Hippocampal memory function as reflected by the intracarotid sodium methohexital Wada test

The intracarotid amobarbital procedure (IAP) determines lateralization of memory function for predicting the risk of amnesia after epilepsy surgery. Shortages of amobarbital led to its substitution with sodium methohexital in the intracarotid methohexital procedure (IMP). We compared IAP scores (32 patients) with IMP scores (20 patients). Wada ipsilateral and contralateral memory scores were analyzed and compared, as was the relationship of these scores to the results of standard neuropsychological memory tests. There was no significant difference in Wada contralateral memory scores (first injection) between the IAP and IMP. Differences between the IAP and IMP in memory scores for the hemisphere ipsilateral to the epileptogenic focus (second injection) were significant (P=0.01), patients who underwent the IMP manifesting a higher ipsilateral memory reserve. IAP scores related better to standard neuropsychological memory test scores than did IMP scores. The anesthetic drug used in Wada testing may affect lateralized memory assessment and prediction of postsurgical memory changes.     

Quantitive imaging in late traumatic brain injury. Part I: late imaging parameters in closed and penetrating head injuries

Objective : To ascertain the value of relatively simple quantitative radiologic measurements after head injury. Despite major advances in neuroradiology, analysis and reporting of imaging studies is based primarily on individual subjective and local experience, rather than on reproducible, standardized parameters; reliance on newer technologies can improve care, but also raises diagnostic costs. Design : Blinded, retrospective, quantitative assessment of computerized tomography studies done some 14 years post-injury. Outcome measures : Frontal horn width (FHW); septum-caudate distance (SCD); temporal horn width (THW); interuncal distance (IUD); third ventricle width (3VW); ventricular score (VS); sulcal width (SW); gray-white matter discriminability (GWMD) and subjective assessment of atrophy (SAOA). Results : Diffuse and frontal damage was noted in both closed (CHI) and penetrating (PHI) head injury groups. Enlargement of frontal lobe parameters (septum caudate distance and frontal horn width suggest frontal injury in both closed and penetrating traumatic brain injury (TBI). Temporal horn width and inter-uncal distance were related to VS, 3VW and FHW in closed, but not in penetrating head injury. Conclusions : Simple linear CSF space measurements are correlated with volumetric and parenchymal measures, and can represent valuable and reliable low-cost quantitative measures of long term brain damage after TBI.     

Repeat abdominal ultrasound evaluation of 100 patients with type I Gaucher disease treated with enzyme replacement therapy for up to 7 years

With the advent of enzyme replacement therapy for Gaucher disease, there was a need to assess response to treatment repeatedly over relatively short periods of time; hence abdominal ultrasound was used in our referral clinic because it was convenient, safe and inexpensive. In 100 treated patients monitored for 2-7 years, nearly all had reduction in hepatosplenomegaly. The per cent reduction was more dramatic in patients who started treatment when older than 16 years. This effect may be explained by a correlation between per cent reduction and degree of baseline organomegaly. Because children often initiate therapy sufficiently early to preclude developing massive organomegaly, the observed per cent reduction is commensurately less. For all patients treated for more than five years, plateau-ing in response was seen after the first three years of treatment. This study permits us to reconsider less frequent evaluations of organ volumes. Our findings also underscore the efficacy of enzyme replacement, but raise the question of the need for dose reduction as nearly normal organ volumes are achieved.     

Orthopedic considerations in Gaucher disease since the advent of enzyme replacement therapy

Gaucher disease, the most prevalent lysosomal storage disorder, is characterized by hepatosplenomegaly, hypersplenism, and rarely, neurological involvement. The most variable symptoms relate to skeletal disease, and both onset and progression are difficult to predict on the basis of genotype. This review describes findings from a large referral clinic (> 500 patients) and from the literature in the decade since the advent of specific enzyme replacement therapy. Such therapy is effective in reducing visceral and hematological involvement, but its greatest advantage as regards the skeleton is prevention of irreversible damage. Avascular necrosis of the joints-particularly the hips but also the knees and shoulders-and pathological fractures of the long bones including the ribs, as well as episodic "crises' of bone pain in children and young adults, are common manifestations. Various imaging modalities should be performed at baseline for life-long monitoring, and then as required because of specific complaints. Surgical interventions such as joint arthroplasties are important adjuvant treatments in this population; presurgical hematological profiling plus antibiotic cover and postoperative pain control are equally critical. Opportunities for orthopedic consultations with senior surgeons are not abused by our patients. These reflect disease-related morbidity, with greater numbers of requests being made by patients requiring enzyme therapy, who by definition have more severe disease characteristics.     

Type I Gaucher disease in children with and without enzyme therapy

This retrospective study describes the course of 56 children with non-neuronopathic Gaucher disease who presented at <16 years and were followed at 6- to 12-month intervals for 3-9 years. Massive splenomegaly and height retardation marked those who required treatment. Enzyme replacement significantly increased hemoglobin levels; platelet counts were divergent at presentation and follow-up, regardless of therapy. Among treated patients there was a significant reduction in liver and spleen index volumes, and a significant increase in height z-scores. None of the children required splenectomy or developed lung involvement. Many patients diagnosed due to large-scale screening were very mildly affected and remain untreated.     

Risk adjustment and risk selection on the sickness fund insurance market in five European countries

From the mid-1990s citizens in Belgium, Germany, Israel, the Netherlands and Switzerland have a guaranteed periodic choice among risk-bearing sickness funds, who are responsible for purchasing their care or providing them with medical care. The rationale of this arrangement is to stimulate the sickness funds to improve efficiency in health care production and to respond to consumers' preferences. To achieve solidarity, all five countries have implemented a system of risk-adjusted premium subsidies (or risk equalization across risk groups), along with strict regulation of the consumers' direct premium contribution to their sickness fund. In this article we present a conceptual framework for understanding risk adjustment and comparing the systems in the five countries. We conclude that in the case of imperfect risk adjustment-as is the case in all five countries in the year 2001-the sickness funds have financial incentives for risk selection, which may threaten solidarity, efficiency, quality of care and consumer satisfaction. We expect that without substantial improvements in the risk adjustment formulae, risk selection will increase in all five countries. The issue is particularly serious in Germany and Switzerland. We strongly recommend therefore that policy makers in the five countries give top priority to the improvement of the system of risk adjustment. That would enhance solidarity, cost-control, efficiency and client satisfaction in a system of competing, risk-bearing sickness funds.     

Abdominal ultrasound findings mimicking hematological malignancies in a study of 218 gaucher patients

Gaucher disease, the most prevalent sphingolipidosis, generally presents with splenomegaly, anemia, and thrombocytopenia. Hence, hematologists are often the specialists involved in diagnosis and management of these patients. We present ultrasonographic characteristics in a cohort of 218 consecutive Gaucher patients evaluated in our clinic during the past 5 years. Our data emphasize the high prevalence of lesions mimicking hematological malignancies in Gaucher disease. One fifth of 184 non-splenectomized patients had intra-splenic lesions, 6% of all patients had similar lesions in the liver, and 32% of 34 splenectomized patients (but none of the other patients) had marked retroperitoneal or peri-portal lymphadenopathy. The presence of splenic lesions correlated with age and splenic size, but not with extent of bone involvement or genotype. Interestingly, they were not affected by reduction in splenomegaly following enzyme replacement therapy. The importance of these findings is to include Gaucher disease in the differential diagnosis of splenic or hepatic lesions, especially in Ashkenazi Jews. Conversely, they are relevant for follow-up of all Gaucher patients, including asymptomatic individuals, because of the reported increased incidence of hematological malignancies in Gaucher disease. Am. J. Hematol. 55:28-34, 1997. © 1997 Wiley-Liss, Inc.     

Novel genetic determinants of low-level aminoglycoside resistance in Pseudomonas aeruginosa

Pseudomonas aeruginosa strains isolated from patients with persistent lung infections and cystic fibrosis have been found to gradually develop aminoglycoside resistance over time. The aim of this study was to identify potential contributors to low-level aminoglycoside resistance, which may cause such graduated increases in resistance. The Harvard P. aeruginosa PA14 nonredundant library, consisting of approximately 5,800 mutants, was screened for twofold or greater increases in tobramycin resistance. Mutants carrying mutations in a total of 135 unique genes were identified and confirmed to have reduced susceptibility to tobramycin. Many of these genes were involved predominantly in energy metabolism; however, most of these mutants did not exhibit growth defects under the conditions tested, although some exhibited the small-colony phenotype and/or defects in growth under anaerobic conditions. Lipopolysaccharide mutants were also identified, and it was found that tobramycin had a reduced ability to permeabilize the outer membranes of these mutants. The results of this study emphasize the complexity of the interactions that tobramycin may have within the bacterial cell and introduce a large number of novel genes which may play a role in tobramycin resistance.