Adults with cerebral palsy: a workshop to define the challenges of treating and preventing secondary musculoskeletal and neuromuscular complications in this rapidly growing population

Although the neurological injury associated with cerebral palsy (CP) is non-progressive, adults with the disorder often develop musculoskeletal and neurological symptoms, such as severe pain, chronic fatigue, and a premature decline in mobility and function, as they age. Little is known about how to manage, much less prevent, these symptoms. This paper summarizes the findings of a multi-disciplinary workshop, sponsored by the Cerebral Palsy International Research Foundation, the American Academy for Cerebral Palsy and Developmental Medicine, and Reaching for the Stars, convened to review current knowledge and begin to develop a blueprint for future research. The goals of the workshop were to (1) define the current incidence and prevalence of CP, (2) review the known complications for persons aging with CP, (3) review current understanding of physiological processes that may contribute to loss of function and premature aging in CP, (4) evaluate current treatment interventions in terms of long-term outcomes, (5) identify cutting-edge technologies in neurorehabilitation that may help prevent or treat the effects of accelerated aging for persons diagnosed with CP, and (6) identify strategies to ensure that individuals with CP receive evidence-based care as they transition from pediatric to adult-care services.     

Candida onychomycosis—an evaluation of the role of Candida species in nail disease

Nail infections caused by Candida species are normally associated with chronic paronychia or chronic mucocutaneous candidiasis (CMCC). However, the role of Candida in the pathogenesis of other primary nail dystrophies has been questioned in view of their response to antifungal therapy alone. In the present study of 86 patients with primary nail dystrophies from which Candida was isolated, three patterns of nail involvement were found. Nineteen patients, of whom 17 had CMCC, had total dystrophic onychomycosis of at least two nails. The second group consisted of 27 patients with paronychia and lateral onycholysis. In a further 40 patients, who did not have paronychia, Candida was isolated from nails showing primary distal and lateral onycholysis. These changes were mainly seen in patients with peripheral vascular disease, particularly Raynaud's disease, or Cushing's syndrome. Nail biopsies from patients in the latter two groups confirmed the presence of yeasts and mycelium in the nail plate and 17 (46%) of those receiving antifungal therapy with ketoconazole or itraconazole showed complete clearance of the nail dystrophy. Good responses to therapy were seen more frequently in patients with peripheral vascular disease or Cushing's syndrome of whom 15 (72%) recovered; distal erosion of the nail plate, mycelium in the nail plate on biopsy or direct microscopy together with the isolation of C. albicans were all associated with good responses to antifungals. In addition to patients with CMCC or paronychia, therefore, Candida appears to be a significant pathogen in some patients with primary onycholysis of the finger nails, particularly where there is underlying peripheral vascular disease or Cushing's syndrome.     

Combined treatment with ranitidine and saline antacids prior to obstetric anaesthesia

Ranitidine 150 mg was given to 126 patients requiring elective Caesarean section under general anaesthesia: 43 women had ranitidine alone, 43 had this supplemented by a pre-induction dose of sodium citrate and 40 patients had ranitidine plus sodium bicarbonate. All three sub-groups provided satisfactory gastric pH and volume. Ranitidine 150 mg was given orally every 6 hours to women in labour. Of 221 patients requiring general anaesthesia during labour, 103 women received 30 ml 0.3 M sodium citrate and 118 women, 20 ml of 8.4% sodium bicarbonate 10 minutes before induction of anaesthesia. In the citrate sub-group there was one patient with a gastric pH less than 2.5 (mean pH 6.2, SEM 0.13 range 2.1-8.4). In the bicarbonate sub-group the lowest gastric acidity was 3.8 (mean pH 8.3, SEM 0.11 range 3.8-9.83).     

T lymphocytes and the lack of activated macrophages in wound margin biopsies from chronic leg ulcers

The objective of this study was to characterize the leucocyte infiltrate which accumulates at the margin of chronic wounds. These leucocytes are a rich source of cytokines and growth factors, and an inappropriate function of these cells may contribute to the maintenance of wound chronicity. The leucocyte populations were stained immunohistochemically with monoclonal antibodies specific for surface receptors which give an indication of cellular function. Wound margin biopsies taken from chronic leg ulcers exhibited a localized infiltrate of CD45+ leucocytes associated with vascularized tissue in the dermis adjacent to the wound margin. Lymphocytes were identified in highest numbers in this area and CD45RO+ T lymphocytes predominated over B lymphocytes, which were either absent or present in very low numbers. In the majority of chronic wounds examined, CD4+ T lymphocytes were present in greater numbers than CD8+ T lymphocytes with a mean (± SD) ratio of CD4+ : CD8+ of 1.5 ± 0.6.
CD68+ macrophages were identified in all layers of the dermis at the chronic wound margin. In 60% of wounds examined, macrophages were negative for the activation associated markers CD16 (FcγIII receptor) and CD35 (C3b receptor). In those biopsies where CD16 and CD35 positive macrophages were observed these were preferentially located in the perivascular regions. These data indicate that as monocytes extravasate into chronic wound tissue they may be subjected to microenvironmental influences which either suppress or do not induce macrophage activation. Suppression of macrophage activation may lead to an inappropriate cytokine/growth factor secretion and contribute to the maintenance of wound chronicity.     

Pharmacokinetics and antipyretic effects of an injectable pro-drug of paracetamol (propacetamol) in children

Propacetamol is a soluble injectable form of paracetamol, which is quickly hydrolysed after intravenous injection. We report the pharmacokinetic results of this drug in children between 10 months and 14 years of age. Three minutes after an i.v. administration of 15 mgkg^-1 the mean plasma paracetamol concentration was about 25 μgml^-1. In a course of repeated administration of propacetamol, the plasma concentration 3 min after the fourth dose remained at about the same value, showing that there was no accumulation of paracetamol. The pharmacokinetic parameters (half life, total clearance and distribution volume) were similar to those in adults. At 15 mgkg^-1 doses, the antipyretic effect is well-established.     

EXTRADURAL CLONIDINE INFUSIONS FOR ANALGESIA AFTER TOTAL HIP REPLACEMENT

We have examined the effectiveness of extradural clonidine infusionsfor postoperative analgesia and the effect of clonidine on extraduralmorphine. In a double-blind, controlled study, patients, undergoingtotal hip replacement were allocated randomly to receive oneof two doses of extradural clonidine (25 µg h^–1or 50µg h^–1), low dose extradural morphine or acombination of morphine and clonidine. Pain scores in the morphinegroup were significantly greater than in the clonidine groups(P < 0.01) and the combination group (P < 0.05) duringthe first 1 h after surgery. The requirements for systemic analgesiawere least in the combination and larger dose clonidine group,and the duration of effect of the initial bolus dose was significantlylonger compared with the morphine and low dose clonidine groups(P < 0.05). Arterial pressure was reduced in the clonidinegroups, although the incidence of clinical hypotension was low.There were no significant differences between the groups inemetic symptoms or urinary retention.     

Long-Term Clinical Performance of a Central Venous Oxygen Saturation Sensor for Rate Adaptive Cardiac Pacing

Rate adaptive ventricular pacemakers using central venous oxygen saturation (O₂Sat) to control the pacing rate have been implanted in 14 patients (mean age 71 years), with a mean follow-up period of 44 months (range 2–63 months). In eight patients the pacemakers were replaced due to signs of battery depletion after an implant duration of 39–58 months. During bicycle exercise testing the O₂Sat decreased on average from 61%± 4% at rest to 36%± 4% (P < 0,0001) at peak exercise, and the maximum pacing rate was 122 ± 5 beats/min. The time delay until the O₂Sat bad dropped 10%, 65%, and 90% of the total reduction during exercise was 4.8 ± 0.9 seconds, 39.8 ± 3.8 seconds, and 71.3 ± 7.5 seconds, respectively. The O₂Sat decreased 9.4%± 2% (P <0.005) from resting supine to resting sitting. Oxygen breathing increased the telemetered O₂Sat from the pacemaker by 8.4 %± 1 % (P < 0.001). During follow-up the O₂Sats were relatively stable in 50% of the patients, but demonstrated significant fluctuations in the others. At 1-year invasive follow-up O₂Sat measured by the pacemaker decreased 22%± 2%, and in blood samples from the right ventricle 22%± 2% from rest to 3 minutes exercise at 25 watts. There was a significant correlation between O₂Sat measured by the pacemaker and in blood samples from right ventricle (n = 105; r = 0.73; P < 0.001). In two patients the O₂Sat dropped significantly during pneumonia. In another patient episodes of angina pectoris was associated with low O₂Sat and a concomitant fast pacing rate.