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G J Parry

Publications and source records attributed to G J Parry.

At least 37 records · Page 2Linked to original sources
PubMed1997

A brief quality-of-life measure for ALS clinical trials based on a subset of items from the sickness impact profile. The Syntex-Synergen ALS/CNTF Study Group.

We previously demonstrated a significant relationship (P<0.0001) between maximum voluntary isometric contraction (MVC) plus pulmonary function scores (the Tufts Quantitative Neuromuscular Exam Combination Megascore (TQNE CM)), and the Sickness Impact Profile (SIP) in a cohort of 524 ALS patients. Because the 136-item SIP questionnaire can be difficult to administer in this population, we examined SIP subscales and clinically derived item sets in relation to the TQNE CM in an effort to define a briefer measure of quality of life for use in clinical trials. Two 'Mini-SIP' indices performed as well as the overall SIP in reflecting the impact of muscle weakness on ALS patients' quality of life: a combination of two SIP subscales ('SIP-33'), and a 19-item set of questions independently chosen by a panel of ALS specialists ('SIP/ALS-19'). Either index potentially could be useful in ALS clinical trials. The SIP/ALS-19 is currently being used in a National ALS data base, providing an opportunity to evaluate its utility prospectively against other QOL measures in ALS patients.

Amyotrophic Lateral Sclerosis↗
PubMed1996

AAEM case report #30: multifocal motor neuropathy.

A 73-year-old man with a 16-year history of fasciculations and 15 years of weakness in his right arm was diagnosed with focal motor neuron disease. After 10 years of purely motor symptoms, he developed mild parasthesias although his sensory examination remained normal. Reflexes were reduced or absent in the weak muscles but were normal elsewhere. Nerve conduction was studied in nerves innervating weak muscles and showed severe motor conduction block. Sensory nerve conduction studies were minimally abnormal, showing reduced amplitudes with normal velocities. Based on the clinical picture and the presence of severe motor conduction block, the patient was diagnosed as multifocal motor neuropathy. Treatment with high-dose intravenous immunoglobulin was given with significant improvement in strength and partial resolution of the conduction block. As this case demonstrates, this treatable disorder may occasionally be mistaken for motor neuron disease although the resemblance is only superficial, and it should never be mistaken for amyotrophic lateral sclerosis. Multifocal motor neuropathy is an inflammatory, demyelinating neuropathy which, like chronic inflammatory demyelinating polyneuropathy (CIDP), is probably immune-mediated. It differs from typical CIDP by virtue of a marked predilection for motor axons, a strikingly restricted distribution, and a protracted course. Treatment with high-dose intravenous immunoglobulin is frequently helpful, but other forms of immune manipulation are less effective.

Demyelinating Diseases↗
PubMed1996

A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group.

Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.

Adult↗
PubMed1996

CRIB (clinical risk index for babies) in relation to nosocomial bacteraemia in very low birthweight or preterm infants.

Positive blood cultures in very low birthweight or preterm infants usually reflect bacteraemia, septicaemia, or failure of asepsis during sampling and lead to increased costs and length of stay. Rates of nosocomial, or hospital acquired, bacteraemia may therefore be important indicators of neonatal unit performance, if comparisons are adjusted for differences in initial risk. In a preliminary study the risk of nosocomial bacteraemia was related to initial clinical risk and illness severity measured by the clinical risk index for babies (CRIB). Nosocomial bacteraemia was defined as clinically suspected infection with culture of bacteria in blood more than 48 hours after birth. One or more episodes of nosocomial bacteraemia were identified retrospectively in 36 of 143 (25%) infants in a regional neonatal unit between 1992 and 1994. Biologically plausible models were developed using regression analysis techniques. After correcting for period at risk, nosocomial bacteraemia was independently associated with gestation at birth and CRIB. Death was independently associated with CRIB, but not with nosocomial bacteraemia. CRIB may contribute, with other explanatory variables, to more comprehensive predictive models of death and nosocomial infection. These may facilitate future risk adjusted comparative studies between groups of neonatal units.

Bacteremia↗
PubMed1996

Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group.

We designed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis (ALS) and to assess safety and tolerability. Gabapentin (800 mg) or placebo was administered t.i.d. in a randomized, double-blinded, placebo-controlled, trial for 6 months. We enrolled 152 patients at eight sites in the United States. The primary outcome measure was the slope of the arm megascore, the average maximum voluntary isometric strength from eight arm muscles standardized against a reference ALS population. A secondary outcome measure was forced vital capacity. Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA. We observed a nonstatistically significant trend (p = 0.057-0.08) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo (mean difference 24%, median 37%). We observed no treatment effect on forced vital capacity. Gabapentin was well tolerated by patients with ALS. These results suggest that further studies of gabapentin in ALS are warranted.

Acetates↗
PubMed1994

Severe radicular pathology in rats with longstanding diabetes.

There few pathological abnormalities in nerves from animals with diabetes. Reported changes consist of mild distal axonal atrophy, axoglial disjunction and minimal segmental demyelination and remyelination. These changes are seen in distal nerves but no studies of radicular pathology in diabetic animals have been reported. We therefore studied peripheral nerve and radicular pathology in rats with longstanding, severe, chemically-induced diabetes. We found marked interstitial edema and severe changes of myelin in the roots of diabetic rats, particularly in the dorsal root. The earliest changes consist of myelin splitting, occurring at the intraperiod line. This progresses to myelin ballooning, accompanied by both tubulovescicular myelin degeneration and macrophage stripping, all of which tend to predominate in large myelinated fibers. There is minimal axonal degeneration. Despite these severe changes in nerve roots, the distal peripheral nerves show no discernible edema and only minimal myelin splitting without demyelination or axonal degeneration. The radicular changes are almost identical to those seen in much older nondiabetic animals. This suggests that they may represent an acceleration of the normal aging process, perhaps related to increased glycation of myelin proteins induced by accumulation of glucose rich interstitial endoneurial edema.

Animals↗
PubMed1994

Antiganglioside antibodies do not necessarily play a role in multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a disorder with a highly characteristic clinical picture and one which is defined by a specific electrodiagnostic abnormality, namely, multifocal conduction block which is confined to motor axons. Sensory axons which traverse segments of severe or even complete motor conduction block conduct normally. A proportion of patients with MMN also have elevated levels of antibodies to GM1 ganglioside. However, about one half of MMN patients lack elevated levels of these antibodies and many others have only modest elevations, to a degree often seen in other neurological and even non-neurological disorders. Furthermore, clinical and electrophysiological improvement of MMN in response to treatment with high dose intravenous immunoglobulin is achieved in the absence of any change in antiglycolipid levels. Injection of serum from patients with MMN and elevated GM1 antibody levels produces demyelination in recipient rat nerves, suggesting a pathogenetic role for these antibodies in demyelination. However, sera of patients with identical antibody titers in other motor system diseases produced no demyelination, suggesting that the demyelinating factor resides in some other serum fraction. At present, there is insufficient evidence to support the contention that these antibodies play a critical pathogenetic role in MMN. Until more evidence is available it is important to define MMN on the basis of a characteristic clinical picture and a unique electrodiagnostic abnormality rather than on a pattern of serum antibodies.

Animals↗
PubMed1994

Static respiratory compliance in the newborn. III: Early changes after exogenous surfactant treatment.

Static respiratory system compliance (Crs) was measured by a single breath passive expiratory flow technique in 73 newborn infants treated with exogenous surfactant. The first 39 received Curosurf, a natural porcine surfactant. The other 34 received Exosurf Neonatal, a synthetic surfactant. All had a diagnosis of respiratory distress syndrome with an arterial/alveolar oxygen ratio < 0.22. Static Crs and arterial blood gases were measured shortly before, and at three and 12 hours after the first dose of surfactant. In 32 infants treated with Curosurf with initial static Crs < 1.8 ml/cm H2O/m body length, which is consistent with surfactant deficiency, static Crs improved by 18% at three hours and by 39% at 12 hours along with a median reduction in fractional inspired oxygen (FIO2) at three hours by 0.32. In 26 infants treated with Exosurf with initial Crs < 1.8 ml/cm H2O/m, Crs did not improve three and 12 hours after treatment and oxygenation improved less than after Curosurf, with a median reduction in FIO2 at three hours of 0.11. Fifteen of the 73 (21%) infants had initial static Crs of > or = 1.8 ml/cm H2O/m, not consistent with surfactant deficiency. Thirteen of these 15 infants showed a fall in static Crs after surfactant treatment, raising the question whether exogenous surfactant did them more harm than good. Initial static Crs and surfactant type both appear to determine the early response to the first dose of surfactant. Only a considerably larger, randomised study can show which surfactant is more effective in reducing adverse clinical outcome.

Animals↗
PubMed1993

Motor neuropathy with multifocal conduction block.

Our present understanding of the syndromes of CIDP and MMN is insufficient to separate them clearly. I believe that MMN is simply a multifocal, predominantly motor variant of CIDP. Furthermore, the highly touted resemblance of MMN to MND has been exaggerated; these syndromes are only superficially similar and can readily be distinguished on clinical and electrophysiologic grounds. MMN is rare but is probably more common than initially believed; certainly, the literature is replete with reports of cases. Further studies are needed to clarify fully the relationship between CIDP and MMN and the role of glycolipid antibodies in MMN and other motor syndromes.

Humans↗
PubMed1993

Uniform slowing of conduction velocities in Charcot-Marie-Tooth polyneuropathy type 1.

We evaluated motor conduction studies in 129 patients with Charcot-Marie-Tooth disease type 1 (CMT1) to assess the uniformity of conduction slowing within individual patients. Conduction velocities were nearly identical in proximal and distal nerve segments (r = 0.86), from side to side (r = 0.95), in ipsilateral median and ulnar nerves (r = 0.94), and even in the median and peroneal nerves (r = 0.70). Segmental amplitude reductions suggestive of possible conduction block or differential dispersion were present in only 19 of 360 nerve segments studied (5.3%), and interphase cancellation or focal compression were likely alternative explanations in these cases. These findings support the concept that uniform conduction slowing characterizes CMT1, in distinction to acquired demyelinating polyneuropathies, which feature multifocal conduction abnormalities. We conclude that normal nerve conduction velocity in a single motor nerve can reliably exclude CMT1, but evaluation of several nerves and nerve segments to establish uniformity of conduction slowing is important in making this diagnosis. The homogeneity of the disturbance of nerve conduction favors a primary Schwann-cell disorder as the basis of CMT1.

Action Potentials↗
PubMed1993

Conduction block as an early sign of reversible injury in ischemic monomelic neuropathy.

We report three patients with reversible motor conduction block in the forearm associated with ischemic monomelic neuropathy (IMN), which occurred in two patients following placement of brachial artery-cephalic vein shunts for hemodialysis. In the third patient, IMN resulted from spontaneous, probably embolic, brachial artery occlusion. Conduction block was observed shortly after the onset of symptoms, and preferentially involved the median nerve. Slowing of conduction velocity was seen in the same nerve segments. Electrophysiologic resolution, correlating with clinical improvement following treatment, occurred promptly in one patient and over several weeks in the others. Recognition of conduction block is important in the evaluation of IMN, and indicates the need for prompt treatment of likely reversible nerve injury.

Aged↗
PubMed1993

Nerve conduction studies in Charcot-Marie-Tooth polyneuropathy associated with a segmental duplication of chromosome 17.

We evaluated motor conduction velocities in a large group of patients and their unaffected kin from five families in which a segmental duplication of chromosome 17p has shown complete linkage to Charcot-Marie-Tooth disease type 1 (CMT1A). Slowing of conduction was completely concordant with the presence of the segmental duplication; two clinically normal patients had slowed conduction. Nonetheless, among the patients with the CMT1A duplication, conduction velocities varied widely, by > 30 m/sec overall, by > 20 m/sec within families, and often by more than 10 m/sec between siblings and between parents and children. One patient was homozygous for the chromosome 17p duplication and had the slowest conduction velocity observed. Conduction slowing was not age-dependent and was present early in childhood. Our findings demonstrate complete penetrance at an early age of the electrophysiologic phenotype associated with the chromosome 17p duplication and confirm the reliability of nerve conduction studies in establishing the affection status in CMT1A. The great variation in conduction velocity among CMT1A patients emphasizes the influence of factors apart from the shared genetic mutation on phenotypic expression.

Adolescent↗
PubMed1993

Age, sex, cigarette smoking and indices of free radical activity in healthy humans.

OBJECTIVES: To determine the effect of age, sex and smoking on free radical (FR) indices. There is currently considerable research interest into the role of FRs in the pathogenesis of many diseases and it is therefore important to identify factors in healthy subjects which influence the markers used to assess FR activity. METHODS: Blood samples were obtained from 123 healthy subjects whose age, sex and smoking habits were recorded. The following were measured on each sample: malondialdehyde (MDA) which is a product of FR mediated lipid peroxidation and the FR scavengers plasma thiols (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD). RESULTS: Malondialdehyde levels were significantly increased in cigarette smokers (p < 0.02) but no significant age related increase in MDA was detected for the group as a whole. However, female smokers had the highest rate of MDA increase with age followed by male smokers and female non-smokers. MDA levels of male non-smokers were unaffected by age. A significant negative correlation was detected between PSH and age (p < 0.001). GSH was significantly higher in females (p < 0.05) and the red cell content of GSH and SOD were significantly inversely related (p < 0.01). CONCLUSION: This study of normal subjects describes an age related increase in malondialdehyde levels, the rate of which is influenced by sex and smoking status. In humans, plasma thiol levels decrease with increasing age, females have higher red cell glutathione and there is a significant inverse relationship between red blood cell superoxide dismutase and glutathione levels. Furthermore, cigarette smoking increases plasma malondialdehyde levels. With the considerable current interest in free radicals, it is important to identify factors which influence the indices used to assess free radical activity in disease states.

Adolescent↗
PubMed1992

Endoneurial blood supply to peripheral nerves is not uniform.

Peripheral nerves are not uniformly susceptible to the effects of ischemia in human and experimental ischemic neuropathies. Since endoneurial blood flow is directly proportional to the number of endoneurial capillaries, we studied endoneurial capillary density at multiple levels of the peripheral nerves of normal rats. Capillary density was lowest in the sciatic and proximal tibial nerves and significantly higher in dorsal and ventral roots and distal tibial and plantar nerves. Endoneurial capillary density corresponds to the hierarchy of susceptibility to ischemic nerve damage in human and experimental ischemic neuropathies. These findings suggest that susceptibility of peripheral nerves to ischemia is determined, at least in part, by the density of endoneurial capillaries.

Animals↗
PubMed1992

EUROMAC. A European concerted action: maternal alcohol consumption and its relation to the outcome of pregnancy and child development at 18 months. Results--strategy of analysis and analysis of pregnancy outcome.

Analyses were made of the relation between maternal alcohol consumption before and in early pregnancy and five infant outcome variables: birthweight, crown-heel length, occipitofrontal circumference and the Apgar scores at 1 and 5 minutes. The data were analysed for all centres combined and separately. From tabulation of the mean values of the outcome variables by alcohol consumption, it appeared that a poorer outcome was related to consumption of 120 g/week absolute alcohol or more. Multiple regression analysis was used to allow for possible confounding by the child's gestational age at birth and sex, the mother's age, parity and smoking habit, and survey centre. Two threshold models were applied to the combined data, taking the confounders into account. The offset threshold model (assuming no effect of alcohol up to a threshold value, and then a constant multiplicative effect at higher levels) suggested a negative effect on birthweight at about 60 g/week absolute alcohol, but with a wide 85% confidence interval of 5-130 g/week. A step function threshold model, which assumes a constant effect above the threshold value, behaved erratically. Similar analyses for crown-heel length and occipitofrontal circumference provided only a very poor fit to the data. Data on reported congenital anomalies are presented by survey centre and maternal alcohol consumption, but due to the unstandardized method of collection they were not analysed further.

Alcohol Drinking↗
PubMed1992

EUROMAC. A European concerted action: maternal alcohol consumption and its relation to the outcome of pregnancy and child development at 18 months. Results--child development at age 18 months.

Children seen in the first part of the study in Berlin, Dundee and Odense were followed up at age 18 months and tested using the Bayley Scales of Infant Development. Five scores were recorded: the Mental Development Index (MDI), the Psychomotor Development Index (PDI) and scores for responsiveness, attention span and activity. The data were analysed for the centres combined and separately, allowing for confounding variables as in the previous chapter. In none of the comparisons was the mean score found to be significantly less in the children of drinkers than in those of abstainers. In many of the comparisons the children of abstainers had the lowest mean scores. In a number of comparisons in Berlin and Dundee, the MDI or PDI was found to be significantly higher in the children of women who had drunk at the upper end of the consumption distribution.

Alcohol Drinking↗
PubMed1992

Electrodiagnostic studies in the evaluation of peripheral nerve and brachial plexus injuries.

Electrodiagnostic studies constitute the most objective and quantitative means of evaluating and sequentially following patients with traumatic peripheral nerve injuries. They can be used to localize the lesions, determine the predominant underlying pathology, estimate the extent and severity of the axonal degeneration, and follow recovery. In addition, intraoperative studies may prevent unnecessary surgery and prevent unnecessary delays if surgery is indicated. Peripheral nerve trauma should not be managed at any center where high quality electrodiagnosis is unavailable.

Brachial Plexus↗