Mixed pyogenic and tuberculous spinal epidural abscesses perforating the dura and extending into the subdural space: A case report and review of the literature.

Background: Spinal infections are associated with a wide variety of clinical conditions, including osteomyelitis, spondylitis, diskitis, septic facet joints, and abscesses. Based on its anatomical relationship with the dura mater, the abscess can be epidural (extradural) or subdural (intrathecal). Subdural intramedullary abscesses of the lumbar spinal canal are more common than subdural extramedullary abscesses. Here, we present a rare case of a patient with a mixed pyogenic and tuberculous epidural abscess in the lumbar spine, which perforated the dura and extended to the subdural space. Case Description: A 29-year-old male presented with progressively worsening back pain and lower-limb weakness over a period of 3 months, with an associated inability to walk, intermittent radicular pain primarily on the left side, intermittent incontinence, and a history of low-grade fever and night sweats. The patient had a history of intravenous (IV) drug abuse and reported practicing unprotected sexual intercourse. Furthermore, the patient had recently came into contact with a person diagnosed with tuberculosis (TB). The patient was administered empirical broad-spectrum antibiotics and underwent emergent L4-L5 laminectomy and spinal abscess decompression. IV antibiotics were selected based on culture results, and anti-TB medications were started. Postoperatively, the patient demonstrated a remarkable lower-limb power improvement and radicular pain alleviation. Conclusion: Spinal epidural abscess perforation of the dura and extension into the subdural space is extremely rare. Distinguishing between epidural and subdural abscesses radiologically is challenging. Multiple risk factors, such as unprotected sexual contact and IV drug misuse, may be associated with the development of polymicrobial abscesses in the lumbar spine. Careful anticipation, identification, and isolation of the causative micro-organisms can ensure effective antibacterial treatment. Early diagnosis, expeditious surgical decompression, and antibiotic treatment are associated with promising outcomes.

Brucellosis: epidemiology, pathogenesis, diagnosis and treatment-a comprehensive review.

Background: Brucellosis is a pervasive zoonotic disease caused by various Brucella species. It mainly affects livestock and wildlife and poses significant public health threats, especially in regions with suboptimal hygiene, food safety, and veterinary care standards. Human contractions occur by consuming contaminated animal products or interacting with infected animals. Objective: This study aims to provide an updated understanding of brucellosis, from its epidemiology and pathogenesis to diagnosis and treatment strategies. It emphasizes the importance of ongoing research, knowledge exchange, and interdisciplinary collaboration for effective disease control and prevention, highlighting its global health implications. Methods: Pathogenesis involves intricate interactions between bacteria and the host immune system, resulting in chronic infections characterized by diverse clinical manifestations. The diagnostic process is arduous owing to non-specific symptomatology and sampling challenges, necessitating a fusion of clinical and laboratory evaluations, including blood cultures, serological assays, and molecular methods. Management typically entails multiple antibiotics, although the rise in antibiotic-resistant Brucella strains poses a problem. Animal vaccination is a potential strategy to curb the spread of infection, particularly within livestock populations. Results: The study provides insights into the complex pathogenesis of brucellosis, the challenges in its diagnosis, and the management strategies involving antibiotic therapy and animal vaccination. It also highlights the emerging issue of antibiotic-resistant Brucella strains. Conclusions: In conclusion, brucellosis is a significant zoonotic disease with implications for public health. Efforts should be directed towards improved diagnostic methods, antibiotic stewardship to combat antibiotic resistance, and developing and implementing effective animal vaccination programs. Interdisciplinary collaboration and ongoing research are crucial for addressing the global health implications of brucellosis.

Current state of career placement and employment opportunities for Doctor of Pharmacy graduates: A cross-sectional analysis from a college of pharmacy, Saudi Arabia.

Background: Traditionally, graduates from colleges of pharmacy in Saudi Arabia work mainly in hospital settings, and only a few graduates work in other practice settings. However, several initiatives and national plans have recently been introduced to facilitate employment in community pharmacies and the pharmaceutical industry/companies. Consequently, the objectives of this study were to explore the current state of career placement, type of employment sectors, and practice settings that Doctor of Pharmacy (PharmD) graduates join based on recent developments in the profession. Methods: This study is a cross-sectional, descriptive study. The target population was PharmD graduates from Unaizah College of Pharmacy, Qassim University, Saudi Arabia. Consequently, all 162 graduates from three recent cohorts (2018-2020) were contacted to participate in this survey. Results: A total of 157 graduates participated in this study, yielding a response rate of 96.91 %. Of the participants, 92 (58.6 %) were female graduates. The overall rate of employment was 84.7 %. Moreover, a higher proportion of male graduates than female graduates (97.1 % versus 73.7 %, P = 0.006) were employed. In this study, the three main sectors that the graduates joined were the pharmaceutical industry and companies (41.2 %), community pharmacies (29.4 %), and medical cities, hospitals and clinics (23.5 %). In addition, almost the same proportions of male and female graduates joined the pharmaceutical industry and companies (40.3 % versus 42.1 %). However, a higher proportion of male graduates than female graduates joined community pharmacies (32.3 % versus 26.3 %). Conversely, a higher proportion of female graduates joined medical cities, hospitals and clinics compared to male graduates (28.1 % versus 19.4 %). Conclusion: The current employment of PharmD graduates in the job market is generally high, but further improvement could be made, especially for female graduates. Moreover, the study findings showed that jobs are shifting toward community pharmacies and the pharmaceutical industry. Therefore, we believe that decision-makers in pharmacy education and curriculum developers must consider these trends and ensure that there is adequate preparation for careers in community pharmacy practice and other sectors of the profession in the curriculum.

Mother's knowledge and attitude regarding recognition of neonatal signs of danger.

Neonates are at risk for various health problems leading to morbidity and mortality that occur significantly in the developing countries. Reducing neonatal morbidity and mortality requires the immediate caregiver's recognition of suggestive neonatal signs of danger (NSD). Generally, reducing neonatal morbidity and mortality requires immediate caregiver's recognition of suggestive NSD and visiting the nearby clinic. The study aimed to assess mothers' knowledge and attitudes regarding the recognition of neonatal danger signs. This is a descriptive cross-sectional hospital-based study conducted at three hospitals located in Khartoum State. The data were collected using a structured interview questionnaire, from a sample, which consisted of 188 participants. The majority of the study population (72%) of the respondents had very poor knowledge about NSD. Fever was the commonest NSD recognised by most of the participant. Most of the study population had positive attitudes toward initiating the management of neonatal risk signs, which include: neonatal jaundice (82%), hypothermia (52.66%), convulsions (71.8%) and fast and difficult breathing (75%) at home. The results also showed that more than half of the participants (54.8%) had negative attitudes regarding the management of diarrhoea at home. The majority of mothers in our study had very poor knowledge about NSD.

Treatment Outcomes of Endovascular Embolization Only in Patients with Unruptured Brain Arteriovenous Malformations: A Subgroup Analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations).

BACKGROUND AND PURPOSE: Endovascular embolization only has been advocated for treatment of brain arteriovenous malformations in recent trials. Our aim was to evaluate the results of embolization only in a cohort of patients who were enrolled in the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) study at 39 clinical sites in 9 countries. MATERIALS AND METHODS: We analyzed the rates and severity of stroke and death in patients who underwent embolization only. Events were identified through in-person neurologic follow-up visits performed at 6-month intervals during the first 2 years and annually, with telephone contact every 6 months thereafter. All event-related data were reviewed by independent adjudicators. RESULTS: Among 30 patients who had embolization planned, 26 underwent embolization only. A total of 13 stroke events were reported in the follow-up period among 26 subjects (ischemic, hemorrhagic, or both in 4, 7, and 2 subjects, respectively). The adverse event occurred after the first embolization in 11 of 13 patients. One patient had a major motor deficit, and 2 patients developed major visual field deficits. One event was fatal. The modified Rankin Scale score was 0-2 at last follow-up in 11 of the 12 stroke survivors. Estimated stroke-free survival was 46% at 12 months. CONCLUSIONS: Although the rates of stroke and/or death were high in patients treated with embolization only in ARUBA, the rates of favorable outcomes following stroke were high during follow-up.

Rate and risk factors of recurrent tuberculosis in Yemen: a 5-year prospective study.

Background: Tuberculosis is a major public health concern in Yemen. Recurrence of tuberculosis complicates the situation further, and has severe negative economic and health consequences. This study estimated the tuberculosis recurrence rate during a 5-year follow-up period, and identified risk factors associated with recurrence.Methods: This was a prospective study with a 5-year follow-up period conducted at health centres with tuberculosis units in ten governorates. Participants were prospectively enrolled in the study from July 2007 to June 2008, with the last patient completing treatment on March 15, 2009.Results: A cohort of 814 patients with pulmonary tuberculosis completed treatment and was followed-up for five years. During the follow-up, 3.4% (n = 28) died and 4.3% (n = 35) were lost to the study, giving a final cohort of 751 patients. The mean age ± standard deviation was 32 ± 13 years. Males represented 57.6% of the subjects. The overall recurrence rate of tuberculosis was 9.5% (71/751), with significant variation between subgroups of patients (range = 7-25.8%). The highest recurrence rates were found in patients with diabetes (25.8%, p < .001), non-adherent patients (22%, p < .001), smokers (16.1%, p = .010), patients with cavitary lung disease (14.4%, p = .004), patients with weight gain ≤5% during the intensive phase (13.3%, p < .001) and unemployed patients (11.9%, p = .017). In multivariate logistic regression analysis, these risk factors were independently associated with recurrent tuberculosis: diabetes (adjusted odds ratio, aOR 3.78, 95% confidence interval, CI 1.84-7.80), non-adherence (aOR 3.22, 95% CI 1.76-5.87), weight gain ≤5% (aOR 2.51, 95% CI 1.39-4.55), smoking (aOR 2.18, 95% CI 1.07-4.47), presence of lung cavitation (aOR 2.01, 95% CI 1.16-3.46), and unemployment (aOR 2.15, 95% CI 1.16-4.01).Conclusion: The recurrence rate of tuberculosis in Yemen was high. The presence of risk factors in newly diagnosed patients should alert healthcare professionals. As most of risk factors were modifiable, the World Health Organisation model of patient-centered care in tuberculosis treatment should be promoted in all tuberculosis centres in the country.

Effects of corn supplementation on meat quality and fatty acid composition of Dorper lambs fed PKC-Urea treated rice straw.

BACKGROUND: The increasing costs of feed has subsequently increased the costs of production of livestock, thereby decreasing the profit margin of this sector. The utilization of agro-industrial by-products has to some extent substitute some of the corn grains and soyabean meal, commonly used in animal feeds. In Malaysia, palm kernel cake (PKC) is a by-product of the oil palm industry and is frequently used to supply both crude protein (14-16% CP) and energy (11 MJ/kg) in ruminants. The energy and protein content are adequate for maintenance in the majority of ruminants. However, highly available energy supplementation is known to improve growth performance and protein deposition. This study was carried out to determine the effect on the quality of meat and fatty acid composition of the semitendinosus (ST), supraspinatus (SS), and longissimus lumborum (LL) muscles of Dorper lambs by including corn as an energy source in a basal diet of PKC urea-treated rice straw. RESULTS: The results show that the LL muscle-drip loss was greater in animals supplemented with 5% corn compared to the other groups. Higher pH values of SS and LL muscles were observed in animals supplemented with 5 and 10% corn. Furthermore, the L* value of ST muscle was increased in lambs fed on 5% corn while, reduced in those fed on 0% corn, but the a* and b* values were not significantly different in the treatment groups. The fatty acid composition of the SS muscles showed that lambs fed on 10% corn had higher levels of sum PUFA n-3 compared to those fed on 0% corn. The concentration of C18:1trans11 and CLA c12 t10 in ST muscle from the lambs fed on supplemented diets were higher than those of the controls. CONCLUSION: This study has concluded the supplementation of corn as a source of energy into a PKC urea-treated rice straw-based diet increased the PUFA concentrations of muscles as compared to control groups.

Somatosensory evoked potential for detection of subclinical neuropathy in Egyptian children with acute lymphoblastic leukaemia.

To evaluate neurological changes developing during paediatric Acute Lymphoblastic Leukaemia (ALL) therapy clinically and through electrophysiological Study of Somatosensory Evoked Potentials (SSEPs) changes in different phases of therapy. Thirty five-ALL patients with age range from 3-14 years were included compared to 30 healthy controls. History, neurological examination, complete blood counts, cytological examination of bone marrow aspirate and cerebrospinal fluid with Measurement of Serum Methotrexate (MTX) were done. The SSEPs were performed and patients subjected to another SSEP with measurement of serum MTX level before and 10 days after intra-thecal injection (IMTX). Clinical neurological findings in patients after induction were depressed deep tendon reflexes (43.3%), hypotonia (28.6%), lost pain sensation (28.6%), muscle weakness (17.1%) and movement disorders (17.1%). Percentage of delayed SSEPs after induction were at levels of brachial plexus (28.6%), spinal cord (68.6%), cortical conduction (31.4%), ERB-N13 Inter Peak Latency (IPL) (74.3%) and N13-N20 IPL (17.1%) in the studied patients. Significant prolonged latency of N13 (p = 0.005), N20 (p = 0.04) and IPL of ERB-N 13 (p = 0.005), N13-N20 (p = 0.01), Inter-Side Difference (ISD) of N13 (p = 0.01), ERB-N13 (p = 0.02) and N13-N20 (p = 0.03) after induction compared to values at diagnosis. Significant positive correlation were found between serum MTX after IMTX with N13-N20 IPL (p = 0.01), N20 ISD (p = 0.03) with significant prolongation in N20 latency, N13-N20 IPL and ISD of N20 compared to values before injection. ALL patients have prolonged latency of SSEPs at cervical cord and cortical levels which increased after IMTX due to axonal injury throughout the cord. SSEPs could be an early diagnostic tool for subclinical neuropathy.

Value of kidney-ureter-bladder radiography in the erect position in addition to standard intravenous urography examination.

OBJECTIVES: To determine if additional kidney-ureter-bladder radiography in the erect position can improve the diagnostic yield of standard intravenous urography (IVU) examination. SUBJECTS AND METHODS: This prospective study was conducted from March to July 2007 on 108 consecutive patients (65 males and 43 females, age ranging from 20 to 50 years) who were referred to the Department of Radiology, Al-Amiri Hospital, Kuwait, for IVU examinations. After 15 min, a film was done in the erect position in addition to the routine IVU protocol. RESULTS: Additional information was demonstrated in the erect radiograph as follows: detecting nephroptosis in 18 (17%) patients, improved visualization of the ureters in 58 (54%) patients, and differentiation between phleboliths and ureteric stone was possible in 12 (11%) patients. CONCLUSIONS: Our study demonstrated significant additional findings in the erect position (at 15 min) compared to the supine position.

T1-weighted fluid-attenuated inversion recovery and T1-weighted fast spin-echo contrast-enhanced imaging: a comparison in 20 patients with brain lesions.

T1-weighted fluid-attenuated inversion recovery (FLAIR) sequence is a relatively new pulse sequence for intracranial MR imaging. This study was performed to compare the image quality of T1-weighted FLAIR with the T1-weighted FSE sequence. Twenty patients with brain lesions underwent T1-weighted fast spin-echo (FSE) and T1-weighted FLAIR during the same imaging session. Four quantitative and three qualitative criteria were used to compare the two sequences after contrast. Two of four quantitative criteria pertained to lesion characteristics: lesion to white matter (WM) contrast-to-noise ratio (CNR) and lesion to cerebrospinal fluid (CSF) CNR, and two related to signals from normal tissue: grey matter to WM CNR and WM to CSF CNR. The three qualitative criteria were conspicuousness of the lesion, the presence of image artefacts and the overall image contrast. Both T1-weighted FSE and FLAIR images were effective in demonstrating lesions. Image contrast was superior in T1-weighted FLAIR images with significantly improved grey matter-WM CNRs and CSF-WM CNRs. The overall image contrast was judged to be superior on T1-weighted FLAIR images compared with T1-weighted FSE images by all neuroradiologists. Two of three reviewers considered that the FLAIR images had slightly increased imaging artefacts that, however, did not interfere with image interpretation. T1-weighted FLAIR imaging provides improved lesion-to-background and grey to WM contrast-to-noise ratios. Superior conspicuity of lesions and overall image contrast is obtained in comparable acquisition times. These indicate an important role for T1-weighted FLAIR in intracranial imaging and highlight its advantage over the more widely practiced T1-weighted FSE sequence.

Insulin-like growth factor-1 receptor immunoreactive cells are selectively maintained in the paraventricular hypothalamus of calorically restricted mice.

The mammalian lifespan is dramatically extended by both caloric restriction (CR) and insulin-like growth factor-1 (IGF-1) suppression. Both interventions involve neuroendocrine alterations directed by the hypothalamus. Yet, it remains unclear whether CR exerts its affects by altering central IGF-1 sensitivity. With this question in mind, we investigated the influence of CR and normal aging on hypothalamic IGF-1 sensitivity, by measuring the changes in IGF-1 receptor (IGF-1R) populations. Taking IGF-1 receptor (IGF-1R) immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the paraventricular nucleus (PVN) of Young-ad libitum fed (Young-Al, 6 weeks old), Old-ad libitum fed (Old-Al, 22 months old), and old calorically restricted (Old-CR, 22 months old) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each cross-section of PVN hypothalamus. Ad libitum fed mice show a 37% reduction in IGF-1R immunoreactive cells and a 12% reduction in the total cell population of the PVN with aging. In comparison, caloric-restricted mice show a 33% reduction in IGF-1R immunoreactive cells and a notable 24% decrease in the total cell population with aging. This selective maintenance of IGF-1R expressing cells coupled with the simultaneous loss of non-immunoreactive cells, results in a higher percentage of IGF-1R immunoreactive cells in the PVNs of CR mice. Thus, the decline in the percentage of IGF-1 sensitive cells in the PVN with age is attenuated by CR.

Prevalence of hepatitis B virus infection in the Gezira state of central Sudan.

AIM: This is a cross-sectional study to determine the prevalence and risk factors for transmission of hepatitis B virus (HBV) infection in the Gezira state of central Sudan prior to the introduction of blood screening and vaccination against HBV. MATERIALS AND METHODS: The study was carried out on the population of Um Zukra village in Gezira state of Central Sudan. The village was surveyed on five consecutive days in Dec 2000. Epidemiological characteristics were recorded and participants were interviewed for risk factors of viral hepatitis. Blood samples were then collected and tested for HBsAg and HBcAb. RESULTS: A total of 404 subjects were screened with a mean age of 35 years; 54.9% were females, HBsAg and HBcAb were reactive in 6.9% and 47.5% of the studied population, respectively. Exposure to HBV increased with increasing age. The only significant risk factor for transmission of infection was a history of parenteral antischistosomal therapy. CONCLUSION: This study shows that prevalence of HBV infection is high in the studied population and it is hoped that introduction of blood screening and vaccination against HBV would decrease the carrier pool in the next few years.

Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice.

Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. Of the hypothalamic nuclei that express the IGF-1 receptor (IGF-1R), the cells of the supraoptic nucleus (SON) display some of the most robust IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the SON of young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed (Old-Al, 22 months), and old-calorie-restricted (Old-CR, 22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each section of supraoptic hypothalamus. Results show that while the total number of cells in the SON of ad-libitum fed mice does not change significantly with aging, a significant reduction in IGF-1R immunoreactive cells does occur in ad-libitum fed mice with aging. In contrast to this, calorie restricted mice show both a decline in the total number of cells and IGF-1R immunoreactive cells in the SON with age, but with the decrease in the latter being notably attenuated when compared to the degree of loss seen in ad-libitum fed mice. Thus, while CR induces greater loss in the total number of cells in the SON with age, it reduces the degree of age-dependent loss seen in IGF-1R expressing cells. As a result, when compared to Old-AL mice, the SON of Old-CR mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging.

Utility of volume adjusted prostate specific antigen density in the diagnosis of prostate cancer in Arab men.

BACKGROUND: This study was undertaken to assess the utility of prostate specific antigen (PSA) and PSA density (PSAD) in discriminating between benign and malignant prostate disease in the Kuwaiti Arab population. METHODS: A total of 100 consecutive patients suspected of having prostate cancer because of serum PSA > 4 ng/ml, or detection of a prostatic nodule on rectal examination were further investigated by determination of PSAD, TRUS of prostate, sexant prostatic biopsy and histological analysis to establish the correct diagnosis. Other diagnostic measures included the determination of the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. RESULTS: Of the 100 prostate biopsies that were performed, 33 cases were confirmed to be prostate cancer and 67 were described as benign lesions comprising benign prostatic hyperplasia (BPH) with or without prostatitis. The age range for patients with prostate cancer was 42-90 years, and 52-90 years for those without prostate cancer. The mean prostate volume was 58.82 cc (range 9-177 cc) and 62.60 cc (range 15-140 cc), the mean PSA value was 36.65 ng/ml (range 5.8-200 ng/ml) and 16.49 ng/ml (range 1.4-46.0 ng/ml), while the mean PSAD was 0.92 (range 0.046-5.714) and 0.452 (range 0.034-2.294) for patients with prostate cancer and patients without prostate cancer respectively. Patients with PSA less than 4 ng/ml (3 cases) all had benign prostate lesions, and 7 cases with PSA more than 50 ng/ml all had prostate cancer and were excluded because values above 50 ng/ml have close to 100% specificity for prostate cancer. Further analysis was done on the remaining 90 cases which were patients with a PSA between 4 and 50 ng/ml. The discriminating power of serum PSA for detecting prostate cancer as estimated by the area under ROC was 0.686 while that for PSAD was 0.732. The maximum likelihood for a positive PSA was at a PSAD cut-off point of 0.32. For the PSA cut-off point of l0 ng/ml, the sensitivity was 80%, and specificity was 42.2%. For the PSAD cut-off point of 0.32, the sensitivity was 58% and the specificity 76.6%. CONCLUSIONS: Determination of PSAD is not a useful adjunct to serum PSA values in the range of 10-50 ng/ ml in our population. PSAD value less than 0.32 with PSA less than l0 ng/ml strongly suggests benign disease.

Contrast-enhanced three-dimensional fast-spoiled gradient magnetic resonance angiography of the renal arteries for potential living renal transplant donors: a comparative study with digital subtraction angiography.

Preoperative assessment of the arterial anatomy of prospective renal donors is essential. Various non-invasive techniques are used for such evaluation. We conducted this study using contrast-enhanced 3-D fast-spoiled gradient (CE 3-D FSPGR) magnetic resonance angiography (MRA) on a 1.0 Tesla magnet, for preoperative definition of the renal arteries. Forty-five preoperative living renal donors underwent CE 3-D FSPGR MRA of the renal vessels and the results were compared with conventional digital subtraction angiography (DSA). The renal vascular anatomy, both normal and with variations, was satisfactorily defined in all 45 cases with CE 3-D FSPGR MRA. Fifteen cases showed an accessory or aberrant arterial supply. A small aneurysm was shown in one case. All cases compared well with conventional DSA. Our study revealed that CE 3-D FSPGR MRA on a lower field strength magnet is accurate in defining the renal vascular anatomy and its variations.

Invasive aspergillosis with polyarthritis.

We report a case of septic arthritis of multiple joints in an 18-year-old male caused by Aspergillus fumigatus. His initial presentation was of low-grade fever followed by involvement of both knee and ankle joints. Later, there was also involvement of metacarpophalangeal joints. Diagnosis was based on biopsy and culture of the skin and joint lesions. The symptoms resolved readily under administration of itraconazole. We recommend that clinicians should be alerted of potential fungal etiology in cases of fever and chronic arthritis, which is unresponsive to conventional medical therapy.

No evidence for a major effect of tumor necrosis factor alpha gene polymorphisms in periportal fibrosis caused by Schistosoma mansoni infection.

Hepatic periportal fibrosis (PPF), associated with portal hypertension, is a major pathological consequence of infections with Schistosoma mansoni and Schistosoma japonicum. Indeed, affected subjects may die from portal hypertension. Previous studies have indicated that tumor necrosis factor alpha (TNF-alpha) may aggravate fibrosis. We therefore investigated whether PPF was associated with certain polymorphisms of the TNF-alpha gene. Four polymorphisms (TNF-alpha -376 G/A, -308 G/A, -238 G/A, and +488 G/A) were investigated in two Sudanese populations living in an area in which S. mansoni is endemic. These polymorphisms were analyzed for 105 Sudanese subjects with various grades of PPF, from mild to advanced; all subjects were from two neighboring villages (Taweela and Umzukra). They were then analyzed for 70 subjects with advanced liver disease and for 345 matched controls from the Gezira region. We found no evidence of associations between these four polymorphisms and PPF in both of these studies. Thus, these four polymorphisms, two of which (TNF-alpha -376 and -308) were found to increase TNF-alpha gene transcription, are unlikely to have a major effect on PPF progression in these populations. However, this result does not exclude the possibility that these polymorphisms have a minor effect on PPF development.

Synergistic interaction of adrenaline and histamine in human platelet aggregation is mediated through activation of phospholipase, map kinase and cyclo-oxygenase pathways.

This study was conducted to examine the mechanism(s) of synergistic interaction of histamine- and adrenaline-mediated human platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of histamine (1-4 microm) plus adrenaline (0.5-2 microm) is inhibited by both an alpha(2)-adrenoceptor blocker (yohimbine) and a histamine (H1) receptor antagonist (diphenhydramine). In examining the role of the downstream signalling pathway, we found that such an interaction is inhibited by the calcium channel blockers verapamil and diltiazem. However, platelet aggregation by adrenaline plus histamine was inhibited by very low concentrations of the phospholipase C (PLC) inhibitor, U73122 (IC(50)= 1.2 microm), the MEK inhibitor, PD98059 (IC(50)= 1.1 microm) and the cyclo-oxygenase (COX) inhibitor, indomethacin (IC(50)= 7 microm). However the inhibition of receptor tyrosine kinase, protein kinase C and phosphatidylinositol 3-kinase by genistien, chelerythrine and wortmannin, respectively, had no significant effect on aggregation. Similarly the nitric oxide donor (SNAP) had no effect on this synergism. These data suggest that the synergistic effect of histamine and adrenaline during human platelet aggregation is receptor mediated and involves activation of PLC, COX and MAP kinase signalling pathways.