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Biomedical subjects

R Fernando

Publications and source records attributed to R Fernando.

At least 37 records · Page 2Linked to original sources

Mercury vapor and female reproductive toxicity.

Epidemiological studies finding menstrual cycle abnormalities among women occupationally exposed to Hg degrees prompted us to investigate the mechanisms of reproductive toxicity of Hg degrees in the female rat. Nose-only Hg degrees vapor inhalation exposures were conducted on regularly cycling rats 80-90 days of age in dose-response and acute time-course studies, which have previously proven useful as a model to identify ovarian toxicants. Vaginal smears were evaluated daily and serum hormone levels were correlated with cycle and with ovarian morphology at necropsy. Exposure concentration-related effects of Hg degrees were evaluated by exposing rats to 0, 1, 2, or 4 mg/m3 Hg degrees vapor 2 h/day for 11 consecutive days. Tissue Hg levels correlated with exposure concentration and duration. Exposure of rats to 4 mg/m3 (but not 1 or 2 mg/m3) Hg vapor for 11 days resulted in significant decreases in body weights relative to controls. Estrous cycles were slightly prolonged in the 2 and 4 mg/m3 dose groups, and serum estradiol and progesterone levels were significantly different in the 4 mg/m3 group compared to controls. The alterations in cycle and hormones at the 4 mg/m3 exposure concentration were attributed to body weight loss and generalized toxicity. In the time-course study, rats were exposed to 2 mg/m3 Hg degrees or air beginning in metestrus and evaluated daily for 8 days. A lengthening of the cycle was detected and morphological changes were observed in the corpora lutea (CL) after exposure for 6 days. To determine if changes in the CL and cyclicity correlated with a functional defect, rats were exposed to Hg degrees vapor and evaluated for pregnancy outcome. There were no significant effects on pregnancy rate or numbers of implantation sites when rats were exposed to 1 or 2 mg/m3 Hg degrees for 8 days prior to breeding, or when exposed for 8 days after breeding. These studies indicate that exposure to Hg degrees vapor altered estrous cyclicity, but had no significant effect on ovulation, implantation, or maintenance of first pregnancy during exposure of short duration in female rats.

Administration, Inhalation↗

Minimum local analgesic dose of intrathecal bupivacaine in labor and the effect of intrathecal fentanyl.

BACKGROUND: Combining bupivacaine with fentanyl for intrathecal analgesia in labor is well recognized, but dosages commonly used are arbitrarily chosen and may be excessive. This study aimed to determine the median effective dose (ED50) of intrathecal bupivacaine, defined as the minimum local analgesic dose (MLAD), and then use this to assess the effect of different doses of fentanyl. METHODS: In this double-blind, randomized, prospective study, 124 parturients receiving combined spinal epidural analgesia at 2-6-cm cervical dilatation were allocated to one of four groups to receive bupivacaine alone or with 5, 15, or 25 microg fentanyl, using the technique of up-down sequential allocation. Analgesic effectiveness was assessed using 100-mm visual analog pain scores, with less than or equal to 10 mm within 15 min defined as effective. MLAD was calculated using the formula of Dixon and Massey. Pruritus and duration of spinal analgesia were also recorded. RESULTS: Minimum local analgesic dose of intrathecal bupivacaine was 1.99 mg (95% confidence interval, 1.71, 2.27). There were similar significant reductions in MLAD (P < 0.001) for all bupivacaine-fentanyl groups compared with bupivacaine control. There was a dose-dependent increase in both pruritus and duration of spinal analgesia with increasing fentanyl (P < 0.0001). CONCLUSION: Under the conditions of this study, the addition of intrathecal fentanyl 5 microg offers a similar significant bupivacaine dose-sparing effect as 15 and 25 microg. Analgesia in the first stage of labor can be achieved using lower doses of fentanyl, resulting in less pruritus but with a shortening of duration of action.

Adult↗

Intermittent oral iron supplementation during pregnancy.

RATIONALE: It has been suggested that in pregnant women weekly iron supplements are as effective as daily supplements in preventing iron deficiency anaemia (IDA). OBJECTIVE: To compare the effectiveness of prophylactic antenatal oral iron supplements given weekly, thrice weekly and daily in preventing IDA in pregnancy. DESIGN: A randomised control trial. SETTING: University antenatal clinic, (UANC) Galle. SUBJECTS AND METHOD: An oral iron supplement containing 100 mg of elemental iron was randomly given weekly (n = 26) thrice weekly (n = 35) and daily (n = 31) to 92 women who were 14 to 24 weeks pregnant. Haemoglobin (Hb), serum ferritin (SF) and haematocrit (Hct) were assessed before and after 12 to 20 weeks of supplementation and a logistic regression analysis carried out. RESULTS: The risk of developing anaemia was significantly higher in the weekly (odds ratio 15, 95% CI 1.4-165.6, p < 0.03) and possibly higher in the thrice weekly (odds ratio 3, 95% CI 0.3-30.3, p = 0.3) groups. The risk of developing iron deficiency (SF < 12 micrograms/l) was also significantly higher in the weekly (odds ratio 18, 95% CI 2.8-115.5, p < 0.003) and thrice weekly (odds ratio 10, 95% CI 1.6-64.8, p < 0.02) groups. CONCLUSION: Prophylactic oral iron supplements when given intermittently were not effective in preventing iron deficiency anaemia in pregnancy.

Adult↗

Internal carotid-artery response to 5% carbon dioxide in women with polycystic ovaries.

Although polycystic ovary syndrome is associated with hypertension, hyperlipidaemia, and insulin resistance, mortality from cerebrovascular disease is not increased. We previously reported lower downstream resistance in the internal carotid artery in women with polycystic ovary syndrome. This study was designed to assess vascular reactivity by measuring the response to inhalation of 5% carbon dioxide. We studied 34 young women with polycystic ovary syndrome, 15 with symptomless polycystic ovaries, and 18 controls.

Administration, Inhalation↗

Internal carotid artery haemodynamics in women with polycystic ovaries.

Although polycystic ovarian syndrome (PCOS) is associated with risk factors for cerebrovascular disease, the available evidence does not demonstrate increased stroke mortality, and it has been suggested that some protective mechanisms must be operating in these women. Haemodynamic changes have been demonstrated in the pelvic vessels and aorta in this syndrome, but there have been no studies of the cerebral circulation. Since insulin resistance is a central feature of PCOS, it is of interest that cerebral blood flow may be altered in diabetic subjects. The present study was designed to assess internal carotid artery haemodynamics in women with PCOS, asymptomatic women with polycystic ovaries (PCO women) and healthy controls. Mean internal carotid pulsatility index, measured using pulsed Doppler ultrasound under standardized conditions, was significantly lower in 35 PCOS and 15 PCO women than in the 18 controls. This was also shown on multiple regression analyses. Peak systolic velocity did not differ between groups. In view of the difficulty of interpreting pulsatility index in low-impedance vascular beds, the 'back' pressure was calculated and found to be lower in women with polycystic ovaries. This is the first demonstration of lower pulsatility index and back pressure (suggestive of reduced vascular tone) in the cerebral circulation of these women, independent of blood pressure, insulin resistance and other endocrine or metabolic factors. Changes in internal carotid haemodynamics may offset the risk of cerebrovascular disease commonly associated with polycystic ovaries.

Adolescent↗

Chemical stability of bupivacaine, lidocaine and epinephrine in pH-adjusted solutions.

Epinephrine and sodium bicarbonate may be added to local anaesthetic solutions in order to reduce the onset time and enhance the quality of epidural anaesthesia for Caesarean section. Such mixtures are sometimes prepared several hours in advance for subsequent use in emergency Caesarean section through a pre-existing epidural catheter. To evaluate this practice, we studied the chemical stability in solution over 24 h of nine epidural mixtures consisting of different combinations of bupivacaine, lidocaine, epinephrine and sodium bicarbonate. In mixtures alkalinised with sodium bicarbonate, epinephrine concentrations decreased significantly over 24 h (p<0.0001), whereas those in nonalkalinised mixtures did not change with time. Bupivacaine and lidocaine concentrations in all mixtures did not decrease over time regardless of alkalinisation. We do not recommend adding epinephrine to alkalinised epidural solutions that are to be stored for a prolonged period before clinical use.

Anesthesia, Epidural↗

Evaluation of a spinal needle locking device for use with the combined spinal epidural technique.

Success of the 'needle-through-needle' technique for combined spinal epidural analgesia requires the immobilisation of the spinal needle during intrathecal injection. A device that achieves this was evaluated in 200 labouring women, randomly allocated to receive a combined spinal epidural using the CSEcure(R) (SIMS Portex, UK) locking needle or a conventional, non-locking technique. Data collection included the incidence of dural click as the spinal needle penetrated the dura mater, presence of cerebrospinal fluid in the spinal needle hub and the number of technical failures with the spinal component. Successful dural punctures with the spinal needle were similar for locking and non-locking needles (99.0 vs. 98.0%; p = 0.55), despite a small but significant reduction in dural click with the locking needle compared with the non-locking technique (97. 0 vs. 84.7%; p < 0.01). Although not statistically significant, there was a higher number of technical failures, mainly due to spinal needle movement, in the non-locking group (9.1 vs. 3.1%; p = 0.08). The locking needle device may be a useful alternative to conventional methods for combined spinal epidural analgesia.

Adult↗

Postpartum headache after epidural blood patch: investigation and diagnosis.

Use of an epidural blood patch to treat spinal headache after accidental dural puncture is well recognized. The high success rate associated with this practice has been questioned and it is not uncommon for patients to suffer recurring headaches after a supposedly successful blood patch. We describe a patient in labour who suffered accidental dural puncture, and whose headache was treated twice with an epidural blood patch. Despite this, the headache persisted. The case highlights the difficulty in the diagnosis of headache in the postnatal period in patients who have had regional analgesia and the importance of considering an alternative pathology, even if epidural blood patching has been successful. In this case, a diagnosis of cortical vein thrombosis was made. The incidence, presentation, aetiology and treatment of this rare condition is described.

Adult↗

Pain perception with pH buffered peribulbar anaesthesia: a pilot study.

AIMS: To determine the relation between pH of anaesthetic solutions and patient perception of pain with peribulbar injection of local anaesthesia. METHODS: This prospective randomised controlled double blind pilot study involved 60 consecutive patients who received a peribulbar block with either a standard acidic local anaesthetic of 5 ml 2% lignocaine and 5 ml of 0.5% bupivacaine (solution A), or an alkalinised solution composed of the same anaesthetic agents but with a pH of 7.44 (solution B). Before surgery patients were asked to grade the pain of both the preoperative dilating drops and the peribulbar injection using a visual analogue scale. RESULTS: The mean pain scores were similar in the two treatment groups-slightly higher (4.97) in group B who received the buffered solution, compared with group A (4.84) who received the plain solution. The small difference (-0.13, 95% confidence limits -1.6 and +1.3) was not significant. There was, however, a highly significant association between pain threshold ("drop pain") and injection pain levels (p<0.0001). CONCLUSION: This study showed no difference in the reduction in the pain experienced by patients undergoing peribulbar anaesthesia with pH buffered local anaesthetic. The study suggests the importance of "pain threshold" as a confounder and also showed the considerable pain felt by some patients on instillation of the preoperative dilating drops.

Analysis of Variance↗

Anti-inflammatory pre-treatment and the resultant effects of interleukin-10: adjuncts to multi-therapeutical strategies.

With the advent of off-pump coronary bypass surgery, there is increasing demand for research in attenuating the deleterious effects of cardiopulmonary bypass (CPB). An improved understanding of the systemic inflammatory response syndrome (SIRS) has distinguished which areas of components have the most adverse effects and which are, in fact, anti-inflammatory. This classification of inflammatory components allows strategic treatment for those likely to cause the most clinically significant 'effect', suitably termed 'effectors'. This article will identify current methods in treating 'effectors', as well as those components having anti-inflammatory effects. This article selectively features certain inflammatory components by: (1) grouping them as being 'mediators' or 'effectors'; (2) relating them to interleukin-10 (IL-10) and treatments potentiating anti-inflammatory effects; (3) summarizing their mechanisms of action; (4) recognizing the time periods during bypass exhibiting peak levels; and (5) investigating current treatment. methods and identifying their significance to 'effectors'. A literature search in MEDLINE was performed, featuring articles of the English-language within the past 5 years. Because of the characteristic of having interlinked multi-component cascades, it is evident that treating SIRS with a one-dimensional method would be inadequate. This article not only confirms the importance of a multi-factorial therapeutic approach, but also targets the inflammatory components having the highest potential for causing direct tissue damage, known as 'effectors'. In addition, previous studies have found IL-10 to have 'regulatory effects' during periods of excessive pro-inflammatory stimuli. These findings may arouse new ideas in exploring the area of anti-inflammatory cytokines. In fact, future treatments may suggest a new classification featuring 'mediators', 'effectors', and 'regulators'.

Cardiopulmonary Bypass↗

Comparison of intrathecal and epidural diamorphine for elective caesarean section using a combined spinal-epidural technique.

To assess calculated equivalent doses of intrathecal and epidural opioids for elective Caesarean section in terms of quality and duration of analgesia, and incidence of side effects, we have compared 50 patients, allocated randomly to one of two groups to receive either diamorphine 0.25 mg intrathecally (group 1) or 5 mg epidurally (group 2), in addition to intrathecal bupivacaine 10 mg, using a combined spinal-epidural technique. There was no significant difference in duration of analgesia between groups (group 1 mean 14.6 (SD 5.9) h, group 2 14.2 (6.5) h; mean difference 0.8 h; 95% Cl -2.8-4.5; P = 0.65) or quality of analgesia (VAPS and VRS scores). The degree of pruritus was similar in both groups (80-88%) but the incidence of postoperative nausea and vomiting was significantly higher in the epidural group (24% vs 4%; P < 0.05). Intrathecal diamorphine 0.25 mg produced the same duration and quality of postoperative analgesia as epidural diamorphine 5 mg for elective Caesarean section but with significantly less nausea and vomiting.

Adult↗

Effect of combined spinal-epidural ambulatory labor analgesia on balance.

BACKGROUND: Low-dose combined spinal-epidural analgesia in labor has proved popular with women because lower-limb motor power is preserved, allowing ambulation. However, there has been debate about the safety of allowing women to walk following low-dose regional analgesia because of somatosensory impairment. The authors undertook a prospective controlled observational study using computerized dynamic posturography to examine balance function in pregnant women after combined spinal-epidural analgesia. METHODS: The authors performed posturographic testing on 44 women in labor after institution of regional analgesia and compared them with a control group of 44 pregnant women. A separate group of six women were tested both before and after combined spinal-epidural analgesia. RESULTS: Neurologic examination after regional analgesia showed two parturients (4%) to have motor weakness (excluded from posturography). Four women (9%) had clinical dorsal column sensory loss; these women all completed posturography. The spinal-epidural analgesia group showed a small, statistically significant reduction in one of six posturographic sensory-organization tests; however, this difference was functionally minor. There were no other differences in posturography between the control and spinal-epidural groups. Similar results were found in the paired study, in which there was minimal change in balance function after spinal-epidural analgesia. CONCLUSIONS: This is the first study to objectively examine the effect of spinal-epidural analgesia on balance function. Using computerized dynamic posturography, the authors were unable to find any functional impairment of balance function after spinal-epidural ambulatory analgesia in women in labor who had no clinical evidence of motor block.

Adult↗

Homicidal poisoning with glibenclamide.

Homicidal poisoning is rare in Sri Lanka although suicidal poisoning, especially with pesticides, is a grave health problem. Clinical and medicolegal findings and the subsequent court proceedings of two cases of homicide due to induced hypoglycaemia with an anti-diabetic drug are presented. The drug used was glibenclamide. Findings emphasize the importance of toxicological analysis and extensive police investigations when the clinical diagnosis and the cause of death are in doubt.

Adult↗

LDL receptor gene expression in human mesangial cells under the influence of calcium channel blockers.

BACKGROUND: Intracellular transport of lipid through the regulation of LDL receptor (LDLr) may be important in the progression of renal dysfunction. METHODS: We explored LDLr gene expression in human mesangial cell line (HMCL) under influence of calcium channel blockers using cell proliferation, LDL binding, Northern blot and LDLr promoter activity assay. RESULTS: Diltiazem and verapamil increased the expression of LDLr mRNA in a dose-dependent manner. Increased LDLr mRNA paralleled LDL binding. Nifedipine did not increase the expression of LDLr mRNA and LDL binding to HMCL at 1 - 100 micromol/l. The LDLr promoter activity assay showed that treatment with 100 micromol/ of diltiazem and verapamil increased LDLr promoter activity by 126.72 +/- 10.68%, and 166.41 +/- 11.41%, respectively, at 24 hours (control as 100%), while treatment with 100 micromol/l of nifedipine had an inhibitory effect on LDLr promoter activity. High concentration of LDL (250 microg/ml) inhibited promoter activity. Diltiazem or verapamil coincubated with LDL (250 microg/ml) could not override transcriptional inhibition by LDL. CCBs inhibited the proliferation of HMCL, therefore, CCBs-induced LDLr expression did not depend on a proliferative response. Signal transduction pathway experiments showed that the calmodulin transduction pathway was involved in LDLr upregulation induced by diltiazem or verapamil. Additionally, tyrosine kinase and PKC pathways were involved in the induction of LDLr induced by verapamil. CONCLUSION: These studies show that diltiazem and verapamil increase LDLr gene transcription and expression which is independent of cell proliferation in HMCL.

Blotting, Northern↗