Effects of treadmill running and limb immobilization on knee cartilage degeneration and locomotor joint kinematics in rats following knee meniscal transection.

OBJECTIVE: This study examined the effects of reduced and elevated weight bearing on post-traumatic osteoarthritis (PTOA) development, locomotor joint kinematics, and degree of voluntary activity in rats following medial meniscal transection (MMT). DESIGN: Twenty-one adult rats were subjected to MMT surgery of the left hindlimb and then assigned to one of three groups: (1) regular (i.e., no intervention), (2) hindlimb immobilization, or (3) treadmill running. Sham surgery was performed in four additional rats. Voluntary wheel run time/distance was measured, and 3D hindlimb kinematics were quantified during treadmill locomotion using biplanar radiography. Rats were euthanized 8 weeks after MMT or sham surgery, and the microstructure of the tibial cartilage and subchondral bone was quantified using contrast enhanced micro-CT. RESULTS: All three MMT groups showed signs of PTOA (full-thickness lesions and/or increased cartilage volume) compared to the sham group, however the regular and treadmill-running groups had greater osteophyte formation than the immobilization group. For the immobilization group, increased volume was only observed in the anterior region of the cartilage. The treadmill-running group demonstrated a greater knee varus angle at mid-stance than the sham group, while the immobilization group demonstrated greater reduction in voluntary running than all the other groups at 2 weeks post-surgery. CONCLUSIONS: Elevated weight-bearing via treadmill running at a slow/moderate speed did not accelerate PTOA in MMT rats when compared to regular weight-bearing. Reduced weight-bearing via immobilization may attenuate overall PTOA but still resulted in regional cartilage degeneration. Overall, there were minimal differences in hindlimb kinematics and voluntary running between MMT and sham rats.

Dark-field microscopy in the assessment of large colon microperfusion and mucosal injury in naturally occurring surgical disease of the equine large colon.

REASON FOR PERFORMING STUDY: Intraoperative assessment of colonic viability can be challenging and largely subjective. Objective methods are often impractical. Viability is related to re-establishment of colonic perfusion; particularly microvascular perfusion. This study evaluated the utility of dark-field microscopy (DFM) of the colonic serosa as an objective method of assessing microperfusion. OBJECTIVES: To measure microvascular perfusion indices (MPI) of the pelvic flexure serosa in horses with surgical colonic lesions and correlate these with macroperfusion indices (MaPI) and histomorphometry. STUDY DESIGN: Prospective, clinical, case-control study. METHODS: Control horses and horses with colonic volvulus (LCV), displacement, and/or simple obstruction undergoing surgery had DFM video loops performed on the pelvic flexure. Total vessel density, perfused vessel density, proportion of perfusion vessels and microvascular flow index were calculated from video analysis. Macroperfusion indices (arterial blood pressure and heart rate) were recorded. Histomorphometry was used to determine a mucosal injury score. Differences between lesions for MPI, MaPI and histomorphometry were compared using ANOVA or Kruskal-Wallis statistic. Spearman correlations between MPI with MaPI were performed. Linear regression was used to assess the relationship between MPI and histomorphometry. P<0.05 was significant. RESULTS: Horses with LCV had lower perfused vessel density, proportion of microvascular perfusion vessels and flow index than horses with nonstrangulating obstructions and control horses. Macroperfusion indices were not correlated with MPI but MPI were correlated with histomorphometry. CONCLUSIONS: Dark-field microscopy is achievable in the operating room and can quantify MPI from the colonic serosa in different colonic lesions. Macroperfusion indices were not related with colonic MPI. Microvascular perfusion indices can predict the severity of histopathological change at the pelvic flexure. Derangements of MPI may be more useful indicators of colonic pathology and viability and offer a more objective assessment of intestinal injury than subjective methods. Further study is needed to determine the utility of DFM in predicting survival in horses with LCV.

Papules and pustules of the elbows and knees: an uncommon clinical sign of dermatomyositis in oriental children.

We report two children with dermatomyositis in whom the initial manifestation was a papular eruption on the extensor surfaces of the elbows and knees. In each there was a follicular component to the eruption and one child had pustular lesions. The extensor eruption predated the onset of muscle weakness by 1 year in the first child and by 2 years in the second. Both children had Vietnamese parents. There is some evidence in the literature that Oriental patients may be predisposed to this type of eruption.

The public health significance of Trichuris trichiura.

An estimated 1049 million persons harbour T. trichiura, including 114 million preschool-age children and 233 million school-age children. The prevalence of T. trichiura is high and may reach 95% in children in many parts of the world where protein energy malnutrition and anaemias are also prevalent and access to medical care and educational opportunities is often limited. The Trichuris dysentery syndrome (TDS) associated with heavy T. trichiura, which includes chronic dysentery, rectal prolapse, anaemia, poor growth, and clubbing of the fingers constitutes an important public health problem, as do lighter but still heavy infections, even if not strictly TDS, especially in children. The profound growth stunting in TDS can be reversed by repeated treatment for the infection and, initially, oral iron. However findings from Jamaica strongly suggest that the significant developmental and cognitive deficits seen are unlikely to disappear without increasing the positive psychological stimulation in the child's environment. The severe stunting in TDS now appears likely to be a reaction at least in part to a chronic inflammatory response and concomitant decreases in plasma insulin-like growth factor-1 (IGF-1), increases in tumor necrosis factor-alpha (TNF-alpha) in the lamina propria of the colonic mucosa and peripheral blood (which likely decrease appetite and intake of all nutrients) and a decrease in collagen synthesis. Improvements in cognitive performance have been found after treatment for relatively heavy infections (without chronic dysentery) in school-going children; it is unclear precisely how much T. trichiura interferes with children's ability to access educational opportunities, but treatment of infections whenever possible is obviously sensible. The blood loss that can occur in T. trichiura infection is likely to contribute to anaemia, particularly if the child also harbours hookworm, malaria and/or has a low intake of dietary iron. Community control is important, particularly for the individuals within a population who harbour heavy worm burdens; this means children, with special attention to girls who will experience increased iron requirements and blood loss due to menstruation, pregnancies, and lactation. Mebendazole and albendazole, both of which are on the WHO Essential Drugs List, are very effective against T. trichiura; multiple doses are needed to attain complete parasitological cure in all cases. However the goal of control programmes in endemic areas is morbidity reduction, which follows when intensity of infection is significantly reduced.

What do the accreditation organizations expect? American Association of Blood Banks.

In 1958, the American Association of Blood Banks introduced the first edition of Standards for Blood Banks and Transfusion Services. That same year, the association implemented the Inspection and Accreditation Program. This program served the association well for 40 years; however, factors such as the application of Current Good Manufacturing Practices by the Food and Drug Administration, the implementation of the Clinical Laboratory Improvement Amendments of 1988 by the Health Care Financing Administration, managed care, competition, and increased cost pressures have changed the way the blood banking community conducts its business. In the early 1990s the board of directors recognized the need to reevaluate the Inspection and Accreditation Program and developed a strategic plan for implementation of a new accreditation program, with an emphasis on prevention rather than detection of errors. The first step in the process was the development of the Accreditation Program Committee. The committee was charged to develop and coordinate a program that would bring the accreditation process in tune with the current climate of blood banking and move it into the 21st century. The board charged the committee with the development of a program that recognizes the differences and similarities within the diverse groups of American Association of Blood Banks institutional members and to take into consideration how they do business and respond to regulations, standards, and other requirements.

Plasma insulin-like growth factor-1, type 1 procollagen, and serum tumor necrosis factor alpha in children recovering from Trichuris dysentery syndrome.

OBJECTIVES: To explore: 1) the relationship between plasma insulin-like growth factor-1 (IGF-1) and other markers of growth; and 2) the effect of serum concentrations of tumor necrosis factor alpha (TNF) on growth variables in children (2-10 years) stunted by Trichuris dysentery syndrome (TDS), recovering cases, and their matched controls. METHOD: Fourteen patients with TDS were admitted to the Tropical Metabolism Research Unit, treated with albendazole and iron, and then followed with matched controls (n = 28) for 1 year. Anthropometric and biochemical measurements were done on admission and then every 3 months for the year. Plasma IGF-1, the carboxyterminal propeptide of type 1 procollagen, serum TNF, total serum protein, serum albumin, and complete blood count were determined. RESULTS: Low admission plasma levels of IGF-1 in TDS cases were accompanied by high serum levels of TNF, and total serum protein, normal serum albumin, low hemoglobin, reduced collagen synthesis (low plasma carboxyterminal propeptide of type 1 procollagen), and growth failure. These variables improved significantly after treatment. Plasma levels of IGF-1 were significantly related to the Z-scores for height-for-age (r = 0.60, 0.73, 0.68) and weight-for-age (r = 0.69, 0.80, 0.69) of cases and controls, height-for-age (r = 0.51, 0.52, 0.54) and weight-for-age (r = 0.51, 0.52, 0.54) at each measurement throughout the year. Serum levels of TNF were not related to any of the growth variables. CONCLUSION: These findings may contribute to the understanding of growth failure in children affected by other forms of chronic inflammatory bowel disease.

Gap junction-mediated cell-cell communication modulates mouse neural crest migration.

Previous studies showed that conotruncal heart malformations can arise with the increase or decrease in alpha1 connexin function in neural crest cells. To elucidate the possible basis for the quantitative requirement for alpha1 connexin gap junctions in cardiac development, a neural crest outgrowth culture system was used to examine migration of neural crest cells derived from CMV43 transgenic embryos overexpressing alpha1 connexins, and from alpha1 connexin knockout (KO) mice and FC transgenic mice expressing a dominant-negative alpha1 connexin fusion protein. These studies showed that the migration rate of cardiac neural crest was increased in the CMV43 embryos, but decreased in the FC transgenic and alpha1 connexin KO embryos. Migration changes occurred in step with connexin gene or transgene dosage in the homozygous vs. hemizygous alpha1 connexin KO and CMV43 embryos, respectively. Dye coupling analysis in neural crest cells in the outgrowth cultures and also in the living embryos showed an elevation of gap junction communication in the CMV43 transgenic mice, while a reduction was observed in the FC transgenic and alpha1 connexin KO mice. Further analysis using oleamide to downregulate gap junction communication in nontransgenic outgrowth cultures showed that this independent method of reducing gap junction communication in cardiac crest cells also resulted in a reduction in the rate of crest migration. To determine the possible relevance of these findings to neural crest migration in vivo, a lacZ transgene was used to visualize the distribution of cardiac neural crest cells in the outflow tract. These studies showed more lacZ-positive cells in the outflow septum in the CMV43 transgenic mice, while a reduction was observed in the alpha1 connexin KO mice. Surprisingly, this was accompanied by cell proliferation changes, not in the cardiac neural crest cells, but in the myocardium- an elevation in the CMV43 mice vs. a reduction in the alpha1 connexin KO mice. The latter observation suggests that cardiac neural crest cells may have a role in modulating growth and development of non-neural crest- derived tissues. Overall, these findings suggest that gap junction communication mediated by alpha1 connexins plays an important role in cardiac neural crest migration. Furthermore, they indicate that cardiac neural crest perturbation is the likely underlying cause for heart defects in mice with the gain or loss of alpha1 connexin function.

Antigenic variability in Trichuris trichiura populations.

The present study examines antigenic variability for the human whipworm Trichuris trichiura. Recognition by IgG of somatic antigens of individual worms collected from 3 intensely infected children from Jamaica, West Indies has been investigated by immunoblotting. When probed with 1 plasma sample, significant differences in recognition of 2 selected antigens among worm populations and between male and female worms was observed. In addition, there was evidence for antigenic variability within worm populations at the individual worm level. Such variation may have considerable implications for the development of immunity to parasitic nematodes.

Practice parameter for the use of red blood cell transfusions: developed by the Red Blood Cell Administration Practice Guideline Development Task Force of the College of American Pathologists.

A practice parameter has been developed to assist physicians in the therapeutic use of red blood cell transfusions. The developers of this parameter used the best available information from the medical literature, as well as clinical experience and the extensive reality testing required by the College of American Pathologists for approval. In acute anemia, a fall in hemoglobin values below 6 g/dL or a rapid blood volume loss of more than 30% to 40% requires red blood cell transfusions in most patients. However, tissue oxygenation provides a better indication of physiologic need in situations where invasive monitoring provides this information. When these data are not available, heart rate and blood pressure measurements and the nature of bleeding (active, controlled, uncontrolled) supplement the hemoglobin value in guiding the transfusion decision. In sickle cell disease and thalassemias, red blood cells are transfused to prevent acute or chronic complications. Red blood cell transfusions are used in chronic anemias unresponsive to pharmacologic agents based on the patient's symptoms. Guidelines must be altered for neonates who require an increase in hematocrit to above 0.30 to 0.35 when respiratory distress is present. Indications for red blood cell transfusion for the pregnant or postpartum patient are similar to those for the nonpregnant patient. Risks of transfusion, particularly transmissible disease and incompatibility, remain but have been reduced. Thus, red blood cell transfusion continues to be a powerful therapeutic tool when used judiciously and carries less risk than in the recent past.

Growth and development four years after treatment for the Trichuris dysentery syndrome.

A follow-up study is reported of 18 children 4 y after treatment for the Trichuris dysentery syndrome (TDS) and matched control children. The TDS children were initially severely stunted and had extremely low developmental levels. They showed catch-up in height of 1.9 z-scores even though they remained in very poor environments. Their intelligence quotients, school achievement and cognitive function remained significantly lower than those of the controls. Controlling for their earlier developmental levels, the TDS children showed a small improvement in mental development relative to the controls.

Plasma proteins in children with trichuris dysentery syndrome.

AIMS: To determine whether in Trichuris trichiura dysentery there is (1) evidence of a systemic inflammatory response, (2) evidence that the plasma protein disturbance has special characteristics compared with uninfected children in the endemic environment. METHODS: Three groups of children (age 1.6 to 11.4 years) were studied: 53 cases of trichuris dysentery syndrome (TDS), 16 cases of chronic non-secretory diarrhoea not infected with the parasite ("disease controls", DC), and 20 asymptomatic, parasite-free primary schoolchildren (normal controls, NC). C reactive protein, alpha 1 antitrypsin, caeruloplasmin, albumin, total globulin, fibrinogen, fibronectin, ferritin, and transferrin were measured on a single occasion for each. The study was thus a cross sectional descriptive survey for group comparison. Plasma viscosity was measured on admission for TDS and DC and repeated after six weeks and six months for TDS. RESULTS: Plasma C reactive protein, alpha 1 antitrypsin, total globulin, fibronectin, and viscosity were significantly higher in TDS than in NC. DC children also had acute phase protein elevations (C reactive protein, caeruloplasmin, viscosity). However, the increase in caeruloplasmin was specific to the DC group while an increase in fibronectin was specific to the TDS group. Serial measurement of viscosity in TDS showed a modest but significant fall during the six months following treatment. CONCLUSIONS: There is an acute phase response in intense trichuriasis and a specific elevation of plasma fibronectin. Plasma viscosity remains abnormally high six months after treatment, although lower than at diagnosis.

Placental proopiomelanocortin gene expression, adrenocorticotropin tissue concentrations, and immunostaining increase throughout gestation and are unaffected by prostaglandins, antiprogestins, or labor.

The objective of this study was to demonstrate the ontogeny of POMC gene expression, the distribution of immunoreactive ACTH, and tissue peptide content within the placenta and fetal membranes and to investigate the regulatory effects of PGs and progesterone during the first trimester and of labor at term. Tissues were collected from the following groups: 1) women undergoing first trimester (gestation 5-12 weeks) therapeutic abortion (by suction curettage with and without the synthetic PGE1 analogue, gemeprost administered vaginally 2-4 h before the procedure or with 600 mg mifepristone 48 h before receiving 1 mg gemeprost vaginally); 2) women undergoing second trimester therapeutic abortion (600 mg mifepristone; 1 mg gemeprost); 3) in association with delivery at term by spontaneous labor; 4) induced labor; or 5) elective caesarean section. ACTH was immunolocalized to the placental cytotrophoblasts in the first trimester and to the syncytiotrophoblasts in the second and third trimester. The intensity of the staining increased with advancing gestation. ACTH immunoreactivity also was localized in the epithelial layer of the amnion, the reticular layer of the chorion, and the decidual stroma. ACTH content measured by RIA in placental extracts increased significantly in the third trimester. In situ hybridization demonstrated expression of POMC messenger RNA in syncytiotrophoblasts and cytotrophoblasts from the first trimester and also demonstrated a significant increase in POMC gene expression with advancing gestation. The localization and staining intensity for ACTH and POMC gene expression were not affected by the administration of PGs or mifepristone or by labor at term. These data demonstrate the localization of ACTH immunoreactivity within the placenta throughout pregnancy, supporting the hypothesis that the placenta may activate and maintain the maternal and/or fetal hypothalamo-pituitary-adrenal axis throughout pregnancy.

Comparison of the amplified Mycobacterium tuberculosis (MTB) direct test, Amplicor MTB PCR, and IS6110-PCR for detection of MTB in respiratory specimens.

Several nucleic acid amplification techniques (NAAT) have been developed for rapid and direct detection of Mycobacterium tuberculosis (MTB) from clinical specimens. This study compared the performances of the Gen-Probe Amplified MTB Direct Test (AMDT), Roche Amplicor MTB PCR test, and an IS6110-PCR assay with acid-fast smear and culture in the detection of MTB from 428 respiratory specimens from 259 patients. Patients' charts were reviewed for clinical correlation. Of 98 specimens that were clinically positive for MTB, acid-fast smear was positive in 50% of cases, culture in 93%, IS6110-PCR in 83%, AMDT in 84%, and Amplicor MTB PCR in 80%. Of 337 specimens that were negative for MTB, 117 (35%) were positive for nontuberculous mycobacteria. Specificities were as follows: smear, 89%; culture, 100%; IS6110-PCR, 99%; AMDT, 98%; and Amplicor MTB PCR, 96%. The accuracies of the tests were 80%, 98%, 96%, and 92%, respectively. MTB culture-positive specimens that were smear-negative were detected by AMDT and IS6110-PCR in 77% of cases and by Amplicor MTB PCR in 70%. NAAT was less sensitive than was culture for detection of MTB, but all these techniques had acceptable accuracy and were completed within hours. NAAT may be useful for rapid screening of respiratory specimens to distinguish MTB from nontuberculous mycobacteria infection in order to isolate patients.

The clinical relevance of circulating tumor necrosis factor-alpha in acute decompensated chronic heart failure without cachexia.

STUDY OBJECTIVE: To evaluate the clinical relevance of circulating tumor necrosis factor-alpha (TNF alpha) in subjects with advanced acutely decompensated congestive heart failure (CHF) and to determine the modulatory effect of clinical interventions on short-term elaboration of this cytokine. DESIGN: Prospective, case-controlled study. SETTING: Inpatient and outpatient (hospital and clinic), at regional academic medical center. PATIENT INTERVENTIONS: Plasma concentrations of TNF alpha were determined in 25 healthy, normal control subjects and in 29 noncachectic patients with advanced CHF (mean ejection fraction = 16 +/- 6%) who required hospitalization for i.v. diuretic and/or inotropic therapy despite optimization of oral medical regimens. CHF patients were divided into two groups: diuretic responsive (group A; n = 6) and diuretic resistant requiring inotropic support (group B; n = 23). Group B was randomly allocated to receive either i.v. dobutamine (n = 13) or milrinone (n = 10) for 72 h. TNF alpha levels in CHF patients were measured serially at baseline, at 6 h, at 48 h, at 72 h, and at 1-week follow-up after hospital discharge. RESULTS: Plasma TNF alpha levels at baseline in CHF patients were 4.0 +/- 1.1 pg/mL (range, 0.5 to 6.5 pg/ mL) and 2.5 +/- 0.6 pg/mL (range, 0.5 to 6.8 pg/mL) in groups A and B, respectively, which were significantly different (p < 0.002) from normal subjects (0.89 +/- 0.40 pg/mL; range, 0.5 to 9.7 pg/mL). Despite clinically successful therapy with i.v. diuretics, dobutamine, or milrinone, plasma levels of this cytokine remained unchanged. Plasma TNF alpha in CHF patients measured in recovery (1 week after hospital discharge) was 5.1 +/- 1.2 pg/mL (range, 1.0 to 9.9 pg/mL) and 3.9 +/- 0.8 pg/mL (range, 0.5 to 8.7 pg/mL) in groups A and B, respectively. CONCLUSION: These findings suggest that although noncachectic patients with chronic heart failure who suffer acute decompensation elaborate significantly higher circulating levels of TNF alpha compared with healthy control subjects, no significant reduction or alteration in circulating TNF alpha is noted in the short-term follow-up despite clinical improvement.

Enterobius, trichuris, capillaria, and hookworm including ancylostoma caninum.

Infections by the nematodes Enterobius, Trichuris, Capillaria, and hookworm are some of the most widespread gastrointestinal infections worldwide. This article is designed not only to provide an overview of the different parasites in terms of epidemiology, clinical manifestation, and disease but also to highlight particular areas of intensive research activity that are providing new insights into both the biology of the host-parasite relationship and possible new approaches to infection management for the future.

Trends in admission and case fatality for acute malnutrition (Kingston 1982-1991).

The case fatality ratio (CFR) in acute protein-energy malnutrition (PEM) achieved in the Tropical Metabolism Research Unit (TMRU) was compared with that of other tertiary care facilities in Kingston. Trends in admission and fatality rates, case severity and complications were also examined. From ward admission registers for Bustamante Hospital for Children (BHC), the University Hospital of the West Indies (UHWI), children's wards and the TMRU all cases of PEM admitted from 1982 through 1991 were enumerated and there was a docket search for random subsamples. Ten-year mean CFR% for BHC was 8.8 (n = 1948); for UHWI wards 5.5 (n = 658); for TMRU 7.1 (n = 662). BHC has the least restrictions on admission and showed most clearly that the peak time in Kingston for admission of PEM was around 1985, falling to a minimum in 1988-1990 and rising again in 1991; however, the other sites also showed similar trends. BHC had a range of CFR% p.a. of 20.0 to 3.0, with a striking fall in the second half of the decade. There was no temporal CFR trend for the UHWI or TMRU. The latter institution had the highest proportion of admissions with marasmic-kwashiorkor and the lowest proportion with recorded infection. The annual variation in numbers of PEM deaths at BHC was best accounted for by (a) percentage change in consumer price index and (b) percentage change in the US$ value of the Jamaican $, in the preceding year, and (c) annual number of admissions, together. Generally, our findings suggest a minor role for expert in-patient management in reducing deaths from PEM.

The risks, benefits, and costs of expanding donor criteria. A collaborative prospective three-year study.

The study purpose was to identify risks, benefits and costs associated with an expanded donor protocol. The protocol design evaluated organs rescued using expanded donor criteria and weighed all costs associated with doing so. Costs were measured against conditions experienced with expanded and traditional criteria and recipient outcome. Traditional donors were between 5 and 55, with negative serologies, and no history of hypertension or diabetes. "Expanded donors" were between 55 and 75 or less than 5, with a history of hypertension, diabetes and/or sero-positive for Hepatitis C. During this study 73 donors met criteria from which 200 organs were transplanted. Defined costs and outcomes for recipients were tracked. Using expanded criteria: costs averaged 20% more per organ; OPO personnel spent an average of 6 hours more time on-site; an additional 12-14 hours in placement activity; and average organs per donor decreased. Heart patient and graft survival rates for traditional and expanded donor organs were comparable. Kidney patients transplanted from this pool experienced a decrease in patient (P = .14) and a significant decrease in graft (P = .02) survival rates. Patient (P = .05) and graft (P = .01) survival rates were significantly lower in liver patients transplanted with expanded donor organs. Two hundred transplants occurred using expanded donor criteria. Costs for the OPO increased appreciably. Heart and kidney utilization from these donors seems justified. It is thought that liver recipients' results were due to utilizing them in sicker patients. Recovery of organs from donors using expanded criteria appears to be a reasonable way of increasing organ supply.