The hindbrain and cortico-reticular pathway in adolescent idiopathic scoliosis.

AIM: To characterise the corticoreticular pathway (CRP) in a case-control cohort of adolescent idiopathic scoliosis (AIS) patients using high-resolution slice-accelerated readout-segmented echo-planar diffusion tensor imaging (DTI) to enhance the discrimination of small brainstem nuclei in comparison to automated whole-brain volumetry and tractography and their clinical correlates. MATERIALS AND METHODS: Thirty-four participants (16 AIS patients, 18 healthy controls) underwent clinical and orthopaedic assessments and brain magnetic resonance imaging (MRI) on a 3 T MRI machine. Automated whole-brain volume-based morphometry, tract-based spatial statistics analysis, and manual CRP tractography by two independent raters were performed. Intra-rater and inter-rater agreement of DTI metrics from CRP tractography were assessed by intraclass correlation coefficient. Normalised structural brain volumes and DTI metrics were compared between groups using Student's t-tests. Linear correlation analysis between imaging parameters and clinical scores was also performed. RESULTS: AIS patients demonstrated a significantly larger pons volume compared to controls (p=0.006). Significant inter-side CRP differences in mean (p=0.02) and axial diffusivity (p=0.01) were found in patients only. Asymmetry in CRP fractional anisotropy significantly correlated with the Cobb angle (p=0.03). CONCLUSION: Relative pontine hypertrophy and asymmetry in CRP DTI metrics suggest central supranuclear inter-hemispheric imbalance in AIS, and support the role of the CRP in axial muscle tone. Longitudinal evaluation of CRP DTI metrics in the prediction of AIS progression may be clinically relevant.

Cost-effectiveness of prenatal screening methods for congenital heart defects in pregnancies conceived by in-vitro fertilization.

OBJECTIVES: To determine if a policy of universal fetal echocardiography (echo) in pregnancies conceived by in-vitro fertilization (IVF) is cost-effective as a screening strategy for congenital heart defects (CHDs) and to examine the cost-effectiveness of various other CHD screening strategies in IVF pregnancies. METHODS: A decision-analysis model was designed from a societal perspective with respect to the obstetric patient, to compare the cost-effectiveness of three screening strategies: (1) anatomic ultrasound (US): selective fetal echo following abnormal cardiac findings on detailed anatomic survey; (2) intracytoplasmic sperm injection (ICSI) only: fetal echo for all pregnancies following IVF with ICSI; (3) all IVF: fetal echo for all IVF pregnancies. The model initiated at conception and had a time horizon of 1 year post-delivery. The sensitivities and specificities for each strategy, the probabilities of major and minor CHDs and all other clinical estimates were derived from the literature. Costs, including imaging, consults, surgeries and caregiver productivity losses, were derived from the literature and Medicare databases, and are expressed in USA dollars ($). Effectiveness was quantified as quality-adjusted life years (QALYs), based on how the strategies would affect the quality of life of the obstetric patient. Secondary effectiveness was quantified as number of cases of CHD and, specifically, cases of major CHD, detected. RESULTS: The average base-case cost of each strategy was as follows: anatomic US, $8119; ICSI only, $8408; and all IVF, $8560. The effectiveness of each strategy was as follows: anatomic US, 1.74487 QALYs; ICSI only, 1.74497 QALYs; and all IVF, 1.74499 QALYs. The ICSI-only strategy had an incremental cost-effectiveness ratio (ICER) of $2 840 494 per additional QALY gained when compared to the anatomic-US strategy, and the all-IVF strategy had an ICER of $5 692 457 per additional QALY when compared with the ICSI-only strategy. Both ICERs exceeded considerably the standard willingness-to-pay threshold of $50 000-$100 000 per QALY. In a secondary analysis, the ICSI-only strategy had an ICER of $527 562 per additional case of major CHD detected when compared to the anatomic-US strategy. All IVF had an ICER of $790 510 per case of major CHD detected when compared with ICSI only. It was determined that it would cost society five times more to detect one additional major CHD through intensive screening of all IVF pregnancies than it would cost to pay for the neonate's first year of care. CONCLUSION: The most cost-effective method of screening for CHDs in pregnancies following IVF, either with or without ICSI, is to perform a fetal echo only when abnormal cardiac findings are noted on the detailed anatomy scan. Performing routine fetal echo for all IVF pregnancies is not cost-effective. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

High prevalence of central hypothyroidism among patients with transfusion dependent thalassemia in Hospital Pulau Pinang: A cross sectional study.

INTRODUCTION: Thalassemia is the most common heritable haematological disorder in Malaysia. Hypothyroidism is one of the complications of the transfusion dependent thalassemia (TDT) patients as a result of iron overload. MATERIALS AND METHODS: All registered TDT patients attending Haematology day care, Hospital Pulau Pinang from January 2019 to January 2020 were included in the study. Hypothyroidism was defined according to TSH and FT4, or based on the history of treatment for diagnosed hypothyroidism. RESULTS: There were 51 TDT patients, with 24 (47%) males and 27 (53%) females. Most of the patients were Malays (27, 53%) followed with Chinese (23, 45%) and Indonesian (1, 2%). Beta thalassemia major and HbE beta thalassaemia accounted for 35 (68.8%) and 14 (27.5%) TDT patients respectively, while two (3.9%) were HbH Constant Spring. Eleven (21.6%) had hypothyroidism; of which seven (63.6%) had central hypothyroidism, three (27.3%) had subclinical hypothyroidism, the remaining one (9.1%) had primary hypothyroidism. Three (27.3%) had concomitant hypogonadism, one (9.1%) had hypocortisolism and another (9.1%) had both diabetes mellitus and hypogonadism. There was no statistical relationship between the prevalence of hypothyroidism and age, serum ferritin, splenectomy history and iron chelation therapy. CONCLUSION: High prevalence of central hypothyroidism is reported. Measurement of both TSH and FT4 is recommended as initial screening for thyroid dysfunction among patient with TDT.

Prevalence of endocrine complications in transfusion dependent thalassemia in Hospital Pulau Pinang: A pilot study.

INTRODUCTION: Frequent blood transfusions results in iron overload and lead to multiple endocrine complications. In spite of improvements in iron chelation therapy, a significant number of transfusion dependent thalassaemia (TDT) patients still develop endocrine complications. The aim of this study is to evaluate the prevalence of various endocrine complications in our adult TDT patients and to study the correlation with serum ferritin and liver iron concentration (LIC). METHODS: A retrospective review of all TDT patients treated in Haematology Unit, Hospital Pulau Pinang (HPP) was conducted. RESULTS: Of the 45 adult TDT patients, 22 were males and 23 were females with mean age of 28.8±6.9 years old. Majority of TDT in HPP were beta thalassemia major (71.1%), followed by E-Beta thalassemia (24.4%) and HbH-Constant Spring (4.4%). Frequency of transfusion was 3-4 weekly. 40.0% of adult TDT suffered from at least one endocrine complication. Among the adult TDT patients with endocrine complication, 50% have one endocrinopathy, 38.9% with two types of endocrinopathies and 11.1% of them have three or more types of endocrinopathies. Hypogonadism (22.2%) was the commonest endocrine complication, followed by osteoporosis (20%), hypothyroidism (13.3%), diabetes mellitus (6.7%) and hypocortisolism (4.4%). Patients with endocrine complications were significantly older. Mean serum ferritin level and LIC was higher among patients with endocrine complications but both were not statistically significant. CONCLUSION: Endocrinopathy is still prevalent in 40% of adult TDT patients. This leads to higher health-care resource utilization, cost and significant morbidities among patients with TDT. Therefore, regular monitoring and early detection with intensification of chelation therapy is essential.

Expression patterns of HENMT1 and PIWIL1 in human testis: implications for transposon expression.

This study aimed to define the expression patterns of HENMT1 and PIWI proteins in human testis and investigate their association with transposon expression, infertility sub-type or development of testicular germ cell tumours (TGCTs). Testis biopsies showing normal spermatogenesis were used to identify normal localisation patterns of HENMT1 and PIWIL1 by immunolocalisation and RT-PCR after laser microdissection. 222 testis biopsies representing normal spermatogenesis, hypospermatogenesis, spermatogenic arrests, Sertoli cell-only (SCO) tumours and TGCTs were analysed by RT-qPCR for expression of HENMT1/PIWIL1/PIWIL2/PIWIL3/PIWIL4 and LINE-1 Additionally, HENMT1-overexpressing TCam2 seminoma cell lines were analysed for the same parameters by RT-qPCR. We found that HENMT1 and PIWIL1 are coexpressed in pachytene spermatocytes and spermatids. Expression of HENMT1, PIWIL1 and PIWIL2 was mainly dependent on germ cell content but low levels of expression were also detected in some SCO samples. Levels of HENMT1, PIWIL1 and PIWIL2 expression were low in TGCT. Samples with HENMT1, PIWIL2 and PIWIL4 expression showed significantly (P < 0.05) lower transposon expression compared to samples without expression in the same histological group. HENMT1-overexpressing TCam2 cells showed lower LINE-1 expression than empty vector-transfected control lines. Our findings support that the transposon-regulating function of the piRNA pathway found in the mouse is conserved in adult human testis. HENMT1 and PIWI proteins are expressed in a germ-cell-specific manner and required for transposon control.

Severe hypertriglyceridemia in a nondiabetic treated with low dose insulin infusion.

We report a case of a 54-year-old man with severe HTG which did not respond to conventional anti lipid therapies. He was treated with intravenous insulin and concurrent dextrose infusions which led to a dramatic reduction in serum triglyceride levels.

KPT-330 has antitumour activity against non-small cell lung cancer.

BACKGROUND: We investigated the biologic and pharmacologic activities of a chromosome region maintenance 1 (CRM1) inhibitor against human non-small cell lung cancer (NSCLC) cells both in vitro and in vivo. METHODS: The in vitro and in vivo effects of a novel CRM1 inhibitor (KPT-330) for a large number of anticancer parameters were evaluated using a large panel of 11 NSCLC cell lines containing different key driver mutations. Mice bearing human NSCLC xenografts were treated with KPT-330, and tumour growth was assessed. RESULTS: KPT-330 inhibited proliferation and induced cell cycle arrest and apoptosis-related proteins in 11 NSCLC cells lines. Moreover, the combination of KPT-330 with cisplatin synergistically enhanced the cell kill of the NSCLC cells in vitro. Human NSCLC tumours growing in immunodeficient mice were markedly inhibited by KPT-330. Also, KPT-330 was effective even against NSCLC cells with a transforming mutation of either exon 20 of EGFR, TP53, phosphatase and tensin homologue, RAS or PIK3CA, suggesting the drug might be effective against a variety of lung cancers irrespective of their driver mutation. CONCLUSIONS: Our results support clinical testing of KPT-330 as a novel therapeutic strategy for NSCLC.

Single-breath vital capacity high concentration sevoflurane induction in children: with or without nitrous oxide?

BACKGROUND: Single-breath vital capacity inhalation induction with high concentration sevoflurane (SBVC-HC) is a rapid and 'needleless' technique, preferred and well tolerated in the cooperative child. The addition of nitrous oxide may speed up induction by its second gas effects. Previous studies done in children looking at the effect of N(2)O on this technique lacked power and showed conflicting results. This study aims to investigate the effect of N(2)O on induction time for SBVC-HC sevoflurane induction in children. METHODS: Eighty unpremedicated, ASA I and II children, aged 5-15 yr having elective surgical procedures under general anaesthesia, were recruited and randomized to: Group A: 8% sevoflurane in O(2) 6 litre min(-1), and Group B: 8% sevoflurane in N(2)O 4 litre min(-1) and O(2) 2 litre min(-1). The primary outcome was the time to 'loss of eyelash reflex'. The time to return of 'regular respiration' and 'conjugate gaze' were also noted. RESULTS: The difference in the 'time to loss of eyelash reflex' was small but statistically significant. Group B: mean duration 53.6 s, standard deviation (SD) 16.1, compared with Group A: 63.5 s, SD 16.1 (mean difference 9.9, 95% confidence interval 2.5-17.3, P=0.01). Differences in the time to return of 'regular breathing' and 'conjugate gaze' were not statistically significant. Patients receiving N(2)O had less excitatory movements (P=0.007), but incidence of other adverse events was low and did not differ significantly between both groups. More than 94% of children would choose this method of induction again in both groups. CONCLUSIONS: We conclude that for SBVC-HC sevoflurane induction in children, the addition of N(2)O resulted in faster loss of consciousness and reduced excitatory movements.

Review of an 11-year Experience in Retrosigmoid Approach for Treatment of Acoustic Neuromas.

This study reviews surgery on acoustic neuromas by the second author using retrosigmoid approach from January 2000 to June 2010 in the state of Sarawak. There was a total of 32 patients in this study. The commonest presenting symptom was hearing loss (81.3%), followed by headache and tinnitus (each 37.5%), ataxia (34.4%) and facial numbness (21.9%). Twenty-seven patients (84.4%) had large tumor (≥ 3cm) while 5 patients (15.6%) had medium size tumor (1.5-2.9cm). The mean tumor size was 3.6 cm. Facial nerve outcome was good to moderate in 93.7% (House and Brackmann Grade I-IV). The most common complications were CSF leak with 3 patients(9.4%) and facial numbness with 2 patients(6.3%). All either resolved with treatment or improved. There was no mortality. Excision of acoustic neuromas using retrosigmoid approach could achieve acceptable facial nerve outcome with a low incidence of morbidity without mortality.

Glycaemic control and cost analysis when changing from gliclazide co-administered with metformin to pre-combined glibenclamide-metformin tablets in type 2 diabetes mellitus.

Type-2 diabetes mellitus (T2DM) patients who were on gliclazide co-administered with metformin were changed to pre-combined glibenclamide-metformin tablets in the Endocrine Clinic, Penang Hospital. We conducted a retrospective study to evaluate the differences in glycaemic control and treatment cost following the change. Eighty patients (60% females) with a mean age of 55 years old were studied. Mean glycosylated haemoglobin (HbAlc) reduction was -0.92% (p<0.01) and -0.83% (p<0.01) after three and six months respectively. Patients with baseline HbA1c > or =8% had greater reduction in mean HbA1c (-1.36%) after six months. The treatment cost per month was reduced by 45% at 3 months (p<0.01)) and 44% at 6 months (p<0.01). The change to pre-combined glibenclamide-metformin tablets resulted in significant improvement in glycaemia and reduction in treatment cost

Care of severe head injury patients in the Sarawak General Hospital: intensive care unit versus general ward.

Intensive care for severe head injury patients is very important in the prevention and treatment of secondary brain injury. However, in a resources constraint environment and limited availability of Intensive Care Unit (ICU) beds in the hospitals, not all severe head injury patients will receive ICU care. This prospective study is aimed to evaluate the outcome of severe head injured patients who received ICU and general ward care in Sarawak General Hospital (SGH) over a 6-month period. A total of thirty five severe head injury patients were admitted. Twenty three patients (65.7%) were ventilated in general ward whereas twelve patients (34.3%) were ventilated in ICU. Overall one month mortality in this study was 25.7%. Patients who received ICU care had a lower one month mortality than those who received general ward care (16.7% vs 30.4%), although it was not statistically different. Multivariate analysis revealed only GCS on admission (OR 0.731; 95% CI 0.460 to 0.877; P=0.042) as the independent predictive factor for one month mortality in this study.

Collembola are unlikely to cause human dermatitis.

Abstract There have been several unconfirmed case reports of dermatitis caused by Collembola (springtails). We recently investigated two nurses with dermatitis suspected to be caused by Drepanura Schött (Collembola: Entomobryidae). IgE antibodies to Collembola proteins were not detected in sera from the nurses and skin tests with the Collembola extract and crushed whole Collembola were negative in both the nurses and volunteers. This study suggests that the springtail Drepanura may not cause human dermatitis and that other organisms and organic matter that are also found in the moist environment inhabited by Collembola might instead be responsible.

Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer.

The Fanconi gene family has a role in DNA repair and inactivation of FANCF has been proposed as a mechanism of sensitisation to platinum chemotherapy. This study sought to confirm this hypothesis in cell lines and a large series of ovarian cancer samples. Promoter methylation was assessed by methylation-sensitive polymerase chain reaction of FANCF in nine ovarian cancer cell lines and 74 ovarian cancer samples taken from patients entered on a trial of cisplatin-based chemotherapy. This study confirmed methylation-dependent silencing of FANCF in one out of nine ovarian cancer cell lines. Methylation of FANCF was demonstrated in 13.2% of 53 evaluable ovarian tumour samples. Progression-free survival gave an HR of 3.63 (95% CI: 1.54-8.54, P=0.0016) in favour of the unmethylated cases. There was no association with overall survival. This study does not support methylation-dependent silencing of FANCF as a mechanism of sensitisation to platinum-based chemotherapy in ovarian cancer.

Endocrine complications in transfusion dependent thalassaemia in Penang Hospital.

Frequent blood transfusions can lead to iron overload which may result in several endocrine complications especially in the absence of adequate chelation therapy. The objectives of this study are to determine the prevalence of endocrine complications in transfusion dependent thalassaemia patients and the correlation of endocrine complications with the degree of iron chelation. This retrospective study looked at cases of adult patients with transfusion dependent thalassaemia treated in the Haematology Unit, Penang Hospital. Of the 25 transfusion dependent thalassaemia patients, there were 10 male and 15 female patients respectively with almost equal number of Malay and Chinese patients (13 and 12 patients respectively). Short stature was seen in 36.0% of our patients. In our cohort, 12 patients had delayed puberty (male 70.0% and female 33.3%). Prevalence of osteoporosis was 36.0%. Hypogonadism was noted in 40.0% of males and 46.7% of females. 53.4% of the female population had menstrual abnormalities with prevalence of primary and secondary amenorrhoea at 26.7% each. The prevalence of other endocrinopathies was much lower: 8.0% had diabetes mellitus and only one patient had hypocortisolism. Iron chelation appeared insufficient in our study population. The high frequency of endocrine complications noted in our study supports the rationale for regular follow-up of transfusion dependent thalassaemic patients to ensure early detection and timely treatment of associated complications.

Rare presentation of idiopathic duodenoduodenal intussusception.

Enteroenteric intussusception is a condition in which the full-thickness bowel wall becomes telescoped into the lumen of distal bowel. Intussusception in adult occurs infrequently and varies from childhood intussusception, particularly in its presentation, aetiology and treatment. Duodenoduodenal intussusception is rare because the duodenum is fixed in the retroperitoneal position. It usually occurs secondary to tumour, lipoma, Brunner's gland hamartomatous polyp or adenoma. The diagnosis in adults is usually made at laparotomy, where presentation is with intestinal obstruction. In non-emergency presentation, it may be difficult to arrive at an accurate diagnosis as symptoms may be vague, self-limiting intermittent abdominal pain. Clinical examinations and investigations may not be conclusive and another working diagnosis such as irritable bowel syndrome would be made. We describe a case where a patient initially presented with symptoms mimicking pancreatitis but his symptoms persisted over the course of 2 weeks. When a laparotomy was performed, duodenoduodenal intussusception was discovered and confirmed with histopathology. In this case, a discernible leading point could not be identified.

Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD).

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.

Beyond Ortner's syndrome--unusual pulmonary complications of the giant left atrium.

INTRODUCTION: The giant left atrium (GLA) is a complication of severe mitral valve disease and causes morbidity by compressing adjacent intra-thoracic structures. CLINICAL PICTURE: We report 2 cases of unusual pulmonary complications of the GLA. Case 1 developed recurrent collapse of the left lung due to left main bronchus compression. Case 2 was diagnosed with right middle lobe compression and collapse. TREATMENT AND OUTCOME: Case 1 was successfully treated by mitral valve replacement and left atrial reduction surgery. Case 2 was treated conservatively. CONCLUSION: Pulmonary atelectasis may occur in patients with GLA due to bronchopulmonary compression. Surgical management with valve replacement and atrial reduction may be necessary to relieve airway compression.

Cryptosporidiosis. Case report in a health team worker.

Cryptosporidium is a coccidial protozoan of the intestinal tract; cryptosporidiosis in veterinarians has been reported as a cause of diarrhea. It has also been reported as a cause of diarrhea in marrow transplant recipients. Cryptosporidiosis has gained attention recently because of its occurrence in patients with the acquired immune deficiency syndrome (AIDS). A healthy intensive care unit nurse who acquired cryptosporidiosis from a bone marrow transplant recipient with diarrhea caused by cryptosporidiosis is described. Results of laboratory examination, including T lymphocyte subsets, were normal. She was treated with bed rest and a liquid diet and her symptoms completely resolved after 15 days. Health care workers should be aware that cryptosporidiosis can be transmitted to them from patients and should follow precautions to avoid acquiring the disease.

Subtypes of endothelin receptors that mediate venous effects of endothelin-1 in anaesthetized rats.

1. The subtypes of endothelin receptors that mediate the effects of endothelin-1 (ET-1) on mean arterial pressure (MAP), heart rate (HR), mean circulatory filling pressure (MCFP), arterial resistance (RA), cardiac output (CO) and venous resistance (RV) were characterized in 9 groups of pentobarbitone-anaesthetized rats via the injection of ET-1 in the absence and presence of bosentan (Ro 47-0203, ETA- and ETB-receptor antagonist), PD 142893 (ETA- and ETB-receptor antagonist) or FR 139317 (ETA-receptor antagonist), as well as injection of the ETB-receptor agonist, IRL 1620. 2. Cumulative i.v. bolus injections of ET-1 or IRL 1620 (0.5, 1 and 2 nmol kg-1) dose-dependently increased MAP (ET: by 22, 34 and 44; IRL: 8, 17 and 28 mmHg), RA (ET: 62, 108 and 162; IRL: 51, 63 and 86% over baseline), RV (ET: 70, 132 and 179; IRL: 81, 89 and 98% over baseline) and MCFP (ET: 1.1, 1.8 and 1.9; IRL: 0.9, 1.0 and 1.2 mmHg) and reduced CO (ET: -18, -35 and -44; IRL: -24; -26; -25% below baseline). Equimolar doses of ET-1 and IRL 1620 caused similar initial transient depressor responses. Saline did not modify any haemodynamic variables in the time-control group. 3. Bosentan (10 mg kg-1, i.v.) inhibited ET-induced increases in MAP, RV, RA and MCFP and decrease in CO. PD 142893 (22 mg kg-1, i.v.) abolished ET-induced changes on MAP, RV, RA and CO, but did not alter effects on MCFP. Bosentan alone did not cause haemodynamic changes, but PD 142893 alone elevated MCFP (0.9 +/- 0.3 mmHg at 1 h after injection) and did not alter other variables. Both antagonists abolished the initial depressor effects of ET-1. 4. FR 139317 (1 mg kg-1, i.v.) partially inhibited the increases in MAP, RV, RA and MCFP and decreases in CO elicited by ET-1, but did not alter the transient depressor response of ET-1. 5. The results show that both ETA- and ETB-receptors mediate the arterial and venous constrictor effects of ET-1. Bosentan is more efficacious than PD 142893 in inhibiting the venous effects of ET-1.

Increase by NG-nitro-L-arginine methyl ester (L-NAME) of resistance to venous return in rats.

1. The effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on mean circulatory filling pressure (MCFP), total peripheral resistance (TPR), cardiac output (CO) and resistance to venous return (Rv) were studied in rats. 2. In conscious, unrestrained rats, L-NAME (0.5-16 mg kg-1) dose-dependently increased mean arterial pressure (MAP) but not MCFP, an inverse index of venous compliance, either in the absence or presence of the ganglionic blocker mecamylamine (10 mg kg-1). 3. In pentobarbitone-anaesthetized rats, L-NAME (2, 4, 8 mg kg-1) increased MAP and reduced CO in a dose-related manner but did not change MCFP, TPR (+84, +140 and +192%) as well as Rv (+62, +72, +110%) were dose-dependently increased by L-NAME. 4. Our results show that L-NAME reduces CO by increasing arterial as well as venous resistances. L-NAME does not affect MCFP.