High prevalence of Neisseria gonorrhoeae in a remote, undertreated population of Namibian pastoralists.

The highly remote pastoralist communities in Kaokoland, Namibia, have long been presumed to have high gonorrhoea prevalence. To estimate gonorrhoea prevalence and correlates of infection, we conducted a cross-sectional study of 446 adults across 28 rural villages. Gonorrhoea status was determined from urethral and vaginal swabs via qPCR assay. All participants answered a closed-ended interview about demographics, sexual behaviour and symptom history. Sixteen per cent of participants had high-level infections (⩾ID(50) dose) and 48% had low-level infections (

Effects of genetic selection on behavioral profiles of Single Comb White Leghorn hens through two production cycles.

Four layer genetic stocks consisting of 3 Ottawa control strains (5, 7, and 10) and a commercial laying stock (CCS) were utilized to evaluate potential changes in behavioral profiles due to the effects of genetic selection through 2 production cycles. The Ottawa strains were started as random bred strains from the crosses of several popular commercial layers in 1950, 1959, and 1972, and the commercial strain used herein was from calendar year 1993, and its ancestors were involved in the formation of all of the random bred strains. The behavior study utilized 2 replicates from each strain that contained 4 cages, 6 hens/cage, for a total of 192 hens. Behavioral observations were recorded on 2 consecutive days beginning at 22 wk of age and every 28 d thereafter during the first production cycle, the molt period, and the second production cycle through 90 wk of age and periodic feather and Hansen's test scores recorded. Behavior profiles were similar between the control strains and the CCS, indicating that long-term genetic selection by commercial egg-type breeding firms to enhance production parameters has had no impact on laying strain behavior patterns. Appetitive behaviors were not affected by strain. During the molt, hens had reduced (P < 0.05) feeding and drinking frequencies in comparison with those observed during the first and second cycles. The data indicated that hens pecked inedible objects at a greater (P < 0.0001) frequency during the first cycle and molt than during the second cycle. Fearfulness scores were only influenced by production phase with the molt having the highest (P < 0.01) score of 3.46. Strain or production phase did not influence the frequency of aggressive and submissive acts.

Mitochondrial genome damage associated with cigarette smoking.

We have investigated the level of mitochondrial DNA (mtDNA) damage and deletions in bronchoalveolar lavage tissues from smokers and nonsmokers using quantitative, extra-long PCR and a "common" mtDNA deletion assay. Smokers had 5.6 times the level of mtDNA damage, 2.6 times the damage at a nuclear locus (beta-globin gene cluster), and almost 7 times the level of a 4.9-kb mtDNA deletion compared to nonsmokers, although the latter increase was not significant. Although both genomes (mitochondrial and nuclear) showed significantly increased levels of DNA damage in smokers (mtDNA P = 0.00072; beta-globin P = 0.0056), the relative differences were greatest in the mtDNA. Damage to the mtDNA may inhibit oxidative phosphorylation and, therefore, potentially cause or contribute to chronic lung disease and cancer. Consequently, the mtDNA may be a sensitive biomarker for environmentally induced genetic damage and mutation.

Reproductive aging: accelerated ovarian follicular development associated with a monotropic follicle-stimulating hormone rise in normal older women.

Women experience a decline in fertility that precedes the menopause by several years. Previous studies have demonstrated a monotropic rise in FSH associated with reproductive aging: however, the mechanism of this rise and its role in the aging process are poorly understood. The purpose of this study was to characterize ovarian follicular development and ovarian hormone secretion in older reproductive age women. Sixteen women, aged 40-45 yr, with regular ovulatory cycles were studied. The control group consisted of 12 ovulatory women, aged 20-25 yr. Serum obtained by daily blood sampling was analyzed for FSH, LH, estradiol (E), progesterone, and inhibin (Monash polyclonal assay). Follicle growth and ovulation were documented by transvaginal ultrasound. Older women had significantly higher levels of FSH throughout the menstrual cycle. E, progesterone, LH, and inhibin levels did not differ between the two age groups when compared relative to the day of the LH surge. Ultrasound revealed normal growth, size, and collapse of a dominant follicle in all subjects. Older women had significantly shorter follicular phase length associated with an early acute rise in follicular phase E, reflecting accelerated development of a dominant follicle. We conclude that older reproductive age women have accelerated development of a dominant follicle in the presence of the monotropic FSH rise. This is manifested as a shortened follicular phase and elevated follicular phase E. The fact that ovarian steroid and inhibin secretion were similar to those in the younger women suggests that elevated FSH in women of advanced reproductive age may represent a primary neuroendocrine change associated with reproductive aging.

Effect of alveolar lining material-coated silica on rat alveolar macrophages.

The disparity between in vitro silica cytotoxicity toward macrophages and their in vivo resistance to injury following inhalation of silica at physiologic concentrations is unresolved. It is probable that inhaled silica particles absorb a variety of biological substances including proteins and alveolar lining material (ALM) thus altering the in vivo response of the macrophage to these particles. Silica (SI) particles coated with rat ALM and uncoated SI particles were studied for their ability to injure rat alveolar macrophages (AM) in vitro. Suspensions of particles were tested at concentrations from 0 to 400 micrograms per 2 X 10(6) cells. Cytotoxicity was assessed by the percent of total cellular lactate dehydrogenase (LDH) released by AM into the culture medium during incubation. Comparable physical association by ALM-coated and uncoated SI particles with AM was shown by scanning electron microscopy combined with X-ray energy spectrometry. These data show that SI coated with ALM is effectively phagocytosed by AM in vitro but is much less cytotoxic than uncoated SI. The surfactant lipids which presumably coat inhaled SI particles in the lung may reduce or delay their toxicity for AM.

Inhibition of LPS-induced tumor necrosis factor-alpha production by colchicine and other microtubule disrupting drugs.

Colchicine has been shown to act as an antiinflammatory agent. In this study, we examined whether colchicine and other microtubule-depolymerizing drugs affected the production of TNF-alpha. When rat peritoneal macrophages were stimulated by LPS, addition of colchicine, vincristine, vinblastine or nocodazole was found to inhibit TNF-alpha release in a concentration-dependent manner. Suppression of TNF-alpha release was not due to interference with secretion as the cytokine did not accumulate intracellularly following colchicine treatment. Colchicine markedly enhanced PGE2 release from LPS-stimulated macrophages. However, addition of the cyclooxygenase inhibitor indomethacin only partially reversed the suppressive effect of colchicine on TNF-alpha production. Colchicine caused a strong reduction of LPS-induced TNF-alpha mRNA accumulation, suggesting that a pretranslational effect may represent the primary mechanism by which colchicine reduced TNF-alpha production. These observations could have clinical relevance in ameliorating undesirable effects due to excessive TNF-alpha production, for example following LPS stimulation of monocytes/macrophages in gram-negative sepsis. Furthermore, these drugs may provide useful tools to study the apparent involvement of the microtubular system in cytokine gene expression and cytokine production.

Suppression of LPS-induced tumor necrosis factor-alpha gene expression by microtubule disrupting agents.

Microtubule disrupting agents such as colchicine have been shown to reduce TNF-alpha production in macrophages. To examine molecular mechanisms underlying the action of colchicine, TNF-alpha gene expression was studied in the murine macrophage cell line PU5-1.8. An LPS stimulation caused an intense up-regulation of TNF-alpha gene expression which was followed by a high TNF-alpha protein production. Simultaneous addition of colchicine (10 microM) suppressed LPS-induced TNF-alpha mRNA accumulation by one-third and TNF-alpha protein release by two-thirds. This effect was shared by vinblastine and vincristine, chemically different agents that also disrupt microtubule polymerization. For full suppressive activity on TNF-alpha gene expression, colchicine had to be present for 3 h in LPS-stimulated macrophage cultures. With nuclear run-on transcription experiments we could demonstrate that colchicine primarily inhibited de novo gene transcription and did not accelerate degradation of TNF-alpha mRNA in actinomycin D-treated macrophages. Thus, the well-known antiinflammatory action of microtubule depolymerizing agents may be largely due to a reduced TNF-alpha gene expression.

Variable tracheal stenosis related to body position.

We demonstrated a variable extrathoracic tracheal stenosis which developed after technically adequate tracheostomy and was worsened by changes in body position. When the patient's arms were above his head, minimal airway diameter was reduced 31 percent, and maximal inspiratory flow rate 37 percent below values measured with arms down, but expiratory flow rates were preserved. Tracheostomy may disrupt the integrity of tracheal support and allow airway collapse under circumstances of increased extratracheal or decreased intratracheal pressure.

Diagnosis of pneumonia due to Pneumocystis by subsegmental pulmonary lavage via the fiberoptic bronchoscope.

To assess the accuracy of pulmonary lavage in diagnosing pneumonia due to Pneumocystis, we used animals as a model and then prospectively studied 33 immunosuppressed adults with diffuse pulmonary infiltrates. In rats treated with cortisone, Pneumocystis organisms could be found in the effluent from lavage as early as in sections of pulmonary tissue, and the effluent from lavage remained diagnostic throughout the ten weeks of observation. Subsegmental lavage in adult patients was performed through the wedged fiberoptic bronchoscope. Pneumocystis organisms were demonstrated in seven patients by lavage, and no false-negative results were recorded. Pneumocystis organisms were readily identified among the sheets of alveolar macrophages seen in smears of the effluent from lavage that were stained with methenamine silver. Subsegmental lavage via the fiberoptic bronchoscope is an accurate and safe technique for establishing the diagnosis of pneumonia due to Pneumocystis in patients whose respiratory embarrassment or thrombocytopenia makes biopsy of the lung hazardous.

Mineral dusts as etiologic agents in pulmonary fibrosis: the diagnostic role of analytical scanning electron microscopy.

This report demonstrates the value of analytical scanning electron microscopy (SEM) in the evaluation of patients with fibrosing pulmonary disease. We describe the findings in six illustrative cases in which prebiopsy or premortem clinical and epidemiologic information did not suggest an etiologic association with exposure to fibrogenic dusts. Exogenous materials were inconstantly recognized by polarized light microscopy, but examination by SEM resulted in localization of significant inorganic deposits in the biopsy and autopsy tissues studied. Talc, mica, graphite, and mixed inorganic dusts were found in these six cases. Characterization of this material by SEM morphology and x-ray energy spectrometry provided the basis for re-appraisal of the exposure history and its potential pathogenetic importance. The technics described utilize routinely processed, paraffin-embedded tissue, and are readily applicable to problems encountered in the hospital setting.

Legionnaires' disease: respiratory infections caused by Legionella bacteria.

This article provides a review of Legionnaire's Disease, a bacterial pneumonia caused by Legionella species, and of Pontiac Fever, the flu-like illness caused by these microorganisms. The authors draw on their personal experience with major human outbreaks of Legionnaire's Disease and with animal models of Legionella pneumonia. Emphasis is placed on the sources in nature from which legionellosis is acquired, the means of dissemination of bacteria, the epidemiology of human infections, the pathogenetic mechanisms of disease and host defense, the clinical manifestations, and the treatment.

Silicosis in mice: effects of dose, time, and genetic strain.

Experimental silicosis allows study of the mechanisms of lung injury, inflammation, and fibrosis. Inbred mice are an attractive species in which to study these mechanisms because of recent progress in murine immunology, molecular biology, and genetics. We exposed mice to an aerosol of silica and examined the effects of exposure dose, the evolution of disease features over time, and the variation in responses among four inbred strains. In C3H/HeN mice incremental cumulative exposure doses of cristobalite silica caused increased initial lung dust burden 12 to 16 weeks post-exposure, progressively intense pathological responses, and increased total lung collagen (hydroxyproline). The histopathological changes and total lung collagen increased progressively over time after exposure. We compared the features of silicosis in four strains of inbred mice selected for common use or immunologic reactivity 16 weeks after aerosol inhalation exposure to crystalline cristobalite silica (70 mg/m3, 5 hours/day, 12 days). C3H/HeN mice demonstrated histopathological silicotic lesions and enlarged intrapulmonary lymphoid tissue, and increased lung wet weight, bronchoalveolar lavage (BAL) recovery of macrophages, lymphocytes, and neutrophils, and total lung collagen (hydroxyproline). BALB/c mice developed slight pulmonary lesions; MRL/MpJ mice demonstrated prominent pulmonary infiltrates with lymphocytes; New Zealand Black mice developed extensive alveolar proteinaceous deposits, inflammation, and fibrosis. Our findings demonstrate orderly dose-time-response relationships, and a substantial variation of responses among inbred strains of mice. This model should prove valuable for future experimental interventions into the mechanisms of silicosis.

Persistent overexpression of interleukin-1beta and tumor necrosis factor-alpha in murine silicosis.

The cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha), derived from macrophages and other cells, may promote mononuclear cell inflammation and fibrosis in pulmonary silicosis. C3H/HeN mice were exposed to control air or to an aerosol of 70 mg/m3 cristobalite silica for 5 h/d for 12 days and examined at 2 and 16 weeks after exposure. This exposure resulted in murine silicosis, as manifested by focal mononuclear cell accumulations, diffuse interstitial fibrosis, lymphoid tissue enlargement, recruitment of inflammatory cells into BAL fluid, and increased total lung collagen. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) with designed primers and membrane hybridization with biotinylated cDNA probes were used to assess the abundance of IL-1beta and TNFalpha mRNA. In situ hybridization with digoxigenin-labeled cDNA probes was used to localize gene expression. Persistent overexpression of both IL-1beta and TNFalpha were found at 2 and 16 weeks in the lungs of silica-exposed mice compared with air-sham control mice. IL-1beta and TNFalpha expression localized to individual mononuclear cells in the alveolar spaces, groups of cells within the aggregate lesions, and scattered mononuclear cells in BALT and lymphoid nodules. Thus, cells producing IL-1beta and TNFalpha appear to be intimately associated with the evolving lesions of silicosis, and the lymphoid tissue of the lung may be important in driving the pathogenesis of this disease.

Lymphocytes, lymphokines, and silicosis.

Silicosis is characterized by mononuclear cell aggregation with mineral particles and fibrosis. Lymphocytes are abundant in these lesions. We exposed inbred strains of mice to a respirable aerosol of cristobalite silica (70 mg/m3, 5 h/d, 12 d) or shamair. Silicosis evolved over months after exposure. The silica-exposed mice showed the accumulation of lymphocytes in alveolar spaces (seen in bronchoalveolar lavage), in lung parenchymal lesions and nodules, and in enlarged bronchial-associated lymphoid tissues and thoracic lymph nodes. The lung lymphocytes were predominantly CD4+ T cells, but numerous CD8+ T cells, natural killer cells, and CD4- gammadelta-TCR+ T cells were present as well. Interferon-gamma (IFN-gamma) production was upregulated, suggesting a THelper-1-like response in silicosis. In silicotic lung tissue, mRNA transcripts for the macrophage-derived cytokines IL-12 and -18 were increased. IFN-gamma gene-deleted mice (C57Bl/6-Ifngtm1 Ts) exposed to silica developed less extensive silicosis and less lung collagen accumulation than wild-type mice. We hypothesize that there is a reiterative amplification cycle in which macrophages with silica may produce cytokines, such as IL-12 and -18, that attract and activate lymphocytes. These activated lymphocytes may then produce additional mediators that in turn attract and activate an expanded secondary population of macrophages. IFN-gamma would be a likely cause of macrophage activation in this cycle. More work is needed to understand the biological events that lead from the inhaled dust to the scarred lung, and to clarify the role of lymphocytes in this process.

Microsurgical replantation of the amputated nose.

A case of successful replantation of the nose is presented. Two arteries and one vein were anastomosed, providing a stable framework for direct revascularization of the amputated nasal segment. This resulted in complete survival of the nose, with an excellent aesthetic result. However, despite successful microsurgical arterial and venous repair, significant postoperative blood loss still occurred as a result of anticoagulation. In cases of the amputation of specialized structures, the improved functional and cosmetic result obtained with replantation must be weighed against the risk of blood-borne disease transmission when postoperative transfusion is required. Recognizing the potential need for postoperative transfusion in these cases is important in allowing the surgeon to exercise appropriate judgment in deciding whether replantation should be performed.

Morphologic changes induced by photoperiod in eyes of turkey poults.

Large White commercial tom poults were grown from 1 day to 8 weeks of age in the following light treatments: (i) continuous incandescent light (24LL); (ii) 23 hours of incandescent light and 1 hour of darkness/day (23L:1D); (iii) 12 hours of incandescent light and 12 hours of darkness/day (12L:12D); or (iv) natural decreasing day lengths (natural). At 8 weeks of age, significant (P less than 0.05) morphologic changes in eyes occurred. Poults exposed to the 24LL or 23L:1D had heavier eyes than did poults exposed to the 12L:12D or natural day length. In addition, the eye size (anterior to posterior diameter and horizontal width) exposed to the 24LL treatment was greater than those exposed to 23L:1D, 12L:12D, or natural day length. Cornea heights of poults exposed to 24LL or 23L:1D were smaller than cornea heights of those exposed to 12L:12D or natural day length. Marked differences did not occur in intraocular pressure among treatments.

Effect of exogenous adrenocorticotropic hormone administration on plasma corticosterone concentrations in American black ducks (Anas rubripes).

A protocol for the adrenocorticotropic (ACTH) stimulation test in American black ducks (Anas rubripes) was established with synthetic ACTH, cosyntropin (Cortrosyn); ACTH stimulation testing was conducted on 31 adult ducks (14 males, 17 females) in September 1993. Plasma corticosterone concentrations were measured on heparinized blood samples collected 30 min, and 1, 2, and 4 hr post-injection. In comparison with saline controls, cosyntropin (0.25 mg/duck) produced a two- to three-fold increase in corticosterone 30 min after administration. Maximal concentrations ranged from 132 to 312 ng/ml and occurred between 1 and 2 hr post-injection. Corticosterone concentrations declined to basal, pre-injection values after 4 hr. Endogenous ACTH release in response to handling stress was evident in control ducks after saline injection but did not interfere with interpretation of the stimulation test. Recommendations for the ACTH stimulation test in black ducks include a 30 min acclimatization period for recently captured or relocated ducks and determination of plasma corticosterone concentration 1 to 2 hr following intramuscular injection with 0.25 mg cosyntropin.

Plasma corticosterone response of turkeys to adrenocorticotropic hormone: age, dose, and route of administration effects.

Three trials were conducted to investigate plasma corticosterone (B) levels in Large White turkey hens in response to adrenocorticotropic hormone (ACTH) injections at different ages, doses, and routes of administration. In Trial 1, hens were subjected to one of the following treatments at 10, 15, and 20 wk of age: cold water immersion (5 C for 1 min), ACTH injection (10 IU/kg), or saline injection. The plasma B responses to ACTH and cold water immersion followed the same general pattern in all three age groups. Plasma B levels of hens in the ACTH treatment were depressed below control B levels until 6 h postinjection, when they became elevated. Plasma B levels of hens in the cold water treatment were either similar to or increased above those of controls by 2 h posttreatment and were depressed below control levels at .5 h posttreatment at 10 and 15 wk of age. In Trial 2, three dose levels of ACTH (1, 5, and 10 IU/kg) were injected either intramuscularly (IM) or intravenously (IV) in 10-wk-old hens. There was both a dose and route of administration effect. Of the IM-injected hens, only those in the 1-IU ACTH treatment group had significantly (P less than .05) increased plasma B levels and this occurred 4 h postinjection. However, plasma B levels of the 1 and 5-IU IV-ACTH treatment hens were significantly (P less than .05) elevated at .5 h postinjection. Plasma B of the 10-IU IM and IV-ACTH treatments were consistently, but not significantly, lower than controls through 4 h postinjection.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal dietary iodide influences turkey embryonic thyroid function.

An experiment was designed to examine a mechanism to improve embryonic survival following maternal thyroid hormone manipulation. Commercial turkey breeder hens were fed diets containing supplemental iodide to mimic changes in the maternal thyroid output during an egg production cycle (32 to 48 wk of age). Dietary iodide treatment depressed maternal blood thyroxine (T4) concentrations in a time-dependent manner. Dietary iodide depressed maternal blood 3, 5, 3'-triiodothyronine (T3) levels across all times examined. The maternal dietary treatment increased embryonic blood concentrations of T4 at 25 to 28 d of incubation but depressed blood concentrations of T3 only at 27 d of incubation. In a second trial, the same response was noted in maternal blood when the hens were fed additional iodide with no corresponding effects on T3 concentrations. The iodide treatment decreased embryonic T4 concentrations in the second trial as well but in a time-dependent manner. Iodide accelerated the increase in T4 concentrations coincidental with earlier pipping in eggs from iodide-fed dams compared with controls. The data indicate that the embryonic thyroid function during hatching is dependent upon the maternal thyroid in turkey dams, even though the embryo develops outside the maternal body.

The effects of feeding the direct-fed microbial, primalac, on growth parameters and egg production in single comb white leghorn hens.

Two commercial strains of Single Comb White Leghorn hens, HyLine W-36 and DeKalb XL, were reared separately as pullet flocks in an enclosed, environmentally controlled brood-grow house with three banks of quad-deck cages (310 cm2 per bird). There were 1,800 hens of each strain, which were divided into two groups, control feed and a direct-fed microbial (DFM) feed treatment. During the pullet-rearing phase to 18 wk of age, the DeKalb birds had greater parameters of growth and overall feed cost than the HyLine birds. The overall feed cost of the DFM treatment was $0.02 per bird greater than controls. However, the DFM-treated feed improved the livability of the DeKalb birds by 2.68%. At 18 wk of age, 3,528 hens were transferred to an enclosed, mechanically ventilated layer house. The two strains were placed in two differently sized quad-deck layer cages with seven birds per cage; the cage sizes were 35.56 cm x 60.96 cm (2,267.73 cm2 or 310 cm2 per bird) and 14 cm x 32 cm (2,890.32 cm2 or 413 cm2 per bird). There were a total of 144 replications with each strain and DFM treatment combination made up of 36 replications equally divided between the high and low density cages. At 70 wk of age, hens receiving the DFM treatment exhibited greater mean egg weights (61.72 g) and percentages of extra large eggs (XLE, 52.06%) compared to that of controls (61.12 g and 48.98%, respectively). The treatment of 310 cm2/hen DFM produced the least (P < or = 0.05) large eggs; however, this treatment group produced the most (P < or = 0.05) XLE. The use of DFM resulted in a shift from smaller to larger eggs. Regardless of density, the DFM hens had lower (P < or = 0.05) feed cost (FC) compared to FC of the controls (a savings of $0.46/bird between the DFM and control in the 310 cm2 /hen treatment and a $0.83 savings/bird between the DFM and control in the 413 cm2/hen treatment). It was concluded that PrimaLac can improve egg size and lower feed costs, regardless of the bird density used in the present study.