Microvascular volume in symptomatic Achilles tendons is associated with VISA-A score.

OBJECTIVES: The role of neovascularisation in tendinopathy is still poorly understood, potentially due to technical limitations of conventional power Doppler ultrasound. This study aimed to investigate the association between contrast-enhanced ultrasound (CEUS) microvascular volume (MV), Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and intrinsic Achilles tendon tenderness, as well as two different Power Doppler modes. DESIGN: Cross-sectional study. METHODS: 20 individuals with uni- or bilateral Achilles tendinopathy completed a VISA-A questionnaire, and underwent microvascular volume measurements of the Achilles tendon mid-portion using both conventional, ultrasensitive (SMI™) power Doppler ultrasound and CEUS. Intrinsic tendon tenderness was assessed with sensation detection threshold to extracorporeal shock waves (ESW). Linear Mixed Model analysis was used to determine the association between microvascular volume (MV), VISA-A, and ESW-detection threshold for both symptomatic and asymptomatic Achilles tendons. RESULTS: There was a significant association between VISA-A and MV (B=-5.3, 95%CI=[-8.5; -2.0], P=0.0004), and between MV and symptom duration (B=-1.7, 95%CI=[-3.2; -5.0], P=0.023). No significant associations were found between power Doppler ultrasound and CEUS-based MV or between CEUS-based MV and ESW-detection threshold. In comparison with conventional power Doppler ultrasound, SMI™ showed on average similar detection capacity for neovessels in the mid-portion of the Achilles tendon, whilst being superior for detecting neovessels within Kager's fat pad (t=3.46, 95%CI=[0.27; 1.03], P<0.005). CONCLUSIONS: Our results indicate that CEUS-based MV of the Achilles tendon is moderately associated with Achilles tendon symptoms. In accordance, CEUS-detected MV could be a novel target for treatment as it seems to be more sensitive than PDU and is correlated with symptoms.

Community-Living Older Adults' Perceptions of Body Weight, Signs of Malnutrition and Sources of Information: a Descriptive Analysis of Survey Data.

BACKGROUND: Community-living older adults may be susceptible to malnutrition (undernutrition) due to both physiological and non-physiological causes. The condition develops over time and the early signs and symptoms may not be obvious. Therefore awareness and early identification of nutrition risk factors may prevent, or at least slow, the progression of malnutrition. OBJECTIVE: To describe community-living older adults' understanding of the signs of malnutrition, where they would seek malnutrition information and their self-perception of body weight. DESIGN: Older adults (aged ≥ 65 years) living in the community setting completed an online or paper based questionnaire between May and August 2016. The questionnaire contained a mix of closed and open questions which related to weight perception, weight changes, perceived signs of malnutrition and sources of malnutrition information. Body mass index (BMI) from self-reported data was classified using BMI reference ranges for older adults and compared to self-perceived weight status. Textual data regarding the signs of malnutrition were analysed and reviewed by two authors using content analysis. Descriptive statistics were used to describe participant characteristics. RESULTS: A total of 344 responses were received, the majority (90%) completed online. Mean participant age was 73 years and 57% of participants were female. Most (92%) reported their health to be good/very good. Body weight was perceived to be just right or more than it should be by 87% of underweight women and 97% of underweight men. Although 71% of the participants indicated their body weight had remained stable in the past six months, 37% reported they had been trying to change their weight. Signs of malnutrition resulted in four key categories of (i) psychological, (ii) physical appearance, (ii) bodily function and (iv) weight change. Very few reported the need to locate malnutrition information and indicated the top three sources for information would be (i) general practitioner, (ii) dietitian or (iii) internet. CONCLUSION: This paper has presented useful data about malnutrition from the perspective of the community-living older adult. We found there may be uncertainty about the best weight, for older age. As many indicated they had been trying to change their weight, awareness needs to be raised regarding the impact of weight changes on health outcomes in this population. In this study, the internet appeared to be a key provider of nutrition information. Healthcare professionals need to consider how this can be used in an informative manner among community living older adults as a tool for raising awareness about nutrition risk and malnutrition.

Experimental pain in the groin may refer into the lower abdomen: Implications to clinical assessments.

OBJECTIVES: To investigate the effects of experimental adductor pain on the pain referral pattern, mechanical sensitivity and muscle activity during common clinical tests. DESIGN: Repeated-measures design. METHODS: In two separate sessions, 15 healthy males received a hypertonic (painful) and isotonic (control) saline injection to either the adductor longus (AL) tendon to produce experimental groin pain or into the rectus femoris (RF) tendon as a painful control. Pain intensity was recorded on a visual analogue scale (VAS) with pain distribution indicated on body maps. Pressure pain thresholds (PPT) were assessed bilaterally in the groin area. Electromyography (EMG) of relevant muscles was recorded during six provocation tests. PPT and EMG assessment were measured before, during and after experimental pain. RESULTS: Hypertonic saline induced higher VAS scores than isotonic saline (p<0.001), and a local pain distribution in 80% of participants. A proximal pain referral to the lower abdominal region in 33% (AL) and 7% (RF) of participants. Experimental pain (AL and RF) did not significantly alter PPT values or the EMG amplitude in groin or trunk muscles during provocation tests when forces were matched with baseline. CONCLUSIONS: This study demonstrates that AL tendon pain was distributed locally in the majority of participants but may refer to the lower abdomen. Experimental adductor pain did not significantly alter the mechanical sensitivity or muscle activity patterns.

Resisted adduction in hip neutral is a superior provocation test to assess adductor longus pain: An experimental pain study.

The criterion of long-standing groin pain diagnoses in athletes usually relies on palpation and clinical tests. An experimental pain model was developed to examine the clinical tests under standardized conditions. Pain was induced by hypertonic saline injected into the proximal adductor longus (AL) tendon or rectus femoris (RF) tendon in 15 healthy male participants. Isotonic saline was injected contralaterally as a control. Pain intensity was assessed on a visual analog scale (VAS). Resisted hip adduction at three different angles and trunk flexion were completed before, during, and after injections. Pain provocation in the presence of experimental pain was recorded as a true positive compared with pain provocation in the non-pain conditions. Similar peak VAS scores were found after hypertonic saline injections into the AL and RF and both induced higher VAS scores than isotonic saline (P < 0.01). Adduction at 0° had the greatest positive likelihood ratio (+LR = 2.8, 95%CI: 1.09-7.32) with 45° (-LR = 0.0, 95%CI: 0.00-1.90) and 90° (-LR = 0.0, 95%CI: 0.00-0.94) having the lowest negative LR. This study indicates that the 0° hip adduction test resisted at the ankles optimizes the diagnostic procedure without compromising diagnostic capacity to identify experimental groin pain. Validation in clinical populations is warranted.

A "polypill" for acute tendon pain in athletes with tendinopathy?

Acute tendon pain in athletes is a condition that is difficult to manage. There are few treatment options that give adequate pain relief and have a theoretical basis for efficacy. We report the use of a novel "polypill" for tendon pain, and provide evidence for the basis for its use. We present it to stimulate discussion and research into a new area of tendinopathy.

Thermal injury increases the number of eosinophil progenitors in rat spleen and bone marrow.

We have investigated the effects of thermal injury upon myelopoiesis. IL-3, GM-CSF, and IL-5 were used to stimulate myeloid colony formation. IL-3 induces early myeloid progenitors and a more developed myeloid progenitor, the granulocyte-macrophage colony-forming unit (GM-CFU), to multiply and develop into mature myeloid cells. GM-CSF induces GM-CFU to become mature myeloid cells, while IL-5 induces eosinophil progenitors to become mature eosinophils. Stem Cell Factor (SCF) + IL-6 and FLT3 ligand, which have no effect on colony formation by themselves, were used to enhance the effects of IL-3 and GM-CSF, respectively. We found that thermal injury increased the number of early myeloid progenitors and GM-CFU in the spleen with either IL-3 or GM-CSF as a stimulant. Thermal injury increased the number of early myeloid progenitors in the bone marrow when GM-CSF, but not IL-3, was used to stimulate colony growth. Also, thermal injury increased the numbers of eosinophil progenitors in rat spleen and bone marrow and increased splenic levels of IL-5 mRNA.

Interleukin-6 signal transduction in human intestinal epithelial cells.

The gut is an important source of inflammatory cytokines, but there is scant information on the mechanisms of cytokine action in gut epithelium. We hypothesized that in human Caco-2 cells, IL-6 acts directly through stimulation of Stat phosphorylation and that bacterial lipopolysaccharide (LPS) causes Stat activation indirectly because of its ability to cause the autocrine secretion and action of interleukin (IL)-6. Stat1, Stat5a, and Stat5b, but not Stat3, were detected in Caco-2 cells. DNA-binding activity corresponding to activated Stat5 was stimulated in a biphasic manner by IL-6, with a transient early phase, followed by sustained activation between 8 and 48 h. LPS also stimulated Stat5-like binding, but there was no early phase of activation. Functional tests of Stat5 activation showed that IL-6 stimulated Stat5-dependent reporter gene transcription but had no effect on Stat1-dependent transcription. LPS did not stimulate Stat-dependent transcription, nor did it alter the transcriptional response to IL-6. Tyrosine phosphorylation of both Stat5a and Stat5b was induced by IL-6. We infer from these data that IL-6 acts on intestinal epithelia through a Stat5-mediated transcriptional mechanism, whereas LPS does not induce gene expression through autocrine activation of enterocyte Stat signaling. These data provide a basis for testing the in vivo regulation of gut signaling and the interaction of gut reticuloendothelial cells with epithelial signal transduction.

Analysis of oncogene, tumor suppressor gene, and chromosomal alterations in HeLa x osteosarcoma somatic cell hybrids.

Using a series of tumorigenic and non-tumorigenic somatic cell hybrids that resulted from the fusion of the human osteosarcoma cell line OHS50-P16T (P16T) with the HeLa cell line D98OR, we investigated the role that genetic mutations, including alterations of oncogenes, tumor suppressor genes, and chromosomes, play in P16T tumorigenicity. Analysis of a previously identified oncogene mutation, c-myc amplification, in the P16T cell line demonstrated that both the tumorigenic and non-tumorigenic hybrids contained the amplified c-myc gene. Analysis of previously identified P16T tumor suppressor gene alterations, p53 mutation, and loss of RB1 expression demonstrated that the mutated p53 gene was selectively maintained in both the non-tumorigenic and tumorigenic hybrids, whereas loss of RB1 expression was not maintained in either the non-tumorigenic or tumorigenic hybrids. Chromosomes 11, 13, 17, and 22 were analyzed for loss of heterozygosity (LOH) to characterize the status of these previously described chromosomal alterations in the tumorigenic and non-tumorigenic hybrids. Loss of HeLa D98OR chromosome 22, with maintenance of P16T chromosome 22, was observed in the tumorigenic hybrids, a result confirmed by LOH analysis, which demonstrated the specific loss of HeLa chromosome 22 genetic material in the tumorigenic segregants. Together, these results demonstrated that amplified c-myc, mutant p53, and RB1 genes seem to be important in osteosarcoma tumorigenicity and that an additional altered gene or genes on chromosome 22 may play a key role in osteosarcoma tumorigenicity.

Analysis of oncogenes, tumor suppressor genes, autocrine growth-factor production, and differentiation state of human osteosarcoma cell lines.

Human osteosarcoma and fibrosarcoma cell lines were investigated for alterations in oncogenes, tumor suppressor genes, and growth factors, all of which have been implicated in tumor formation. Characterization of oncogenes that are involved in osteosarcoma formation, including the c-fos and c-myc oncogenes, indicated that all six osteosarcoma cell lines examined had 5- to 20-fold amplification of the c-myc oncogene, whereas neither of two fibrosarcoma cell lines c-myc amplification. Interestingly, only three of six osteosarcoma cell lines displayed altered c-myc immediate-early gene function. c-fos was found to be normal, both at the gene and functional levels, in all six osteosarcoma and both fibrosarcoma cell lines tested. Characterization of two tumor suppressor genes, p53 and RB1, that have been implicated in osteosarcoma formation indicated that p53 was altered in five of six osteosarcoma cell lines, whereas RB1 was altered in only two or six of these cell lines. Neither RB1 nor p53 was found to be altered in the fibrosarcoma cell lines tested. An additional transformation marker, autocrine growth-factor production, was observed in all six osteosarcoma cell lines and both fibrosarcoma cell lines examined. Finally, the differentiation state of the osteosarcoma cell lines was investigated via the bone differentiation markers alkaline phosphates and osteocalcin. Alkaline phosphatase activity was observed in four of six osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined. The alkaline phosphatase activity was a result of the expression of the bone/liver/kidney alkaline phosphatase isoform. High-level osteocalcin expression was observed in one of the osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined, although all cell lines demonstrated low-level osteocalcin expression. Together, these data demonstrate that relatively undifferentiated osteosarcomas commonly display c-myc amplification, p53 and RB1 mutation, and autocrine growth-factor production, all of which may play a role in osteosarcomagenesis.

The diagnosis of chronic groin pain in athletes: a review of 189 cases.

The case-notes of 189 athletes with chronic groin pain were reviewed to determine the prevalence of the underlying conditions. Diagnoses were determined following a review of their history, clinical examination, local anaesthetic infiltration, radiological investigation, surgical exploration and clinical progress. The most common pathology found was an incipient hernia (50% of cases). Twenty-seven percent were found to have multiple pathologies. An approach to the differential diagnosis and radiological investigation of athletes with chronic groin pain is suggested.

Effects of daily SKF 38393, quinpirole, and SCH 23390 treatments on locomotor activity and subsequent sensitivity to apomorphine.

In three experiments, male Wistar rats (250-350 g) were injected (SC) daily with the D1-type dopamine receptor agonist, SKF 38393 (0.0, 4.0, 8.0, or 16.0 mg/kg), the D2-type dopamine receptor agonist, quinpirole (0.0, 0.3, or 3.0 mg/kg), and/or the D1-type dopamine receptor antagonist, SCH 23390 (0.0 or 0.5 mg/kg) for 8-10 days. After each daily injection, the rats were tested for locomotor activity in photocell arenas for 20 min. Following this subchronic pretreatment, all rats were challenged with the mixed dopamine receptor agonist apomorphine (1.0 mg/kg, SC) and tested for locomotor activity. SKF 38393 treatments produced a dose-dependent decrease in locomotor activity which did not significantly change across days. Quinpirole also depressed locomotor activity when first injected, but this quinpirole-induced inhibition of activity progressively decreased across days. When subsequently challenged with apomorphine, rats in both the SKF 38393 and the quinpirole pretreatment groups displayed greater locomotor activity than rats pretreated with only vehicle. Although SCH 23390 pretreatments did not affect subsequent sensitivity to apomorphine, SCH 23390 completely blocked the effect of quinpirole. These results suggest that although repeated D1 receptor stimulation may be sufficient to induce behavioral sensitization to apomorphine, D2 receptor stimulation also contributes to the effect.

Inguinal surgery in athletes with chronic groin pain: the 'sportsman's' hernia.

Fifty athletes with chronic undiagnosed groin pain underwent surgical exploration and inguinal hernia repair. Six months later, all athletes were sent questionnaires to assess their return to sport, level of pain (using analogue pain scores) and the overall result of their surgery. Operative findings revealed a significant bulge in the posterior inguinal wall in 40 athletes. Forty-four athletes (88%) replied to the questionnaire. Forty-one athletes (93% of respondents) had returned to normal activities. Pain scores indicated a marked improvement in their level of pain (P less than 0.001). Thirty-three athletes (75%) rated the result as good and 10 (23%) as improved. It is concluded that athletes with chronic groin pain who are unable to compete in active sport should be considered for routine inguinal hernia repair if no other pathology is evident after clinical examination and investigation.

Determination of L-thyroxine in reference serum preparations as the o-phthalaldehyde-N-acetylcysteine derivative by reversed-phase liquid chromatography with electrochemical detection.

A simple procedure for the assay of L-thyroxine in serum preparations with D-thyroxine as internal standard is described. The L-thyroxine is extracted with acetonitrile, fractionated on a reversed-phase silica cartridge and analysed by reversed-phase high-performance liquid chromatography of the o-phthalaldehyde-N-acetyl-L-cysteine derivative. This derivative is not fluorescent, but may be detected with suitable sensitivity and selectivity with an electrochemical detector.

Maternal deaths associated with Clostridium sordellii infection.

Clostridium sordellii is a common soil and enteric bacterium that is infrequently recovered from the vagina. We describe three women in which C. sordellii caused puerperal infection and a distinctive and lethal toxic shock-like syndrome. Patients were less than 1 week post partum and each had a single, limited focus of infection including infection associated with a retained vaginal sponge, a cesarean section operative site, and endometritis. Each patient had a distinctive course characterized by sudden onset of clinical shock marked by severe and unrelenting hypotension associated with marked, generalized tissue edema and "third spacing" with increased hematocrit, presence of marked leukemoid reaction with total neutrophil counts of 84,000/mm3, 66,000/mm3, and 93,600/mm3, absence of rash or fever, limited or no myonecrosis, and a rapid and uniformly lethal course. Hypoalbuminemia was also noted. Similar findings were noted in prior isolated reports of C. sordellii-mediated postpartum or surgical infection. Treatment of animals with C. sordellii or closely related C. difficile toxins produces similar findings. We suggest that localized infection with toxin-producing strains of C. sordellii can produce a rapidly lethal toxic shock-like syndrome. Further study and earlier recognition of this syndrome may be life-saving in other patients.

UV radiation measurement in a study of elderly subjects.

Elderly subjects were exposed to controlled amounts of sunshine over a 3-month period. Ultraviolet radiation (UVR) was monitored using two types of sensors, polysulphone film and a digital radiation meter. The time periods for sun exposure were computer-derived so as to yield 'safe' exposure times, but these times may have been underestimated. Erythemally effective radiation doses calculated from the sensor readings indicated good agreement between the sensors.

The determination of nivacortol in plasma using HPLC.

A high performance liquid chromatographic method with ultraviolet detection was developed for the determination of nivacortol (WIN 27914) in biological samples. The drug was isolated from human plasma by using a solid-phase extraction and eluted with ethanol. The solvent was evaporated and the residue dissolved in the chromatographic eluent. The sample was subjected to chromatography on a C8 silica column and eluted with a gradient of acetonitrile in 0.1 M sodium acetate buffer, pH 6.5. A single concentration of a structural analogue (WIN 31338) was used as internal standard for the quantitative determination of the analyte. The plasma concentrations were below that needed to suppress ACTH secretion by pituitary cells in culture and did not suppress plasma ACTH in Nelson's syndrome.