Cervical nerve root stimulation. Part I: technical aspects and normal data.

OBJECTIVE: Cervical nerve root stimulation (CRS) is a technique of assessing the proximal segments of motor axons destined to upper extremity muscles. Few studies report normal values. The objective was to determine CMAP onset-latencies and CMAP amplitude, area, and duration changes in healthy controls for the abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps, and riceps muscles. In addition, to determine the tolerability of CRS, as measured by the visual analog scale (VAS). METHODS: We studied 21 healthy volunteers prospectively with CRS using four target muscles (APB, ADM, biceps, and triceps) bilaterally. Collision studies were used in all APB recordings. VAS was obtained in all subjects. RESULTS: Mean CMAP onset-latencies were: APB 14 +/- 1.5 ms; ADM 14.2 +/- 1.5 ms; biceps 5.4 +/- 0.6 ms; triceps 5.4 +/- 1.0 ms. Onset-latency significantly correlated with height for all nerves. The mean change in CMAP amplitude and area (%) between most distal stimulation and CRS was: APB reduction of 15.1 +/- 11.6 and 4.9 +/- 3.6%; ADM reduction of 21.1 +/- 10.7 and 17.2 +/- 8.8; biceps reduction of 10 +/- 11.5 and reduction of 8.7 +/- 6.8; triceps increase of 3.3 +/- 5.2 and 11.0 +/- 9.9% respectively. Mean CMAP duration change between most distal stimulation and CRS was: APB, increase of 20.4 +/- 7.4%; ADM, increase of 14.4 +/- 8.5%; biceps, increase of 13.9 +/- 10.8%; triceps, increase of 7.7 +/- 6.7%. The mean VAS score was 3.8 +/- 1.2, and all subjects completed the study. CONCLUSIONS: The present study establishes normative data and indicates that CRS is a well-tolerated technique. SIGNIFICANCE: The normal values may be used as reference data for the needle CRS technique in the assessment of proximal conduction abnormalities.     

Cytochrome P450 3A4 and P-glycoprotein Activity and Assimilation of Tacrolimus in Transplant Patients with Persistent Diarrhea

Renal transplant recipients suffering from persistent diarrhea have been repeatedly reported to have increased tacrolimus (Tac) trough levels. This study aimed to explore this phenomenon in detail in 15 renal transplant recipients with diarrhea, whose immunosuppression consisted of corticosteroids, mofetil mycophenolate and Tac. Both hepatic and intestinal CYP3A4 and PGP activity, important determinants of Tac bioavailability, were assessed, together with global CYP activity and investigations for gastrointestinal infection, function and morphology. Global CYP, CYP3A4, PGP and trough/dose levels of Tac were compared with diarrhea-free controls. In addition, a pharmacokinetic study of Tac was performed in 11 patients affected by diarrhea versus 9 controls. As expected, diarrhea was associated with increased Tac trough levels. An even stronger, significant increase of dose-normalized Tac levels was observed between 90 and 360 min after Tac intake. Time to peak concentration and drug half-life, however, were not altered. In addition, a concomitant decrease (+/-50%) of intestinal PGP activity was noticed in patients with diarrhea. For global CYP, CYP3A4 and hepatic PGP activity no such differences were noted. This pattern was not influenced by the specific cause of diarrhea. These data strongly suggest that persistent diarrhea is associated with an increased oral bioavailability of Tac.     

The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.

BACKGROUND: In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided. METHODS: Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations. RESULTS: 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit. CONCLUSION: Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.     

Genetic variation in serotonin transporter alters resting brain function in healthy individuals.

BACKGROUND: Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals. METHODS: Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores. RESULTS: Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood. CONCLUSIONS: The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.     

Laparoscopic incisional hernia repair after liver transplantation.

Incisional hernias occur in up to 17% of patients after liver transplantation. Laparoscopic ventral hernia repair is associated with fewer wound complications and a decreased incidence of recurrence when compared to open hernia repair in nontransplant patients. This is a retrospective review of 13 patients who underwent laparoscopic incisional hernia repair (LAP group) after liver transplantation compared to 14 patients who had open repairs (OP group; all but one with mesh). Primary immunosuppression in both groups at the time of transplantation was tacrolimus, but more patients in the LAP group were on sirolimus at the time of hernia, while more patients in the OP group were on prednisone at the time of hernia repair. All operations were completed with a laparoscopic approach; there were no conversions to open. Length of stay differed significantly between the 2 groups, with a mean of 5.4 days for the LAP group compared to 2.7 days in the OP group (0.0059). Complications occurred in 2 (15%) of the patients in the LAP group and 5 (36%) in the OP group. One patient in the LAP group required mesh removal to exclude causes of recurrent ascites, and 1 in the OP group for mesh infection. One (7.6%) of the patients in the LAP group developed a recurrence, compared to 29% (4) of the OP group (P =0.3259). In conclusion, laparoscopic incisional hernia repair is safe in patients after liver transplantation, with a low risk of infection or recurrence.     

Effects of Ethanol Exposure during the Third Trimester Equivalent on Neuron Number in Rat Hippocampus and Dentate Gyrus

An artificial rearing procedure was used to expose neonatal rats to a formula containing 3.74% ethanol during postnatal days 4 through 10. This treatment produced a mean blood ethanol concentration of 379.8 +/- 17.3 mg/dl. When the pups were killed on the afternoon of postnatal day 10, brain weight to body weight ratio in the ethanol-exposed rats was reduced 22.4% and 21.5% compared to suckle and pair-fed controls, respectively. Ethanol exposure also resulted in a 16% reduction of neurons in hippocampal field CA4, compared to controls, but did not produce deficits in fields CA1 or CA3. There was also a 10% increase in the number of neurons (a population of cells in the midst of a proliferative phase at the time of the exposure) in the granule cell layer of the dentate gyrus. The ethanol exposure did not affect cell size in any of the four neuron populations measured. These results suggest, that within the dose and timing parameters examined, ethanol exposure during the third trimester equivalent appears to be preferentially harmful to specific populations of developing neurons.