Significant decline in lymphatic filariasis associated with nationwide scale-up of insecticide-treated nets in Zambia.

Lymphatic filariasis (LF) is a mosquito-borne disease, broadly endemic in Zambia, and is targeted for elimination by mass drug administration (MDA) of albendazole and diethylcarbamazine citrate (DEC) to at-risk populations. Anopheline mosquitoes are primary vectors of LF in Africa, and it is possible that the significant scale-up of malaria vector control over the past decade may have also impacted LF transmission, and contributed to a decrease in prevalence in Zambia. We therefore aimed to examine the putative association between decreasing LF prevalence and increasing coverage of insecticide-treated mosquito nets (ITNs) for malaria vector control, by comparing LF mapping data collected between 2003-2005 and 2009-2011 to LF sentinel site prevalence data collected between 2012 and 2014, before any anti-LF MDA was started. The coverage of ITNs for malaria was quantified and compared for each site in relation to the dynamics of LF. We found a significant decrease in LF prevalence from the years 2003-2005 (11.5% CI95 6.6; 16.4) to 2012-2014 (0.6% CI95 0.03; 1.1); at the same time, there was a significant scale-up of ITNs across the country from 0.2% (CI95 0.0; 0.3) to 76.1% (CI95 71.4; 80.7) respectively. The creation and comparison of two linear models demonstrated that the geographical and temporal variation in ITN coverage was a better predictor of LF prevalence than year alone. Whilst a causal relationship between LF prevalence and ITN coverage cannot be proved, we propose that the scale-up of ITNs has helped to control Anopheles mosquito populations, which have in turn impacted on LF transmission significantly before the scale-up of MDA. This putative synergy with vector control has helped to put Zambia on track to meet national and global goals of LF elimination by 2020.

Health informatics education and capacity building in Eastern Cape Province, South Africa.

OBJECTIVES: To describe the experience of, and lessons learned from, a collaborative project developing and delivering an MSc in Health Informatics in South Africa. METHODS: The description and discussion is based on the experiences of the staff delivering the course, and formal and informal evaluations, the former conducted as part of the University of Winchester's quality assurance processes. RESULTS: Some of the lessons learned from adapting the course to meet local needs are described and discussed. CONCLUSIONS: Simply attempting to transpose a successful course from one country and culture to another is not a guarantee of success. Educational staff delivering such courses need to take account of local context and culture, be flexible and prepared to adapt to students' needs and circumstances, which may be beyond anyone's control. However, by meeting real identified needs, success can contribute to sustaining capacity building and the development of the local health informatics workforce.

Total shoulder replacement in rheumatoid disease: a 16- to 23-year follow-up.

We describe the longer term clinical and radiological findings in a prospectively followed series of 49 rheumatoid patients (58 shoulders) who had undergone Neer II total shoulder replacement. The early and intermediate results have been published previously. At a mean follow-up of 19.8 years (16.5 to 23.8) 14 shoulders survived. Proximal migration of the humeral component was associated with progressive loosening of the glenoid and humeral components, but was independent of the state of the rotator cuff at the time of operation. Despite these changes the range of movement was preserved. Most patients had little or no pain in the shoulder, could sleep undisturbed and could attend to personal hygiene and grooming.

Towards new copper based radiopharmaceuticals.

This paper reviews the research in progress in Oxford on the chemical, spectroscopic and redox properties of bis(thiosemicarbazonato) complexes of zinc and copper in the context of the hypoxia selectivity of the copper(II) complex. Also, covered are synthetic strategies for modified complexes with a range of functional substituents and the in vitro and in vivo characteristics of two of these derivatives are described. Finally, the synthesis of some new bifunctional macrocyclic ligands is described and some of these give Cu(II) derivatives which cannot be reduced and are therefore resistant to reductive loss of copper in vivo.

Bioinformatic and biochemical evidence for the identification of the type III secretion system needle protein of Chlamydia trachomatis.

Chlamydia spp. express a functional type III secretion system (T3SS) necessary for pathogenesis and intracellular growth. However, certain essential components of the secretion apparatus have diverged to such a degree as to preclude their identification by standard homology searches of primary protein sequences. One example is the needle subunit protein. Electron micrographs indicate that chlamydiae possess needle filaments, and yet database searches fail to identify a SctF homologue. We used a bioinformatics approach to identify a likely needle subunit protein for Chlamydia. Experimental evidence indicates that this protein, designated CdsF, has properties consistent with it being the major needle subunit protein. CdsF is concentrated in the outer membrane of elementary bodies and is surface exposed as a component of an extracellular needle-like projection. During infection CdsF is detectable by indirect immunofluorescence in the inclusion membrane with a punctuate distribution adjacent to membrane-associated reticulate bodies. Biochemical cross-linking studies revealed that, like other SctF proteins, CdsF is able to polymerize into multisubunit complexes. Furthermore, we identified two chaperones for CdsF, termed CdsE and CdsG, which have many characteristics of the Pseudomonas spp. needle chaperones PscE and PscG, respectively. In aggregate, our data are consistent with CdsF representing at least one component of the extended Chlamydia T3SS injectisome. The identification of this secretion system component is essential for studies involving ectopic reconstitution of the Chlamydia T3SS. Moreover, we anticipate that CdsF could serve as an efficacious target for anti-Chlamydia neutralizing antibodies.

Haplotypic diversity in human CEACAM genes: effects on susceptibility to meningococcal disease.

Adhesion between the opacity-associated adhesin (Opa) proteins of Neisseria meningitidis and human carcino-embryonic antigen cell adhesion molecule (CEACAM) proteins is an important stage in the pathogenesis of meningococcal disease, a globally important bacterial infection. Most disease is caused by a small number of meningococcal genotypes known as hyperinvasive lineages. As these are also carried asymptomatically, acquisition of them alone cannot explain why only some hosts develop meningococcal disease. Our aim was to determine whether genetic diversity in CEACAM is associated with susceptibility to meningococcal disease. Frequency distributions of alleles, genotypes and haplotypes were compared in four CEACAM genes in 384 case samples and 190 controls. Linkage disequilibrium among polymorphic sites, haplotype structures and relationships were also analysed. A number of polymorphisms were observed in CEACAM genes but the diversity of CEACAM1, to which most Opa proteins bind, was lower, and a small number of high-frequency haplotypes were detected. Dose-dependent associations of three CEACAM haplotypes with meningococcal disease were observed, with the effect of carrying these haplotypes amplified in homozygous individuals. Two haplotypes were protective while one haplotype in CEACAM6 was associated with a twofold increase in disease susceptibility. These data imply that human CEACAM may be one determinant of human susceptibility to meningococcal disease.

Treatment of Chlamydia trachomatis with a small molecule inhibitor of the Yersinia type III secretion system disrupts progression of the chlamydial developmental cycle.

The obligate intracellular bacterium Chlamydia trachomatis possesses a biphasic developmental cycle that is manifested by differentiation of infectious, metabolically inert elementary bodies (EBs) to larger, metabolically active reticulate bodies (RBs). The cycle is completed by asynchronous differentiation of dividing RBs back to a population of dormant EBs that can initiate further rounds of infection upon lysis of the host cell. Chlamydiae express a type III secretion system (T3SS) that is presumably employed to establish and maintain the permissive intracellular niche by secretion of anti-host proteins. We hypothesize that T3SS activity is essential for chlamydial development and pathogenesis. However, the lack of a genetic system has confounded efforts to establish any role of the T3SS. We therefore employed the small molecule Yersinia T3SS inhibitor N'-(3,5-dibromo-2-hydroxybenzylidene)-4-nitrobenzohydrazide, designated compound 1 (C1), to examine the interdependence of the chlamydial T3SS and development. C1 treatment inhibited C. trachomatis but not T4SS-expressing Coxiella burnetii development in a dose-dependent manner. Although chlamydiae remained viable and metabolically active, they failed to divide significantly and RB to EB differentiation was inhibited. These effects occurred in the absence of host cell cytotoxicity and were reversible by washing out C1. We further demonstrate that secretion of T3S substrates is perturbed in C1-treated chlamydial cultures. We have therefore provided evidence that C1 can inhibit C. trachomatis development and T3SS activity and present a model in which progression of the C. trachomatis developmental cycle requires a fully functional T3SS.

A note on a phrase in Shakespeare's play King Lear: 'a plague upon your epileptic visage'.

In Shakespeare's play King Lear the word 'epileptic' appears (used in a derogatory manner). This is held to be the first appearance of the word in the English language (although we have found earlier English references to the word which Shakespeare may have read). Textual analysis of the lines following the use of 'epileptic' suggests that it is actually a reference to the pock-marks of syphilis, endemic in Elizabethan England, and is not actually a reference to epilepsy itself.

John Hall and his epileptic patients--epilepsy management in early 17th century England.

John Hall, a physician, practised in Stratford in the early 17th century and was the son-in-law of William Shakespeare. During his career he kept records of his patients (in Latin) which he may have been preparing for publication when he died. Despite his instruction for them to be destroyed some were later translated into English and published by another physician. The case records were popular and have recently been reprinted with a commentaryl. We have searched the case records for descriptions of epilepsy and examined the treatments offered (and the attitudes to) this condition in early 17th century England. Treatment consisted of standard remedies ('fumes' of hartshorn and extracts of peony) related to the Galenic system of medicine, plus individual remedies. Interestingly, there is no evidence that the condition was stigmatized.

Benefits realisation in maternity information systems.

This paper describes the compilation of a monograph on benefits realisation of maternity information systems from maternity services around England and Wales. It was compiled to compliment a monograph produced in June 1995 on Nursing Information Systems. The paper summarises the structure of the monograph and outlines the concept of benefits realisation. The examples featured in the monograph are not "true" benefits realisation studies and many of the accounts are anecdotal in nature. However, the paper suggests that midwives do benefit from using a maternity information system particularly in the areas of auditing practice, effortless retrieval of statistics, less duplication of data entry, summaries of care and research purposes. Managers also benefit from some of these functions and those relating to estimating workload and allocation of resources. It is suggested that any benefits for staff and management should also benefit clients and improve the provision of the maternity services.

Regulatory circuits involved with pH-regulated gene expression in Salmonella typhimurium.

Salmonella typhimurium encounters a variety of acid conditions during both its natural and pathogenic existence. The ability of this organism to respond transcriptionally to low pH is an area of active interest but little knowledge. As part of an ongoing investigation of low-pH adaptation, 18 pH-controlled lacZ operon fusions in Salmonella typhimurium have been identified (15 in this study) and categorized into at least 11 different loci. They include iroA (at 57 min), aciA (99 min), aciB (90-93 min), aciD (ompC, 45 min), aciJ, aciK (33-36 min), aniC (93 min), anil (33-36 min), hyd (59 min), cadA (54 min) and aniG (63 min). All but two were induced by low pH. One of the exceptions, the iron-regulated iroA locus, was induced at high pH. The unusual aciA locus was induced by low pH under semiaerobic conditions but high pH under aerobic conditions. Most of the other aci genes were expressed best under anaerobic conditions. Many of these genes exhibited strict co-inducer requirements for small molecules to be expressed in minimal medium. These included iron for iroA, tyrosine for aniC, I and aciK, mannose for aniG, formate for hyd, lysine for cadA, and unknown components of complex medium for aciA, aciB and aciD. Six regulatory circuits were revealed involving at least five regulatory loci (fur, oxrG, earAB, earC and ompR). As part of the adaptive response to low pH, S. typhimurium will induce an acid protection system called the acid tolerance response (ATR). As has been shown for fur mutations, the oxrG regulatory mutation interfered with the normal induction of this system.

Galactorrhea: a complication of spinal cord injury.

Galactorrhea, a secretion of milk or milk-like products from the breast in the absence of parturition, has been reported to occur in women with spinal cord injuries in association with amenorrhea and hyperprolactinemia. Four cases of galactorrhea in association with spinal cord injury are reported. Galactorrhea developed in four spinal cord injured women who had thoracic paraplegia. The onset of galactorrhea was from one month to five months after injury. Although the onset of galactorrhea may have been related to prescribed medications in all four cases, insufficient data exist to draw conclusions. The three women whose galactorrhea persisted declined treatment and galactorrhea continuing for more than two years in one instance. We conclude that galactorrhea with or without amenorrhea may develop after a spinal cord injury and that spinal cord injured women may have an enhanced sensitivity to medication-induced galactorrhea.

Classification of pressure ulcers.

Several systems exist for classifying pressure ulcers, though none of them have been evaluated for interrater reliability. A new grading scale was compared with the commonly used Shea classification. This new scale was developed to provide a more complete description of pressure ulcer healing. The advantages of this scale include a classification of red areas as ulcers to help prevent further deterioration and classification of healed sores to note potential problems. The Yarkony-Kirk scale classifies a red area as a grade 1 ulcer, and involvement of the epidermis and dermis with no subcutaneous fat observed as a grade 2 ulcer. Grade 3 indicates exposed subcutaneous fat with no muscle observed. Exposed muscle without bone involvement is classified as a grade 4 ulcer, and grade 5 describes exposed bone with no joint space involvement. Grade 6 indicates joint space involvement. There is a classification of pressure sore healed to indicate a healed pressure ulcer. Interrater reliability was assessed by two nurses. In spite of an increased number of categories for the Yarkony-Kirk scale, there was no decline in reliability. Reliability was excellent with an interrater correlation of 0.90 for the Yarkony-Kirk scale and 0.86 for the Shea classification when measured for 72 patients. Eighty-five percent of the ratings for the Yarkony-Kirk scale were identical, whereas only 68% were identical for the Shea classification. Three percent of the ratings for the Shea classification were greater than +/- 1 category; 6% of the ratings for the Yarkony-Kirk scale were greater than +/- 1 category. This scale appears to possess good reliability and to describe pressure ulcers more completely. This scale may also be used to teach prevention activities as well as ulcer classification.

Spinal cord injury care system: fifteen-year experience at the Rehabilitation Institute of Chicago.

A statistical study of 15 years of the spinal cord injury care system of the Rehabilitation Institute of Chicago is reported. The Rehabilitation Institute of Chicago (RIC) is the rehabilitation component of the Midwest Regional Spinal Cord Injury Care System, a collaborative programme with Northwestern Memorial Hospital and Northwestern University. Data are reported on 1382 patients, a representative sample of the over 2000 patients treated since the inception of the centre. The sample was predominantly male (83%, N = 1147) and caucasian (64%, N = 888). The most common aetiology was motor vehicle accidents (36%, N = 505). During the 15-year period there were significant decreases in both acute and rehabilitation lengths of stay. Ninety three per cent of the patients were discharged home. Rehabilitation benefits were demonstrated by improvements in the Modified Barthel Index. The research, educational and clinical programmes are described.

Risk factors for heterotopic ossification in spinal cord injury.

Heterotopic ossification (HO) is a complication in 16% to 53% of spinal cord injured (SCI) patients. One third of these patients have moderate to severe HO that adversely affects function or health. Pharmacologic prophylaxis of HO for all SCI patients continues to be controversial. High-risk criteria for HO formation identified in total hip replacement patients are not applicable to SCI. A review of the literature did not reveal specific risk factors for HO with SCI. The charts of 100 randomly selected SCI patients, 50 with HO and 50 without HO, were reviewed retrospectively to learn if criteria which would predict high-risk patients could be identified. A total of 14 variables, seven demographic (age, sex, race, level of lesion, completeness of lesion, cause of injury, and geographic locus of patient) and seven medical (bladder stones, fractures, pressure sores, deep vein thrombosis, pulmonary embolism, spasticity, and urinary tract infections) were studied. Four of the 14 variables (age, completeness of lesion, presence of pressure sores, and spasticity) were significantly related to HO formation. The risk factors appear to be additive. When all were present, 92% of patients were found to have HO. Before the findings are applied clinically, it is suggested that a prospective study be conducted to confirm the risk predictive value of these factors in HO.

Prospective payment for acute care: impact on rehabilitation hospitals.

This study assessed rehabilitation workers' perceptions of acute care Medicare prospective payment effects on rehabilitation hospitals and units. Members of four groups--physicians, nurses, social workers, and administrators--were asked to complete a survey of prospective payment effects. All survey participants worked at one of the 373 DRG-exempt rehabilitation hospitals in 46 states that have similar prospective payment systems. A total of 761 persons (60% of the eligible sample) responded with complete answers. Across all groups, respondents reported increases in the frequency of acute illness, as well as increases in complications and readmission into acute care. An increase in the number of referrals for inpatient rehabilitation was also reported, although only minimal changes in the length of rehabilitation stay were perceived. Individuals at rehabilitation hospitals perceived a greater increase in complication and readmission rate and acute illness, whereas individuals at rehabilitation units perceived a greater increase in referrals. Differences among members of the four disciplines were small, with social workers reporting the largest increase in complications and readmission to acute care hospitals, as well as in referrals for inpatient rehabilitation. Implications of these findings for rehabilitation hospitals and units are discussed.

Multivariate analysis of improvement and outcome following stroke rehabilitation.

This study documented the status of 432 patients and characteristics of functional improvements and outcomes achieved by 163 patients who participated in comprehensive stroke rehabilitation. Scores on the 100-point Activities of Daily Living Index improved from hospital admission to discharge and declined slightly at follow-up. An average Activities of Daily Living Index point gain of 0.6 per day was found that was unrelated to age, sex, side of hemiparesis, or admission functional status. Seventy-nine percent of the patients were discharged home; 85% were home at follow-up. Eleven percent of the patients were working at follow-up. Patients traveled outside their homes an average of 24.6 days during the three months immediately following discharge. A significant number of patients achieved favorable functional housing, employment, and social outcomes. This study supported referral for rehabilitation services regardless of age, side of hemiparesis, or degree of impairment.