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Biomedical subjects

G J Parry

Publications and source records attributed to G J Parry.

At least 19 recordsLinked to original sources

Relationship between probable nosocomial bacteraemia and organisational and structural factors in UK neonatal intensive care units.

OBJECTIVES: To assess the relationship between organisational and structural factors of UK neonatal intensive care units (NICUs) with risk adjusted probable nosocomial bacteraemia. DESIGN OF STUDY: A prospective observational study of infants concurrently admitted to 54 randomly selected UK NICUs between March 1998 and April 1999. RESULTS: Of the 13 334 infants admitted, 402 (2.97%) had probable nosocomial bacteraemia. The median unit level percentage of infants with probable nosocomial bacteraemia was 2.48% (minimum 0%, maximum 9%). The risk adjusted odds of probable nosocomial bacteraemia were increased by 1.13 (95% CI 1.07 to 1.20) for each additional level 1 cot per hand washbasin and decreased by 0.53 (95% CI 0.35 to 0.79) in infants admitted to units with an NICU infection control nurse compared with units without. There was no relation with an increase in the floor space of the unit per cot (odds ratio 0.99 (95% CI 0.98 to 1.00) per m(2)) or with the quality of hand washing signs (odds ratio 1.04 (95% CI 0.93 to 1.16) per increase in quality score). CONCLUSIONS: There is widespread variation in rates of probable nosocomial bacteraemia in UK NICUs. Probable nosocomial bacteraemia is reduced in units with a dedicated infection control nurse and with the presence of more hand washbasins. Further research is required to identify methods to eliminate nosocomial bacteraemia.

Bacteremia↗

Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: This assessment evaluates the clinical utility, efficacy, and safety of quantitative sensory testing (QST). METHODS: By searching MEDLINE, Current Contents, and their personal files, the authors identified 350 articles. Selected articles utilized computer operated threshold systems, manually operated threshold systems, and electrical threshold devices. The authors evaluated the use of normal values and the degree of reproducibility between the same and different systems. Articles were rated using a standard classification of evidence scheme. RESULTS: Because of differences between systems, normal values from one system cannot be transposed to others. Reproducibility of results was also an important concern, and there is no consensus on how it should be defined. The authors identified no adequately powered class I studies demonstrating the effectiveness of QST in evaluating any particular disorder. A number of class II and III studies demonstrated that QST is probably or possibly useful in identifying small or large fiber sensory abnormalities in patients with diabetic neuropathy, small fiber neuropathies, uremic neuropathies, and demyelinating neuropathy. CONCLUSIONS: QST is a potentially useful tool for measuring sensory impairment for clinical and research studies. However, QST results should not be the sole criteria used to diagnose pathology. Because malingering and other nonorganic factors can influence the test results, QST is not currently useful for the purpose of resolving medicolegal matters. Well-designed studies comparing different QST devices and methodologies are needed and should include patients with abnormalities detected solely by QST.

Diabetic Neuropathies↗

Can we eliminate placebo in ALS clinical trials?

BACKGROUND: Previous studies concluded that the decline in strength in patients with amyotrophic lateral sclerosis (ALS) is a linear function. If so, a patient's natural history might serve as the control, instead of placebo, in a clinical trial. METHODS: A placebo-controlled ALS clinical trial included a natural history phase, followed by a 6-month treatment phase. Each patient's forced vital capacity (FVC) score and maximal voluntary isometric contraction (MVIC) raw scores were measured monthly, standardized, and averaged into megascores. For 138 patients, the arm, leg, FVC, arm+leg combination, and arm+leg+FVC combination megascore slopes during the natural history phase and during the placebo phase were compared. RESULTS: The mean slope of megascores during the natural history phase and the mean slope during the placebo phase were not different for the arm, leg, and arm+leg megascores, but were different for the FVC and arm+leg+FVC combination megascores. CONCLUSIONS: Natural history controls may be useful in ALS exploratory trials that use arm megascore slope as the primary outcome measure. However, there are distinct limitations to the use of natural history controls, so that Phase 3 ALS clinical trials require placebo controls.

Amyotrophic Lateral Sclerosis↗

Mononeuritis multiplex in diabetes mellitus: evidence for underlying immune pathogenesis.

Four patients with type 2 diabetes mellitus developed mononeuritis multiplex subacutely. Sural nerve biopsies showed multifocal axonal loss in all patients, with epineurial perivascular inflammation affecting small calibre vessels in three. Three patients improved with immunotherapy. These observations suggest that mononeuritis multiplex in diabetes may be caused by an immune mediated vasculopathy and that it is pathogenetically akin to the more common and better recognised diabetic amyotrophy.

Aged↗

Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To determine the efficacy of IV immunoglobulin (IVIg) given patients with untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A randomized, double-blind, multicenter, investigator-initiated study compared IVIg (Aventis Behring LLC, King of Prussia, PA) with placebo (5% albumin). On days 1, 2, and 21, IVIg (1 g/kg) or placebo was given. The primary outcome measure was the change in muscle strength from baseline to day 42, using the average muscle score (AMS). Secondary outcome measures included change from baseline AMS at days 10 and 21, the Hughes' functional disability scale, forced vital capacity (FVC), and nerve conduction studies (NCS) of four motor nerves (median, ulnar, peroneal, and tibial). RESULTS: The patients (n = 33) were randomized. Of these, 30 (14 women, 16 men, aged 54 +/- 20 years, range 13 to 82) received IVIg and 23 were given placebo (12 women, 11 men, aged 50 +/- 18 years, range 23 to 73). Baseline AMS values of the groups were similar (IVIg 7.06 +/- 1.31 versus placebo 7.28 +/- 1.18, p = 0.53). There were two dropouts in placebo group and one in the IVIg group. Mean AMS improved at day 42 comparing IVIg with placebo (0.63 versus -0.1, p = 0.006). Improved strength was seen by day 10. The placebo group lost strength over this same interval. In the IVIg, 11 subjects improved by the functional disability scale; none worsened. This differed (p = 0.019) from those in the placebo-treated group (two improved, two got worse, remainder unchanged). Forced vital capacity did not improve with IVIg treatment. IVIg improved ulnar motor distal latency (p = 0.005), tibial distal compound muscle amplitude (p = 0.003), and peroneal nerve conduction velocity (p = 0.03). CONCLUSIONS: IVIg improves strength in patients with untreated CIDP by day 10 with continued benefit through day 42; more than one third improve by at least a functional grade on a disability scale. This study provides data supporting IVIg as the initial treatment for CIDP.

Adolescent↗

Distinctive pathologic findings in proximal diabetic neuropathy (diabetic amyotrophy).

OBJECTIVE: To investigate the pathogenesis of proximal diabetic neuropathy (PDN) with nerve and muscle biopsies. BACKGROUND: Recent evidence suggests that nerve ischemia secondary to immune-mediated vasculopathy rather than diabetic microangiopathy may be responsible for PDN. METHOD: - Fifteen patients with PDN and two diabetic controls underwent nerve and muscle biopsy and clinical, electrophysiologic, and laboratory evaluation. There were eight men and seven women between 49 and 79 years of age with type II diabetes. All had progressive, painful, asymmetric, proximal weakness with duration of 5 weeks to 12 months. None had evidence of systemic autoimmune disorder. RESULTS: Four patients showed the distinctive findings of polymorphonuclear small-vessel vasculitis affecting epineurial vessels with transmural infiltration of postcapillary venules with polymorphonuclear leukocytes. Immunoglobulin M (IgM) deposits were found along the endothelium and intramurally in affected vessels. IgM staining was seen in the subperineurial space and in the endoneurium. Activated complement deposition was seen along endothelium of small vessels. Three of these four patients were evaluated within 6 seeks of onset of PDN, and the fourth patient during acute flare of PDN 6 months after the initial onset. Six patients showed "perivasculitis" with mononuclear cell infiltrates around small epineurial vessels without vasculitis (fibrinoid necrosis or transmural inflammation). One patient showed recanalized vessels with transmural lymphocytes without fibrinoid necrosis, possibly suggesting healed vasculitis. CONCLUSION: These distinctive pathologic findings support that proximal diabetic neuropathy has an immune-mediated inflammatory basis and suggest that polymorphonuclear vasculitis with immune complex and complement deposition may be the primary event in the acute phase of proximal diabetic neuropathy.

Aged↗

Quantitative sensory testing: effect of site and pressure on vibration thresholds.

OBJECTIVE: To determine the effect of different sites and locally applied pressure on vibration thresholds. METHODS: Vibration thresholds were compared in 47 normal volunteers at 3 sites of the index finger (pulp, dorsum of the middle phalanx and nail) and at two sites of the great toe (dorsum of the proximal phalanx and nail). The effect of local pressure (30, 50 and 100 g/1.22 cm(2)) were compared in 41 subjects at the dorsum of the middle phalanx of the index finger and the proximal phalanx of the great toe. RESULTS: The hand was more sensitive than the foot for vibration. There were no significant differences in vibration thresholds at different sites of the index finger and different sites of the great toe. The pulp of the index finger yielded the least inter-individual variation. Testing under 30 and 50 g/1.22 cm(2) of pressure yielded equal vibration thresholds. Vibration threshold was higher when tested under 100 g/1.22 cm(2) at the index finger but not the great toe. This difference was small and clinically negligible. CONCLUSION: Testing of vibration thresholds in normal subjects can be adequately conducted at several sites of the index finger and the great toe. The test can be adequately done under low pressure of 30-50 g/1.22 cm(2).

Adult↗

Quantitative sensory testing: effect of site and skin temperature on thermal thresholds.

OBJECTIVE: To determine the effect of different sites and local skin temperature on thermal thresholds. METHODS: Cool and warm detection and cold and heat pain thresholds were compared in 46 normal volunteers at the thenar eminence (TE), dorsum of the hand (DH), volar surface of the wrist (VW) and dorsum of the foot (DF). RESULTS: The hand is more sensitive than the foot for cool and warm. TE is more sensitive for warm than DH and VW but the difference is clinically negligible. DH and VW are equally sensitive to warm. TE, DH, and VW are equally sensitive to cool. Inter-individual variance is smallest at TE. Warm and cool thresholds are independent of local skin temperature (range of 27-37 degrees C). TE is less sensitive for cold pain but otherwise the hand and the foot are equally sensitive to thermal pain. CONCLUSION: Testing of thermal thresholds in normal subjects can be adequately conducted at several sites at the hand, however, TE is preferred given the small inter-individual variability. TE may be preferred for evaluating hyperalgesia to cold given its higher threshold. Warming or cooling of the skin is unnecessary within the range normally encountered in routine clinical evaluation.

Adult↗

Variability of presentation in hereditary neuropathy with liability to pressure palsy results in underrecognition.

The genetic defect responsible for hereditary neuropathy with liability to pressure palsy (HNPP) is located in the same segment that is duplicated in Charcot-Marie-Tooth type 1A (CMT1A). HNPP had been presumed to be rare until an epidemiological study found a much higher incidence than was expected; the researchers suggested that HNPP was underrecognized because many affected persons have mild symptoms. We believe that another reason for underdiagnosis of HNPP is the marked phenotypic variability of the disease. We recommend, therefore, that DNA analysis for the 17p11.2 deletion be considered in patients with unexplained demyelinating neuropathy regardless of family history.

Adolescent↗

Management of diabetic neuropathy.

The only strategy shown to be consistently beneficial in the treatment of diabetic neuropathy is meticulous control of blood glucose. The largest study of the effects of glycemic control on progression of neuropathy was the Diabetes Control and Complications Trial, which enrolled 1,500 patients. Meticulous control of blood glucose by multiple injections or continuous subcutaneous infusion both delayed the onset of neuropathy and slowed its progression. A weakness of this and other studies of the effect of glycemic control is that they used surrogate measures of improvement (or slowing of progression) of neurologic function. Most used sensory and motor nerve conduction studies and some used vibration perception thresholds. Whether such measures correlate reliably with neuropathy symptom scores, neurologic examination, quality-of-life measures, neuropathic complications (foot ulcers and amputation), and mortality remains controversial. Also, most studies of tight glycemic control do not address the complications of more intensive therapy, among them severe hypoglycemia. Severe hypoglycemia can precipitate acute painful neuropathy, and it markedly increases axonal degeneration in experimental diabetic neuropathy. Finally, all studies have been confined to patients with mild neuropathy; some patients had no clinical evidence of neuropathy. Whether benefit can accrue to patients with more advanced neuropathy is not known. The most physiologic means of achieving glycemic control is through pancreas transplantation; this can result in significant improvement in clinical and electrophysiologic measures of motor and sensory function and slightly improve autonomic function. Strategies to reduce the metabolic consequences of hyperglycemia on nerves and to enhance axonal regeneration are needed to supplement careful glycemic control. Aldose reductase inhibitors hold promise for reducing metabolic nerve injury, but further study is needed.

Aldehyde Reductase↗

Annual league tables of mortality in neonatal intensive care units: longitudinal study. International Neonatal Network and the Scottish Neonatal Consultants and Nurses Collaborative Study Group.

OBJECTIVE: To assess whether crude league tables of mortality and league tables of risk adjusted mortality accurately reflect the performance of hospitals. DESIGN: Longitudinal study of mortality occurring in hospital. SETTING: 9 neonatal intensive care units in the United Kingdom. SUBJECTS: 2671 very low birth weight or preterm infants admitted to neonatal intensive care units between 1988 and 1994. MAIN OUTCOME MEASURES: Crude hospital mortality and hospital mortality adjusted using the clinical risk index for babies (CRIB) score. RESULTS: Hospitals had wide and overlapping confidence intervals when ranked by mortality in annual league tables; this made it impossible to discriminate between hospitals reliably. In most years there was no significant difference between hospitals, only random variation. The apparent performance of individual hospitals fluctuated substantially from year to year. CONCLUSIONS: Annual league tables are not reliable indicators of performance or best practice; they do not reflect consistent differences between hospitals. Any action prompted by the annual league tables would have been equally likely to have been beneficial, detrimental, or irrelevant. Mortality should be compared between groups of hospitals using specific criteria-such as differences in the volume of patients, staffing policy, training of staff, or aspects of clinical practice-after adjusting for risk. This will produce more reliable estimates with narrower confidence intervals, and more reliable and rapid conclusions.

Cohort Studies↗

Multifocal motor neuropathy without overt conduction block.

One of the defining electrophysiological characteristics of multifocal motor neuropathy (MMN) is focal motor nerve conduction block. We have noted occasional patients with typical clinical features of MMN in whom there is no demonstrable conduction block. Upon review of 5 such cases, we conclude that otherwise typical MMN may present without overt conduction block. This subset of patients does not otherwise differ from patients with MMN in whom this hallmark electrodiagnostic feature is present.

Adult↗

MRI in juvenile ALS: a patient report.

We describe the MR images of a patient with juvenile ALS. MRI of the brain showed bilateral hyperintensities along the corticospinal tracts extending from the corona radiata to the brainstem on T2-weighted images. These findings should be differentiated from the slight hyperintensities seen in the posterior limbs of the internal capsules in normal subjects.

Adolescent↗

Neuropathy in erythropoietic protoporphyrias.

Peripheral neuropathy (PN) has rarely been described as a complication of erythropoietic protoporphyria (EPP). We describe three episodes of PN and the electrophysiologic findings in two patients with EPP. PN is seen in patients with EPP and hepatic failure and raised free erythrocyte protoporphyrin or serum protoporphyrin levels and is identical to that seen in acute intermittent porphyria. Recognition is important because of the good eventual prognosis.

Adolescent↗

Reliability of maximal voluntary isometric contraction testing in a multicenter study of patients with amyotrophic lateral sclerosis. Syntex/Synergen Neuroscience Joint Venture rhCNTF ALS Study Group.

Maximal voluntary isometric contraction (MVIC) is becoming widely used for monitoring disease progression in amyotrophic lateral sclerosis (ALS). We evaluated the variability of MVIC in a large multicenter (29 sites) drug trial in ALS. Intra- and interrater variability were assessed twice during the 19-month study. Intrarater reliability increased from the first to the second test, approaching the reliability reported for a single experienced clinical evaluator, but interrater reliability did not. Multiple clinical evaluators in a single site increased the variability of MVIC measurements. Rigorous quality assurance standards and monitoring of clinical evaluators should be incorporated into the design of multicenter studies using MVIC, since low variability is necessary to detect a modest treatment effect.

Adult↗