Background. Long-distance truck drivers are at risk of acquiring and transmitting HIV and have suboptimal access to care. New HIV prevention strategies using antiretroviral drugs to reduce transmission risk (early antiretroviral therapy (ART) at CD4 count >350 cells/μL) have shown efficacy in clinical trials. Demonstration projects are needed to evaluate “real world” programme effectiveness. We present the protocol for a demonstration study to evaluate the feasibility, acceptability, and cost of an early ART intervention for HIV-positive truck drivers along a transport corridor across South Africa, Zimbabwe, and Zambia, as part of an enhanced strategy to improve treatment adherence and retention in care. Methods and Analysis. This demonstration study would follow an observational cohort of truck drivers receiving early treatment. Our mixed methods approach includes quantitative, qualitative, and economic analyses. Key ethical and logistical issues are discussed (i.e., choice of drug regimen, recruitment of participants, and monitoring of adherence, behavioural changes, and adverse events). Conclusion. Questions specific to the design of tailored early ART programmes are amenable to operational research approaches but present substantial ethical and logistical challenges. Addressing these in demonstration projects can inform policy decisions regarding strategies to reduce health inequalities in access to HIV prevention and treatment programmes.
This review is designed to highlight several key challenges in the diagnosis of human epidermal growth factor receptor 2 (her2)–positive breast cancer currently faced by pathologists in Canada:
Pre-analysis issues affecting the accuracy of her2 testing in non-excision sample types: core-needle biopsies, effusion samples, fine-needle aspirates, and bone metastasesher2 testing of core-needle biopsies compared with surgical specimensCriteria for retesting her2 status upon disease recurrence
Literature searches for each topic were carried out using the medline, Embase, International Pharmaceutical Abstracts, and biosis databases. In addition, the congress databases of the American Society of Clinical Oncology (2005–2011) and the San Antonio Breast Cancer Symposium (2007–2011) were searched for relevant abstracts.
All authors are expert breast pathologists with extensive experience of her2 testing, and several participated in the development of Canadian her2 testing guidelines. For each topic, the authors present an evaluation of the current data available for the guidance of pathology practice, with recommendations for the optimization or improvement of her2 testing practice.
her2 testing; breast cancer; pathology
The goal of a safer vaginal environment could be reached by identifying harmful vaginal practices and an effective microbicide, thereby increasing options for HIV prevention
The potential spread of prion infectivity in secreta is a crucial concern for prion disease transmission. Here, serial protein misfolding cyclic amplification (sPMCA) allowed the detection of prions in milk from clinically affected animals as well as scrapie-exposed sheep at least 20 months before clinical onset of disease, irrespective of the immunohistochemical detection of protease-resistant PrPSc within lymphoreticular and central nervous system tissues. These data indicate the secretion of prions within milk during the early stages of disease progression and a role for milk in prion transmission. Furthermore, the application of sPMCA to milk samples offers a noninvasive methodology to detect scrapie during preclinical/subclinical disease.
Considerable evidence indicates that methyl farnesoate (MF) production by the crustacean mandibular organs is negatively regulated by neuropeptides from the sinus gland (SG) in the eyestalk. In the crab Cancer pagurus, two neuropeptides (MO-IH-1 and -2) have been isolated from the SG that inhibit MF synthesis by mandibular organs of female crabs in vitro. To test their activity in vivo, we treated eyestalk-ablated male crabs with SG extracts (SGEs) or MO-IH-1 and -2. SGEs reduced haemolymph levels of MF by 60-80%, while MO-IH-1 and -2 had little effect. Protease treatment of SGEs destroyed the in vivo activity, suggesting that the extract contains an additional peptide responsible for the in vivo activity. When separated by reversed-phase high performance liquid chromatography (HPLC), the in vivo activity eluted in fractions prior to MO-IH-1 and -2. When mandibular organs were removed from animals previously treated in vivo with these active fractions, they had reduced levels of MF synthesis and activity of farnesoic acid O-methyl transferase compared with mandibular organs from animals treated with saline. Together, these results indicate that the regulation of the crustacean mandibular organ is complex and may involve several SG compounds. Some of these compounds (i.e., MO-IH-1 and -2) act directly on the tissue while others affect the mandibular organ indirectly.
OBJECTIVES—To assess whether attendance at the site after an incident in a sewer was associated with symptoms in emergency personnel and whether the prevalence of symptoms was associated with estimated levels of exposure to any chemical hazard.
METHODS—Symptoms experienced by people attending an incident involving two dead sewer workers suggested the presence of a chemical hazard, before environmental sampling confirmed any toxic agent. Self reported symptoms, estimated exposures, and biomarkers of exposure for likely agents from all 254 people who attended the incident and a referent occupational group matching the 83 emergency personnel who went to the Accident and Emergency department (A and E) in the first 48 hours were recorded. The prevalence of symptoms and concentrations of creatine phosphokinase in serum of the 83 early patients at A and E were compared with their referent occupational group. In all workers who attended the incident, the trends in symptom prevalences and concentrations of creatine phosphokinase in serum were examined by distance from the site and predefined exposure category.
RESULTS—Among all workers who attended the incident, symptoms of shortness of breath and sore throat were significantly associated with indirect estimates of exposure but not associated with concentrations of creatine phosphokinase. Freon was detected in two blood samples. The early patients at A and E reported more symptoms than their matched reference group and their median concentrations of creatine phosphokinase were higher.
CONCLUSIONS—The association between symptoms and concentrations of creatine phosphokinase with attendance at the site indicated the presence of a continuing hazard at the site and led to extra precautions being taken. Comparison values from the referent occupational group prevented unnecessary medical follow up.
Keywords: pollution; chemical; population
Glomerular filtration rates (GFR) were estimated in 168 children (227 estimates) before treatment for haematological
malignancies with high dose, intravenous methotrexate. Clinical
management was altered on the basis of GFR in only two cases, both of
whom had tumour lysis syndrome. Routine estimations of GFR do not
contribute to management.
OBJECTIVES: To establish the prevalence of "dry sex" practice in a South African periurban population. To investigate the reasons for and factors influencing the practice of dry sex and to evaluate dry sex practice as a risk factor for sexually transmitted disease (STD). DESIGN: Cross sectional sample survey. METHODS: A random community sample of men and women aged between 16 and 35 in Gauteng Province, South Africa, were interviewed regarding the practice of dry sex using a structured interviewer administered questionnaire. RESULTS: Dry sex practices were reported by 60% of men and 46% of women. Among younger individuals dry sex practice is far more common among the less educated, but there was no significant difference between education groups in the older respondents. A higher proportion of men practising dry sex than not practising dry sex reported having a past history of STD infection (56% versus 41%) although this difference was only marginally significant (p = 0.05). There was no difference in reported history of STD between women who practised dry sex and those who did not. CONCLUSIONS: This study shows that dry sex practice is common in this community. The younger less educated group were the most likely to practise dry sex. Dry sex practice was associated with an increased prevalence of self reported STDs in men but not in women.
Ixodid (hard) ticks are blood-feeding arthropods that require a blood meal to complete each stage of development. However, the hormonal events coordinating aspects of feeding and development are only poorly understood. We have delineated a new neuropeptide-endocrine interaction in the adult tick, Amblyomma hebraeum, that stimulates the synthesis of the moulting hormones, the ecdysteroids. In adult female ticks, ecdysteroid synthesis could be demonstrated in integumental tissue incubated in vitro with a synganglial (central nervous system) extract, but not in its absence. Stimulation by the synganglial extract is both time- and dose-dependent, but is completely abolished by trypsin treatment, suggesting that the activity is due to a peptide/protein. Integumental tissue ecdysteroidogenesis is also stimulated by elevation of the cAMP concentration using forskolin and 3-isobutyl-l-methyl-xanthine, or by 8-bromo-cAMP. This suggests the involvement of at least a cAMP second messenger system in the neuropeptide-ecdysteroidogenesis axis, without precluding a role for other second messengers as well. Despite involving a quite different steroidogenic tissue, the foregoing system has some parallels with the known prothoracicotropic hormone (neuropeptide)-prothoracic gland endocrine axis of insects.
OBJECTIVES: To measure the exposure of a group of farmers to organophosphate pesticide in sheep dip, and to record the incidence of symptoms after exposure. DESIGN: A prospective study of the autumn 1992 dipping period. Working methods were assessed by questionnaire. Absorption of organophosphate pesticide was estimated before, immediately after, and six weeks after dipping by measuring plasma cholinesterase, erythrocyte cholinesterase, and dialkylphosphate urinary metabolites of organophosphates. Symptoms were recorded by questionnaire at the same time as biological monitoring. Possible confounding factors were identified by medical examination of the subjects. SETTING: Three community council electoral wards in Powys, typical of hill sheep farming areas in Wales. SUBJECTS: All (38) men engaged in sheep dipping living in the three community council electoral wards. RESULTS: 23 sheep farmers and one dipping contractor completed the study--a response rate of 63%. A sample of seven men who refused to enter the full study had similar working practices to the 24 subjects. Subjects reported inadequate handling precautions, and significant skin contamination with dip. Two men reported under diluting dip concentrate for use. Both had significant depression of erythrocyte cholinesterase after dipping. This indicated some absorption of organophosphate pesticide--but this did not reach levels usually associated with toxicity. It was not clear whether the symptoms of these two mens were caused by organophosphate exposure. Measurement of dialkylphosphate urinary metabolites in a single specimen of urine voided shortly after the end of dipping could not be correlated with individual exposure. CONCLUSIONS: Sheep dipping is strenuous and dirty work and sheep farmers find it difficult to wear personal protective equipment and avoid skin contamination with dip. In this limited study, farmers did not seem to have significant organophosphate toxicity, despite using inadequate handling precautions.
Complete trisomy 22, with or without mosaicism, has been reported as a distinct syndrome. In this report an infant is described who was externally male but with female rudimentary internal organs and whose karyotype was 47,XX+22.
Patients with hypergastrinaemic duodenal ulcer disease were studied to determine whether chronic moderate hypergastrinaemia produces hyperplasia of gastric enterochromaffin-like cells in man. Eight patients had peak postprandial plasma gastrin concentrations greater than 200 pmol/l, which is the 92nd percentile for patients with duodenal ulcer disease in this laboratory. The control group was eight patients with duodenal ulcers whose peak postprandial gastrin concentrations were less than 200 pmol/l. Basal and peak postprandial plasma gastrin concentrations were 107 (37) and 306 (66) pmol/l (mean (SEM] respectively in the hypergastrinaemic patients compared with 26 (4) and 137 (14) pmol/l respectively in the controls. There was no significant difference in the density of gastrin enterochromaffin-like cells between the two groups. The number of enterochromaffin-like cells per high power field was 53 (8) in the hypergastrinaemic patients compared with 50 (8) in the controls. We conclude that chronic moderate hypergastrinaemia does not produce hyperplasia of enterochromaffin-like cells in man. Our hypergastrinaemic group had plasma gastrin concentrations similar to, or greater than those reported during treatment with drugs such as omeprazole and histamine H2 receptor blockers.
The investigation and treatment of 131 patients with 'obscure' gastrointestinal bleeding has been reviewed. One hundred and six patients were assessed electively for recurrent haemorrhage, 25 presented as emergencies. The major presenting feature was melaena (55 patients), anaemia (35), rectal bleeding (34), haematemesis (six) and ileostomy bleeding (one). The lesions responsible for haemorrhage were colonic angiodysplasia (52 patients), small bowel vascular anomalies (16), Meckel's diverticula (nine), small bowel smooth muscle tumours (seven), gastric vascular anomalies (four), chronic pancreatitis (three), colonic diverticular disease (three) and 16 other miscellaneous lesions. No lesion was found in 21 cases. Lesions were first shown by visceral angiography (69 patients), at laparotomy (23), on endoscopy (11), on gastrointestinal contrast radiological studies (four), and at ERCP (three). Lesions which were undetectable at operation increased markedly with age (p less than 0.0001). Expert visceral angiography is strongly recommended before surgery in patients over 45 years of age and after laparotomy when no cause has been found. Exploratory laparotomy is recommended at an early stage for younger patients, and for older patients after non-diagnostic angiography.
The results of selective visceral angiography and colonoscopy were compared in the diagnosis of angiodysplasia of the large bowel. Fifty six patients were diagnosed as having angiodysplasia on angiography and 34 of these patients also underwent colonoscopy. Twenty three of the colonoscopies were positive giving a diagnostic yield of 68%. Three colonoscopies were negative and eight were incomplete. Colonoscopy was useful in the diagnosis of concomitant disease and also provided the clinician with the therapeutic possibility of electrocoagulation. Colonoscopy at operation proved to be a valuable technique in assessing the extent of angiodysplasia prior to resection.
Indium leucocyte scanning and measurement of faecal Indium leucocyte excretion are techniques which have recently been introduced for assessing patients with inflammatory bowel disease. The methodology has recently been made more specific for acute inflammation by labelling pure granulocytes rather than the mixed leucocyte preparation. To determine the accuracy of this modified technique in detecting inflammatory bowel disease, we have prospectively compared Indium granulocyte scanning and faecal In granulocyte excretion with rectal histology and contrast bowel radiology as screening procedures in 100 patients with suspected inflammatory bowel disease. Thirty three patients were shown to have inflammatory bowel disease - 24 with Crohn's disease and nine with ulcerative colitis or indeterminate colitis. Overall the respective sensitivities for detecting inflammatory bowel disease were 97% for faecal Indium granulocyte excretion, 94% for Indium granulocyte scanning, 79% for radiology and 70% for rectal histology. The superiority of In granulocytes over radiology and rectal histology in detecting inflammatory bowel disease was, in the main, due to the difficulty in diagnosing Crohn's with conventional techniques. Although three of the patients with ulcerative colitis and indeterminate colitis had normal sigmoidoscopic appearances - all had abnormal rectal histology. No patient with a non-inflammatory bowel disorder had a positive In granulocyte scan or a raised faecal excretion. These results show that investigations using In granulocytes are accurate in identifying inflammatory bowel disease and offer important advantages over conventional procedures for detecting Crohn's disease.
The records of 37 patients investigated for obscure gastrointestinal haemorrhage originating from the small bowel were reviewed retrospectively. Bleeding was caused by Meckel's diverticula in eight cases, smooth muscle tumours in seven cases, vascular anomalies in 14 cases, and other single lesions in eight cases. The lesions were identified by angiography in 18 patients, operation in 17, and barium follow through examination in two. Only one patient under 50 years of age had a lesion that would not have been found by careful laparotomy. Early laparotomy is advisable in patients aged under 50 with obscure gastrointestinal bleeding; expert selective angiography is recommended before operation in patients aged over 50 and those who have already undergone a laparotomy yielding negative results.
Two cases are described who developed epileptic seizures whilst taking maprotiline hydrochloride in therapeutic dosage. In both cases the electroencephalogram was normal and the fits stopped on withdrawal of the drug.