Three infants with constipation and muscular weakness: infantile botulism

Two previously healthy infants, a boy of 10 weeks and a girl of 4 months presented with apathy and muscle weakness. A third previously healthy child, a girl of 6 weeks old was admitted with respiratory insufficiency. None of the three had had a bowel movement for a number of days. After extensive investigations which revealed few abnormalities Clostridium botulinum toxin was obtained in serum from all three children. Type-B-toxin was shown in the faeces of the older girl and boy; both recovered quickly. The other girl had type-A toxin; she died. Two of the three children were given honey to comfort them. Infantile botulism must be considered in every infant with symptoms of constipation and hypotonia. The diagnosis can quickly be confirmed by electromyography with repetitive 50-Hz-stimulation. Honey is a well-known source of the C. botulinum spore and should not be given to children under the age of 12 months. These three children are the first cases to be described in the Netherlands.     

Effects of brain death on stress and inflammatory response in the human donor kidney

BACKGROUND: After kidney transplantation, a decreased graft survival is seen in grafts from brain dead donors compared to living donors, possibly related to a progressive inflammatory reaction in the graft. In this study, we focused on the effects of brain death on the inflammatory response (adhesion molecules, leukocyte infiltration, and gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were linked to outcome data after transplantation. METHODS: Human kidney biopsy specimens were obtained during organ retrieval from brain dead and living organ donor controls. On these specimens, immunohistochemistry and semiquantitative RT-PCR were performed. Regression analyses were performed connecting results to outcome data of kidney recipients. RESULTS: In brain death, immunohistochemistry showed an increase of E-selectin and interstitial leukocyte invasion versus controls; RT-PCR showed an increase of gene expression of HO-1 and Hsp70. One and 3 years after transplantation, high ICAM and VCAM expression proved to have a negative effect on kidney function in brain dead and living kidneys, while HO-1 proved to have a strongly positive effect, but only in kidneys from living donors. CONCLUSIONS: E-selectin expression and interstitial leukocyte accumulation in brain dead donor kidneys indicate an early phase inflammatory state prior to organ retrieval. Also, brain death causes a stress-related response resulting in upregulation of potentially protective heat shock proteins. The upregulation of HO-1 is beneficial in living donor kidneys, but might be inadequate in brain death.     

Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study

BACKGROUND: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy. METHODS: This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147). RESULTS: The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively. CONCLUSION: Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.     

Medical decision-making for seriously ill non-elderly and elderly patients

OBJECTIVES: Age of patients by itself is no longer a contra-indication for most medical interventions. The increase of possible interventions for elderly patients has contributed to a sharp age-specific increase of health care costs. Our study aimed to increase the insight in medical decision-making about life-prolonging interventions for patients from non-elderly and elderly age groups. DESIGN: Case-control study. SETTING: Clinical practices in three settings: oncology, nursing home and cardiology. SUBJECTS: Eighty-one physicians, representing a response of 60%. METHODS: Face-to-face interviews using a structured questionnaire addressing decision-making about the application of taxoid treatment for breast cancer patients, the application of bypass surgery for patients with angina pectoris under or over 70 years of age, and referral to specialist treatment because of a suspected malignancy of nursing home patients under or over 75 years of age. RESULTS: The chance of having been treated was in all settings lower for patients with a relatively poor quality of life and for patients who had no (known) preference to be treated. No differences were found for chance of having been treated between non-elderly and elderly patients with similar patient characteristics. The only exception to this is the patient preference concerning treatment: elderly patients were more likely to have been treated against their will than non-elderly patients were. CONCLUSIONS: A relatively high frequency of non-treatment decisions for elderly patients may be predominantly explained by the fact that patient characteristics that determine non-treatment decision-making are more prevalent in elderly age groups, and not by the effect of age per se.     

Alteration of the extracellular matrix interferes with raft association of neurofascin in oligodendrocytes. Potential significance for multiple sclerosis?

Remyelination, as potential treatment for demyelinating diseases like multiple sclerosis (MS), requires the formation of new axoglial interactions by differentiating oligodendrocyte progenitor cells. Since the oligodendrocyte-specific isoform of neurofascin, NF155 (neurofascin isoform of 155 kDa), may be important for establishing axoglial interactions, we analyzed whether its expression is changed in chronic relapsing experimental allergic encephalomyelinitis (EAE). Although overall expression of NF155 was not changed, immunoreactivity of NF155 was dramatically increased in EAE lesion sites indicating an enhanced accessibility of NF155 epitopes. As this may be due to infiltrating plasma components, for example, fibronectin, we analyzed whether fibronectin affects the intracellular distribution and membrane association of NF155 in primary oligodendrocytes. In oligodendrocytes cultivated on polylysine, NF155 was recruited to membrane microdomains (rafts) during development and became enriched in secondary and tertiary processes. Fibronectin perturbed localization and raft association of NF155 and inhibited the morphological differentiation of oligodendrocytes. Consistent with the in vitro data, raft association of NF155 was reduced in spinal cord of EAE rats. The results suggest that the association of NF155 to microdomains in the oligodendrocyte membrane is required for its participation in intermolecular interactions, which are important for myelination and/or myelin integrity.     

Kinematic characteristics of postural control during reaching in preterm children with cerebral palsy

The relationships between kinematic characteristics of sitting posture during reaching movements of the dominant arm and 1) the kinematics of the reaching movement itself and 2) functional performance during daily life activities (PEDI) were assessed in 51 sitting preterm children with cerebral palsy (CP). The children were 2-11 y, 33 had spastic hemiplegia (SH) and 18 bilateral CP (Bi-CP). The data were compared with those of 26 typically developing children (TD). Sitting posture before the onset of reaching of children with CP differed from that of TD children: they sat with a more reclined pelvis and a more collapsed trunk. The more reclined pelvic position was associated with a better quality of reaching movements. The different sitting postures of pelvis and trunk were not related to functional performance during daily life activities. Displacement of the head, trunk, and pelvis of the children with CP did not differ from that of the TD children. Nevertheless, in the children with CP a more stable head, a more mobile trunk, and a more stable pelvis were related to better functional performance and/or a better quality of reaching. This suggests that physiotherapeutic guidance of children with CP should focus rather on the latter postural parameters than on the different sitting posture of pelvis and trunk.     

Body mass index is associated with altered renal hemodynamics in non-obese healthy subjects

BACKGROUND: Weight excess is associated with increased renal risk. Data in overt obesity suggest a role for altered renal hemodynamics. Whether body mass index (BMI) is also relevant to renal function in non-obese subjects is unknown. METHODS: We studied the relation between BMI and renal hemodynamics in 102 healthy, non-obese (BMI <30 kg/m2) subjects [59 males, 43 females, mean age 39 (18-69) years] in a post-hoc analysis of subjects evaluated as prospective kidney donors or as healthy volunteers in renal hemodynamic studies. RESULTS: Mean (+/-SD) BMI was 24.0 +/- 2.8 kg/m2, mean arterial pressure (MAP) 93 +/- 11 mm Hg, glomerular filtration rate (GFR, iothalamate clearance) 111 +/- 19 mL/min/1.73 m2, effective renal plasma flow (ERPF, hippuran clearance) 458 +/- 108 mL/min/1.73 m2, FF (GFR/ERPF) 0.25 +/- 0.04. On univariate analysis, BMI correlated negatively with ERPF/1.73 m2 body surface area (BSA) (r=-0.46; P < 0.001), GFR/1.73 m2 BSA (r=-0.24, P= 0.013) and positively with FF (r= 0.45, P < 0.001), and age (r= 0.47, P < 0.001). On multivariate analysis both BMI and age were independent predictors of ERPF/1.73 m2 BSA (negative) and FF (positive, all P < 0.05). Age was the only predictor of GFR/1.73 m2 BSA (negative). Analyzed for renal function indexed for height (h), BMI correlated negatively with ERPF/h (r=-0.274, P= 0.005), but not with GFR/h (r= 0.13, P= 0.899). On multivariate analysis both BMI (positive) and age (negative) were independent predictors for GFR/h (both P < 0.001). Age was the only predictor for ERPF/h (negative). Predictors for FF (BMI and age, both positive) were by definition unaltered. CONCLUSION: The impact of BMI on renal function is not limited to overt obesity, as in subjects with BMI <30 kg/m2 a higher BMI is associated with higher FF, that is, a higher GFR relative to ERPF. This suggests an altered afferent/efferent balance and higher glomerular pressure (i.e., a potentially unfavorable renal hemodynamic profile) that may confer enhanced renal susceptibility when other factors, such as hypertension or diabetes are superimposed.