Enhanced TLR2 responses in multiple sclerosis.

The roles of the microbiome and innate immunity in the pathogenesis of multiple sclerosis (MS) remain unclear. We have previously documented abnormally low levels of a microbiome-derived Toll-like receptor (TLR)2-stimulating bacterial lipid in the blood of MS patients and postulated that this is indicative of a deficiency in the innate immune regulating function of the microbiome in MS. We postulated further that the resulting enhanced TLR2 responsiveness plays a critical role in the pathogenesis of MS. As proof-of-concept, we reported that decreasing systemic TLR2 responsiveness by administering very low-dose TLR2 ligands attenuated significantly the mouse model of MS, experimental autoimmune encephalomyelitis. Studies of Toll-like receptor responses in patients with MS have been conflicting. Importantly, most of these investigations have focused on the response to TLR4 ligation and few have characterized TLR2 responses in MS. In the present study, our goal was to characterize TLR2 responses of MS patients using multiple approaches. Studying a total of 26 MS patients and 32 healthy controls, we now document for the first time that a large fraction of MS patients (50%) demonstrate enhanced responsiveness to TLR2 stimulation. Interestingly, the enhanced TLR2 responders include a significant fraction of those with progressive forms of MS, a subset of patients considered unresponsive to adaptive immune system-targeting therapies. Our results suggest the presence of a pathologically relevant TLR2 related innate immune abnormality in patients with both relapsing-remitting and progressive MS. These findings may have significant implications for understanding the role of innate immunity in the pathogenesis of MS.

Nutritional status and interventions in hospice: physician assessment of cancer patients.

BACKGROUND: Cancer cachexia is a multifactorial syndrome characterised by a progressive loss of skeletal muscle mass. It adversely influences quality of life, treatment response and survival. Early identification and multimodal interventions can potentially treat cancer cachexia. However, healthcare professionals demonstrate a lack of understanding and the ability to identify cancer cachexia early. The present study aimed to evaluate the assessment by physicians of nutritional status in cancer patients admitted to hospice. METHODS: A retrospective medical record review was conducted on all cancer admissions to a specialist in-patient palliative care unit over a 4-month period between October 2016 and January 2017. Charts were reviewed for evidence of documented nutritional assessment by physicians. Data were collected from the referral letter, admission notes, drug kardex and discharge letter. The information extracted included: (i) patient demographics and characteristics; (ii) terms used by physicians to describe nutritional status; (iii) any record of nutritional impact symptoms (NIS) experienced by the patient; and (iv) nutritional interventions prescribed. RESULTS: One hundred and forty admissions were evaluated. Nutritional terminology and NIS were most commonly documented on the admission notes. Only 41% of documents recorded any nutritional term used by physicians to assess nutritional status. Furthermore, 71% of documents recorded at least one NIS experienced by the patient. Fatigue was the most frequent NIS. CONCLUSIONS: We identified an inadequate nutritional assessment of cancer patients admitted to hospice. Implementation of a nutritional symptom checklist and nutrition screening tools, along with enhanced physician education and multidisciplinary nutrition care, could improve the identification and management of cancer cachexia in the palliative care setting.

Short communication: Effect of dietary manipulation of crude protein content and nonfibrous-to-fibrous-carbohydrate ratio on energy balance in early-lactation dairy cows.

Disparities between nutrient intake and demand often result in a state of negative energy balance (EB) in the early-lactation dairy cow. Reducing dietary crude protein (CP) content and providing glucogenic nutrients may overcome this issue. This study evaluates whether or not offering a diet lower in CP and higher in nonfiber carbohydrates (LP-NFC) can improve EB and the metabolic status of the early-lactation dairy cow compared with a diet higher in CP and fibrous carbohydrates (HP-FC). Twenty Holstein-Friesian dairy cows were assigned to 1 of 2 dietary treatments in a randomized block design. Diets were isoenergetic (6.57 MJ of net energy for lactation) and formulated to contain 15% CP and 6% starch (HP-FC), or 12% CP and 28% starch (LP-NFC) and were offered for the first 63 d of lactation. Intake and milk yield were determined daily, whereas milk and blood samples, weights, and body condition scores were collected weekly. Intakes (mean ± standard errors of the mean, SEM) of dry matter (17.4 ± 0.6 kg/d) and energy (113.0 ± 4.6 MJ of net energy for lactation) were not different between treatments. However, the HP-FC group had a higher milk yield (31.8 vs. 28.9 ± 1.4 kg/d) and a lower EB compared with the LP-NFC group. Blood urea N concentration (3.5 vs. 1.8 ± 0.2 mmol/L) was higher, whereas bilirubin (6.0 vs. 6.7 ± 0.2 mmol/L) and ß-hydroxybutyrate concentrations (0.7 vs. 0.8 ± 0.05 mmol/L) were lower in the HP-FC group compared with the LP-NFC group. These data suggest that EB can be improved during early lactation through the manipulation of milk output by offering a lower CP, higher NFC diet.

Effect of supplemental concentrate type on milk production and metabolic status in early-lactation dairy cows grazing perennial ryegrass-based pasture.

Forty-four early-lactation dairy cows of mixed parity were used to examine the effect of 4 supplemental concentrate types (n=11) on milk production and metabolic status. Animals were blocked by parity and calving date, and blocks were balanced for previous milk yield and milk protein yield. Cows received grazed pasture plus 5.17 kg of DM/d of 1 of the following isoenergetic (1.1 units of energy for lactation) concentrates: 1) high crude protein (CP) with rolled barley (HP, 19% CP); b) low CP with rolled barley (LP, 15% CP); c) low CP with barley and a supplemental methionine hydroxy analog (HMBi; LP + HMBi, 15% CP); and d) low CP with ground corn (LP-corn, 15% CP). Milk yield was recorded from d 1 to 100 postpartum, with weekly milk sampling, body weight, and body condition score (BCS) measurements. Blood and rumen sampling were conducted weekly from wk 2 to 6 postpartum. Milk yield was lower for cows in the LP treatment compared with those offered other concentrate types (25.2 vs. 27.5 ± 0.39 kg/d). Animals in the HP group had a higher milk yield than those in the LP + HMBi group (28.2 vs. 26.8 ± 0.39 kg/d). Milk fat yield was lower from animals in the LP-corn group compared with those in the LP + HMBi group (0.94 vs. 1.03 ± 0.03 kg/d). Milk protein yield was lower in the LP group compared with those in the HP group (0.88 vs. 0.97 ± 0.02 kg/d). Animal body weight, BCS, and BCS loss were not affected by concentrate type. However, nonesterified fatty acids were higher from animals in the HP group than for those in the LP + HMBi group (0.41 vs. 0.33 ± 0.03 mmol/L), and ß-hydroxy butyric acid was higher from animals in the HP group than for those in the other treatments (0.71 vs. 0.59 ± 0.03 mmol/L). Glucose was higher from animals in the LP-corn group than for those in the HP and LP groups (3.3 vs. 3.2 ± 0.05 mmol/L). Blood urea-N was higher from animals offered HP compared with those offered the other treatments (5.49.6 vs. 4.21 ± 0.44 mmol/L). However, rumen NH(3)-N and volatile fatty acid concentration in the rumen were not affected by supplemental concentrate type. Reducing supplemental concentrate CP reduced milk yield. However, milk fat production and energy-corrected milk were not different, reducing the likelihood of an improved energy balance or a more favorable blood metabolic profile in early-lactation dairy cows grazing perennial ryegrass. Offering HMBi with low-CP concentrates or replacing rolled barley with ground maize improves milk production relative to low-CP concentrates and metabolic status relative to high-CP concentrates.

Effect of supplementary concentrate type on nitrogen partitioning in early lactation dairy cows offered perennial ryegrass-based pasture.

Forty-four early lactation (64 ± 20 d in milk) dairy cows of mixed parity were used to assess the effect of 4 supplementary concentrate types (n=11) on N partitioning. Animals were blocked on parity and calving date, and blocks were balanced for previous milk yield and milk protein yield. Cows received grazed pasture plus 5.17 kg of dry matter (DM)/d of one of the following isoenergetic concentrates: high crude protein (CP) with rolled barley (HP, 19% CP); low CP with rolled barley (LP, 15% CP); low CP with barley and supplementary 2-hydroxy-4-methylthio butanoic acid (HMBi; LP+HMBi, 15% CP); and low CP with ground corn (LP Corn, 15% CP). Nitrogen partitioning studies were conducted at wk 6 and 10 postpartum by using the n-alkane technique to determine pasture dry matter intake (DMI). Pasture DMI (13.3kg of DM/d) and dietary digestibility of DM were not affected by concentrate type. Milk yield was lower for LP compared with other concentrate types (25.4 vs. 28.3 kg/d). Yields of milk protein and milk casein were not affected by concentrate type. However, milk solid yield and milk fat yield were higher for LP+HMBi (1.97 and 0.92 kg/d) compared with LP (1.72 and 0.87 kg/d). Concentrations of fat, protein, lactose, and casein were not affected by concentrate type. Dietary N intake was higher for HP compared with other treatments (0.545 vs. 0.482 kg/d, HP vs. average of the 3 LP treatments). Dietary N intakes were not different among low CP concentrates. Fecal N excretion was not affected by concentrate type. However, urinary N excretion was related to N intake and was higher for HP compared with other treatments (0.261 vs. 0.195 kg/d, HP vs. average of the 3 LP treatments). Urinary N excretion was not different among low CP concentrates. Milk N output was higher for HP (0.139 kg/d) compared with LP (0.12 kg/d) but not LP+HMBi (0.137 kg/d) or LP Corn (0.138 kg/d). The portion of feed N excreted as feces N was lower for HP compared with other treatments (0.272 vs. 0.327, HP vs. average of the 3 LP treatmentsHowever, the portion of feed N excreted as urine N was higher for HP (0.466) compared with LP+HMBi (0.408) and LP Corn (0.366) but not compared with LP. The portion of feed N excreted as milk N was higher for LP Corn (0.282) compared with HP (0.257) but not LP+HMBi or LP. Dietary reformulation to reduce N excretion in pasture-based dairy production systems is possible. However, maintenance of milk yield and milk N when concentrate CP was reduced (19 vs. 15%) required the use of either protected AA (HMBi) or ground corn.

Centromere conversion and retention in somatic cell hybrids.

The generation of somatic cell hybridization-derived cell lines between highly divergent species affords the opportunity to examine the concept of 'genome dominance' in the context of genetic and epigenetic changes. While whole-scale genome dominance has been well documented in natural hybrids among closely related species, an examination of centromere position and sequence retention in 2 marsupial-eutherian hybrids has revealed a mechanism for 'centromere dominance' as a driving force in the generation of stable somatic cell hybrids following an initial period of genomic instability. While one somatic cell hybrid cell line appeared to retain marsupial centromere sequences which remained competent to recruit the centromere-specific histone variant CENP-A in a Chinese hamster background, fusion events between marsupial and mouse-derived chromosomes in another hybrid line led to a centromere sequence conversion from one species to the other. We postulate that the necessity to maintain an epigenetically defined centromere following genome hybridization may be responsible for retention of specific chromosomes and may result in rapid sequence turnover to facilitate the recruitment of CENP-A containing histones.

ß-Blockade in the perioperative management of the patient with cardiac disease undergoing non-cardiac surgery.

The cardiology literature has suggested for decades that ß-blockade protects patients with ischaemic heart disease. Extending this concept to perioperative patients initially produced promising results, with reductions in perioperative myocardial ischaemia and longer-term cardiovascular complications observed in several small randomized trials. However, subsequent larger trials have either shown no benefit or greater morbidity (especially stroke), despite reductions in cardiovascular events. Retrospective database analyses have confirmed or disputed these findings. Speciality societies, most importantly, the American Heart Association/American College of Cardiology Foundation, have promulgated guidelines for perioperative ß-blockade, which have been revised, as the evidence has changed. While the European guidelines continue to emphasize perioperative ß-blockade in high-risk patients, the American guidelines have reduced the strength and breadth of recommendations, focusing on haemodynamic titration. Future work will need to focus on identifying populations most likely to benefit or to be harmed, including pharmacogenetic analyses and distinctions between individual ß-blockers.

Effect of forage source and a supplementary methionine hydroxy analog on nitrogen balance in lactating dairy cows offered a low crude protein diet.

Four primiparous and 4 multiparous midlactation dairy cows were stratified by pre-experimental milk yield (23.5 ± 2.3 kg/d), protein yield (0.75 ± 0.066 kg/d), parity, and days in lactation (121 ± 10 d) into 4 groups of 2 in a 2 × 2 factorial, Latin square design (n = 8) to assess the effect of forage source and a supplementary methionine hydroxy analog on nitrogen (N) balance where low crude protein (CP) diets (13.3%) are offered. Diets contained either predominantly grass silage [GS (G- and G+)] or corn silage [CS (C- and C+)] as the forage source and were offered with (G+ and C+) or without (G- and C-) the isopropyl ester of 2-hydroxy-4 methylthio butanoic acid (HMBi). The G- and G+ contained 46% GS and 10% CS in the dry matter (DM), whereas C- and C+ contained 12% GS and 52% CS in the DM. Supplementary HMBi was included at a rate of 0.2% of DM in G+ and C+ diets. Diets were isonitrogenous (9.8 ± 0.4% protein truly digested in the small intestine) and isoenergetic (0.96 ± 0.01 units of energy for lactation; kg/DM). Each of the 4 experimental periods lasted 24 d: 14 d for dietary adaptation, followed by 10 d of housing in individual metabolism stalls; N balance was conducted on the last 5 d of each experimental period. Intake of DM was higher for CS-based vs. GS-based diets (20.23 vs. 18.41 kg/d). No effect of dietary treatment was found on milk yield or yields of milk fat, protein, and lactose. Supplementing with HMBi tended to improve milk solids yield (1.69 vs. 1.59 kg/d), casein yield (0.59 vs. 0.55 kg/d), and concentrations of casein (2.89 vs. 2.73%) and protein (3.58 vs. 3.49%) in the milk. Dietary N intake was higher for CS-based vs. GS-based diets (0.460 vs. 0.422 kg/d). However, forage source or supplementary HMBi had no effect on N excretion in the feces, urine, or milk. Excretion of urinary urea was positively related to N intake. Concentrations of urea N in the plasma (2.34 vs. 1.72 mmol/L), milk (2.54 vs. 2.24 mmol/L), and urine (123.32 vs. 88.79 mmol/L), and total excretion of urinary urea N (40.23 vs. 35.09 g/d) were higher for animals offered CS-based vs. GS-based diets. Corn silage improved N intake through improved DM intake. However, neither forage source nor HMBi supplementation affects N output in the feces, urine, or milk.

A Picture of the Moon's Atmosphere.

Atomic sodium is a useful tracer of the tenuous lunar atmosphere because of its high efficiency in scattering sunlight at the D(1) (5896 angstroms) and D(2) (5890 angstroms) wavelengths. In 1988, Earth-based instruments revealed the presence of sodium at a density of less than 50 atoms per cubic centimeter at lunar altitudes below 100 kilometers. Telescopic observations that are made with a coronograph technique to block out the disk of the moon allow a true picture of the circumiunar atmosphere to be obtained and show the presence of sodium out to a distance of several lunar radii. The distribution of sodium has a solar zenith angle dependence, suggesting that most of the sodium that reaches great altitudes is liberated from the moon's surface by solar photons (by heating or sputtering) or by solar wind impact, in contrast to a source driven by uniform micrometeor bombardment.

Imaging Obsearvations of Jupiter's Sodium Magneto-Nebula During the Ulysses Encounter.

Jupiter's great sodium nebula represents the largest visible structure traversed by the Ulysses spacecraft during its encounter with the planet in February 1992. Ground-based imaging conducted on Mount Haleakala, Hawaii, revealed a nebula that extended to at least +/-300 Jovian radii (spanning approximately 50 million kilometers); it was somewhat smaller in scale and less bright than previously observed. Analysis of observations and results of modeling studies suggest reduced volcanic activity on the moon lo, higher ion temperatures in the plasma torus, lower total plasma content in the torus, and fast neutral atomic clouds along the Ulysses inbound trajectory through the magnetosphere. Far fewer neutrals were encountered by the spacecraft along its postencounter, out-of-ecliptic trajectory.

Detection of soft X-rays and a sensitive search for noble gases in comet Hale-Bopp.

An image of comet Hale-Bopp (C/1995 O1) in soft x-rays reveals a central emission offset from the nucleus, as well as an extended emission feature that does not correlate with the dust jets seen at optical wavelengths. Neon was found to be depleted in the cometary ice by more than a factor of 25 relative to solar abundance, which suggests that ices in Hale-Bopp formed at (or later experienced) temperatures higher than 25 kelvin. A helium line emission at a wavelength of 584 angstroms was detected and may be attributable to charge transfer of solar wind alpha particles in the cometary coma. Ionized oxygen and another helium line contribute to an emission observed at 538 angstroms.

LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis.

Germline mutations in STK11, which encodes the tumor suppressor liver kinase B1 (LKB1), promote Peutz-Jeghers syndrome (PJS), a cancer predisposition syndrome characterized by the development of gastrointestinal (GI) polyps. Here, we report that heterozygous deletion of Stk11 in T cells (LThet mice) is sufficient to promote GI polyposis. Polyps from LThet mice, Stk11+/- mice, and human PJS patients display hallmarks of chronic inflammation, marked by inflammatory immune-cell infiltration, signal transducer and activator of transcription 3 (STAT3) activation, and increased expression of inflammatory factors associated with cancer progression [interleukin 6 (IL-6), IL-11, and CXCL2]. Targeting either T cells, IL-6, or STAT3 signaling reduced polyp growth in Stk11+/- animals. Our results identify LKB1-mediated inflammation as a tissue-extrinsic regulator of intestinal polyposis in PJS, suggesting possible therapeutic approaches by targeting deregulated inflammation in this disease.

HLA identical leukemia cells and T cell growth factor activate cytotoxic T cell recognition of minor locus histocompatibility antigens in vitro.

Lymphocytes from a healthy HLA-identical bone marrow transplant donor were tested for their ability to destroy her brother's acute myelogenous leukemia blasts in vitro. Primary mixed lymphocyte culture (MLC) and cell-mediated lysis (CML) responses between the patient's remission (pretransplant) and donor's lymphocytes were negative. Stimulation of donor lymphocytes for 7 d in vitro with irradiated leukemia cells, leukemia cells plus allogeneic irradiated lymphocytes, or a pool of irradiated lymphocytes from 10 donors, did not activate any cytotoxic cells able to destroy the HLA identical leukemic blasts. Further culturing for 7 additional d in T cell growth factor (TCGF) generated lymphocytes that induced effective cytotoxicity against the leukemic blasts, but not against autologous lymphocytes. Effective killing against the leukemia was observed only in cultures initially stimulated with the irradiated leukemia cells. These cytotoxic cells were maintained in TCGF and mediated persistent killing against the leukemic target cells. They were also able to destroy lymphocytes from the patient's mother and father, but not from an unrelated cell donor. This suggested specific recognition of non-HLA antigens inherited by the patient, that were foreign to the HLA identical bone marrow donor. These lymphocytes were cloned by a limiting dilution technique and one clone maintained cytotoxicity to the AML blasts and the father's lymphocytes, but not lymphocytes from the mother or an HLA-identical donor. This cytotoxicity was inhibited by a monoclonal anti-HLA antibody. Thus, in vitro sensitization of this sibling's lymphocytes with AML blasts followed by TCGF expansion, and cloning, enabled the detection of HLA-restricted cytotoxic cells that recognize minor locus histocompatibility antigens. This immune recognition may be relevant to the "graft vs. leukemia" effect that has been observed in leukemic animals and patients following histocompatible hematopoietic transplants.

Clustering of adverse drug events: analysis of risk factors for cerebellar toxicity with high-dose cytarabine.

BACKGROUND: Cerebellar toxicity is a severe, therapy-limiting adverse reaction of cytarabine given in high doses. The Food and Drug Administration received a report of an increased frequency of cerebellar toxicity at the University of Wisconsin Hospital and Clinics after a switch from the product (Cytosar-U) manufactured by The Upjohn Co., Kalamazoo, Mich., to the generic form made by Quad Pharmaceuticals, Inc., Indianapolis, Ind. PURPOSE: To compare the incidence of cerebellar toxicity in Quad-treated patients with Upjohn-treated patients, a record-based cohort study was conducted at the University of Wisconsin Hospital and Clinics between January 1986 and August 1989. METHODS: The incidence of cerebellar toxicity was studied in 63 leukemia patients according to the manufacturer of the product received (34 Upjohn only, 25 Quad only, and four both manufacturers). The relative risk of cerebellar toxicity was adjusted for other known risk factors. RESULTS: Patients in the manufacturer-defined treatment groups did not differ significantly with respect to age, sex, type of leukemia, disease stage, calculated creatinine clearance, presence of abnormal liver function tests, or total dose received. The crude relative risk of cerebellar toxicity comparing the Quad product with the Upjohn product was 5.0 (95% confidence interval = 1.8-13.7). Adjustment for potential confounders did not alter the association. Other risk factors for cerebellar toxicity, independent of manufacturer, were age greater than 50 years, type of leukemia, disease stage, total dose greater than or equal to 20 g/m2, abnormal pretreatment liver function, and reduced creatinine clearance. CONCLUSION: This study found a significantly higher incidence of cerebellar toxicity with high-dose cytarabine manufactured by Quad Pharmaceuticals when compared with the incidence of cerebellar toxicity with the Upjohn product. Further research at independent institutions would be necessary to allow generalization of this finding. In addition, our findings suggest that a dose reduction in high-dose cytarabine therapy may be indicated for patients with reduced glomerular filtration rates.

Does service integration improve the sexual and reproductive healthcare of women living with HIV?

The sexual and reproductive health (SRH) care needs of a cohort of HIV-positive women were studied pre- and post-integration of genitourinary medicine (GUM) and SRH services. Pre-integration, 24.9% of women at risk of pregnancy were using an effective method of contraception, with a non-significant improvement post-integration to 39.3%. Pre-integration, 47.6% of pregnancies were unplanned, whilst 50% were still unplanned post-integration. Cervical cytology uptake within the previous 12 months improved significantly. It appears that the integration of services alone does not improve all aspects of the SRH of women living with HIV and additional novel strategies should be explored.

Cost effectiveness of a community based research project to help women quit smoking.

OBJECTIVE: To estimate the cost effectiveness of a four year, multifaceted, community based research project shown previously to help women quit smoking. DESIGN: A quasi-experimental matched control design. SETTING: Two counties in Vermont and two in New Hampshire, USA. SUBJECTS: Women aged 18-64 years. METHODS: Costs were the grant related expenditures converted to 2002 US dollars. Survey results at the end of the intervention were used to estimate the numbers of never smokers, former smokers, light smokers, and heavy smokers in the intervention and comparison counties, and 1986 life tables for populations of US women categorised by smoking status to estimate the gain in life expectancy. MAIN OUTCOME MEASURES: Cost effectiveness ratios, as dollars per life-year saved, for the intervention only and for total grant costs (intervention, evaluation and indirect costs). RESULTS: The cost effectiveness ratio for the intervention, in 2002 US dollars per life-year saved, discounted at 3%, was 1156 dollars (90% confidence interval (CI) 567 dollars to infinity), and for the total grant, 4022 dollars (90% CI 1973 dollars to infinity). When discounted at 5%, these ratios were 1922 dollars (90% CI 1024 dollars to 15,647 dollars), and 6683 dollars (90% CI 3555 dollars to 54,422 dollars), respectively. CONCLUSION: The cost effectiveness ratios of this research project are economically attractive, and are comparable with other smoking cessation interventions for women. These observations should encourage further research and dissemination of community based interventions to reduce smoking.

Smoking cessation counseling during periodic health examinations.

Periodic health examinations are an excellent opportunity to counsel smokers to quit. The impact of a specialized smoking cessation counselor on the smoking behavior of patients having periodic health examinations was studied in a general internal medicine practice. One hundred fifty-five smokers having periodic health examinations were randomly assigned to a control group who received usual physician advice or an intervention group who received usual physician advice and two counseling sessions with a smoking cessation counselor. The two groups were similar in all demographic variables, smoking-related baseline variables, and baseline levels of motivation and intention to quit smoking. The smoking status of 97% of the subjects was assessed 6 months later. In the intervention group, 46% made quit attempts and 19% quit, compared with 34% and 12%, respectively, in the control group. Intervention-group smokers made more quit attempts (mean +/- SD, 5.0 +/- 2.5 vs 1.8 +/- 0.2) and had a greater reduction in daily cigarette use (8.4 +/- 1.5 vs 3.5 +/- 1.3). Of the 74% of smokers with higher levels of motivation to quit smoking, more intervention-group smokers attempted to quit (70.8% vs 45.5%) and succeeded in quitting at the 6-month follow-up (27.1% vs 10.9%). Periodic health examinations are an excellent opportunity to counsel smokers to quit, especially those smokers with higher levels of motivation to quit smoking.

Acquired immunodeficiency syndrome/human immunodeficiency virus risk behavior among gay men in small cities. Findings of a 16-city national sample.

BACKGROUND: Most research on acquired immunodeficiency syndrome has been conducted in several of the country's largest cities, and little is known about the current level of human immunodeficiency virus risk taking among gay men in other geographical areas. The purpose of this study was to determine the frequency of risk behavior practices among gay men in smaller communities. METHOD: A large sample of men who patronized gay bars in 16 small and moderate-size cities drawn from six states in four different regions of the country was surveyed to determine the frequency of high-risk behavior and factors influencing risk taking. Eighty-five percent of men in all cities' bars completed all survey measures. The community samples were 1991 men; mean age, 31.3 years; mean education, 10.6 years; 90% were white and 10% were of other ethnicities. All participants provided detailed information on their sexual behavior practices over the preceding 2 months and completed measures assessing their perceived peer norms concerning safer sex practices and risk avoidance, intentions to avoid risk, personal risk estimation, acquired immunodeficiency syndrome risk knowledge, perceived threat of acquired immunodeficiency syndrome/human immunodeficiency virus, and serostatus testing history. RESULTS: High-risk patterns were still common among gay men in these smaller cities; nearly one third of all men had engaged in unprotected anal intercourse an average of eight times in the past 2 months, usually outside monogamous relationships. High-risk behavior was most strongly associated with beliefs that safer sex practices would not be well accepted by peers, weak intentions to use condoms, underestimation of personal vulnerability to the acquired immunodeficiency syndrome, younger age, and higher levels of overall sexual activity. Nine percent of men tested said they were seropositive. CONCLUSIONS: Growing human immunodeficiency virus prevalence and continued high rates of risk behavior indicate that a new "front line" for human immunodeficiency virus prevention among homosexually active men has shifted to the country's smaller cities. Community prevention efforts in these areas are urgently needed to avert sharp increases in future human immunodeficiency virus infections in this population.

Manipulating enteric methane emissions and animal performance of late-lactation dairy cows through concentrate supplementation at pasture.

The objective of this study was to determine the potential of increased fiber-based concentrates to reduce methane (CH(4)) production in relation to milk yield from late-lactation dairy cows. The effect of 2 levels of concentrate supplementation (0.87 vs. 5.24 kg on a dry matter basis) on herbage voluntary intake, total dry matter intake, milk yield, milk composition, and CH(4) production were determined by way of a randomized block designed grazing trial using lactating Holstein-Friesian cows (231 +/- 44 d in milk) grazing a mixed-grass sward with a regrowth aged 36 d. Increased concentrate supplementation resulted in a significant increase in total dry matter intake, milk yield, fat-corrected milk (FCM) yield, and daily CH(4) production. However, herbage intake and milk composition were unaffected. Although daily CH(4) production increased with fibrous concentrate use the increase was not as great as that observed for milk yield. The decline in CH(4) production per kilogram of milk was nonsignificant; however, when relating CH(4) production to FCM(FCM at 35 g of fat/kg of milk), a declining trend was identified within increasing concentrate supplementation (19.26 and 16.02 g of CH(4)/kg of FCM). These results suggest that increased fibrous concentrate use at pasture, even at modest levels, could reduce enteric CH(4) production per kilogram of animal product. However, the effectiveness of such a strategy is dependent on the maintenance of production quotas and a subsequent decline in the number of livestock needed to fulfill the specified production level.

Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: addition of cytosine arabinoside to the pretransplant conditioning prevents rejection.

A total of 41 patients with hematologic malignancies (other than acute leukemia in relapse) received allogeneic bone marrow transplants at the University of Wisconsin from 1 April 1980 through 31 March 1984. In an effort to minimize graft-versus-host disease, marrow was depleted of T-lymphocytes in vitro with monoclonal anti-T-cell antibody and complement prior to infusion for seven of 19 recipients of marrow from HLA-identical, MLC-nonreactive siblings, and for all 22 recipients of marrow from MLC-reactive HLA-haploidentical donors. The recipients of HLA-identical T-depleted marrow all showed excellent engraftment following standard pre-BMT conditioning with cyclophosphamide and total body irradiation. In contrast, five of five recipients of T-depleted haploidentical marrow failed to engraft following this same conditioning regimen. The addition of cytosine arabinoside to the pretransplant conditioning appeared to correct this problem, allowing engraftment in 14 of 17 subsequent patients. These clinical results, coupled with prior in vitro data, demonstrate the need to adequately suppress residual host-versus-graft immunity in order to prevent the rejection of T-cell-depleted HLA-haploidentical bone marrow.