Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self-limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model.

REASONS FOR PERFORMING STUDY: Improvement has been reported following intra-articular (i.a.) injection of mesenchymal stromal cells (MSCs) in several species. These observations have led to the use of i.a. MSCs in equine practice with little understanding of the mechanisms by which perceived improvement occurs. OBJECTIVES: To evaluate the effect of i.a. allogeneic umbilical cord blood (CB-) derived MSCs using a lipopolysaccharide (LPS) induced synovitis model. We hypothesised that i.a. CB-MSCs would reduce the inflammatory response associated with LPS injection. STUDY DESIGN: Randomised, blinded experimental study. METHODS: Feasibility studies evaluated i.a. LPS or CB-MSCs alone into the tarsocrural joint. In the principal study, middle carpal joint synovitis was induced bilaterally with LPS and then CB-MSCs were injected into one middle carpal joint. Lameness, routine synovial fluid analysis, and synovial fluid biomarkers were evaluated at 0, 8, 24, 48 and 72 h. RESULTS: LPS injection alone resulted in transient lameness and signs of inflammation. In joints untreated with LPS, injection of 30 million CB-MSCs resulted in mild synovitis that resolved without treatment. Mild (grade 1-2) lameness in the CB-MSC-treated limb was observed in 2 horses and severe lameness (grade 4) in the 3rd, 24 h post injection. Lameness did not correlate with synovitis induced by CB-MSC injection. Simultaneous injection of LPS and CB-MSCs resulted in significant reduction in synovial fluid total nucleated, neutrophil and mononuclear cell numbers compared with contralateral LPS-only joints. No difference was detected in other parameters associated with synovial fluid analysis or in synovial fluid biomarkers. The incidence of lameness was only different from baseline at 8 h, where horses were lame in CB-MSC limbs. CONCLUSIONS: Allogeneic CB-MSCs reduced synovial fluid cell populations and stimulated mild self-limiting inflammation in the synovitis model. Continued evaluation of the effects of i.a. CB-MSC therapy on synovitis in horses is needed to evaluate anti- and proinflammatory properties of CB-MSCs. Immediate interests are dose, timing of treatment, and treatment frequency.

Diabetes-specific family conflict and psychological distress in paediatric Type 1 diabetes.

AIMS: Diabetes-specific family conflict is associated with suboptimal adherence and glycaemic control. Little is known about the individual and family factors associated with diabetes-specific family conflict. The purpose of this study was to examine whether background factors (e.g. age, gender), diabetes variables (e.g. duration of diabetes, adherence, glycaemic control) and psychological distress (i.e. depression and anxiety) in parents and children and adolescents were associated with diabetes-specific family conflict. METHODS: Participants were 187 children and adolescents with Type 1 diabetes and their parents. Study measures assessed diabetes-specific family conflict, youth depression and parent depression and anxiety. Demographic and disease-specific data (adherence, glycaemic control) were also collected. RESULTS: Findings suggested a close link between psychological distress in parents and children and adolescents and reports of increased diabetes-specific family conflict. In the presence of suboptimal glycaemic control, children and adolescents and parents reported more family conflict. Adherence was not significantly associated with family conflict. CONCLUSIONS: This study highlights the importance of considering the impact of individual psychological functioning on family conflict and also suggests a bidirectional relationship between conflict and glycaemic control.

Hexosamines regulate leptin production in human subcutaneous adipocytes.

The hexosamine biosynthetic pathway has recently been proposed as a mechanism through which cells "sense" nutrient flux to regulate leptin release. This study was undertaken to examine the regulation of leptin production by hexosamines in human adipocytes. Adipose tissue UDP-N-acetylglucosamine, an end product of hexosamine biosynthesis, was elevated 3.2-fold, and ob messenger ribonucleic acid was elevated 2-fold in the sc adipose tissue of 17 obese [body mass index (BMI), 41.3+/-12.0 kg/m2; age, 31+/-5 yr] subjects compared to 14 lean (BMI, 23.4+/-1.6 kg/m2; age, 33+/-11 yr) subjects. Serum leptin was increased 2.7-fold in the obese subjects. A significant positive relationship was found between adipose tissue UDP-N-acetylglucosamine and BMI (Spearman correlation = 0.576; P = 0.0007) and between UDP-N-acetylglucosamine and serum leptin (Spearman correlation = 0.4650; P = 0.0145). Treatment of isolated sc adipocytes with 1 mmol/L glucosamine, an intermediate product in UDP-N-acetylglucosamine biosynthesis, increased leptin release 21.4+/-17.6% (mean +/- SD) over control (P = 0.0365) and 74.5+/-82.8% over control (P = 0.0271) in adipocytes from lean (BMI, 23.2+/-1.6 kg/m2; n = 6) and obese (BMI, 55.4+/-13.0 kg/m2,; n = 9) subjects, respectively, by 48 h of culture. Inhibition of UDP-N-acetylglucosamine biosynthesis with 6-diazo-5-oxo-norleucine reduced glucose-stimulated leptin release from cultured adipocytes 21.8+/-32.4% (P = 0.0395; n = 12) and ob gene expression 19.9+/-18.9% (P = 0.0208; n = 8) by 48 h of treatment. These findings suggest that hexosamine biosynthesis regulates leptin production in human adipose tissue.

Leptin production in adipocytes from morbidly obese subjects: stimulation by dexamethasone, inhibition with troglitazone, and influence of gender.

This study examined the regulation of leptin production by dexamethasone and troglitazone. Subcutaneous and omental adipose tissue was obtained during bariatric surgical procedures (30 women and 16 men; body mass index, 52.5 +/- 1.7 kg/m2, age, 39 +/- 2 yr), and adipocytes were cultured in suspension. Subcutaneous adipocytes from females released significantly more leptin than did omental cells from the same subject (P < 0.05), but basal leptin release was not different in adipocytes from these depots in males. Dexamethasone (0.1 micromol/L) significantly increased leptin release within 24 h from sc (135 +/- 13% of control) and omental (227 +/- 53%) adipocytes of females, but not males. Dexamethasone-stimulated leptin production at 48 h was significantly greater in the omental adipocytes of females (398 +/- 64% of control) than in sc adipocytes of females (207 +/- 21%) or the omental (211 +/- 33%) and sc (180 +/- 23%) adipocytes of males. Troglitazone (10 micromol/L; 48 h) significantly inhibited dexamethasone-stimulated leptin release in sc (57 +/- 10.7% inhibition) and omental adipocytes (134 +/- 26% inhibition). There was no gender-related difference in the effect of troglitazone to inhibit dexamethasone-stimulated leptin release. Troglitazone significantly inhibited basal leptin production from omental adipocytes by 15.0 +/- 5.2%. The effect of dexamethasone and troglitazone to regulate leptin release was mediated through changes in ob gene expression, but did not involve changes in glucose uptake or metabolism to lactate. The data suggest that adipocytes from females are more responsive to the stimulatory effect of dexamethasone in vitro than are adipocytes from males. If adipocytes from females are more responsive to relevant in vivo stimuli for leptin secretion such as insulin or glucose, this could contribute to the gender difference in serum leptin. The data also suggest that leptin release from omental adipocytes may be more responsive to hormonal and nutrient regulation in vivo than are sc adipocytes.

Tumor necrosis factor-alpha inhibits leptin production in subcutaneous and omental adipocytes from morbidly obese humans.

This study was undertaken to examine the regulation of leptin production from human adipocytes by tumor necrosis factor-alpha (TNFalpha). Adipocytes were isolated from adipose tissue obtained during bariatric surgical procedures (17 women and 3 men; body mass index, 52.5 +/- 2.4 kg/m2; age, 40 +/- 3 yr) and cultured in suspension. Leptin release from sc adipocytes was inhibited 17.7 +/- 5.2% (P < 0.01), 21.6 +/- 4.3% (P < 0.005), and 37.1 +/- 7.2% (P < 0.05) by 1, 10, and 100 ng/mL TNFalpha, respectively, after 48 h in culture. At 100 ng/mL, significant inhibition of leptin release (25.8 +/- 9.7%; P < 0.05) was detected by 24 h. TNFalpha (10 ng/mL) had no effect on dexamethasone (0.1 micromol/L)-stimulated leptin production in sc adipocytes. In omental adipocytes TNFalpha inhibited leptin release 21.0 +/- 9.6% and 40.8 +/- 6.3% at 10 and 100 ng/mL by 48 h (P < 0.05). Significant inhibition ofleptin release from omental adipocytes was observed at 24 h with 100 ng/mL TNFalpha (P < 0.05). Anti-TNFalpha antibody completely blocked TNFalpha inhibition of leptin release. The ob messenger ribonucleic acid was significantly reduced (23.6 +/- 5.9%) after 48 h of TNFalpha (100 ng/mL) treatment (P < 0.025). TNFalpha had no effect on glucose uptake or lactate production in sc and omental adipocytes. The data suggest that the direct paracrine effect of adipose-derived TNFalpha is inhibition of leptin production.

Study of mechanical versus manual/mechanical compression following various interventional cardiology procedures.

Knowledge and technology for cardiovascular disease are growing at a rapid rate. Interventional cardiology offers patients several options of therapy, including percutaneous transluminal coronary angioplasty, directional coronary atherectomy, and percutaneous transluminal coronary rotoblator angioplasty procedures. Patients with these procedures require femoral intra-arterial sheath insertion and postprocedure management of these sheaths. The best practice for sheath removal is a controversial issue. This article describes a study conducted at Presbyterian Hospital in Charlotte, North Carolina, comparing the use of manual/mechanical versus mechanical compression technique for sheath removal. Subjects included patients who had one of the previous procedures performed. Subjects were randomly assigned to one of two study groups: manual/ mechanical or mechanical compression. Variables such as size of sheath, anticoagulants, antiplatelets, and flat time after sheath removal were examined. The outcome measure reported was the development of a groin complication. Results indicated no significant difference in groin complication. As a result, practice at Presbyterian Hospital changed to mechanical compression for removing sheaths.

High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer: poor response rate in unselected patients.

We have conducted a retrospective study of high-dose folinic acid and 5-fluorouracil in 96 patients with advanced colorectal cancer. Patients received 200 mg m-2 (maximum 300-350 mg) folinic acid by infusion over 2 h followed by an i.v. bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 600 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for four cycles; thereafter patients with objective response continued to a maximum of eight cycles. The overall response rate was 10.6% in 85 evaluable patients. The median duration of response was 11 months. The median survival was 6 months. Toxicity was low, only one patient experiencing toxicity greater than WHO grade II (grade IV platelet toxicity). Diarrhoea, nausea, vomiting and mucositis also occurred but were mild and infrequent. Our low response rate may be related to factors such as patient characteristics or duration of treatment.

Determinants of couple agreement in U.S. fertility decisions.

An analysis of data from 8,450 women interviewed in 1988 for the National Survey of Family Growth finds that teenagers, never-married women, black women and those with less than a high school education are less likely than other women to have a birth that is jointly desired by both partners; 29%, 35%, 45% and 51% of births, respectively, are wanted by both partners, compared with an overall average of 69%. Third and higher order births are also less likely than earlier births to be jointly planned--58%, compared with 69% of first births and 76% of second births. In situations in which the birth is not jointly planned, black women, unmarried women, teenagers and women having third or higher order births are all significantly more likely than other women in their race, marital status, age and birth-order categories to have a birth when the man's preference is unknown. Never-married women are significantly more likely than married women to have a birth when the woman desires one but the man does not, while black women are significantly more likely than white women to have a birth that the man wanted but that the woman did not.

PIP: Cycle IV of the US National Survey of Family Growth in 1988 was used to obtain data on wantedness of births by couples including 8450 women aged 15-44 years. The study population included 5354 Whites, 2771 Blacks, and 325 of other ethnicity. Respondents answered for their husbands or partners about attitudes toward the wantedness of births. Couple agreement was grouped as births that both couples wanted; births that both couples considered unintended or mistimed; births that were wanted by the woman and not by her partner; births desired by the man and not the woman; and births for which the woman did not know her partner's preference. Social and demographic factors were race, education, marital status, age, and birth order. Bivariate and logistic regression analysis were performed. The results showed that 74% of non-Hispanic White women, 66% of Hispanic White women, and 45% of Black women had jointly planned births. 51% with less than a high school education, 66% of high school graduates, 73% with a college education, and 84% of college graduates had jointly planned births. 35% of unmarried women versus 74% of ever-married women had planned births. 29% of adolescent women versus 66-79¿ of older women had jointly planned births. 69% of first births versus 76% of second births were jointly planned; only 58% of third births were jointly planned. A separate analysis was performed for those not knowing their partner's preference. Black women were more likely than non-Hispanic White or Hispanic women to report a lack of joint approval and more likely to have a child without partner approval in the logistic regression. There was a lower likelihood of a planned birth among teenagers compared to those aged 20-24 years. Women with 1-3 years of college education were more likely to have a birth the man wanted, but they did not want, than women with a college degree. Education did not have an impact when other variables were controlled. In comparisons of differences between spouses and wantedness, Black women with less than a high school education were more likely to want a child without spouse approval than women with 1-3 years of college education; when excluding women aged under 20 years, the results were the same. In the race analysis, age, marital status, and birth order were important factors, but, for White women, only birth order was relevant.

Changes in the planning status of births to ever-married U.S. women, 1982-1988.

PIP: Analysis of births reported in the Cycles III and IV of the US National Survey of Family Growth in 1982 and 1988 indicate no statistically significant changes in the proportion of births among women noncontracepting and not seeking a pregnancy. Birth distributions are largely changed among women planning births, which show declines, and women with contraceptive failures, which result in increased births. There were significant increases in ever married women's use of contraception (65% in 1982 and 71% in 1988), and fewer women desiring a pregnancy (6% in 1982 and 3% in 1988). Among those at risk of a unintended pregnancy the proportion using more effective methods of contraception increased from 71% to 73%. The failure rates for less effective methods such as the condom, diaphragm, and spermicides are unchanged between 1982 and 1988. The proportion of unintended pregnancies ending in abortion change very little between 1982 and 1988, according to analysis of data for 1982 and 1987 by Forest and Singh. Analysis of NSFG data on abortions for the 5 years preceding the surveys show a decline, but it is not statistically significant. The analysis suggests that there were indeed more unplanned pregnancies that came to term between 1982 and 1987 than between 1977 and 1981. The unplanned pregnancies are accounted for by the increased number of women at risk of contraceptive failure, the increased failure rates for the pill and for abstinence, and an increased proportion of unwanted pregnancies carried to term between 1982 and 1988. The proportion not using contraception would not appear to have affected the changes in unintended births. Why use-effectiveness of contraception has changed is not known.^ieng

Silent maladie de Roger.

A patient with no cardiac murmur was found to have a ventricular septal defect by Doppler echocardiography yet no evidence of pulmonary or right ventricular hypertension. This array of findings is distinctly unusual and appears to be at odds with the clinical teachings concerning small ventricular septal defects.

Religion and fertility in the United States: new patterns.

In the United States, the baby boom-era pattern of high Catholic and low Protestant fertility has ended. Among non-Hispanic whites in the 1980s, Catholic total fertility rates (TFRs) were about one-quarter of a child lower than Protestant rates (1.64 vs. 1.91). Most of the Protestant-Catholic difference is related to later and less frequent marriage among Catholics. Future research on the demography of religious groups should focus on explaining the delayed marriage pattern of Catholics, the high fertility of Mormons and frequently attending Protestants, and the very low fertility of those with no religious affiliation.

Intermittent superior vena cava syndrome caused by a Hickman catheter.

A case of intermittent superior vena cava syndrome caused by a Hickman catheter is reported. The symptoms resolved on removal of the catheter. The use of anticoagulants in conjunction with indwelling venous catheters is discussed.

Determinants of unintended childbearing among ever-married women in the United States: 1973-1988.

A downward trend in unwanted childbearing has reversed among large segments of the population, according to data from the 1988 National Survey of Family Growth. The proportion of births in the previous five years that were unwanted at conception fell from 14 percent in 1973 to eight percent in 1982, but increased to 10 percent in 1988. Between the 1982 and 1988 surveys, increases were most pronounced among women with less than a high school education and among women living below the federal poverty level. Differences between black women and white women in levels of unwanted childbearing, which were converging prior to 1982, have since grown considerably, particularly among the poor and the less educated.

PIP: The increases in unwanted childbearing by 10% between 1982-88, particularly pronounced among women with less than a high school education and among those living below the federal poverty level, reflect the concerns in this article. Data from the National Survey of Family Growth, Cycle IV, (NSFG-IV) in 1988 were used to describe the trends between 1973-1988 in ever married US women aged 15-44 and % of unwanted and mistimed at conception births, by race and maternal characteristics (education, poverty level, residence). Determinants of unwanted childbearing were estimated with 3 sets of logistic regressions (total, black, and white). Data methods are described. Childbearing has been increasing among those with the least access to private medical care. The theoretical explanation offered is that income disparities among the lower income strata, particularly in the ghettos, produces alienation, and an increase in risk taking behavior, manifested as unprotected intercourse contributed consequently to unplanned conceptions. Other joint factors are declining parental authority, limited access to contraceptives, and conflicting messages about sex. The results show a decline in the proportion of unwanted births between 1973 and 1982, from 13% to 8%, and then a 10% increase. Mistimed births remain constant throughout the period. The proportion of births unwanted increased with the age of the mother, while mistimed births showed a decrease. Mistimed births consistently outnumber unwanted births. The actual numbers of mistimed births were 2 times as prevalent pre-1973 and 3 times, by 1982 as unwanted births. The % point difference between blacks and whites in unwanted births was 18 points in 1973, 9 points in 1982 and 14 points in 1988. Increases in formal education were related to smaller %s of unwanted births for either race, but statistically significant for those with high school education; this was not true in 1973. The proportion of unwanted births among women in poverty rose by almost 75% between 1973-82. By 1982, only black women below the poverty level with unwanted births were statistically significant; this was not true in 1973. Mistimed childbearing has risen among white women living outside SMSA's and unwanted childbearing within SMSA's. Births to women 30 years are more likely to be unwanted, with other variables controlled in the regression analyses. Race and ethnicity are known to be highly intercorrelated with level of income and educational attainment, but there remains an independent effect of race on unwanted childbearing. Access to abortion providers data was not available to assess the impact that abortion services have played, and will continue play on unwanted childbearing.

Digenetic trematodes of marine fishes of Okinawa, Japan.

Between May and September 1985, 348 fishes representing 50 families, 107 genera, and 152 species from the coastal waters of Okinawa were examined for digenetic flukes. Ten families (Lepocreadiidae, Opistholebetidae, Gyliauchenidae, Fellodistomidae, Acanthocolpidae, Opecoelidae, Bucephalidae, Cryptogonimidae, Syncoeliidae, and Hemiuridae), representing 29 genera and 34 species of digenetic flukes were recorded. Seven new geographic locality records and 25 new host records were established. Possibly 2 new species, one being a species of the genus Metadena from Meiacanthus grammistes and the other a species of the genus Mesolecitha from Plectorhynchus chaetodontoides, were detected. Most infections were of a single species, and although prevalence and intensity were low, host specificity was high. Only 3 of the 34 species identified transgressed family bounds in their definitive hosts.

Intractable complex partial seizures: the "initial motionless stare" and surgical outcome following temporal lobectomy.

Complex partial seizures (CPSs) beginning with an initial motionless stare (IMS) have been reported to respond well to temporal lobectomy. CPSs without the IMS or with early lateralizing motor phenomena often persisted after temporal lobectomy. We have studied video-EEG-recorded seizures of 18 patients with depth electrodes who then underwent temporal lobectomy. The IMS did not correlate with success or failure of surgery. However, initial head and/or eye deviation was correlated with poor surgical outcome.

A clinical nurse specialist in a line management position.

The authors describe their experiences utilizing a clinical nurse specialist in a middle management role in an organizational framework to support primary nursing. They describe the original design and planning of the organizational model 12 years ago, the administrative supports that have been added in the intervening years, and how professional and administrative authority are integrated by the clinical nurse specialist in a line position.