Evaluation of biomarkers of oxidative stress and female reproductive hormones in post menopausal women with breast cancer in Southern Nigeria.

BACKGROUND: Reproductive hormones and reactive oxygen species produced by either hormonal or aerobic metabolism have been implicated in carcinogenesis of the breast and disease progression. Perturbations in the homeostasis of female reproductive hormones and oxidative stress indices in breast cancer (BCa) could be used for monitoring disease prognosis. OBJECTIVES: The aim of this study was to assess levels of some biomarkers of oxidative stress and female reproductive hormones in postmenopausal women with BCa at different stages. METHODS: Reduced glutathione (GSH), total antioxidant capacity (TAC), total plasma peroxides (TPP), nitric oxide (NO), malondialdehyde (MDA), estradiol (E2), and prolactin (PRL) levels were determined in 50 post-menopausal women with BCa (stages II-IV) and 50 women without BCa (controls) by colorimetry and ELISA methods. Oxidative stress and body mass indices (OSI &BMI) and clinical history were obtained. RESULTS: Post-menopausal women with BCa had significantly higher BMI (26.60 ± 5.17 vs 22.73 ± 1.21 kg/m2, P=<0.001), TAC (5.59 ± 2.38 vs 4.43 ± 2.66 mmol/l, P = 0.023), TPP (4.92 ± 3.59 vs 2.98 ± 2.82 mmol/l, P = 0.003), NO (31.96 ± 10.73 vs 23.92 ± 6.37 µmol/l, P=<0.001) and E2 (78.89 ± 54.54 vs 11.08 ± 14.80 pg/ml, P = 0.003) levels and lower mean age at menarche (13.16 ± 0.87 vs 14.14 ± 1.60 years, P=<0.001) compared to controls. Controls had significantly lower E2 (P = 0.003), TPP (P = 0.005) and OSI (P = 0.043) compared to women with stage II BCa; lower E2 (P=<0.001), NO (P = 0.010), TAC (P = 0.010) and TPP (P=<0.001) compared to stage III BCa; and lower E2, (P=<0.001), NO (P = 0.044) and MDA (P = 0.020) compared to stage IV BCa respectively. Prolactin correlated positively with E2 (r = 0.296, P = 0.037), and TAC (r = 0.336, P = 0.011) in women with BCa. CONCLUSION: Postmenopausal women with BCa at different stages have increased estradiol, antioxidants, lipid peroxidation, and oxidative stress index suggesting that these indices may be useful for clinical assessment and monitoring progression of breast cancer.

Vitamin D supplementation improves insulin resistance in type 2 diabetes subjects in Lagos, Nigeria

Type 2 diabetes is a disease caused by both insulin resistance and an insulin secretory defect. Reports suggest that vitamin D3 supplementation improves insulin resistance and pancreatic beta-cell function, but there is paucity of data on vitamin D and glycaemia in type 2 diabetes in Nigeria. We have therefore performed a single blind prospective randomised placebo-controlled trial, involving type 2 diabetes participants in Lagos, Nigeria. The participants consisted of 42 type 2 diabetes patients with vitamin D deficiency. These participants were randomised into two equal groups of treatment and a placebo arm. Vitamin D3(3000 IU daily) was given to the participants in the treatment arm. Insulin resistance (HOMA-IR) and pancreatic beta-cell (HOMA-B) function were determined at baseline and after 12 weeks of vitamin D3 supplementation, or placebo treatment. There was a reduction from baseline in the mean insulin resistance level in both the treatment and placebo groups. How-ever, this reduction was only statistically significant in the treatment group (p <0.01). The proportion of subjects with improvement in insulin resistance status (homeostatic model assessment insulin resistance score (HOMA-IR)<2.0) was significantly higher in the treatment arm (p<0.05). There was a reduction in the mean insulin secretory capacity in the treatment group while it increased in the placebo group, though this difference was not statistically significant. We conclude that vitamin D3 supplementation results in a reduction in insulin resistance, but has no effect on pancreatic beta-cell function in type 2 diabetes

Endocrine-related diseases in the emergency unit of a Tertiary Health Care Center in Lagos: A study of the admission and mortality patterns.

INTRODUCTION: Non-communicable diseases are emerging as an important component of the burden of diseases in developing countries. Knowledge on admission and mortality patterns of endocrine-related diseases will give insight into the magnitude of these conditions and provide effective tools for planning, delivery, and evaluation of health-care needs relating to endocrinology. MATERIALS AND METHODS: We retrieved medical records of patients that visited the emergency unit of the Lagos University Teaching hospital, over a period of 1 year (March 2011 to February 2012) from the hospital admissions and death registers. Information obtained included: Age, gender, diagnosis at admission and death, co-morbidities. Diagnoses were classified as endocrine-related and non-endocrine related diseases. Records with incomplete data were excluded from the study. RESULTS: A total of 1703 adult medical cases were seen; of these, 174 were endocrine-related, accounting for 10.2% of the total emergency room admission in the hospital. The most common cause of endocrine-related admission was hyperglycaemic crises, 75 (43.1%) of cases; followed by diabetes mellitus foot syndrome, 33 (19.0%); hypoglycaemia 23 (13.2%) and diabetes mellitus related co-morbidities 33 (19.0%). There were 39 endocrine-related deaths recorded. The result revealed that 46.1% of the total mortality was related to hyperglycaemic emergencies. Most of the mortalities were sepsis-related (35.8%), with hyperglycaemic crises worst affected (71.42%). However, the case fatalities were highest in subjects with thyrotoxic crisis and hypoglycaemic coma. CONCLUSION: Diabetic complications were the leading causes of endocrine-related admissions and mortality in this health facility. The co-morbidity of sepsis and hyperglycaemia may worsen mortality in patients who present with hyperglycaemic crises. Hence, evidence of infection should be sought early in such patients and appropriate therapy instituted.

Chlamydia Infection; Plasma Peroxidation and Obesity in Tubal Infertility

Background: Genital tract infections and obesity are both sources of oxidative stress. Alterations in immune and antioxidant parameters may arise from this or from an indeterminate autoimmune mechanism. Objective: This study aimed to investigate the association of Chlamydial infection; obesity and oxidative response with tubal infertility in Nigerian women. Methods: It was a case-control study of 40 women with tubal infertility and 32 fertile women; respectively; recruited from the Infertility and Family Planning Clinics respectively; of the University College Hospital; Ibadan; Nigeria. Anthropometric indices were measured in each subject and endocervical swabs were taken to screen for current genital tract infection. Antioxidant; hormonal and immunologic analysis were performed on serum. Results: None of the subjects had current genital tract infections. Chlamydia trachomatis IgG positivity was significantly higher in infertile than in fertile subjects [OR 4.33; 95CI (0.078-0.681)]. No significant variations were observed in the anthropometric indices; antioxidant parameters and hormones between infertile and the fertile women. Body mass index correlated positively with oxidative stress in infertile subjects. Waist and hip circumferences correlated negatively with oestradiol in women with tubal infertility. Conclusion: Chlamydial infection is associated with tubal factor infertility; however; obesity seems to increase oxidative stress and reduce fertility potential in women with tubal factor infertility

Chlamydial infection, plasma peroxidation and obesity in tubal infertility.

BACKGROUND: Genital tract infections and obesity are both sources of oxidative stress. Alterations in immune and antioxidant parameters may arise from this or from an indeterminate autoimmune mechanism. OBJECTIVE: This study aimed to investigate the association of Chlamydial infection, obesity and oxidative response with tubal infertility in Nigerian women. METHODS: It was a case-control study of 40 women with tubal infertility and 32 fertile women, respectively, recruited from the Infertility and Family Planning Clinics respectively, of the University College Hospital, Ibadan, Nigeria. Anthropometric indices were measured in each subject and endocervical swabs were taken to screen for current genital tract infection. Antioxidant, hormonal and immunologic analysis were performed on serum. RESULTS: None of the subjects had current genital tract infections. Chlamydia trachomatis IgG positivity was significantly higher in infertile than in fertile subjects [OR 4.33; 95%CI (0.078-0.681)]. No significant variations were observed in the anthropometric indices, antioxidant parameters and hormones between infertile and the fertile women. Body mass index correlated positively with oxidative stress in infertile subjects. Waist and hip circumferences correlated negatively with oestradiol in women with tubal infertility. CONCLUSION: Chlamydial infection is associated with tubal factor infertility, however, obesity seems to increase oxidative stress and reduce fertility potential in women with tubal factor infertility.

Primary lung carcinoma after heart or lung transplantation: management and outcome.

OBJECTIVE: We sought to examine our management and outcome of lung carcinoma occurring after thoracic organ transplantation. METHODS: We performed a retrospective review of cases of primary lung carcinoma diagnosed between 1990 and 2000 in patients who have previously undergone thoracic transplantation at our institution. RESULTS: Seventeen patients were identified (1 lung and 16 heart transplants). Median time from transplantation to diagnosis of lung carcinoma was 89 months (range, 46-138 months). Predominant presentation was as an incidental finding at chest radiography (13/17). All patients had smoked cigarettes before transplantation, with 5 continuing to smoke after transplantation. Histologic types were squamous (n = 11), adenocarcinoma (n = 3), small cell (n = 2), and undifferentiated (n = 1). Revised International Union Against Cancer (UICC) clinical stage at the time of diagnosis was stage I or II in 11 of 17 patients. Of these, 9 underwent surgical resection; 2 patients unfit for surgical intervention had radiotherapy. Surgical procedures were lobectomy (n = 5), wedge excision (n = 3), and no resection (n = 1). Median survival after diagnosis was 12 months for all patients and 24 months if the tumor was resected. Six patients who had surgical resection subsequently died (survival of 2, 9, 21, 21, 36, and 67 months); 2 remain alive after 12 and 54 months, respectively. CONCLUSIONS: When possible, surgical intervention should be undertaken for early stage lung cancer occurring after thoracic transplantation because medium-term survival is achievable. Sublobar excisions and definitive radiotherapy should be considered if comorbidity prevents optimal surgical treatment.

Determinants of outcome after heterotopic heart transplantation.

BACKGROUND: Donor availability is currently the major factor limiting the use of heart transplantation as a treatment for severe heart failure. Heterotopic heart transplantation may address this issue by allowing the use of smaller donor organs, which otherwise may not be used. METHODS: We analyzed the outcome of 42 consecutive, adult heterotopic transplantations performed between 1993 and 1999 at our center and compared them with the 303 consecutive orthotopic transplants performed in adult patients during the same period. METHODS: Univariate analysis showed a relative risk for death of 1.8 at 1 year after transplantation for the heterotopic group compared with the orthotopic transplantation group (p = 0.04). Multiple regression analysis using a proportional hazards model showed that donor-recipient size-mismatch, i.e., donor body surface area < or =75% of recipient body surface area (p = 0.0001), donor age (p = 0.0001), and use of a female donor (p = 0.04) were significant risk factors but heterotopic transplantation per se was not. A Kaplan-Meier survival analysis of heterotopic vs orthotopic transplantation showed that 30-day survival was 76% vs 87%. By 1 year, this was 59% vs 74%. At 3 years, the comparison was 56% vs 69%. Repeating this analysis after sub-dividing the heterotopic group into those size-matched vs size-mismatched, the 1-year survival was 81% vs 45%, respectively (p = 0.02). CONCLUSIONS: Heterotopic transplantation using a size-matched graft resulted in similar survival to that seen after orthotopic transplantation during the same period. Heterotopic transplantation with an undersized graft resulted in significantly decreased survival.

Intrathoracic organ transplantation in the United Kingdom 1995-99: results from the UK cardiothoracic transplant audit.

OBJECTIVE: To describe the current practice and outcomes of intrathoracic transplantation in the United Kingdom. DESIGN: Prospective observational cohort study. SETTING: Multicentre study involving all nine UK intrathoracic transplant units. PATIENTS: 2588 patients added to the national waiting list between April 1995 and March 1999 and 1737 patients who underwent heart, lung, or heart-lung transplantation in the same period. MAIN OUTCOME MEASURES: Waiting list mortality and post-transplant graft survival. RESULTS: There was a slight fall in transplant activity over the four years. Within six months of listing, 52.5% of patients on the heart transplant list had been transplanted and 11.0% had died, compared with 31.3% and 15.2% for lung, and 23.4% and 20.4% for heart-lung. The median time to transplant in days (95% confidence interval) was 133 (115 to 149) for heart, 386 (328 to 496) for lung, and 471 (377 to 577) for heart-lung. After three years, the waiting list mortality was 16.9% (6.1% to 46.8%) for heart, 33.1% (9.0% to 100%) for lung, and 36.5% (10.5% to 100%) for heart-lung. The three year graft survival after transplantation was 74.2% (71.2% to 77.0%) for heart, 53.8% (48.2% to 59.2%) for lung, and 57.2% (49.0% to 64.6%) for heart-lung. CONCLUSIONS: This validated database defines the current state of thoracic transplantation in the United Kingdom and is a useful source of data for workers involved in the field. Thoracic transplantation is still limited by donor scarcity and high mortality. Overoptimistic reports may reflect publication bias and are not supported by data from this national cohort.

Subjective patient outcomes following coronary artery bypass using the radial artery: results of a cross-sectional survey of harvest site complications and quality of life.

OBJECTIVES: To assess patient-based outcomes following radial artery harvesting for coronary artery bypass surgery (CABG). METHODS: A cross-sectional telephone survey of 127 patients who underwent radial artery grafting was undertaken. The parameters assessed included symptoms related to the radial artery harvest site (functional impairment, sensory symptoms, and wound infection) and health related quality of life. RESULTS: A high percentage of patients (67.7%) reported altered sensation, in the hand, in particular around the thenar eminence, in the forearm, or in relation to the incision; this was self-limiting and clinically insignificant in the vast majority of patients. Twelve patients reported residual insignificant symptoms after a median follow-up of 17.5 months. Four patients reported a subjective decrease in grip strength. Patients reported a good quality of life, and there was no association between this and the presence or absence of symptoms related to radial artery harvest. Some patients volunteered a 'preference' for the radial artery harvest site when compared with concomitantly harvested long saphenous vein (LSV), and there was a lower wound infection rate at radial artery harvest sites compared with vein harvest sites (6 vs. 15%). CONCLUSIONS: Sensory symptoms following radial artery procurement occur more frequently than previously reported, but are largely self-limiting and are usually clinically insignificant. Patients appear to have a good quality of life following CABG using the radial artery. Radial artery harvest may be associated with lower wound infection rates and greater patient satisfaction than LSV harvest, however, the presence of residual sensory symptoms may be of relevance when obtaining informed consent.

Does routine use of the radial artery increase complexity or morbidity of coronary bypass surgery?

BACKGROUND: Despite increasing data supporting its use, the uptake of radial artery coronary bypass grafting by most surgeons remains low. This may partly be from perceptions that it increases risk or complexity of coronary surgery. METHODS: Data on 151 patients who had radial grafts are compared with 179 concurrent nonrandomized controls that underwent conventional surgery using saphenous vein. Additionally, telephone interviews were conducted on 127 radial recipients to assess subjective outcome. RESULTS: Cardiopulmonary bypass and cross-clamp times were similar in both groups (72 versus 74 minutes and 20 versus 22 minutes). Morbidity was comparable (mortality 1% versus 2%; cerebral vascular accident 1% versus 2%; sternal infection 1% versus 2%; resternotomy 4% versus 6%). Of 127 patients contacted, 41 (32%) reported that they had experienced parasthesia, and 65 (51%) reported numbness related to radial harvest; of these, 75% reported their symptoms as resolved or resolving. Early angiography performed in 36 patients revealed a radial patency rate of 92%. CONCLUSIONS: Concerns about increased morbidity and mortality should not hinder adoption of radial artery grafting.

Assessment of quality of life in lung transplantation using a simple generic tool.

BACKGROUND: The EuroQol is a generic questionnaire developed to provide a simple method for assigning utility values to health. This study examines the applicability of the EuroQol to the measurement of quality of life in single, bilateral, and heart-lung transplantation. METHODS: A cross sectional study was performed in 87 patients awaiting lung transplantation and in 255 transplant recipients attending follow up clinics in four transplant units. RESULTS: In the waiting list group 61% reported extreme problems in at least one of the five EuroQol quality of life domains compared with 20% single lung recipients, 4% bilateral lung recipients, and 2% heart-lung recipients at 3 or more years after transplantation. The mean utility value of patients on the waiting list was 0.31. In comparison, utility values for recipients 3 years after transplantation were 0.61 for single, 0.82 for bilateral, and 0.87 for heart-lung transplants. The utility scores and health profiles of bilateral and heart-lung recipients were consistently superior to those of single lung recipients. Problems in all five domains were more frequent in single lung recipients. Subjective assessment with a visual analogue scale showed a similar trend. CONCLUSIONS: The EuroQol is a simple method of deriving a single utility value for quality of life and is responsive to changes after lung transplantation. It is worth considering as a means of monitoring quality of life after transplantation and as an index of quality of survival in research studies in solid organ transplantation. These data suggest that quality of life after transplantation of one lung is inferior to that after transplantation of two lungs.

Does splitting the lung block into two single lung grafts equate to doubling the societal benefit from bilateral lung donors? Comparisons between two single versus one bilateral lung transplant. UK Cardiothoracic Transplant Audit Steering Group.

Multi-organ thoracic transplantation, although beneficial to one recipient, has an opportunity cost of denied transplants to others. This paper compares population based outcomes of splitting lung blocks for two single lung transplants compared to doing one bilateral lung transplant, and suggests that the benefit of splitting lung blocks may not necessarily be double that of using each block for one recipient.

Where are we today with pulmonary transplantation? Current results from a national cohort. UK Cardiothoracic Transplant Audit Steering Group.

Lung transplantation is now an accepted therapy for the treatment of end-stage lung disease. This paper presents some current results of lung transplantation as determined from a validated national database.

A simple approach to risk stratification in adult heart transplantation.

OBJECTIVE: While there are numerous reports in the literature of risk factors for graft failure after heart transplantation, simple models for risk stratification are lacking. This study describes a simple method for risk stratification in adult heart transplantation that can be applied when the size of a dataset is insufficient for formal regression modelling. METHODS: Multi-centre prospective cohort study. Fourteen risk factors documented in the literature as increasing post transplant graft failure were used to formulate a model. Risk factors included in the model were recipient age >50 years, pre-operative ventilatory support, pre-operative circulatory support, >1 previous sternotomy, pulmonary vascular resistance >2.5 wood units, male with body surface area >2.5 m2, retransplant, ischaemic time >3.5 h, donor age >45 years, donor inotropic support >10 microg/kg per min dopamine, female donor, ratio donor/recipient body surface area <0.7, donor with diabetes and history of donor drug abuse. Four risk groups were defined depending on the number of risk factors present: Low, none; moderate, 1; high, 2 or 3; very high, 4 or more. Graft survival to 30 days was chosen as the primary outcome. The model was tested on 373 adult transplants performed in the UK between April 1995 and December 1996. RESULTS: Twenty eight transplants were low risk, 82 moderate, 201 high and 62 very high. The 30-day survival (70% CI) for the risk groups was low, 97% (93-100), moderate 95% (92-98), high 87% (84-89) and very high 80% (75-83) (P = 0.02). CONCLUSIONS: This preliminary model enables some stratification of heart transplant procedures according to donor and recipient risk profile. Further work will be directed at refining and validating the model.

Variations in cardiac transplantation: comparisons between the United Kingdom and the United States.

BACKGROUND: International practice variations have been documented in various health care specialties. This study compares cardiac transplantation in the UK with practice in the US. METHODS: UK data were from an ongoing multi-center prospective study, the UK Cardiothoracic Transplant Audit. The UK population comprised 620 listings and 463 transplants. US data were obtained from UNOS and comprised 3946 listings and 4704 transplants. RESULTS: There was a mean of 14 transplants per center per year in the US compared with 34 in the UK. Notable differences in practice include rarity of listing in the UK of patients > 65 years (0.2% vs 4.1% in US) and patients with previous transplants (UK 0.9%, US 3.2%). Patients listed in the US were more likely to be on ventricular assist devices (odds ratio 8.0, 95% CI 3.0-21.7) or inotropes (odds ratio 4.9, 95% CI 3.7-6.4). Living donor (domino) transplants, although comprising 7% of transplants in the UK, are virtually non-existent in the US (1 domino in 4704 transplants). Heterotopic transplants were more common in the UK (4.4% vs 0.5%). Indications for transplant were similar (except retransplantation). The donor age was > 35 years in 43% of UK donors vs 33% of US donors. CONCLUSION: This study reveals substantial practice differences between the UK and US. Further studies are required to examine the reasons for these practice differences, the influence on transplant outcome, and their ethical and economic implications.

Are abdominal radiographs still overutilized in the assessment of acute abdominal pain? A district general hospital audit.

Several studies have shown that plain film radiography (PFR) is unnecessary for most patients with abdominal pain. To evaluate the current-day utilization of PFR, we retrospectively reviewed 224 patients presenting to an emergency department with acute abdominal pain. Plain film radiography was performed in 55.8% (125/224) of patients, but only 10.4% (13/125) of these were diagnostic. Most patients with non-specific abdominal pain had radiographs (62%, 31/50), suggesting that PFR was being used as a routine investigation. Plain film radiography has little in the diagnosis of most causes of abdominal pain and should therefore not be used routinely. Confining radiography to patients with suspected gastrointestinal obstruction, perforation or ischaemia, unexplained peritonism, or renal colic would have included all our diagnostic films and reduced the utilization of PFR to 20.5%. The reasons for inappropriate requests and issues concerning the use of emergency radiography are discussed. Staff education, departmental protocols and increased out-of-hours ultrasonography facilities are recommended to reduce the inappropriate use of PFR.

Karydakis operation for sacrococcygeal pilonidal sinus disease: experience in a district general hospital.

Asymmetrical excision of sacrococcygeal pilonidal sinus has been shown to be associated with low recurrence rates. We report our experience with an asymmetric technique--the Karydakis operation. Of 28 patients who had the operation over a 4-year period, no recurrences were observed in 27 patients available for follow-up (median follow-up 3 years). Three patients had complications requiring surgical intervention. The operation is easy to teach and learn and is worth considering by both specialist and non-specialist surgeons.