Dulwich Community Hospital

Bacillus cereus is a gram-positive aerobic or facultatively anaerobic spore-forming rod. It is a cause of food poisoning, which is frequently associated with the consumption of rice-based dishes. The organism produces an emetic or diarrheal syndrome induced by an emetic toxin and enterotoxin, respectively. Other toxins are produced during growth, including phospholipases, proteases, and hemolysins, one of which, cereolysin, is a thiol-activated hemolysin. These toxins may contribute to the pathogenicity of B. cereus in nongastrointestinal disease. B. cereus isolated from clinical material other than feces or vomitus was commonly dismissed as a contaminant, but increasingly it is being recognized as a species with pathogenic potential. It is now recognized as an infrequent cause of serious nongastrointestinal infection, particularly in drug addicts, the immunosuppressed, neonates, and postsurgical patients, especially when prosthetic implants such as ventricular shunts are inserted. Ocular infections are the commonest types of severe infection, including endophthalmitis, panophthalmitis, and keratitis, usually with the characteristic formation of corneal ring abscesses. Even with prompt surgical and antimicrobial agent treatment, enucleation of the eye and blindness are common sequelae. Septicemia, meningitis, endocarditis, osteomyelitis, and surgical and traumatic wound infections are other manifestations of severe disease. B. cereus produces beta-lactamases, unlike Bacillus anthracis, and so is resistant to beta-lactam antibiotics; it is usually susceptible to treatment with clindamycin, vancomycin, gentamicin, chloramphenicol, and erythromycin. Simultaneous therapy via multiple routes may be required.

Alan Turing was neither a biologist nor a chemist, and yet the paper he published in 1952, 'The chemical basis of morphogenesis', on the spontaneous formation of patterns in systems undergoing reaction and diffusion of their ingredients has had a substantial impact on both fields, as well as in other areas as disparate as geomorphology and criminology. Motivated by the question of how a spherical embryo becomes a decidedly non-spherical organism such as a human being, Turing devised a mathematical model that explained how random fluctuations can drive the emergence of pattern and structure from initial uniformity. The spontaneous appearance of pattern and form in a system far away from its equilibrium state occurs in many types of natural process, and in some artificial ones too. It is often driven by very general mechanisms, of which Turing's model supplies one of the most versatile. For that reason, these patterns show striking similarities in systems that seem superficially to share nothing in common, such as the stripes of sand ripples and of pigmentation on a zebra skin. New examples of 'Turing patterns' in biology and beyond are still being discovered today. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

BACKGROUND: Muscle functions to generate force-producing movement and also has a role in proprioception. If ageing compromises these sensorimotor functions of muscle, the ability of older subjects to detect and correct postural sway may be impeded, resulting in impairment of functional performance. METHOD: To see if age-related changes occurred and, if so, what their effects might be. Quadriceps strength, proprioception, postural stability and functional performance were assessed in young (n = 20, mean age 23 years), middle-aged (n = 10, mean age 56 years) and elderly (n = 15, mean age 72 years) subjects. RESULTS: With increasing age there were decreases in quadriceps strength (r = -0.511; P < 0.001), acuity of joint position sense (r = -0.603; P < 0.001) and postural stability (ANOVA < 0.002) during stance conditions which placed a greater reliance on muscle proprioceptors. These changes may decrease postural stability confidence, resulting in impaired performance of common activities of daily living (r = 0.635; P < 0.001). CONCLUSIONS: The age-related deterioration in sensorimotor function of muscle may contribute to the increased fear and frequency of falls in elderly subjects, thereby decreasing independence.

Nosocomial infection or colonization due to enterococci with high-level resistance to vancomycin (minimal inhibitory concentrations [MICs] between 64 and greater than 2000 mg/L) has occurred in 41 patients with renal disease. These vancomycin-resistant enterococci were cultured from many sources including blood. All but one strain contained one or more plasmids ranging in molecular weight from 1.0 to 40 Megadaltons (MDa). Vancomycin resistance was transferable by conjugation to a susceptible recipient strain of Enterococcus faecalis but this was not always associated with plasmid DNA. The emergence of transferable high-level vancomycin resistance in enterococci causing significant clinical infections is of particular importance since vancomycin is widely regarded as a reserve drug for the management of infections with multi-resistant Gram-positive organisms.

In mice, seminal fluid elicits an inflammation-like response in the female genital tract that activates immune adaptations to advance the likelihood of conception and pregnancy. In this study, we examined whether similar changes in leukocyte and cytokine parameters occur in the human cervix in response to the male partner's seminal fluid. After a period of abstinence in proven-fertile women, duplicate sets of biopsies were taken from the ectocervix in the periovulatory period and again 48 h later, 12 h after unprotected vaginal coitus, vaginal coitus with use of a condom, or no coitus. A substantial influx of CD45(+) cells mainly comprising CD14(+) macrophages and CD1a(+) dendritic cells expressing CD11a and MHC class II was evident in both the stratified epithelium and deeper stromal tissue after coitus. CD3(+)CD8(+)CD45RO(+) T cells were also abundant and increased after coitus. Leukocyte recruitment did not occur without coitus or with condom-protected coitus. An accompanying increase in CSF2, IL6, IL8, and IL1A expression was detected by quantitative RT-PCR, and microarray analysis showed genes linked with inflammation, immune response, and related pathways are induced by seminal fluid in cervical tissues. We conclude that seminal fluid introduced at intercourse elicits expression of proinflammatory cytokines and chemokines, and a robust recruitment of macrophages, dendritic cells, and memory T cells. The leukocyte and cytokine environment induced in the cervix by seminal fluid appears competent to initiate adaptations in the female immune response that promote fertility. This response is also relevant to transmission of sexually transmitted pathogens and potentially, susceptibility to cervical metaplasia.

A prospective study of bacterial and fungal infections after liver transplantation in 284 adults was undertaken. One hundred seventy-five (62%) became infected; bacterial or fungal infections occurred in 159 (56%) and 36 (13%) patients, respectively. Gram-positive cocci, in particular Staphylococcus aureus and Enterococcus faecium, were the commonest bacterial pathogens, and bacteremia and wound infection were the most frequent bacterial infections. Acute rejection and prolonged admission were independent risk factors for bacterial infection; pretransplantation antibacterials had a protective effect. Fungal infection most frequently involved the urinary tract and chest; Candida albicans was the most common pathogen. Four independent variables predicted fungal infection: low pretransplantation hemoglobin, high pretransplantation bilirubin, return to surgery, and prolonged therapy with ciprofloxacin. Patients with acute liver failure were more prone to bacterial, but not fungal, infection. No associations were found between infections and duration of surgery. Bacterial, and to a lesser extent, fungal infections are important complications of liver transplantation. However, liver transplantation surgery per se may not be the major determinant of infection.

The present update on the global distribution of Mycobacterium tuberculosis complex spoligotypes provides both the octal and binary descriptions of the spoligotypes for M. tuberculosis complex, including Mycobacterium bovis, from >90 countries (13,008 patterns grouped into 813 shared types containing 11,708 isolates and 1,300 orphan patterns). A number of potential indices were developed to summarize the information on the biogeographical specificity of a given shared type, as well as its geographical spreading (matching code and spreading index, respectively). To facilitate the analysis of hundreds of spoligotypes each made up of a binary succession of 43 bits of information, a number of major and minor visual rules were also defined. A total of six major rules (A to F) with the precise description of the extra missing spacers (minor rules) were used to define 36 major clades (or families) of M. tuberculosis. Some major clades identified were the East African-Indian (EAI) clade, the Beijing clade, the Haarlem clade, the Latin American and Mediterranean (LAM) clade, the Central Asian (CAS) clade, a European clade of IS6110 low banders (X; highly prevalent in the United States and United Kingdom), and a widespread yet poorly defined clade (T). When the visual rules defined above were used for an automated labeling of the 813 shared types to define nine superfamilies of strains (Mycobacterium africanum, Beijing, M. bovis, EAI, CAS, T, Haarlem, X, and LAM), 96.9% of the shared types received a label, showing the potential for automated labeling of M. tuberculosis families in well-defined phylogeographical families. Intercontinental matches of shared types among eight continents and subcontinents (Africa, North America, Central America, South America, Europe, the Middle East and Central Asia, and the Far East) are analyzed and discussed.

The concept of "water structure" has been invoked to explain all manner of aqueous phenomena. Here we look at the origins of this tendency to understand solute hydration in terms of structural changes in bulk water, and consider the validity of one particular example: the classification of small solutes as chaotropic or kosmotropic, and the putative relation of this terminology to notions of structure-making and structure-breaking in the solvent. We doubt whether complex phenomena such as Hofmeister and osmolyte effects on macromolecules can be understood simply on the basis of a change in solvent structure. Rather, we argue that chaotropicity, if understood in the original sense, arises from the activities that solutes exert on macromolecular systems, as well as from deviations of solvation water from bulk-like behaviour. If applied judiciously, chaotropicity remains a potent, biologically pertinent parameter useful for classifying and understanding solution phenomena in all types of living system.

Skin biopsy specimens were taken from 29 postmenopausal women who had not been given hormone replacement therapy and from 26 women who had been treated with oestrogen and testosterone implants for two to 10 years. The mean hydroxyproline content and therefore the mean collagen content in the skin was found to be 48% greater in the treated than the untreated women, who were matched for age. This difference was significant (p less than 0.01). The implication of this finding is that oestrogen or testosterone, or both, prevents the decrease in skin collagen content that occurs with aging and protects skin in the same way as it protects bone in postmenopausal women.

The influence of norethisterone on mood and behaviour was investigated in prospective placebo-controlled study in 58 postmenopausal hysterectomized women who were being treated with subcutaneous oestradiol and testosterone implants. Norethisterone, 2.5 or 5 mg daily, was given for 7 days and a placebo for two periods of 7 days. Psychological, behavioural and physical variables were assessed using the Menstrual Distress Questionnaire. There were widespread adverse effects which were dose-related. Significant changes in five of the eight symptom complexes studied (pain, concentration, behavioural change, water retention and negative affect) were found with 5 mg/day of the progestogen. The symptoms were similar to the typical complaints of the premenstrual syndrome, such that a combination of oestradiol and testosterone implants with cyclical oral norethisterone appears to be a model for this condition. The dose of this progestogen should therefore be the minimum to achieve the desired therapeutic effect.

Gregory Bateson's notions of negative explanation, restraint, and double description are discussed. The difficulties that families often experience in the discovery of new solutions to problems are explained according to the terms of these notions. A map for therapy is derived that emphasizes the therapist's contribution to the therapeutic system's state of "readiness" for the discovery of new solutions. Details of therapist/family participation in the endurance of new discoveries are examined. An approach to the treatment of the context for childhood fears and obsessive/compulsive behavior demonstrates one application of this map.

Sixty faecal samples, 39 from adults and 21 from neonates, were investigated by means of a simple scheme to isolate and identify any group D streptococci present. A number of differences were found between the two groups. Group D streptococci were absent from 43% of the neonates compared with only 13% of the adults; Streptococcus bovis was commoner in the neonates (23.8%) than in the adults (5%), and Streptococcus faecium was not isolated from any of the infant samples although it was common in the adult samples (25%). The viable counts of Strep. faecium were found to be, on average, 100-fold lower than those of Streptococcus faecalis. The methods and results are discussed with reference to the clinical significance of group D streptococci, especially in bacterial endocarditis and carcinoma of the colon.

BACKGROUND: The Timed Up and Go Test (TUGT) has been recommended as a simple screening tool to identify those at risk of falling. However, subsequent detailed assessment is required to identify underlying falls risk factors to provide direction for optimal targeted intervention strategies. METHODS: 110 consecutive falls clinic patients underwent the TUGT, the Abbreviated Mental Test and the Physiological Profile Assessment (PPA), a validated tool for quantifying risk of falling based on a combination of physiological measures-contrast sensitivity, knee extension strength, proprioception, reaction time and postural sway. Regression analysis was used to determine how well the TUGT and presence of cognitive impairment could identify patients at high risk of falls as defined by the PPA. RESULTS: TUGT and cognitive status were found to be independent and significant predictors of PPA scores. These variables accounted for 21% of the variance in PPA scores (multiple R=0.47, P<0.001). The standardised beta weights were 0.403 for TUGT and 0.236 for cognitive status. A receiver-operator curve (ROC) indicated that 15 seconds in the TUGT was the optimal cut-point for identifying those with a high risk of falling: 70% of the total sample. CONCLUSIONS: The TUGT and a simple test of cognition can be used to streamline referrals in a high-risk population, allowing for more efficient use of available resources in clinical practice. A subsequent PPA provides quantification of risk and direction for tailored intervention.

The skin collagen content, skin thickness, metacarpal index, and forearm bone mineral content in postmenopausal women showed a similar decline of between 1-2% per year after the menopause. All four parameters showed a decline that was significant when compared with the years from the menopause. Significant correlations between all four parameters suggest that a similar pathology causes the decrease in bone mass and skin thickness--a decline in the connective tissue element that is common to both bone and skin.

A method of obtaining an approximate solution to two-point boundary value problems by use of of cubic splines, which was suggested by Bickley (1968) is developed. Error analysis is carried out and from the results a method of deferred correction is obtained. The use of unequal intervals is considered. An algorithm for computing the solution to prescribed accuracy in the case of equal intervals is described and a numerical example given.

The cervix is central to the female genital tract immune response to pathogens and foreign male Ags introduced at coitus. Seminal fluid profoundly influences cervical immune function, inducing proinflammatory cytokine synthesis and leukocyte recruitment. In this study, human Ect1 cervical epithelial cells and primary cervical cells were used to investigate agents in human seminal plasma that induce a proinflammatory response. TGF-β1, TGF-β2, and TGF-β3 are abundant in seminal plasma, and Affymetrix microarray revealed that TGF-β3 elicits changes in Ect1 cell expression of several proinflammatory cytokine and chemokine genes, replicating principal aspects of the Ect1 response to seminal plasma. The differentially expressed genes included several induced in the physiological response of the cervix to seminal fluid in vivo. Notably, all three TGF-β isoforms showed comparable ability to induce Ect1 cell expression of mRNA and protein for GM-CSF and IL-6, and TGF-β induced a similar IL-6 and GM-CSF response in primary cervical epithelial cells. TGF-β neutralizing Abs, receptor antagonists, and signaling inhibitors ablated seminal plasma induction of GM-CSF and IL-6, but did not alter IL-8, CCL2 (MCP-1), CCL20 (MIP-3α), or IL-1α production. Several other cytokines present in seminal plasma did not elicit Ect1 cell responses. These data identify all three TGF-β isoforms as key agents in seminal plasma that signal induction of proinflammatory cytokine synthesis in cervical cells. Our findings suggest that TGF-β in the male partner's seminal fluid may influence cervical immune function after coitus in women, and potentially be a determinant of fertility, as well as defense from infection.

The hypothesis that the many non-specific changes normally associated with cyclical ovarian activity are the primary aetiological factors in the premenstrual syndrome was tested by suppressing ovulation with subcutaneous oestradiol implants. Sixty eight women with proved premenstrual syndrome were treated under placebo controlled conditions for up to 10 months in a longitudinal study. Active treatment was combined with cyclical oral norethisterone to produce regular withdrawal periods. Symptoms were monitored with daily menstrual distress questionnaires, visual analogue scales, and the 60 item general health questionnaire. Of the 35 women treated with placebo 33 improved, giving an initial placebo response rate of 94%. The placebo effect gradually waned, but the response to the active combination was maintained for the duration of the study. Analysis of the prospective symptom ratings showed a significant superiority of oestradiol implants over placebo after two months for all six symptom clusters in the menstrual distress questionnaire. Changes seen in the retrospective assessments were less significant but the trend was the same. Treatment with oestradiol implants and cyclical progestogen was well tolerated and appears to be both rational and effective for severe cases of the premenstrual syndrome.

An inability to regulate ionic and metabolic homeostasis is related to a reduction in the developmental capacity of the embryo. The early embryo soon after fertilisation and up until compaction appears to have a reduced capacity to regulate its homeostasis. The reduced ability to regulate homeostasis, such as intracellular pH and calcium levels, by the precompaction-stage embryo appears to impact on the ability to regulate mitochondrial function and maintain adequate levels of energy production. This reduction in ATP production causes a cascade of events leading to disrupted cellular function and, perhaps ultimately, disrupted epigenetic regulation and aberrant placental and fetal development. In contrast, after compaction the embryo takes on a more somatic cell-like physiology and is better able to regulate its physiology and therefore appears less vulnerable to stress. Therefore, for human IVF it would seem important for the establishment of healthy pregnancies that the embryos are maintained in systems that are designed to minimise homeostatic stress, particularly for the cleavage-stage embryos, as exposure to stress is likely to culminate in impaired embryo function.

BACKGROUND: There is no validated assessment of an older person's risk of falling that is easily applied in primary care. We aimed to develop a two-part tool for use in primary care or the community. Part 1 includes a rapid assessment of the individual's risk of falling for administration by clinical or non-clinical staff. Part 2 (for clinical staff) includes guidance on further assessment, referral and interventions. We assessed the predictive validity of part 1. METHODS: The tool was developed by an expert panel following the updating of an existing systematic review of community-based prospective studies identifying risk factors for falling and modified in accordance with the feedback from extensive piloting. We assessed predictive validity by a questionnaire survey sent at baseline and 6 months to a random sample of 1000 people aged over 65 in one Primary Care Group area. RESULTS: Five items were included in part 1: history of any fall in the previous year, four or more prescribed medications, diagnosis of stroke or Parkinson's disease, reported problems with balance, inability to rise from a chair without using arms. The presence of three or more risk factors had a positive predictive value for a fall in the next 6 months of 0.57 (95 per cent confidence interval 0.43-0.69). Less than three risk factors had a negative predictive value of 0.86 (0.82-0.89), and a specificity of 0.92 (0.88-0.94). CONCLUSION: The tool may be useful for identifying people who would benefit from further assessment of their risk of falling and appropriate intervention.

An oral regimen of continuous conjugated equine estrogens (Premarin 0.625 or 1.25 mg daily) and low-dose progestogen (Norethisterone 0.35 to 2.1 mg daily) have been used to treat 95 nonhysterectomized postmenopausal women for up to 2.5 years. This method of hormone replacements was undertaken in an attempt to avoid the withdrawal bleeding and progestogenic side effects associated with conventional cyclical therapy with estrogen and progestogen, while simultaneously protecting the endometrium from estrogenic over-stimulation. With the lower dose of estrogen, amenorrhea was achieved immediately in 30 of 46 patients (65%), and after adjustments to the dose of the progestogen in all ten patients observed for at least one year (maximum 2.5 years). With the higher dose of estrogen, irregular spotting during the first three months resulted in the cessation of treatment by six of the 49 patients (12%), but 23 (47%) women had no bleeding during that time; by 15 months, all 13 patients who had remained in treatment had become amenorrheic (maximum 2.25 years). Endometrial biopsy specimens after six months of combined treatment in 56% of patients revealed atrophic histology regardless of the dose of the estrogen.