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.

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.

Cold hemagglutination pathophysiology. Evaluation and management of patients undergoing cardiac surgery with induced hypothermia.

The widespread induction of systemic hypothermia and use of iced cardioplegic solutions in cardiac surgery may promote occasional cold autoagglutination. Routine laboratory methods used to detect cold-agglutinating autoantibodies may not take into account the extremely low temperatures that the heart and body may attain during cardiopulmonary bypass. Several cold-mediated complications have now been encountered during cardiac surgery in patients with both known and unsuspected cold-reactive autoantibodies. This review will provide the clinician with a working knowledge of the cold autoimmune disorders, a rapid method for differential diagnosis in unproved cases, and an ability to select techniques for reliable myocardial and renal protection in both known and unsuspected cases.

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.

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.

Parasitic helminth infection and cognitive function in school children.

The study examines the effect of moderate to high worm burdens of Trichuris trichiura infection on the cognitive functions of 159 school children (age 9-12 years) in Jamaica, using a double-blind placebo-controlled protocol. Results were evaluated by using a forward-stepwise multiple linear regression. Removal of worms led to a significant improvement in tests of auditory short-term memory (p less than 0.017; p less than 0.013), and scanning and retrieval of long-term memory (p less than 0.001). Nine weeks after treatment, there were no longer significant differences between the treated children and an uninfected Control group in these three tests of cognitive function. It is concluded that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy.

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.

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.

Histopathology and immunohistochemistry of the caecum in children with the Trichuris dysentery syndrome.

Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflammatory cells. Except in the vicinity of the worm, where the epithelium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intraepithelial T cells. There was also an increase in crypt epithelial cell proliferation. Lamina propria T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS.

Rate of expulsion of Trichuris trichiura with multiple and single dose regimens of albendazole.

The efficacy of multiple and single dose regimens of albendazole on Trichuris trichiura infection was evaluated by counting the number of worms expelled/day from two pair-matched groups of children, for nine days following therapy. The temporal patterns of worm expulsion were similar whether the children received a single 400 mg dose or two consecutive doses: no worms were passed before the second day, or after the sixth day, after intervention, and the maximum worm expulsion rate was attained on the fourth day. A second treatment six days after the first expelled no more worms. The results obtained here resemble those obtained previously with a three-day (600 mg) regimen of mebendazole in a study of heavily infected children. We conclude: that irrespective of dose, benzimidazole carbamates require the gut transit time plus 48 hours to immobilize T. trichiura; and that a single dose of albendazole is effective against light infections of T. trichiura but requires further evaluation with high intensity infections.

Epidemiology and population dynamics of Ascaris lumbricoides and Trichuris trichiura infection in the same community.

The gastrointestinal helminth infection status of an age-stratified sample from a single Caribbean community was assessed using anthelmintic expulsion techniques. The same sample was re-assessed in a similar manner after a 17 month period of re-infection. The age-prevalence profile of Ascaris lumbricoides was convex while that of Trichuris trichiura was asymptotic. The age-intensity profiles of both species were convex. These differing patterns are attributed to differences in the absolute worm burdens of the 2 species. The frequency distributions of infection intensity were similar for both species, and largely independent of host age. The basic reproductive rate of A. lumbricoides (Ro = 1-1.8) was similar to that recorded elsewhere and much lower than that of T. trichiura (Ro = 4-6), implying that the latter is intrinsically more resistant to control. Individual hosts were predisposed to high (or low) intensity infection with either species, although predisposition to both species simultaneously was not conclusively demonstrated. Further studies are required to determine the cause of these observations.

Age-related prevalence and intensity of Trichuris trichiura infection in a St. Lucian community.

Age-related changes in the average worm burden and the prevalence of Trichuris trichiura infection, in a village community in St. Lucia, were examined by field studies based on worm expulsion techniques. Horizontal age-intensity profiles were convex in form with peak parasite loads occurring in the 2 to 15-year-old children. Prevalence is shown to be a poor indicator of changes in average worm load with age. Faecal egg counts (epg and epd) provide a qualitative measure of worm burdens since fecundity is shown to be approximately independent of worm load. The parasites were highly aggregated within the study community, with most people harbouring low burdens while a few individuals harboured very heavy burdens. Of the total parasite populations in the study sample, 84% were harboured by the 2 to 15-year-old children. Of those individuals harbouring 100 worms or more, 87% were in the 2 to 10-year-old age range. Crude estimates of population parameters (basic reproductive rate, 4-5; rate of reinfection, 90 year-1) suggest that the rate of reinfection is higher than for other helminth parasites of man. The control of morbidity and parasite transmission is discussed in the context of targeting drug treatment at the child segment of the study population.

Population dynamics and chemotherapeutic control of Trichuris trichiura infection of children in Jamaica and St. Lucia.

Population dynamical parameters of Trichuris trichiura infections in children were estimated from longitudinal intensity and prevalence data from a population (n = 23) in a children's home in Jamaica. The theoretical predictions of a deterministic model incorporating these parameters were approximated to observed horizontal-age prevalence data from a naturally infected population (n = 203) of children in a St. Lucian village, and a rough estimate of the basic reproductive rate (Ro = 8-10) of T. trichiura obtained. The findings suggest that T. trichiura populations are intrinsically more difficult to control by traditional mass-treatment chemotherapy (eradication requires greater than 91% of the population to be treated every 6 months for greater than 5 years) than are populations of Ascaris, but may be more susceptible to selective chemotherapy programmes which aim to treat only the most heavily infected individuals.

Immunoepidemiology of intestinal helminthic infections. 3. Mucosal macrophages and cytokine production in the colon of children with Trichuris trichiura dysentery.

Mucosal macrophages and accessory cells have been studied by immunohistochemistry in the lamina propria of the colon of children with Trichuris trichiura dysentery syndrome (TDS). No difference was found in the numbers of cells recognized by the monoclonal antibodies CD11c, CD68, or RFD7 between TDS children and local controls. However, large numbers of cells were recognized by an antibody against calprotectin (an anti-bacterial glycoprotein found in tissue infiltrating-monocytes) in TDS colonic mucosa, but few in control colon. Large numbers of cells containing tumour necrosis factor alpha (TNF alpha) were also seen in TDS mucosa; cells isolated from TDS mucosa secreted more TNF alpha than cells from control mucosa; and children with TDS had high levels of circulating TNF alpha. Non-specific macrophage-mediated inflammation and local cytokine production may therefore play a role in the pathogenesis of TDS.

Population distribution of Trichuris trichiura in a community of Jamaican children.

The Trichuris trichiura worm burdens of 23 children living in a Place-of-Safety in Kingston, Jamaica, were assessed by stool collection for more than five days after treatment with mebendazole. This procedure was repeated after a seven-month period of natural re-infection. For both collections the maximum rate of worm expulsion was achieved on the fourth day after starting treatment. The worm population distributions were overdispersed and well described by the negative binomial probability model (k = 0.29) in each case. For any one individual, the number of worms passed on the first expulsion was unrelated, absolutely or relatively, to the number passed on the second. These data suggest that: knowledge of the time dependency of helminth expulsion is essential for the accurate estimation of worm burdens by this method; populations of Trichuris are more highly aggregated than those of Ascaris and may thus be more susceptible to control by selective rather than random chemotherapy; and the inherent predisposition of hosts to infection may be of minor importance in determining the distribution of worms in the population-heavily infected hosts appear no more or less likely to acquire large worm burdens on subsequent exposures.

Growth suppression in the Trichuris dysentery syndrome.

The Trichuris Dysentery Syndrome (Ramsey, 1962) is an insidious, chronic condition which has clinical features similar to Crohn's ileocolitis and ulcerative colitis, diseases similarly associated with growth retardation. The attained heights and weights of 19 children at the time of diagnosis of intens, -2.4 Standard Deviation (Z) scores from the Tanner-Whitehouse median with weight, adjusted for height-age, -1.3 Z. We present data on the growth velocities of 11 of the children in the half-year following worm expulsion by mebendazole. These children returned to their home environments without food supplementation or close follow-up, but showed an average height velocity of +5.5 Z and weight velocity (for height-age) of +2.4 Z. Of 8 children with unequivocal height spurts only 3 had any weight spurt. We suggest that the pattern of catch-up growth points to the existence of some specific link between allergy or inflammation in the lower intestinal tract and suppression of linear growth, rather than to stunting due to general deprivation and undernutrition.

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.

The 1983 Comprehensive Blood Bank Survey of the College of American Pathologists.

Approximately 2,800 laboratories participated in the 1983 Comprehensive Blood Bank Survey of the College of American Pathologists. Sixteen reference laboratories participated to validate the results and provide a referee consensus for grading of antibody studies. Participant consensus was used to evaluate ABO, Rh, and crossmatching results. Ungraded antigen typing results are included as well as discussions of the ungraded additional challenges and supplementary questions. Accuracy of participant results remains high on these surveys.

CAP Comprehensive Blood Bank Survey--1984.

An average of 2750 laboratories participated in the 1984 Comprehensive Blood Bank Survey of the College of American Pathologists. Results from 16 laboratories were utilized to validate results and assure maintenance of specimen character during shipment. Results of ABO grouping, D typing, special antigen typing, antibody detection, and antibody identification by participants remained good and are discussed. Special ungraded samples were provided as additional challenges. The results of these studies and the responses to supplementary questions are discussed.

The 1987 Comprehensive Blood Bank Survey of the College of American Pathologists.

The 1987 Comprehensive Blood Bank Survey consisted of four shipments of samples. Each presented graded challenges in ABO and D typing, crossmatching, and antibody detection and identification and ungraded challenges for antigen typing and ungraded serum samples for educational purposes. Practice patterns were elicited through supplemental questions, generally about issues raised by the survey samples. Two of the surveys showed significant problems. Set J-C included serum with anti-Lea, which was not detected by some participants. Anti-Dia was one of two antibodies in the J-D graded sample, and this additional antibody was not detected by a significant number of participants. Although minor problems were encountered in other challenges, in general performance was good.