, three have been identified as quinones based on UV-absorption spectrometry and mass spectrometry. Oxidation rates as high as 100% per hour of exposure are observed when less than 0.1 micrograms of BaP is coated inside the quartz tubes and exposed to ozone or sunlight. Oxidation rates for benzo[a]pyrene (using tritiated BaP) were determined for two types of experimental conditions. In the first set, tritiated BaP was spotted onto a glass fibre paper and sampling continued for 24 h; the loss of BaP was found to be 88%. In the second set tritiated BaP was spotted at intervals of one hour, for eight hours, while sampling is being carried out and the loss of BaP during the period was estimated to be 50%.

X- and gamma-ray response of the TLD badge based on CaSO4:Dy Teflon TLD discs.

A TLD badge based on CaSO4: Dy Teflon TLD discs has been designed for personnel monitoring of radiation workers encountering X-rays of effective energies above 20 keV. The badge had two Teflon TLD discs, one of which is used bare (without any filter) and other which is used with a metal filter. By taking into account the TL readout of both of these discs, the problems of photon energy dependence as well as directional dependence of the badge have been reduced to a minimum. The uncertainty due to photon energy dependence above 29 KeV (eff.) was found to be within a value of +/- 15% (at an angle of incidence of 45 degrees). The directional dependence of the badge is within +/- 30% in the energy range from 35 KeV to 1.25 MeV. The badge is designed so as to provide approximate information on the effective photon energy of the X-ray exposures.