Routine Cyclosporine concentration - C2 level Monitoring. Is it helpful during the early post Transplant Period?

Background

Pre dose or trough blood cyclosporine (CSA) concentration is routinely monitored and the result is used to alter patient''s drug dosing. Patients with identical pre dose blood CSA may have very different systemic exposure to the drug. Recently CSA 2 hour post dose level [C2] has been reported to correlate better with drug exposure. We undertook this study to evaluate the influence of trough and C2, CSA concentration monitoring on short-term renal allograft outcomes.

Methods

25 patients of renal transplant receiving a triple drug regimen of CSA micro emulsion (Panacea Biotec) 8mg/kg, azathioprine 1mg/kg and prednisolone 0.5mg/kg were analyzed prospectively for graft outcomes. CSA levels were monitored in whole blood by radioimmunoassay using monoclonal antibodies, at 72 hours after the transplant.

Results

The mean age of patients was 37.08 + 9.1 years. There were 20 males and 5 females. The mean age of donors was 40.2 + 8.2 years. There were 11 related donors with at least a haplomatch, 4 spousal and 10 unrelated donors with a nil antigen match. The mean pre dose CSA concentration was 289.22 + 171.9ng/ml; range (98.8 + 783.41ng/ml). The CSA concentration at 2 hours after the CSA administration was 838 + 310.87ng/ml (range, 169 + 1268ng/ml). 3 (12%) patients had acute rejection. In these patients the mean pre dose CSA concentration was 328.67ng/ml and the mean C2, CSA concentration was 1006.26ng/ml. CSA induced hemolytic uraemic syndrome was diagnosed in one patient. The trough and C2, CSA concentration levels were 174 and 870.83ng/ml respectively in this patient.

Conclusion

In our study CSA levels, trough and peak showed significant inter patient variability. The trough and C2 concentration levels did not correlate with the episodes of acute rejection. We conclude that in a triple drug regimen with fixed dosing schedules routine trough CSA level monitoring is not helpful in the acute post renal transplant period.Key Words: Cyclosporine levels, Cyclosporine trough levels, C2 levels     

Diffusion-weighted imaging and proton magnetic resonance spectroscopy in perinatal hypoxic-ischemic encephalopathy: association with neuromotor outcome at 18 months of age

We evaluated early diffusion-weighted imaging findings, the quantitative apparent diffusion coefficient, and magnetic resonance spectroscopy (the presence of lactate and ratios of N-acetylaspartate to total creatine and choline to total creatine) in the prediction of the 18-month neuromotor outcome of term newborns with hypoxic-ischemic encephalopathy. Conventional T1- and T2-weighted and diffusion-weighted imaging was performed in 20 asphyxiated term newborns, with additional basal ganglia magnetic resonance spectroscopy in 15 newborns between 2 and 18 days of life (mean 7.3 days). Neuromotor outcome was dichotomized into normal and abnormal for statistical analysis. Statistically significant differences in the ratios of N-acetylaspartate to total creatine, but not apparent diffusion coefficient values and ratios of choline to total creatine, were found between infants with a normal and an abnormal outcome (Mann-Whitney U-test, P = .010). There was a significant association between the presence of a lactate peak and an abnormal outcome (chi-square test, P = .017). The presence of a lactate peak for predicting an abnormal outcome had a sensitivity of 100% and a specificity of 80%, and the odds ratio was 37.4. Ischemic lesions were more conspicuous and/or extensive on diffusion-weighted imaging in all except one neonate. The presence of normal findings on both diffusion-weighted imaging and conventional magnetic resonance imaging is predictive of a normal neuromotor outcome, whereas lactate and a reduced ratio of N-acetylaspartate to total creatine in the basal ganglia, but not an apparent diffusion coefficient, are associated with an abnormal outcome at 18 months of age.     

Noninvasive assessment of corneal sensitivity in young and elderly diabetic and nondiabetic subjects

PURPOSE: To investigate the effect of age and diabetes on corneal sensitivity using the noncontact corneal aesthesiometer (NCCA). METHODS: One hundred sixteen nondiabetic subjects and 111 diabetic subjects (33 type I and 78 type II) were recruited and divided into three age groups: Young (or=60 years). The exclusion criteria included patients with severe retinopathy requiring treatment, a history of invasive ocular surgery, or a history of conditions known to affect corneal sensitivity. The corneal cooling sensation threshold, for the right eye of each subject, was assessed with a double-staircase method-of-limits technique with the NCCA. This instrument uses a controlled pulse of air to produce a small, localized reduction in the surface temperature of the eye, which is detected by the nerves in the corneal epithelium. RESULTS: Analysis of the scatterplot of each subject's central cooling sensation threshold revealed a gradual loss of sensitivity with increasing age (nondiabetic, r(2) = 0.349; diabetic, r(2) = 0.131). Within the nondiabetic group, inter-age-group comparisons found significant differences between the central corneal cooling sensation thresholds for the three age groups (t-test, P < 0.01). Within the diabetic group, a significant difference was found between the Middle and Older categories only (t-test, P < 0.05). In summary, the Young group was more sensitive than the Middle group, which was more sensitive than the Older group. Within both type I and type II diabetic subjects, there was neither a significant relationship between duration of the disease and corneal sensitivity (t-test, P > 0.05) nor a gender-based difference (t-test, P > 0.05). CONCLUSIONS: There is a gradual reduction in corneal sensitivity with increasing age in both nondiabetic subjects and diabetic subjects, along with an increasing variation in the measured threshold. There is no relationship between corneal sensitivity and the time since diagnosis of diabetes for a thermally cooling stimulus, suggesting that the A partial differential and C fibers of the corneal innervation are affected differently by abnormal glucose metabolism in the diabetic cornea.     

The cultural and social meanings of childbearing for Chinese and Scottish women in Scotland

OBJECTIVE: to analyse the meanings that women gave to their childbearing experiences in order to provide some useful insights as to how their experiences might be improved. SETTING: maternity units in Scotland. DESIGN: four semi-structured interviews with each of ten Chinese and ten Scottish women in their own language; and unstructured interviews with 45 health workers, women's relatives and their friends. FINDINGS: having children was meaningful to Scottish and Chinese women in Scotland in different ways which were related to their social positions, beliefs and practices involved and the change in social status on the birth of a child. Different meanings demanded different coping strategies in healthy childbearing. Scottish women took greater interest in their sense of control over their childbearing. Some Chinese women were experiencing more extensive cultural conflicts and changes as they tried to identify with the new culture, while the others were experiencing gradual changes over a period of time consciously or unconsciously. Both Chinese and Scottish women in the study were in a struggle between autonomy and control over their childbearing--between the mind and the body. CONCLUSION: childbearing is socially shaped and culturally specific. Maternity services need to consider ways in which cultural sensitive care can be provided to women in a multi-ethnic modern society.     

Rice-body formation in atypical mycobacterial tenosynovitis and bursitis: findings on sonography and MR imaging

OBJECTIVE: This article describes rice bodies found in patients with atypical mycobacterial tenosynovitis and bursitis, emphasizing the sonographic and MR imaging appearances of these small bodies. CONCLUSION: Rice bodies occur in patients with atypical mycobacterial tenosynovitis and bursitis. When small, rice bodies are better visualized on MR imaging than on sonography, allowing the radiologist to consider appropriate diagnoses.     

cGMP-dependent and not cAMP-dependent kinase is required for adenosine-induced dilation of intracerebral arterioles

Adenosine (ADO) is a potent cerebral vasodilator and has been proposed as a metabolic regulator of cerebral blood flow. However, the signal transduction pathway by which ADO causes vasodilation in cerebral microvessels is currently unknown. The current study was designed to investigate the role of cyclic nucleotides and cyclic nucleotide-dependent protein kinases in ADO-induced dilation of resistance-sized rat cerebral arterioles that develop spontaneous tone. Arterioles were cannulated and perfused intraluminally at constant flow (2 microl/min) and pressure (60 mm Hg). ADO (29.7 +/- 2.0%; 1 microM), CGS-21680 (16 +/- 4%, 1 microM), 8-bromo-cyclic guanosine monophosphate (8 Br-cGMP; 29.9 +/- 3.9%; 100 microM), sodium nitroprusside (SNP; 30.6 +/- 3.3%, 1 microM), cyclic guanine monophosphate-dependent protein kinase activator (Sp-8-pCPT-cGMPS, 25.9 +/- 4.2%; 10 microM), forskolin (30.5 +/- 5.9%; 0.1 microM), and pH 6.8 all produced large dilations. The selective cGMP-dependent protein kinase inhibitor, Rp-8-pCPT-cGMPS (10 microM), had no effect on resting diameter or reactivity to acidic pH, but significantly ( < 0.05) attenuated arteriolar dilations to ADO (59%, n = 8), CGS-21680 (60%, n = 4), SNP (62%, n = 3), 8 Br-cGMP (88%, n = 3), and Sp-8-pCPT-cGMPS (98%, n = 3). H8, the less-selective cyclic nucleotide-dependent protein kinase inhibitor, had similar effects as Rp-8-pCPT-cGMPS. Additionally, the inhibitor of the soluble guanylate cyclase, 1H-[1,24]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), blocked the response to SNP (70% inhibition) and significantly inhibited the ADO response (43% inhibition). In contrast, inhibition of the cyclic ADO monophosphate (cAMP)-dependent protein kinase Rp-8-CPT-cAMPS had no effect on the ADO, SNP, or pH responses, but significantly blocked forskolin-induced vasodilation (53%). It is concluded that ADO-induced vasodilation in cerebral microvessels, at least in part, involves cGMP and cGMP-dependent protein kinase, but not cAMP or cAMP-dependent kinase. Our data therefore provides a new insight into mechanisms by which ADO invokes vasodilation in cerebral microvascular arterioles.     

Laparoscopic management of omental torsion secondary to an occult inguinal hernia

Torsion of the greater omentum is an uncommon surgical emergency. Most of the reported cases have been primary omental torsion with infarction, in which the underlying cause is largely unknown. Right-sided abdominal symptoms are the predominant complaint. Left-sided omental torsion is rather infrequent, and the preoperative diagnosis is extremely difficult. We report a case of omental torsion secondary to an occult left indirect inguinal hernia that was successfully diagnosed and managed laparoscopically.     

Ictal (99m)Tc ECD SPECT in paroxysmal kinesigenic choreoathetosis

Paroxysmal kinesigenic choreoathetosis is a rare neurologic disorder characterized by sudden attacks of brief involuntary dyskinetic movement that are precipitated by voluntary movement. A 14-year-old male who presented with frequent brief attacks of hemidystonia triggered by sudden movement is reported. Investigations, including video electroencephalogram and magnetic resonance imaging of brain, were normal. There was excellent and sustained response to carbamazepine. Ictal single-photon emission computed tomography using (99m)Tc ethyl cysteinate dimer revealed increased perfusion of the contralateral basal ganglia, which is associated with onset of choreoathetosis attacks. Our findings provide evidence that hyperactivity of the basal ganglia is associated with the dyskinetic attacks in paroxysmal kinesigenic choreoathetosis.