Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC experience.

AIM: Perihilar cholangiocarcinoma (PHC) is a challenging disease and requires aggressive surgical treatment in order to achieve curation. The assessment and work-up of patients with presumed PHC is multidisciplinary, complex and requires extensive experience. The aim of this paper is to review current aspects of diagnosis, preoperative work-up and extended resection in patients with PHC from the perspective of our own institutional experience with this complex tumor. METHODS: We provided a review of applied modalities in the diagnosis and work-up of PHC according to current literature. All patients with presumed PHC in our center between 2000 and 2016 were identified and described. The types of resection, surgical techniques and outcomes were analyzed. RESULTS AND CONCLUSION: Upcoming diagnostic modalities such as Spyglass and combinations of serum biomarkers and molecular markers have potential to decrease the rate of misdiagnosis of benign, inflammatory disease. Assessment of liver function with hepatobiliary scintigraphy provides better information on the future remnant liver (FRL) than volume alone. The selective use of staging laparoscopy is advisable to avoid futile laparotomies. In patients requiring extended resection, selective preoperative biliary drainage is mandatory in cholangitis and when FRL is small (< 50%). Preoperative portal vein embolization (PVE) is used when FRL volume is less than 40% and optionally includes the left portal vein branches to segment 4. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as alternative to PVE is not recommended in PHC. N2 positive lymph nodes preclude long-term survival. The benefit of unconditional en bloc resection of the portal vein bifurcation is uncertain. Along these lines, an aggressive surgical approach encompassing extended liver resection including segment 1, regional lymphadenectomy and conditional portal venous resection translates into favorable long-term survival.

The prostate cancer detection rates of CEUS-targeted versus MRI-targeted versus systematic TRUS-guided biopsies in biopsy-naïve men: a prospective, comparative clinical trial using the same patients.

BACKGROUND: The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10-12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these "blind" systematic biopsies with reliable imaging-based targeted biopsies. METHODS/DESIGN: In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols. DISCUSSION: This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantification. TRIAL REGISTRATION: The Dutch Central Committee on Research Involving Human Subjects registration number NL52851.018.15, registered on 3 Nov 2015. Clinicaltrials.gov database registration number NCT02831920 , retrospectively registered on 5 July 2016.

Unsuccessful TB treatment outcomes with a focus on HIV co-infected cases: a cross-sectional retrospective record review in a high-burdened province of South Africa.

BACKGROUND: South Africa did not meet the MDG targets to reduce TB prevalence and mortality by 50% by 2015, and the TB cure rate remains below the WHO target of 85%. TB incidence in the country is largely fuelled by the HIV epidemic, and co-infected patients are more likely to have unsuccessful TB treatment outcomes. This paper analyses the demographic and clinical characteristics of new TB patients with unsuccessful treatment outcomes, as well as factors associated with unsuccessful treatment outcomes for HIV co-infected patients. METHODS: A cross-sectional retrospective record review of routinely collected data for new TB cases registered in the Free State provincial electronic TB database between 2009 and 2012. The outcome variable, unsuccessful treatment, was defined as cases ≥15 years that 'died', 'failed' or 'defaulted' as the recorded treatment outcome. The data were subjected to descriptive and logistic regression analyses. RESULTS: From 2009 to 2012 there were 66,940 new TB cases among persons ≥15 years (with a recorded TB treatment outcome), of these 61% were co-infected with HIV. Unsuccessful TB treatment outcomes were recorded for 24.5% of co-infected cases and 15.3% of HIV-negative cases. In 2009, co-infected cases were 2.35 times more at risk for an unsuccessful TB treatment outcome (OR: 2.35; CI: 2.06-2.69); this figure decreased to 1.8 times by 2012 (OR: 1.80; CI: 1.63-1.99). Among the co-infected cases, main risk factors for unsuccessful treatment outcomes were: ≥ 65 years (AOR: 1.71; CI: 1.25-2.35); receiving treatment in healthcare facilities in District D (AOR: 1.15; CI 1.05-1.28); and taking CPT (and not ART) (AOR: 1.28; CI: 1.05-1.57). Females (AOR: 0.93; CI: 0.88-0.99) and cases with a CD4 count >350 (AOR: 0.40; CI: 0.36-0.44) were less likely to have an unsuccessful treatment outcome. CONCLUSIONS: The importance of TB-HIV/AIDS treatment integration is evident as co-infected patients on both ART and CPT, and those who have a higher CD4 count are less likely to have an unsuccessful TB treatment outcome. Furthermore, co-infected patients who require more programmatic attention are older people and males.

MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy.

OBJECTIVES: Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. METHODS: A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H&E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. RESULTS: Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. CONCLUSIONS: mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. KEY POINTS: • mpMRI and contrast-enhanced ultrasound are appropriate imaging modalities for assessing IRE effects • mpMRI and CEUS are the most feasible imaging modalities to visualize IRE ablation zone • The imaging is concordant with results of histopathological examination after IRE • Grey-scale US is insufficient for assessing IRE ablations.

All-PM coherent 2.05 µm Thulium/Holmium fiber frequency comb source at 100 MHz with up to 0.5 W average power and pulse duration down to 135 fs.

We report on a dual output all-PM fiber laser system running at 100 MHz repetition rate offering coherent broadband and narrowband pulses centered at 2.05 µm with a spectral FWHM bandwidth of 60 nm and 1.5 nm at up to 360 mW and 500 mW, respectively. The broadband pulses are compressed down to 135 fs. The multi-stage double-clad amplifier based on Tm/Ho codoping is seeded by a supercontinuum light source, spanning from around 1 µm up to 2.4 µm.

Comparison of two-dimensional measurement with three-dimensional volume rendering for the assessment of loss of domain in incisional hernia patients.

PURPOSE: We aimed to compare simple two-dimensional (2D) measurement with comprehensive three-dimensional (3D) volume rendering to determine loss of domain (LOD), a clinically important decision-making feature for incisional hernia repair. METHODS: In this single-center retrospective study, we analyzed the CT scans of a consecutive cohort of adult patients with a midline incisional hernia. The hernia sac- and abdominal cavity volumes were obtained by two different methods. The 2D method estimated the volumes using the corresponding height, width, and depth. The 3D method comprised of a volume rendering tool. For both methods, LOD was calculated according to the Sabbagh ratio (hernia sac volume / (hernia sac volume + abdominal cavity volume)). Taking the 3D method as the reference standard, the performance of the 2D method was expressed as positive predictive value (PPV) and negative predictive value (NPV) for LOD of more than- and less than 20%. The agreement between both methods was expressed as Cohen's kappa coefficient (kappa). RESULTS: We analyzed 92 CT scans. Agreement between both methods was high (kappa = 0.854, p = 0.0001); all 67 measurements for which the 2D method assessed LOD to be less than 20% were correctly classified (NPV = 100%), and 20 of 25 measurements for which the 2D method assessed LOD to be more than 20% were correctly classified (PPV = 80%). CONCLUSIONS: The 2D method can exclude patients from perioperative actions needed for a more complex hernia. Since this method is easy to use and less time-consuming, it seems useful for the routine radiological assessment of LOD in clinical practice.

Circulating markers of endothelial activation in canine parvoviral enteritis.

ABSTRACT: Canine parvovirus (CPV) is a common cause of enteritis, immune suppression and systemic inflammation in young dogs. Endothelial markers, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and molecules that upregulate their expression, such as high mobility group box 1 protein (HMGB-1), provide insight into the state of the endothelium during inflammation. This study aimed to determine if circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 were altered in CPV enteritis compared to healthy controls, and whether a correlation existed between these molecules and the degree of inflammation. Thirty dogs with naturally occurring CPV enteritis and ten control dogs were included. Physical examinations, complete blood count and C-reactive protein (CRP) measurements were performed on all dogs at presentation. The concentrations of ICAM-1, VCAM-1 and HMGB-1 were measured using commercially available canine-specific enzyme-linked immunosorbent assay (ELISA) kits. In dogs with CPV enteritis, ICAM-1 concentrations were significantly lower (median: 5.9 [IQR: 4.3-8.3]) and CRP higher (134 [IQR: 85-195]) compared to controls (8.0 [IQR: 6.9-10.3], p = 0.008; 1 [IQR: 0-7], p < 0.001). No significant difference was found for VCAM- 1 and HMGB-1. A strong correlation was identified between VCAM-1 and segmented neutrophil count (r = 0.612, p < 0.001). Despite the presence of systemic inflammation in CPV enteritis, evidenced by high CRP concentrations, our results suggest circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 failed to show an increase. Endothelial activation with subsequent leukocyte adhesion and transmigration through the endothelium may be affected in CPV enteritis and these findings require further investigation.

First Report of Aster Yellows Phytoplasma in Grapevines in South Africa.

For many years phytoplasma diseases have caused serious losses in most of the major grape-growing regions of the world, except South Africa, where a mixed phytoplasma infection was first reported in 2006 (1). During the early growing season of 2006, symptoms consistent with phytoplasma disease were observed in vineyards in the Olifants River Valley. Symptoms included yellowing of leaves, incomplete lignification of shoots, shortening of internodes, and the abortion of growth tips and immature bunches. Symptomatic shoots and leaves from grapevine cultivars (Merlot, Shiraz, Cabernet Sauvignon, Ruby Cabernet, Pinotage, Corinth, Chardonnay, Columbar, Chenin blanc, Sauvignon blanc, Sultana, and Regal) were collected during the early growing season (November) of 2006, 2007, and 2008. Total DNA was extracted from 32 of these samples (from single plants in the same vineyards over the 3 years) with the Invisorb Spin Plant Mini Kit (Invitek, Berlin, Germany) and tested by nested PCR using two universal primer pairs, P1/P7 and R16F2n/R16R2 (3). The first round of PCR of the 2006 samples yielded 1.8-kb fragments for 17 of the samples, while the nested PCR yielded an additional seven positive samples, confirming the necessity of nested PCR for reliable diagnosis. A similar trend was observed in the 2007 and 2008 PCR test results. All asymptomatic plants, which were included as negative controls, and water controls were negative by nested PCR. Twenty-four 1,245-bp amplicons, generated by nested PCR, were excised from gels, purified with a NucleoSpin Extract II Kit (Macherey-Nagel, Düren, Germany) and directly sequenced. Sequence data was compiled with the BioEdit Version 7.0.4.1 sequence alignment editor software (2), aligned using ClustalW Version 1.4 (4), and a consensus sequence was generated (GenBank Accession No. GQ365729). A BLAST search of the NCBI GenBank database using the individual sequences revealed high sequence identities (≥99%) with the aster yellows phytoplasma group (16SrI) and specifically with the subgroup 16SrI-B. In a comparison of the sequences of the 1.2-kb PCR fragments of 24 local samples with each other, sequence identities of ~99% were observed. These results clearly illustrate that all vines screened were infected with the same phytoplasma. Single nucleotide differences observed between different isolates may indicate the presence of closely related sequence variants of this phytoplasma. Aster yellows occurs worldwide and has been reported to infect grapevine-South Africa can now be added to this list. During the three seasons of our study, the area in which symptomatic vineyards were observed increased significantly, indicating spread by a biological vector. Moreover, infected vineyards were noticed in two other South African grape-growing regions. In contrast to the previous report, which reported a mixed infection of phytoplasmas of groups 16SrXII-A and 16SrII-B (1), PCR screening and sequencing of more than 40 individual samples from these areas confirmed these all to be infected with aster yellows phytoplasma only. To our knowledge, this is the first report of the detection and identification of an aster yellows phytoplasma causing grapevine yellows disease in South Africa. References: (1) S. Botti and A. Bertaccini. Plant Dis. 90:1360, 2006. (2) T. A. Hall. Nucleic Acids. Symp. Ser. 41:95, 1999. (3) I.-M. Lee et al. Phytopathology 83:834, 1993. (4) J. D. Thompson et al. Nucleic Acids Res. 22:4673, 1994.

Retrospective study on the incidence of Salmonella isolations in animals in South Africa, 1996 to 2006.

A retrospective study that involves the analysis of laboratory diagnostic data collected during the period 1996-2006 was conducted. A total of 3417 Salmonella isolations involving 183 different serotypes was recorded from 1999-2006, inclusive, at the Onderstepoort Veterinary Institute, Agricultural Research Council, South Africa. The most common serotypes were Salmonella enterica subspecies enterica serovar Typhimurium (917 incidents), Salmonella enterica subspecies enterica serovar Dublin (248 incidents), Salmonella enterica subspecies enterica serovar Enteritidis (232 incidents), Salmonella enterica subspecies enterica serovar Muenchen (164 incidents), Salmonella enterica subspecies enterica serovar Heidelberg (118 incidents) and Salmonella enterica subspecies enterica serovar Chester (113 incidents). The number of recorded Salmonella isolations over the period 1996 to 2006 varies considerably from year to year The peak of 693 isolations was recorded in 1997, and the lowest, 108 incidents, in 2001. Of the total incidents recorded during the period of survey, 2410 (70.5%) occurred in poultry and other birds, 641 (18.75%) occurred in cattle, 255 (7.46) in pigs and 111 (3.24%) in sheep. Despite the large number of serotypes isolated (183), 52 % of incidents were due to only 6 serotypes in decreasing order of prevalence: S. Typhimurium, S. Dublin, S. Enteritidis, S. Muenchen, S. Heidelberg and S. Chester. Serovar Typhimurium was the most common serotype and was detected in all animal species sampled, with, 65% (598) of the incidents occurring in poultry and 20% (187) occurring in cattle. Of the total of 248 incidents of S. Dublin serotype, 95.6% (237) of incidents occurred in cattle and of the 232 isolates of S. Enteritidis, 223 (96%) originated from poultry. Serovar Choleraesuis was identified in 16 isolates from pigs. The following 4 serotypes were each recorded in more than 50 incidents: S. Hadar (102), S. Schwarzengrund (99), S. Mbandaka (94) and S. Sandiego (73). The trends of annual incidence of Salmonella infection in cattle, sheep, pigs, poultry and other birds during the 11-year period and the distribution of the main serotypes in individual species of animals from 1996-2006 are discussed.

Iris yellow spot virus in Onion Seed Crops in South Africa.

In December 2006, symptoms typical of iris yellow spot caused by Iris yellow spot virus (IYSV; genus Tospovirus, family Bunyaviridae) were observed on scapes (seed stalks) in an onion (Allium cepa L.) seed crop in the Klein Karoo of the Western Cape Province, South Africa. Symptoms included diamond-shaped chlorotic or necrotic lesions on the scapes, some of which had 'green-islands' with nested diamond-shaped lesions, as well as indistinct, circular to irregular, chlorotic or necrotic lesions of various sizes. At the time symptoms were observed, approximately 5% of the scapes had lodged as a result of extensive lesions resembling those caused by IYSV. The crop was 2 to 3 weeks from harvest. Symptomatic tissue from two plants (two samples from one plant and four samples from the other plant) was tested for IYSV by reverse-transcriptase (RT)-PCR. Total RNA was extracted from symptomatic scape tissue with the SV Total RNA Isolation System (Promega, Madison, WI) according to the manufacturer's instructions. First strand cDNA was synthesized with the RevertAid H Minus First Strand cDNA Synthesis kit (Fermentas Inc., Hanover, MD), followed by PCR amplification with primers IYSV-For (TGG YGG AGA TGY RGA TGT GGT) and IYSV-Rev (ATT YTT GGG TTT AGA AGA CTC ACC), which amplify the nucleocapsid (NP) gene of IYSV. An amplicon of expected size (approximately 750 bp) was observed for each of the symptomatic plants assayed and was sequenced. Comparison of the sequence (GenBank Accession No. EF579801) with GenBank sequences revealed 95% sequence identity with the NP gene of IYSV GenBank Accession No. EF419888, with eight amino acid differences. The known geographic distribution of IYSV in onion bulb or seed crops has increased rapidly in recent years in many areas of the world (1). To our knowledge, this is the first confirmation of IYSV in South Africa. Approximately 6,100 ha of onion bulb crops are grown annually in South Africa in the Western Cape, Kwazulu Natal, Limpopo, and Northern Cape provinces, and 600 ha of onion seed crops are grown primarily in the semi-arid regions of the Western Cape. Examination of an additional 10 onion seed crops in the Klein Karoo during January 2007 revealed the presence of iris yellow spot in three more crops at approximately 5% incidence in each crop. The four symptomatic crops had all been planted as bulb-to-seed crops, using vernalized bulbs produced on the same farm. This suggests that IYSV may have been disseminated into the seed crops on the vernalized bulbs, either as infected bulb tissue or in viruliferous thrips on the bulbs. Reference: (1) D. H. Gent et al. Plant Dis. 90:1468, 2006.

Measuring HIV- and TB-related stigma among health care workers in South Africa: a validation and reliability study.

SETTING: Recent evidence indicates that human immunodeficiency virus (HIV) and tuberculosis (TB) related stigma act as a key barrier to the utilisation of associated occupational health services by South African health care workers (HCWs). It also highlights a dearth of appropriate tools to measure HIV and TB stigma among HCWs. OBJECTIVE: To test four scales measuring different aspects of stigma: respondent's external stigma (RES) and others' external stigma (OES) towards TB as well as HIV across different professional categories of HCWs. DESIGN: The current study employs data from a study on HIV and TB stigma among HCWs, a cluster randomised controlled trial for the collection of data among 882 HCWs in the Free State Province of South Africa. Confirmatory factor analyses and structural equation modelling were used to assess the validity and reliability of the scales. RESULTS: All four scales displayed adequate internal construct validity. Subsequent analysis demonstrated that all four scales were metric-invariant, and that the OES scales were even scalar-invariant across patient and support staff groups. The scales displayed good reliability and external construct validity. CONCLUSION: Our results support the use of the scales developed to measure TB and HIV stigma among HCWs. Further research is, however, needed to fine tune the instruments and test them across different resource-limited countries.

Stigma as a barrier to the use of occupational health units for tuberculosis services in South Africa.

SETTING: Tuberculosis (TB) is the leading cause of death in South Africa, and health care workers (HCWs) are disproportionally affected. The resulting absenteeism strains the already overburdened health system. Although hospital occupational health care units (OHUs) are cost-effective and of crucial importance in tackling the TB epidemic, the fear of being stigmatised by other colleagues might lead HCWs to avoid using OHUs. OBJECTIVE: To investigate whether the perception of TB stigma among colleagues has a negative effect on the willingness to use OHUs for TB services. DESIGN: In the Free State Province, South Africa, a representative sample of 804 HCWs from six hospitals were surveyed on workplace stigma as a predictor for the use of OHUs for TB services. Applying structural equation modelling, we also controlled for exogenous variables. RESULTS: There was a significant negative relationship between the perception of stigmatising attitudes and behaviours among co-workers and the use of OHUs for TB screening (ß -0.21, P = 0.000), treatment (ß -0.16, P = 0.001) and isoniazid preventive therapy (ß -0.17, P = 0.000). CONCLUSION: The negative effect of TB stigma on OHU use among HCWs can impact upon their health and increase hospital costs. This needs to be addressed by interventions combating TB stigma among HCWs in the workplace.

Infection control and tuberculosis in health care workers: an assessment of 28 hospitals in South Africa.

SETTING: Twenty-eight public hospitals in the Free State Province, South Africa. OBJECTIVE: To examine the association between tuberculosis (TB) infection control (IC) scores in Free State hospitals and the incidence of TB disease among health care workers (HCWs) in 2012. DESIGN: A cross-sectional survey and mixed-methods analysis of TB IC policies, practices and infrastructure using a comprehensive, 83-item IC audit and observation tool. RESULTS: As the total IC score increased, the probability of TB in an HCW at that hospital decreased. When adjusted for other covariates in multivariate analysis, if the total score of a hospital increased by one unit, the odds of an HCW having TB decreased by 4.9% (95%CI 0.9-8.8). Significant associations were also seen for the personal protective equipment (PPE) score, where odds decreased by 11.5% (95%CI 1.8-20.1) for each unit increase in score. Administrative score, environmental score and miscellaneous score were not statistically significant in the multivariate model. CONCLUSIONS: These findings reaffirm that overall IC and PPE are essential to protect HCWs from acquiring TB. More attention to TB IC is required to protect the health care workforce and to stop the South African TB epidemic.

Resonant nonlinearity in high-energy Er3+-fiber chirped-pulse-amplifiers.

We present experimental results, which show that the up-chirp of dispersively stretched femtosecond pulses decreases linearly with increasing pulse energy after amplification in Erbium-doped fibers. For 6 microJ output pulses a nonlinear dispersion of -410(6) fs(2) was measured. This nonlinear dispersive effect is attributable to the resonant dispersion of the Erbium-ions and the decrease of the inversion during pulse amplification and was about one order of magnitude larger than predicted by the literature. Most likely this deviation is attributable to the complex population dynamics of the Er3+-ions during pulse amplification, since in the literature the relation between the refractive index and Er3+-inversion was described for a quasi-static population distribution. Due to the high resonant dispersion the required compressor dispersion for minimum output pulse duration depends strongly on the output pulse energy in Erbium-doped fiber-based chirped-pulse-amplifier set-ups.

Prefrontal cortical hypometabolism during low-dose interferon alpha treatment.

OBJECTIVE: To evaluate prospectively interferon alpha (IFN-alpha) associated effects on cerebral glucose metabolism and its correlation to neuropsychiatric symptoms during low-dose IFN-alpha-treatment. METHODS: Eleven patients treated with low-dose IFN-alpha for chronic hepatitis C were prospectively evaluated by neuropsychiatric tests and cerebral [18F]deoxyglucose positron emission tomography (FDG-PET) before and in the 12th week of treatment. PET images were spatially normalized, corrected for variance in global activity and pixel-based t-statistics were calculated for each set of PET scans using SPM96 software. Pixel-cluster with P<0.001 for hypo- or hypermetabolism were displayed in parametric images. Covariance analysis with neuropsychiatric tests was calculated for each cluster. RESULTS: In week 12 of IFN-alpha treatment, significant hypometabolism with a decrease of local activity ranging from 8 to 12% was found in all patients bilaterally in the prefrontal cortex (BA 9), which correlated in a covariate analysis with changes in depression score as measured by Beck's Depression Inventory. Additionally, hypermetabolism with a maximum increase in local activity of 6-8% was seen in all patients in putamina as well as the left occipital region (BA 18). Before IFN-alpha treatment, only 1/11 patient showed depressive symptomatology. After 3 months of treatment, 6/11 patients were classified as having mild to moderate depressive symptoms (P<0.1; Wilcoxon test). CONCLUSIONS: Low-dose IFN-alpha therapy is associated with significant prefrontal hypometabolism. This hypometabolism covaried with depression score, but was even found in clinically non-depressed patients. These findings may reflect a possible predisposing factor for IFN-alpha associated neuropsychiatric syndromes and might contribute to a pathophysiological model of affective disorders, as endogenous IFN-alpha levels are elevated in a subset of psychotic patients during acute disease.

Escherichia coli serotypes in pigs in South Africa.

This retrospective study was based on 674 cases of colibacillosis in pigs submitted to the diagnostic bacteriology laboratory of the Onderstepoort Veterinary Institute (OVI) over the 20-year period ranging from 1971-1991. During this time, 28,840 cases from various livestock species were received, of which 4162 (14.4%) were from pigs. The 674 porcine cases selected for this study were included if an E. coli infection had been suspected by the referring veterinarian, and typable E. coli strains were then isolated by this laboratory. Enteritis (45.5%) and septicaemia (46.9%) were the most common syndromes, with agalactiae (1.4%) and abortion (1.1 %) representing a far lower prevalence. Oedema-disease signs were described by the submitting veterinarian in only 12 cases. Samples were received from weaners and sucklers in relatively equal numbers until 1981, but subsequently samples from sucklers declined, while those from weaners remained high. There were 69 different somatic and capsulated (OK) antigen groups associated with E. coli infections in pigs. Escherichia coli O149 was the most common isolate (45.8%), while E. coli O141 was the next most common isolate (18.3%). This was followed by O9 (8.9%), O20 (5.2%) and O8 (3.1%). All other serotypes together accounted for less than 20% of the total number of cases, and were isolated fewer than 20 times each. The fimbrial attachment factor, F4 (K88) was found associated with 46.9% of isolates.

Relation between macrophage migration inhibition and immunity to Brucella abortus in guinea-pigs.

Relation between macrophage migration inhibition and immunity to Brucella abortus in guinea-pigs. Onderstepoort Journal of Veterinary Research 43 (4), 175-184 (1976). A soluble protein antigen was prepared from Brucella melitensis Rev I with which macrophage migration inhibition (MMI) assays were successfully done using guinea-pig peritoneal exudate cells. By comparing the MMI, agglutinin response and immunity of groups and of individual guinea-pigs which had been immunized with either B. melitensis Rev I live vaccine or B. melitensis Rev I inactivated antigen, an association between the MMI and resistance to infection was demonstrated.

The serological and immunological relationship of type strains A and D of Pasteurella multocida to field isolates from sheep.

Investigations with antisera prepared in rabbits and sheep and active immunity experiments in mice showed that strains of Pasteurella multocida which, according to the haemagglutination test, are serologically related, do not necessarily give rise to cross immunity. Conversely, it was found that serologically unrelated strains may exhibit an appreciable degree of cross protection. The unreliability of the haemagglutination test as an indicator of immunological identity of strains was further confirmed in that peritoneal fluid from immunized mice showed passive protection properties despite the absence of haemagglutinating antibodies. There was no consistent agreement between the results obtained with antisera prepared in different species and active immunity experiments in mice, and this leads to the conclusion that different species probably vary quantitatively and qualitatively in their immune response to immunization with P. multocida. Attempts to determine whether combined bacterins afforded a better immunity than monovalent bacterins were inconclusive.

Resistance to various antibiotics of Salmonella and Escherichia coli isolated from registrable farm feeds.

Resistance to 20 antibiotics of 128 Salmonella and 97 Escherichia coli isolates from various registrable farm feeds was determined. A high frequency of comparatively low levels of resistance was found in both the Salmonella and E. coli isolates. This, together with an elevated frequency of multiple resistance, indicates that problems related to an effective transfer in bacterial populations of resistance to certain antibiotics are a distinct possibility. The addition of antibiotics, such as penicillin and tetracyclines, to animal feeds can create conditions for rapid selection amongst bacteria resistant to antibiotics. The numbers of resistant bacteria in the animal environment may be increased and may lead to the development of veterinary and human health problems from the possible transfer of antimicrobial resistance from animal pathogens to human pathogens or spreading in the human population of animal pathogens resistant to antibiotics. There is a need for caution in the use of antibiotics, particularly in animal feeds. Extended survey of, and epidemiological research on, farm feeds, manufacturing mills and animal production units are emphasized.

The implementation of the Choice on Termination of Pregnancy Act: some empirical findings.

The Choice on Termination of Pregnancy Act of 1996 substantially liberalised abortion law. Whilst a substantial number of terminations of pregnancies (TOPs) have already been performed in terms of the new Act, it has also surfaced that an array of factors of various kinds may impede its further implementation and operation. A study was undertaken to determine the nature and extent of any such impediments to the implementation of the Choice on Termination of Pregnancy Act. More specifically a survey was conducted amongst a sample of 75 women who had undergone a TOP since the implementation of the Act; health professionals and social workers who provide TOP services (n = 16); and health professionals and social workers who are in a position to refer women to TOP facilities (n = 63). Overall, the clients were well treated at the TOP facilities, and were satisfied with the service given to them. However, post-counselling and to a lesser extent pre-counselling, is lacking. Counselling is important as a considerable proportion of the clients suffered from emotional feelings usually associated with depression and/or self-reproach before and after the termination procedure. Furthermore these clients did not usually discuss their termination with family members. TOP service providers were dissatisfied with the TOP facilities, especially the insufficient number of consultation and counselling rooms. Health care workers in a position to refer clients to TOP facilities were not always willing to do so, thereby obstructing the referral system. In the main, it is recommended that the entire TOP procedure should be done at clinics/hospitals so that clients will not have to do inductions at home, more trained staff should be available, facilities should be adequate and accessible, and there should be psychological support for staff.