Superficial plantar cutaneous sensation does not trigger barefoot running adaptations.

It has long been proposed that the gait alterations associated with barefoot running are mediated by alterations in sensory feedback, yet there has been no data to support this claim. Thus, the purpose of this study was to examine the role of superficial plantar cutaneous feedback in barefoot and shod running. METHODS: 10 healthy active subjects (6 male, 4 female); mass: 65.2+9.7kg; age: 27+7.1years participated in this study. 10 over-ground running trials were completed in each of the following conditions: barefoot (BF), shod (SHOD), anesthetized barefoot (ANEST BF) and anesthetized shod (ANEST SHOD). For the anesthetized conditions 0.1-0.3mL of 1% lidocaine was injected into the dermal layer of the plantar foot below the metatarsal heads, lateral column and heel. 3-dimensional motion analysis and ground reaction force (GRF) data were captured as subjects ran over a 20m runway with a force plate at 12m. Kinematic and kinetic differences were analyzed via two-way repeated measure ANOVAs. RESULTS: The differences in gait between the BF and SHOD conditions were consistent with previous research, with subjects exhibiting a significant decrease in stride length and changing from rearfoot strike when SHOD to fore/midfoot strike when BF. Additionally, BF running was associated with decreased impact peak magnitudes and peak vertical GRFs. Despite anesthetizing the plantar surface, there was no difference between the BF and ANEST BF conditions in terms of stride length, foot strike or GRFs. CONCLUSION: Superficial cutaneous sensory receptors are not primarily responsible for the gait changes associated with barefoot running.

Plasma Hsp72 is higher in runners with more serious symptoms of exertional heat illness.

Exertional heat illness is a potentially fatal disorder that primarily affects fit young men. Plasma Hsp72 may be important in the aetiology of this disorder, acting as a danger signal to the organism and leading to an inflammatory response. The aim of this study was to determine whether patients with exertional heat illness following a 14 km run show a difference in their plasma Hsp72 concentration compared with control subjects who completed the event without incident. Patients (n = 22) and controls (n = 7) were all male. The patients were subdivided into two groups, one of which exhibited more serious symptoms indicating neurological impairment such as confusion (n = 13) (CNS) while the other group exhibited mild symptoms (MILD) (n = 9). The CNS group had a higher rectal temperature (T(rec)) compared with the control group (41.0 +/- 0.3 vs. 39.8 +/- 0.2 degrees C, P < 0.05, mean +/- SE). Immediately after the run plasma Hsp72 was higher in the CNS group compared to controls and patients with mild symptoms (37.9, 17.0, and 20.9 ng/ml, respectively, P < 0.005). There was a correlation between plasma Hsp72 and T(rec) measured immediately after the race (r = 0.597, P < 0.001, n = 29). However, core temperature was not the only factor leading to increased plasma Hsp72 immediately post race. Plasma Hsp72 was still higher in CNS patients compared with the control group (P < 0.05) when T(rec )was included as a covariate. In conclusion, plasma Hsp72 was elevated immediately after a 14 km run with higher levels in patients with more serious symptoms of heat illness.

Effect of temperature and duration of hyperthermia on HSP72 induction in rat tissues.

The aim of the present study was to determine whether heat shock protein 72 (HSP72) is induced in a heated rat model at rectal temperatures below 42 degrees C. Rats were divided into a control group and six groups (n = 6) heated to different rectal temperatures: 39 degrees C for 1 h (39), 40.0 degrees C for either 15 min (40S) or 1 h (40L), 41.0 degrees C for either 15 min (41S) or 1 h (41L) and 42.0 degrees C for 15 min (42). Tissues were sampled 4 h after heating. Following 1 h at 40.0 degrees C, HSP72 was significantly elevated in heart (p < 0.005), but not in gut or liver tissue. In all three tissues, HSP72 was significantly elevated under the conditions 41L and 42 compared to control tissue (p < 0.005). Marked differences were found in the amount of HSP72 induced in different tissues in response to the same heat stress. Duration of heating was important in modulating HSP72 induction, with a significantly greater induction of HSP72 following 1 h compared to 15 min at 41 degrees C in all three tissues (p < 0.02). A correlation was found between thermal load and HSP72 content in liver, heart (both p < 0.01) and gut (p < 0.001) for the rats heated to 41 and 42 degrees C. These data show that HSP72 is induced at temperatures below 42 degrees C, with striking differences between tissues.

The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review.

UNLABELLED: Bearden CE, Hoffman KM, Cannon TD. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disord 2001: 3: 106 150. C Munksgaard, 2001 OBJECTIVES: To present a comprehensive review of the existing neuropsychological and neuroimaging literature on bipolar affective disorder. This review critically evaluates two common conceptions regarding the neuropsychology of bipolar disorder: 1) that, in contrast to schizophrenia, bipolar affective disorder is not associated with general cognitive impairment independent of illness episodes, and 2) relative right hemisphere (RH) dysfunction is implicated in bipolar illness patients, supported by reports of relatively greater impairment in visuospatial functioning, lateralization abnormalities, and mania secondary to RH lesions. METHODS: The major computerized databases (Medline and PSYCInfo) were consulted in order to conduct a comprehensive, integrated review of the literature on the neuropsychology and neuroanatomy of bipolar disorder. Articles meeting specified criteria were included in this review. RESULTS: In a critical evaluation of the above notions, this paper determines that: 1) while there is little evidence for selective RH dysfunction, significant cognitive impairment may be present in bipolar illness, particularly in a subgroup of chronic, elderly or multiple-episode patients, suggesting a possible toxic disease process, and 2) the underlying functional correlate of these cognitive deficits may be white matter lesions ('signal hyperintensities') in the frontal lobes and basal ganglia, regions critical for executive function, attention, speeded information processing, learning and memory, and affect regulation. While this hypothesized neural correlate of cognitive impairment in bipolar disorder is speculative, preliminary functional neuroimaging evidence supports the notion of frontal and subcortical hypometabolism in bipolar illness. CONCLUSIONS: The etiology of the structural brain abnormalities commonly seen in bipolar illness, and their corresponding functional deficits, remains unknown. It is possible that neurodevelopmental anomalies may play a role, and it remains to be determined whether there is also some pathophysiological progression that occurs with repeated illness episodes. More research is needed on first-episode patients, relatives of bipolar probands, and within prospective longitudinal paradigms in order to isolate disease-specific impairments and genetic markers of neurocognitive function in bipolar disorder.

Microleakage of a consolidated silver direct filling material.

Microleakage of an experimental direct filling material comprised of a chemically precipitated silver powder that had been surface treated with a dilute acid to promote cold welding upon consolidation was evaluated. Microleakage was compared to both dispersed-phase and spherical amalgam by use of an in vitro gas-diffusion method and in class 5 restorations placed in extracted human teeth. The effect of two cavity varnishes and two dentin adhesives as cavity liners on microleakage was also evaluated using extracted teeth. Microleakage of silver powder consolidated with dental instruments was less than that found with dental amalgam. The use of copal or polyamide cavity varnish resulted in the lowest combination of microleakage on dentin and enamel margins.

Intranasal beclomethasone as an adjunct to treatment of chronic middle ear effusion.

BACKGROUND: Following otitis media, 10% to 50% of children develop residual middle ear effusion with concurrent hearing loss and potential cognitive, behavioral, and language impairment. Prophylactic antibiotics and tympanostomy tubes are currently recommended treatments for chronic middle ear effusion. OBJECTIVE: In a double-blind, placebo-controlled, randomized study of chronic middle ear effusion, we assessed the effectiveness of topical intranasal beclomethasone as an adjunct to prophylactic antibiotic therapy. METHODS: Sixty-one children, aged 3 to 11 years with persistent middle ear effusion greater than 3 months, were randomized into three treatment groups: (1) prophylactic antibiotics; (2) prophylactic antibiotics plus intranasal beclomethasone (336 micrograms/day); and (3) prophylactic antibiotics plus intranasal placebo. Patients were evaluated with aeroallergen skin tests at entry; and tympanogram, otoscopic examination, and symptom questionnaire at 0, 4, 8, and 12 weeks. RESULTS: While middle ear pressures, otoscopic examinations, and symptom scores were improved for each treatment group over 12 weeks of therapy, the beclomethasone plus antibiotics group improved all three measures more rapidly than the antibiotics-alone and placebo nasal spray plus antibiotics groups over the first 8 weeks. Only the beclomethasone group significantly improved left (P = .004) and right (P = .01) middle ear pressures over 12 weeks. Resolution of chronic middle ear effusions was more frequent in the beclomethasone group (P < or = .05 at 4 and 8 weeks). No difference in response to nasal steroids was observed between atopic and nonatopic subjects. CONCLUSIONS: We conclude that intranasal beclomethasone may be a useful adjunct to prophylactic antibiotic treatment of chronic middle ear effusion.

Evaluation of the usefulness of lymphocyte proliferation assays in the diagnosis of allergy to cow's milk.

BACKGROUND: The significance of cell-mediated mechanisms in IgE-mediated milk allergy (IgE-MA) and in milk-induced enterocolitis syndrome (ME) is controversial. Some investigators have claimed that lymphocyte proliferation assays are useful in the diagnosis of food hypersensitivity, despite the great variability in study designs and results reported. This study was undertaken to address many of these variables and to determine whether lymphocyte proliferation assays correlate with clinical diagnoses. METHODS: Lymphocyte proliferative responses to milk antigen were evaluated in two groups of children, 27 with IgE-MA, and nine with ME and in 21 pediatric control subjects. IgE-mediated food allergy was documented by positive double-blind, placebo-controlled food challenges and positive skin prick test results. ME was diagnosed by oral challenge or by a history of repeated episodes of delayed vomiting (>2 hours) after ingestion of milk and by negative skin prick test responses. Peripheral blood mononuclear cells were isolated and cultured. Cultures stimulated with milk (the food antigen of interest), soy antigen (a nonrelevant food antigen), or tetanus antigen (a positive control antigen) and unstimulated controls were performed in quadruplicate. On days 5, 7, and 9, cells were pulsed with tritium-labeled thymidine and incubated for 4 hours. Results were compared as counts per minute (cpm) and as stimulation indices (SIs). RESULTS: Maximal proliferation was generally seen on day 7. The median cpm (20,941) and the median SI (19.2) in response to milk antigen in the 27 children with IgE-MA were significantly greater than those in the control patients (6969 cpm; SI = 14.2; p = 0.001 and p < 0.05, respectively). However, the ranges were large and overlapped extensively (IgE-MA, 5616 to 52,053 cpm; controls, 469 to 39,260 cpm). The non-soy-allergic patients with IgE-MA also had a significantly greater response to soy antigen than did the control subjects when cpm were compared (0.01 < p < 0.05). There were no differences in background or in response to tetanus antigen. The median response to milk in the patients with ME (11,975 cpm) was significantly greater than that in control subjects (6969 cpm; 0.01 < p < 0.05), when cpm were compared but not when SIs were compared. There were no significant differences between the patients with IgE-MA and those with ME. CONCLUSION: Overall, these results indicate that lymphocyte proliferation assays are neither diagnostic nor predictive of clinical reactivity in individual patients with milk allergy. Lymphocytes of many control patients are highly responsive to milk antigens, and lymphocytes of many patients with milk allergy are not. Statistically significant differences are only evident when the patients are compared as groups.

Serum specific-IgE antibodies to peptides detected in a casein hydrolysate formula.

Up to 2.5% of infants are affected by cow milk hypersensitivity in the first two years of life, although most of these children will "outgrow" their reactivity within 2-3 years. Extensively hydrolyzed ("hypoallergenic") cow milk-based formulae are often recommended as a substitute formula and are generally well tolerated. However, a small minority of cow milk-allergic children experience allergic reactions to the hypoallergenic formulae as well. Utilizing inhibition-ELISAs and sera from patients with IgE-mediated cow milk allergy, we have identified residual protein fractions less than 20 kD in several of the extensively hydrolyzed cow milk-based formulae. Although many of the cow milk allergic children had positive skin prick tests [SPT] to one of the hydrolysate formulae (Nutramigen), the positive skin test result generally did not correlate with clinical reactivity, although the negative predictive value of the negative SPT was excellent. Children with IgE-mediated cow milk allergy and a positive skin prick test to the hypoallergenic formula should probably receive their first dose of the formula in a medical setting so that appropriate therapy can be administered in the unlikely event of an allergic reaction.

Consolidation conditions for a cold-welded mercury-free alloy.

Alloys being investigated as possible direct-filling materials rely upon a cold-welded, deformable silver matrix phase for cohesion and strength. The silver matrix is formed by direct consolidation of comminuted silver under an oxide-removing acid. The object of this study was to determine the effect of conditions such as load, increment thickness, and concentration of oxide-removing acid on the properties of the silver matrix. Results indicate that the addition of higher impact loads significantly improved yield strength and specimens built up by using thinner increments were significantly stronger and denser.

Microvascular transplantation of cryopreserved knee joints.

Successful transplantation of cryopreserved complex tissues has not yet been reported. We wanted to test whether microvascular transplantation of cryopreserved knee joints can be achieved in rats. Twenty-five knee joints were cryopreserved and then microsurgically transplanted to the groin of inbred recipient animals. Ten fresh knee joints were transplanted as controls. One week after transplantation, the transplants were evaluated in situ for pedicle patency and tissue perfusion and then harvested for histology. In all surviving rats (n = 21), the cryopreserved knee joints were well perfused immediately after transplantation. At harvest, 14 knee joints appeared viable with a patent pedicle, whereas 6 were questionably viable and demonstrated arterial thrombosis. Histologically, the viable joints revealed an intact bone and cartilage matrix; however, the number of viable chondrocytes and osteocytes was reduced. Additionally, endothelial cell plugs in some areas of the capillary bed led to scattered microinfarctions despite a patent vascular pedicle. The nonperfused transplants showed infarction. In conclusion, we have demonstrated successful microvascular transplantation of cryopreserved knee joints with reduced short-term viability. Long-term studies must determine whether full recovery occurs.

Creation of myelomeningocele in utero: a model of functional damage from spinal cord exposure in fetal sheep.

A recent study in human fetuses with myelomeningocele (MMC) suggested that the primary malformation is not neural but a failed closure of the posterior vertebral column and paraspinal soft tissue, which leads to exposure and secondary destruction of the spinal cord. The goal of this study was to test whether chronic exposure of the normal spinal cord to the amniotic space produces a lesion similar to human MMC. In fetal sheep at 75 days' gestation (group A) and 60 days' gestation (group B) (term = 150 days), the lumbar spinal cord was exposed to the amniotic cavity by excising skin and paraspinal soft tissues, and by performing a laminectomy. Some animals from both groups were fetectomized and assessed morphologically at 100 days' gestation. The remainder were delivered near term and assessed clinically, electrophysiologically, and morphologically. In group A, all animals showed MMC-type pathology. The exposed spinal cord was herniated out of the spinal canal and rested on the dorsal membranes of a cystic sac. The neural tissue was stretched and flattened out. Histologically, the hallmarks of the spinal cord were not discernable and the cytoarchitecture was lost. These changes were less severe at 100 days than at term. The three survivors in group A were paraplegic. In group B, the two survivors and two fetuses harvested at 100 days had healed skin wounds and near normal spinal cord histology. The other animal harvested at 100 days had a MMC-type lesion with less severe histological changes. The two survivors had a mild paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

In utero surgery rescues neurological function at birth in sheep with spina bifida.

We hypothesize that the neurologic deficit associated with open spina bifida is not directly caused by the primary defect but rather is due to chronic mechanical and chemical trauma since the unprotected neural tissue is exposed to the intrauterine environment. We report here that exposure of the normal spinal cord to the amniotic cavity in midgestational sheep fetuses leads to a human-like open spina bifida with paraplegia at birth, indicating that the exposed neural tissue is progressively destroyed during pregnancy. When open spina bifida was repaired in utero at an intermediate stage, the animals had near-normal neurologic function. The spinal cord was deformed but largely preserved. These findings suggest that secondary neural tissue destruction during pregnancy is primarily responsible for the functional loss and that timely in utero repair of open spina bifida might rescue neurologic function.

Safety, infectivity, transmissibility and immunogenicity of rhesus rotavirus vaccine (MMU 18006) in infants.

In an attempt to evaluate the immunogenicity, infectivity, transmissibility and safety of rhesus rotavirus vaccine (RRV) MMU 18006, 27 infants ages 5 to 20 months participated in two randomized, double-blind placebo controlled trials, one in a day care setting to allow for child to child contact and close surveillance and the other on an outpatient basis. Fourteen infants (mean age, 8.3 months) received 10(5) plaque-forming units of RRV and 13 (mean age, 11.1 months) received placebo. In the eight infants who participated in the vaccine trial in the day care setting, there was no evidence of transmissibility of RRV, by either stool excretion or seroconversion. The data from both trials showed RRV to be 100% infective and immunogenic in the vaccinees. There were no gastrointestinal side effects although there was an association between vaccine administration and fever occurring on Days 3 and 4. Based on these encouraging preliminary results, further work is proceeding to evaluate this vaccine at lower doses in this age group of infants.

DNA-damaging and mutagenic effects of 1,2-dimethylhydrazine on Bacillus subtilis repair-deficient mutants.

Mutagenic, DNA-damaging, and in vivo alteration of DNA have been demonstrated for 1,2-dimethylhydrazine (DMH), a potent inducer of adenocarcinomas of the large intestine and colon of rats. These activities are pH-dependent, with 6.5 giving optimum response. There was no requirement for metabolic activation with rat-liver S9 mix when the appropriate Bacillus subtilis mutant strains were used. The Rec- strains recA8 and mc-1 were greater than 300-fold more sensitive to the DNA-damaging activity of DMH than was their isogenic wild-type parent. The DNA isolated from DMH-treated mc-1 had altered spectroscopic characteristics, and gave a greatly reduced transformation efficiency. Treatment of B. subtilis strain TKJ6321 with DMH at pH 6.5 induced His+, Met+ mutations in substantial numbers at low concentrations of this chemical. The use of B. subtilis mutants in these studies has therefore made it possible to demonstrate mutagenic and DNA-damaging activity in bacteria for this potent carcinogenic chemical.