Polycyclic aromatic hydrocarbons in a polyherbal drug: human health exposure-associated risk assessment study.

PAHs are pervasive pollutants known to bioaccumulate in environmental matrices, plants, and humans. Dr. Iguedo Goko Cleanser® is a polyherbal drug with unsubstantiated claims to treat various diseases in sub-Saharan Africa. PAHs were measured following EPA-16 PAHs guidelines using Gas Chromatography (Agilent-6890N, USA). The drug's exposure-associated public health concerns was determined using suitable mathematical paradigms. PAHs present were acenaphthene (2.74 × 10-2), pyrene (2.7598 × 10-2), and chrysene (5.1277 × 10-2) ppm. Dietary intake of chrysene, acenaphthene and pyrene for adults, and children ranged from 2.466-4.615 × 10-3 and 1.215-2.308 × 10-3 ppm/mg/kg, respectively. B[α]Peq, EDB[α]Peq, and incremental lifetime cancer risk were determined to be 5.6777 × 10-4, 5.109912 × 10-5 and 5.3289 × 10-12, respectively. Our results suggest a high risk of non-carcinogenic adverse health effects, especially on chronic exposure among adolescents and adults, necessitating caution and/or avoidance of its chronic use. Therefore, policy formulation and implementation as regards the safety of plant-based remedies and allied products before their distribution among end-users must be ensured.

Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease.

Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality.

Psychopharmacology of smoking cessation medications: focus on patients with mental health disorders.

The adverse effects of smoking cessation in individuals with mental health disorders have been a point of concern, and progress in the development of treatment has been slow. The primary first-line treatments for smoking cessation are Nicotine Replacement Therapy, Bupropion, Varenicline, and behavioural support. Nortriptyline and Clonidine are second-line treatments used when the first-line treatments are not effective or are contraindicated. Smoking cessation medications have been shown to be effective in reducing nicotine cravings and withdrawal symptoms and promoting smoking cessation among patients living with mental disorders. However, these medications may have implications for patients' mental health and need to be monitored closely. The efficacy and side effects of these medications may vary depending on the patient's psychiatric condition, medication regimen, substance use, or medical comorbidities. The purpose of this review is to synthesise the pharmacokinetics, pharmacodynamics, therapeutic effects, adverse effects, and pharmacological interactions of first- and second-line smoking cessation drugs, with an emphasis on patients suffering from mental illnesses. Careful consideration of the risks and benefits of using smoking cessation medications is necessary, and treatment plans must be tailored to individual patients' needs. Monitoring symptoms and medication regimens is essential to ensure optimal treatment outcomes.

Fetus-in-Fetu Airway Teratoma Management of a Newborn in a Low-Resource Country: A Case Report.

A term baby was delivered by cesarean and found to have an unexpected large teratoma attached to its mouth. Surgical excision was planned within 24 hours. Anesthesia concern of airway control required multidisciplinary team consultation, airway and patient preparation, and anticipation for failure. Challenging airway cases in low-resource countries can be successfully managed with deliberate attention to detail, preparation, and experience.

Opioid prescribing habits of physicians in Kwara State, Nigeria.

OBJECTIVE: Although opioid analgesics are effective in the treatment of moderate to severe acute, cancer and chronic non-malignant pains, they are under-prescribed in Nigeria. The objective of this study was to assess the prescription pattern of opioids among physicians in a north central State, Nigeria.. DESIGN: This was a descriptive cross sectional study. SETTING: The study was conducted at the International Association for the Study of Pain (IASP)-sponsored workshops on pain and palliative care at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. PARTICIPANTS: These were physicians at the monthly workshops organized by the Pain and Palliative Care Unit of the hospital between August 2011 and July, 2012. INTERVENTIONS: Pre-tested semi-structured questionnaires were used to obtain responses to questions on pain management including opioids utilization in the various hospitals of the 114 participants. MAIN OUTCOME MEASURES: The main outcome measure was opioid prescription by the participants. RESULTS: Out of the 114 questionnaires distributed, 113 were returned with complete information giving a response rate of 99.1%. The mean age of the respondents was 42.0±10.8 years. Although 97.3% of the respondents reported that pain was a frequent complaint in their practice, 69.5% of those who reported seeing patients with moderate to severe pain on a daily basis rarely or never prescribed opioid analgesics. The reasons given for poor opioid prescription were fear of respiratory depression (86.8%), fear of addiction (85.1%) and non-availability (28.9%). CONCLUSION: Opioid prescription rate for patients with moderate-severe pain is low possibly due to myths and misconceptions about their adverse effects. FUNDING: International Association for the Study of Pain (IASP) Initiative for Improving Pain Education Grant awarded to Dr. K.W. Wahab in 2011.

Comparison of caudal ketamine with or without bupivacaine in pediatric subumbilical surgery.

In this prospective, randomized, double-blind study, we evaluated the perioperative analgesic efficacy of caudal ketamine with or without bupivacaine in 62 American Society of Anesthesiologists I-II children undergoing lower abdominal surgery. Patients were randomized into three groups, and all blocks were placed under general anesthesia. Group 1 (n=20) had caudal injection of plain 0.125% bupivacaine 1 mlkg(-1). Group 2 (n=22) received caudal ketamine 0.5 mgkg(-1) diluted with 0.9% saline using the same weight-related volumes. Group 3 (n=20) received a similar dose of ketamine mixed with 0.125% bupivacaine 1 mlkg(-1). No supplementary intraoperative analgesic was required in any of the groups. Patients in group 3 had the longest duration of analgesia compared to the other two groups. There was no significant difference in the incidence of side effects among the three groups. We conclude that ketamine can safely be used as an adjuvant to prolong the duration of caudal analgesia in this group of West African children.

Intercostal nerves block for mastectomy in two patients with advanced breast malignancy.

Regional anesthesia is recognized as an alternative to general anesthesia for modern breast cancer surgery. Various techniques of block have been described. Each has its unique problems. Regional anesthesia was chosen for simple mastectomy in two patients with advanced breast malignancy, due to compromised pulmonary status resulting from widespread malignant infiltration of both lungs. We used intercostal nerves block. The block was supplemented with an infraclavicular infiltration to interrupt the branches of the superficial cervical plexus that provide sensation to the upper chest wall and subcutaneous infiltration in the midline to block the nerve supply from the contralateral side. Anesthesia was generally effective and the operations were uneventful. Both patients and surgeons expressed satisfaction. We conclude that where patients have significant comorbidities that make general anesthesia undesirable, the use of intercostal nerves block remains a safe and reliable anesthetic option that allows the patient access to surgery for simple mastectomy.

Emergency thyroidectomy in a patient with severe upper airway obstruction caused by goiter: case for regional anesthesia.

A case of severe airway obstruction caused by a giant malignant goiter is presented. The patient had emergency thyroidectomy under regional anesthesia (bilateral superficial cervical plexus block). The procedure was well tolerated and the intraoperative course was uneventful. The anesthetic challenges are discussed and a case is made for regional anesthesia as a safe and reliable anesthetic option for thyroidectomy in this situation.

Vitamin E succinate induces apoptosis in human prostate cancer cells: role for Fas in vitamin E succinate-triggered apoptosis.

The apoptosis-triggering properties of vitamin E succinate (VES, RRR-alpha-tocopheryl succinate) for human LNCaP and PC-3 prostate carcinoma cells and normal PrEC human prostate epithelial cells were investigated. LNCaP and PC-3 cells were sensitive to VES-induced apoptosis, with 100% and 60% of cells undergoing apoptosis after three days of treatment with 10 micrograms of VES/ml, respectively. PrEC cells were resistant to VES-induced apoptosis. Treatment of prostate cells with agonistic anti-Fas antibody triggered apoptosis in approximately 50% of PC-3 cells within 48 hours, whereas LNCaP and PrEC cells were resistant. Prostate cells simultaneously treated with VES and agonistic anti-Fas antibodies revealed 1) no effect on PrEC cells, 2) an additive effect on Fas-sensitive PC-3 cells, and 3) a synergistic effect on LNCaP cells. VES treatment of LNCaP cells caused depletion of cytosolic 43-kDa Fas, enhanced membrane levels of 43-kDa Fas, and induced Fas sensitivity. PC-3 cells expressed high levels of membrane 43-kDa Fas that were enhanced by VES treatments. Fas ligand expression by LNCaP cells was enhanced by VES treatments. In summary, VES triggers apoptosis in human prostate carcinoma cells but not normal prostate cells in vitro, and VES modulates Fas signaling.

Vitamin E succinate (VES) induces Fas sensitivity in human breast cancer cells: role for Mr 43,000 Fas in VES-triggered apoptosis.

Fas (CD95/APO-1) is an important mediator of apoptosis. We show that Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 human breast cancer cells become responsive to anti-Fas (CD95) agonistic antibody-triggered apoptosis after pretreatment or cotreatment with vitamin E succinate (VES; RRR-alpha-tocopheryl succinate). In contrast, no enhancement of anti-Fas agonistic antibody-triggered apoptosis was observed following VES pretreatment or cotreatment with Fas-sensitive primary cultures of human mammary epithelial cells, immortalized MCF-10A cells, or T47D human breast cancer cells. Although VES is itself a potent apoptotic triggering agent, the 6-h pretreatment procedure for Fas sensitization did not initiate VES-mediated apoptosis. The combination of VES plus anti-Fas in pretreatment protocols was synergistic, inducing 2.8-, 3.0-, and 6.3-fold enhanced apoptosis in Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells, respectively. Likewise, cotreatment of Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells with VES plus anti-Fas enhanced apoptosis 1.9-, 2.0-, and 2.6-fold, respectively. Functional knockout of Fas-mediated signaling with either Fas-neutralizing antibody (MCF-7-, MDA-MB-231-, and MDA-MB-435-treated cells) or Fas antisense oligomers (MDA-MB-435-treated cells only), reduced VES-triggered apoptosis by approximately 50%. Analyses of whole cell extracts from Fas-sensitive cells revealed high constitutive expression of Mr 43,000 Fas, whereas Fas-resistant cells expressed low levels that were confined to the cytosolic fraction. VES treatment of the Fas-resistant cells caused a depletion of cytosolic Mr 43,000 Fas with a concomitant increase in Mr 43,000 membrane Fas. These data show that VES can convert Fas-resistant human breast cancer cells to a Fas-sensitive phenotype, perhaps by translocation of cytosolic Mr 43,000 Fas to the membrane and show that VES-mediated apoptosis involves Mr 43,000 Fas signaling.

RRR-alpha-tocopheryl succinate inhibits the proliferation of human prostatic tumor cells with defective cell cycle/differentiation pathways.

The RRR-alpha-tocopheryl succinate derivative of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of three metastatic human prostatic cancer cell lines, LNCaP, PC-3, and DU-145. LNCaP is a lymph node-derived androgen-sensitive prostate cell line; these cells are defective for response to transforming growth factor-beta (TGF-beta) but are normal for cell cycle-related tumor suppressor genes: p53 and retinoblastoma (Rb). PC-3 is a bone marrow-derived androgen-insensitive prostate cell line; these cells are defective for both p53 alleles but normal for both Rb alleles. DU-145 is a brain-derived androgen-insensitive prostate cell line; these cells are defective for both p53 and both Rb alleles. VES at 5, 10, and 20 micrograms/ml inhibited DNA synthesis in the three cell lines in a dose-dependent manner. Purified TGF-beta 1 at 1 ng/ml inhibited DNA synthesis of PC-3 cells within 24-72 hours and DU-145 cells at 72 hours but did not inhibit DNA synthesis of LNCaP cells. Previous studies in our laboratory showed that VES growth-inhibited tumor cells secrete biologically active antiproliferative factor TGF-beta s, suggesting that VES's mechanism of growth inhibition may involve the TGF-beta system of growth control.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase II trial of 10-Edam in patients with advanced colorectal carcinoma.

10-Edam (10-ethyl-10-deaza-aminopterin), an antifolate derivative, was administered to 14 chemotherapy-naive patients with advanced colorectal carcinoma. The drug was given weekly by intravenous route at an initial dose of 80 mg/m2, with escalation or attenuation according to tolerance. Mucositis was dose limiting and occurred in 11 of 14 patients (78.6%). Removal from the study was required in one patient due to progressive pulmonary fibrosis that was histologically identical to methotrexate-induced lung damage. Toxicity was otherwise mild to moderate and included diarrhea, constipation, abdominal discomfort, anorexia, nausea/vomiting, rash, and fatigue. There were no responses to 10-Edam in this study, 95% confidence interval (0-0.23). Stable disease was achieved in four patients; the remaining 10 patients demonstrated progression within 9 weeks of initiating systemic therapy. 10-Edam employed at this dosage and schedule was not effective as a treatment against advanced colorectal carcinoma.

Randomized study of continuous infusion fluorouracil versus fluorouracil plus cisplatin in patients with metastatic colorectal cancer.

One hundred twenty-two chemotherapy-naive patients with histologically confirmed colorectal adenocarcinoma were entered into a randomized trial comparing infusional fluorouracil (FU) versus cisplatin (CDDP) and FU. In both groups, patients received continuous infusion FU 1,000 mg/m2/d for 5 consecutive days every 4 weeks. Patients randomized to CDDP/FU also received CDDP 20 mg/m2 intravenous (IV) bolus on days 1 to 5 of each cycle. Patients were comparable in terms of age, performance status, baseline laboratory values, dominant sites of measurable disease, and percent of liver involvement. The partial response rate was significantly greater in patients who received CDDP/FU versus FU alone (25% v 3%, P = .001). Patients who received CDDP/FU experienced significantly greater toxicity compared with FU alone: grades 3 and 4 hematologic toxicity occurred in 22% and 0% of patients, respectively (P = .0001); grades 2 to 4 nausea and vomiting occurred in 80% and 15% of patients, respectively (P = .0001). There were no significant differences in either the duration of response (median, 6 and 4.7 months for CDDP/FU and FU groups, respectively) or survival (median 10, and 12 months, respectively). Compared with infusional FU alone, CDDP/FU provided a significantly greater partial response rate with increased toxicity, but it did not improve overall survival in patients with advanced colorectal carcinoma. Therefore, the use of CDDP/FU as routine therapy for the treatment of colorectal carcinoma cannot be recommended.

Association of inflammatory bowel disease (IBD) with indolent soft-tissue sarcomas: report of two cases and review of literature.

Two patients with inflammatory bowel disease (IBD) and indolent forms of soft-tissue sarcomas (extraosseous osteogenic sarcoma and desmoid tumor) are presented. The literature is reviewed regarding these tumors, which have not previously been recognized in association with IBD. Despite the well-established relationship between IBD and neoplasms of epithelial and lymphoreticular origin, there have been limited data in this context pertaining to mesenchymal tumors. Two preceding reports have described the coexistence of IBD with another form of soft tissue sarcoma (Kaposi's sarcoma). Given that this relationship has now been observed in four cases, the possibility that soft-tissue sarcoma and IBD do not coexist fortuitously must be considered. This suggestion is raised in light of the rare incidence of these disorders, the limited understanding of factors governing their expression, and the known association of IBD with other forms of neoplasia.

Histoplasmosis in immunosuppressed patients.

Infection with Histoplasma capsulatum in 58 patients whose immune responses were suppressed (Immunosuppressed patients) (16 from the present series and 42 described previously) was analyzed. The most common underlying diseases were Hodgkin's disease (29 per cent), chronic lymphocytic leukemia (19 per cent) and acute lymphocytic leukemia (17 per cent). Sixty-three per cent of the patients had received cytotoxic drugs, and 57 per cent had taken corticosteroids. Widely disseminated infection occurred in 88 per cent of the patients, with predominant involvement of lungs and organs of the reticuloendothelial system. Localized pulmonary infection was present in the remaining patients. The most useful diagnostic method was bone marrow biopsy with microscopic examination for the intracellular yeast form of H. capsulatum. Biopsy of oral lesions, lung, liver and lymph node also proved diagnostically helpful. Growth of H. capsulatum in culture was frequently too slow to be beneficial in diagnosing histoplasmosis in ill patients. Serologic methods were of little diagnostic help in this population of immunosuppressed patients. The response to amphotericin B therapy was excellent (6.7 per cent mortality rate) in those patients in whom the diagnosis was established early and in whom a full course of antifungal therapy could be given. In contrast, the mortality rate in patients who received no antifungal therapy or less than 1 g of amphotericin B was 100 per cent.