Interval training and cardiometabolic health in reproductive-aged females.

Physical activity and exercise training are especially important for reproductive-aged females as exercise-induced health benefits can also affect their infants. However, levels of physical inactivity remain high among females in this age group, before, during, and after pregnancy. There is a great need for practical and feasible exercise modes to increase adherence to exercise in this population, and interval training may be a time-efficient training modality. Interval training is a form of exercise involving intermittent bouts of intense effort interspersed with recovery periods of rest or lower-intensity exercise. A substantial amount of research indicates that interval training induces superior cardiometabolic health benefits compared with iso-energetic moderate-intensity continuous exercise. This review provides a comprehensive overview of research on interval training interventions in reproductive-aged females across various life stages, focusing on the cardiometabolic health benefits. We discuss the potential role of interval training in premenopausal females with overweight/obesity, polycystic ovary syndrome, and subfertility, as well as the potential influence of oral contraceptives on cardiometabolic adaptations to interval training. Furthermore, this review also highlights recent findings supporting the beneficial role of high-intensity interval training for cardiometabolic health outcomes during pregnancy. In summary, the existing evidence suggests that interval training can improve several cardiometabolic and reproductive outcomes in females spanning different life stages. However, more research is needed to further strengthen the evidence-base for physical activity recommendations for females in their reproductive years of life.

Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer's disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy.

AIMS: Several observations point to the involvement of angiotensin-converting enzyme-1 (ACE-1) in Alzheimer's disease (AD): ACE-1 cleaves amyloid-beta peptide (Abeta) in vitro, the level and activity of ACE-1 are reportedly increased in AD, and variations in the ACE-1 gene are associated with AD. We analysed ACE-1 activity and expression in AD and control brains, particularly in relation to Abeta load and cerebral amyloid angiopathy (CAA). METHODS: ACE-1 activity was measured in the frontal cortex from 58 control and 114 AD cases of known Abeta load and CAA severity. The distribution of ACE-1 was examined immunohistochemically. In five AD cases with absent or mild CAA, five with moderate to severe CAA and five controls with absent or mild CAA, levels of vascular ACE-1 were assessed by quantitative immunofluorescence. RESULTS: ACE-1 activity was increased in AD (P < 0.001) and correlated directly with parenchymal Abeta load (P = 0.05). Immunohistochemistry revealed ACE-1 in neurones and cortical blood vessels - in the intima but most abundant perivascularly. Cases with moderate to severe CAA had significantly more vessel-associated ACE-1 than did those with little or no CAA. Perivascular ACE-1 did not colocalize with Abeta, smooth muscle actin, glial fibrillary acidic protein, collagen IV, vimentin or laminin, but was similarly distributed to extracellular matrix (ECM) proteins fibronectin and decorin. CONCLUSIONS: Our findings indicate that ACE-1 activity is increased in AD, in direct relationship to parenchymal Abeta load. Increased ACE-1, probably of neuronal origin, accumulates perivascularly in severe CAA and colocalizes with vascular ECM. The possible relationship of ACE-1 to the deposition of perivascular ECM remains to be determined.

Should follow-up of patients with arthroplasties be carried out by general practitioners?

Due to economic constraints, it has been suggested that joint replacement patients can be followed up in primary care. There are clinical, ethical and academic reasons why we must ensure that our joint replacements are appropriately clinically and radiologically followed up to minimise complications. This Editorial discusses this.

Demonstration of local immunosuppression with methylprednisolone in the sponge matrix allograft model.

This study evaluated the effect of locally delivered methylprednisolone on the systemic and local immune response in the sponge matrix allograft model. Polyurethane sponges were coated with peritoneal exudate cells from DBA/2 (H-2d) or C57Bl/6 mice (H-2b) and placed subcutaneously in C57BL/6 recipients 24 hr later. Each mouse received both a syngeneic and an allogeneic sponge graft. Local immunosuppression was effected by placement on day 0 of cellulose/matrix pellets containing a preparation of increasing quantity of controlled release MP or by daily intrasponge injection of MP. Local immunosuppression was demonstrated by decreased cytotoxicity on day 12 in the allogeneic sponge receiving MP directly, as compared with the groups that received MP in the opposite syngeneic sponge or no MP. This effect was noted at a specific MP dose (0.5 mg/kg/day). Absolute numbers of precursor cytolytic cells and mature cytolytic cells (determined by limiting dilution analyses) infiltrating the allografts were also decreased in the sponges receiving MP directly, relative to the groups receiving MP in the opposite syngeneic sponge. Maintenance of systemic (in contrast to local) immunity was also demonstrated. Animals treated with local MP into a simultaneously placed syngeneic sponge or in whom no MP was delivered became sensitized to a synchronous DBA/2 sponge and rejected a subsequent DBA/2 skin graft in second-set fashion. Conversely, animals that received local MP into their synchronous DBA/2 sponge rejected a subsequent DBA/2 skin graft or a third-party graft with first-set kinetics. The presence of local MP at the initial graft site prevented the animals from becoming sensitized to the presented alloantigen but did not keep the animal from developing a rejection response to a third-party skin graft with first-set kinetics. It appears that delivery of MP locally to the site of antigen is an effective method to modulate alloreactivity. In addition, the sponge matrix allograft appears to be a useful model for studying local immunosuppression.

Evaluation of a novel osteogenic factor, bone cell stimulating substance, in a rabbit cranial defect model.

A novel osteogenic factor, bone cell stimulating substance (BCSS), was recently isolated from bovine bone. Unlike the bone morphogenetic proteins, which are generally 20- to 40-kDa glycoproteins belonging to the transforming growth factor-beta superfamily, BCSS is a 2.5-kDa, water-soluble polypeptide. This study evaluated the osteogenic potential of BCSS in combination with coralline-derived porous hydroxyapatite to reconstruct a large, nonhealing cranial defect in the rabbit. Twenty-four rabbits underwent a 16 x 20 mm full-thickness (extradural) excision of the parietal bones and were divided into six groups of four rabbits each. Group 1 through 5 were reconstructed with 16 x 20 x 1.5 mm hydroxyapatite implants treated with: (1) 20 osteogenic units (424 micrograms) BCSS, (2) 8 osteogenic units (170 micrograms) BCSS, (3) 4 osteogenic units (85 micrograms) BCSS, (4) 0 osteogenic units (424 micrograms) inactive BCSS analog, or (5) left untreated. Group 6 was left unreconstructed. Implants were harvested at 12 weeks and analyzed for percentage of lamellar bone formation by a computerized microscope video image analysis system. Groups reconstructed with BCSS-treated hydroxyapatite implants demonstrated more bone ingrowth than did the control hydroxyapatite groups not treated with BCSS (inactive BCSS analog or untreated). Linear regression dose-response analysis indicated an average 3.2 percent increase in bone ingrowth for a 10-U increase in BCSS (p = 0.043). The unreconstructed control group demonstrated no healing. With a molecular mass of only 2.5 kDa and its identity not completely known, BCSS is a novel factor that seems to possess osteogenic potential similar to that of previously investigated osteogenic proteins.

Computer-assisted anthropometry for outcome assessment of cleft lip.

Anthropometry and clinical examination best evaluate the morphology of repaired cleft lip and nose. An original, accurate, and practical image analysis of the lip and nose, which takes advantage of the mathematic, geometric, and organizational capabilities of public domain NIH-Image software (http://rsb.info.nih.gov/nih-image/), has been developed and tested over the past 6 years. A modified structured physical examination form that complements this analysis is under study. Accuracy of NIH-Image-based anthropometry was compared with direct measurements of 22 linear distances on the lip and nose. Twenty-five sets of direct measurements were taken, prospectively, on 15 children with repaired cleft lip over a 6-year period. The results were submitted to regression analysis. Then, relevant lip and nasal tip aesthetics were evaluated by the measuring capabilities of NIH-Image to create a quantitative assessment tool. For each episode, 15 possible faults were weighted, according to aesthetics and deformity, to provide an adverse score. The sum of the 5 lip scores, 10 nose scores, and combination gave respective grades. The analysis was modified to stratify congenital deformity to relate severity of disease to outcome. This analysis was applied to digitized images of 19 consecutive children, immediately prior to repair of complete unilateral cleft lip and nose, at the time of palate repair, and annually from the age of 3 to 6 years. There were 19 NIH-Image-based measurements of the congenital deformity and 35 measurements of surgical results; four children had three sets of records, eight had two sets, and seven had one set Descriptive statistics were applied. Following 556 paired direct and computer-assisted measurements, exceptional linear correlation was shown with a Pearson R coefficient of 0.96. The best correlation was lines within the plane of the camera lens, with the average difference ranging between 0.025 and 0.997 mm. Visual inspection of frontal and submental photographs of excellent, good, and poor results substantiates the ability of this analysis to quantify and grade a spectrum of relevant cleft lip and nasal anatomy. For these 19 patients, there was a broad range of performance scores, approximating a normal distribution. The mean of the NIH-Image-based analysis scores, 16.91, was a (very) good grade. A single standard deviation of 6.88 extended up into excellent and down to fair. The congenital analysis indicated a range of deformity. Comparing deformity with outcome, simple regression analysis had a coefficient of determination (R2) of 0.223, indicative of a weak positive relationship. An accurate and practical morphologic computer-assisted outcome assessment of repaired cleft lip and nasal deformity has been developed. There is a weak direct correlation between severity of deformity and outcome. Testing in multiple clinics is warranted.

Abdominal pain of spinal origin. Value of intercostal block.

A prospective study was made of 73 patients presenting in one year with abdominal pain provisionally diagnosed as of spinal origin. The criteria for audit of diagnosis and treatment are defined. The diagnosis was confirmed in 53 patients, 49 of whom had been treated with a lignocaine intercostal block in the relevant segment. Thirty-three of these (67.3%) had both complete and prolonged relief. It is suggested that the block causes interruption of a vicious circle of pain and muscle spasm in a 'spinal reflex pain syndrome'.

Povidone-iodine bowel irrigation before resection of colorectal carcinoma.

Preoperative mechanical bowel preparation, peroperative topical antiseptic measures, and postoperative antibiotic therapy have all been shown to reduce infection after colorectal surgery. We report the results of a randomised trial of preoperative irrigation with a 10% aqueous solution of povidone-iodine (Betadine) versus water in patients undergoing major resection for large bowel carcinoma. All patients had mechanical bowel preparation, preoperative topical povidone-iodine and per and postoperative antibiotics. Of 22 study patients only one (4.6%) developed abdominal wound infection, whereas in 23 controls nine (39.1%) did so (P less than 0.01). In three of the study patients cultures of swabs taken at operation from the transected bowel ends showed no bacterial growth. Arguably the bacterial population would have been markedly reduced in other patients. These results suggest that povidone-iodine irrigation before large bowel resection reduces wound sepsis.

How will surgical site infection be measured to ensure "high quality care for all"?

As of April 2010 all NHS institutions in the United Kingdom are required to publish data on surgical site infection, but the method for collecting this has not been decided. We examined 7448 trauma and orthopaedic surgical wounds made in patients staying for at least two nights between 2000 and 2008 at our institution and calculated the rate of surgical site infection using three definitions: the US Centers for Disease Control, the United Kingdom Nosocomial Infection National Surveillance Scheme and the ASEPSIS system. On the same series of wounds, the infection rate with outpatient follow-up according to Centre for Disease Control was 15.45%, according to the UK Nosocomial infection surveillance was 11.32%, and according to ASEPSIS was 8.79%. These figures highlight the necessity for all institutions to use the same method for diagnosing surgical site infection. If different methods are used, direct comparisons will be invalid and published rates of infection will be misleading.

Outcome measures for orthopaedic interventions on the hip.

Orthopaedic outcome measures are used to evaluate the effect of operative interventions. They are used for audit and research. Knowledge of these measures is becoming increasingly important with league tables comparing surgeons and hospitals being made accessible to the profession and the general public. Several types of tool are available to describe outcome after hip surgery such as generic quality-of-life questionnaires, disease-specific quality-of-life questionnaires, hip-specific outcome measures and general short-term clinical measures. We provide an overview of the outcome measures commonly used to evaluate hip interventions.

Chronic obscure groin pain is commonly caused by enthesopathy: 'tennis elbow' of the groin.

Forty-nine patients with chronic obscure groin pain, bilateral in four, presented to one general surgeon in a 12-month period. Inflammation ('enthesopathy') at the pubic insertion of the inguinal ligament was the cause in 30 patients (32 groins). This has not previously been recognized as a cause of chronic groin pain, possibly because the exact site of tenderness can be obscured by the pubic pad of fat. Enthesopathy also occurred in five rectus and one adductor longus tendons (one patient had inflammation in both). Infiltration with long-acting steroid (1 per cent triamcinolone) and local anaesthetic (2 per cent lignocaine) was offered to all patients with localized tenderness of tendon or ligament. A questionnaire survey 3-15 months after injection showed a better outcome after treatment than when injection was declined. Other causes of pain included nerve entrapment (five cases), spinal referred pain (five in four patients) and ureteric stones (two). Inguinal hernia is sometimes coincidental rather than causative of the pain. In three patients the pain had subsided and no diagnosis was made. Simple diagnostic and therapeutic measures may relieve chronic groin pain and spare patients elaborate investigation or unnecessary operation.

Intra-abdominal adhesions as a manifestation of a fibrotic diathesis.

In 81 patients with fibrous intra-abdominal adhesions there was a high incidence of other lesions in which there was a substantial element of fibrosis. These included chronic peptic ulceration, ovarian cysts, fibrous stenotic lesions, and thickened scars. It is suggested that in some patients a generalized fibrotic tendency as well as local factors may play a part in the pathogenesis of adhesions.

Diagnosis and management of testes in the superficial inguinal pouch.

A physical sign was assessed and operation findings were noted in boys with testes which tended to deviate lateral to the external ring who were seen over a five-year period. Tensing the abdominal muscles by straight-leg raising not only facilitated palpation of such testes but also helped to domonstrate lateral deviation. The view that testes found lateral to the external ring and which could be pushed some way into the scrotum were merely retractile was questioned. Such testes were deviated by inguinal tethering. The spermatic cord was short enough in over half the tethered testes to require retroperitoneal dissection to achieve the fully descended position, not a significantly different proportion compared with the obstructed group.

Prophylaxis against systemic infection after transrectal biopsy for suspected prostatic carcinoma.

Five minutes after transrectal prostatic biopsy 16 out of 21 patients were shown by blood culture to have bacteraemia. Antibiotic prophylaxis--routinely with ampicillin and metronidazole for 48 hours--prevented progression to septicaemia, and four days after the procedure all blood samples were negative. Irrespective of whether antibiotic prophylaxis is used, blood culture should be routine in all patients undergoing transrectal prostatic biopsy.

Posture, blood velocity in common femoral vein, and prophylaxis of venous thromboembolism.

Might leg elevation and avoidance of poor postures provide better prophylaxis against venous thromboembolism than heparin or mechanical methods? 12 supine subjects tilted in 3 degrees increments from 6 degrees leg-down to 12 degrees leg-up showed linear increase in mean peak blood velocity and reduction in calibre in the common femoral vein (colour-duplex ultrasound). Between horizontal and 6 degrees leg-up, velocity was increased by 17% and diameter reduced by 14%. A ranking of mean peak velocities in six postures (sitting; standing; trunk raised 35 degrees to legs which were first horizontal and then tilted up 6 degrees; supine, first horizontal then 6 degrees leg-up) showed significant increases in velocity between consecutive positions.

Severe gastrointestinal haemorrhage: haemangiomata demonstrated by selective visceral arteriography.

Selective visceral arteriography was found to be invaluable in the management of two cases of severe gastrointestinal haemorrhage associated with cavernous haemangiomata (a large gastric haemangioma and a small jejunal haemangioma). It is suggested that arteriography may be indicated in cases where a previous laparotomy has not shown the cause of bleeding, when the patient's general condition precludes a prolonged operation, and when superficial haemangiomata are found.

Anti-idiotypic antibodies as probes of protein active sites: application to cholera toxin subunit B.

Since Jerne proposed a "network" theory of immune regulation, the properties of anti-idiotypic antibodies (anti-IdAb) have been investigated widely. Anti-IdAb raised against antibodies to a variety of ligands have been shown to bind the ligands' receptors. Thus, the combining site of an anti-IdAb may contain information regarding the three-dimensional structure of an antigen. However, this remarkable property of "internal imagery" has not been exploited for structural investigation at the molecular level. In the present report, a monoclonal "auto"-anti-IdAb was raised against ganglioside GM1 (a cell-surface glycolipid that binds cholera toxin) and was shown to crossreact with the B subunit of cholera toxin. This antibody was presumed to recognize amino acid residues located within the GM1 binding domain. To identify these residues, the antibody was screened against homologous toxins purified from enterotoxigenic strains of Escherichia coli and chimeric peptides produced by recombinant methods. Amino acid variation at position 4 from the N terminus of these proteins was found to disrupt antibody binding. Since the toxins and chimera are all closely related in structure and function, the residue at position 4 (an asparagine in cholera toxin B subunit) appears to be in the epitope of the antibody and, by implication, in the GM1 binding site. Of particular significance, this structural detail could not be deduced with GM1 alone. It would seem that ligand and anti-ligand anti-IdAb encode similar stereochemical information but do so with different "chemical alphabets," giving rise to distinct binding specificities.