Progression of bone disease without deterioration of hematological parameters in a child with Gaucher disease during low-dose glucocerebrosidase therapy

Gaucher disease is the most prevalent lysosomal storage disease. Although the efficacy of the macrophage-targeted human placental glucocerebrosidase is well known, it is still difficult to develop definitive guidelines regarding the appropriate therapy schedule. We describe an 8-year-old Japanese boy with Gaucher disease who had avascular necrosis of the right femoral head without deterioration of hematological variables during low-dose enzyme replacement therapy (12-13 IU/kg). This case demonstrates that continuous normal hematological findings may not preclude progression of other aspects of Gaucher disease in some patients during enzyme replacement therapy.     

Anesthetic considerations for the pediatric plastic surgical patient

An understanding of the anesthesiologist's concerns during pediatric plastic surgical procedures can facilitate the coordination of efforts between the multiple services involved in the care of these children. Prior to surgery, the child's history is obtained and physical examination is performed. The condition of the airway is the primary concern. Preoperative medication is usually given by oral routes to avoid injections. Induction intubation, maintenance, and emergence are discussed. Specific postanesthesia care is described. Special precautions are given for children having surgical repair of craniofacial anomalies. Cleft lip and palate and mandibular advancement are described.     

Corneal opacities in Gaucher disease

PURPOSE: To describe the corneal findings in a variant of Gaucher disease. METHODS: Case report. In an 18-year-old man, ophthalmic and general clinical evaluation, and enzymatic and molecular genetics studies were performed. RESULTS: Diffuse, well-defined, small, linear, or dotlike corneal opacities were observed through, out the posterior two thirds of the corneal stroma in both eyes. The patient had calcific valvular heart disease. Enzymatic and ultrastructural studies were consistent with Gaucher disease. Analysis of the glucocerebrosidase gene disclosed homozygosity for a D409H mutation. CONCLUSION: Corneal opacities are a distinguishing ocular feature of the variant of Gaucher disease associated with the D409H mutation and with calcific cardiac disease.     

Cytokine mRNA in Gaucher disease

Bromine-76 is potentially useful as a radiolabel for monoclonal antibodies (MAbs) in PET imaging. The purpose of the present study was to evaluate the 76Br-labeled anticarcinoembryonic antigen (-CEA) MAb 38S1 as a tumor imaging agent in an experimental tumor model and to study the pharmacokinetics of 76Br-38S1 in comparison with 125I-38S1. METHODS: Nude rats carrying human colon carcinoma xenografts were co-injected with directly labeled 76Br-38S1 and 125I-38S1. Biodistribution of labeled 38S1 was monitored for 4 days after administration, in the case of 76Br activity, including PET imaging. In addition, catabolism of radiolabeled MAbs was analyzed by gel filtration chromatography of blood plasma and homogenized tissues. RESULTS: Tumor sites could be readily identified by PET imaging from 46 hr after administration of 76Br-38S1 and onwards. The concentration of 76Br activity in tumors, blood and most normal tissues was higher than the corresponding 125I concentration at all time points. This was mainly due to catabolism of radiolabeled MAb, resulting in free radiohalides, of which 76Br- was retained in contrast to the rapidly excreted 125I- ion. CONCLUSION: Bromine-76-labeled anti-CEA MAbs may be applied for experimental tumor imaging with PET.     

Anesthetic management of a child with Lenz dysplasia associated with panhypopituitarism

We present a child with Lenz dysplasia associated with panhypopituitarism. Lenz dysplasia is characterized by small eyeball, small head, hydronephrosis, cleft lip and palate, and mental retardation. A 12 month-old boy with Lenz dysplasia was scheduled for plasty of the lip and basis of the nasal cavity under general anesthesia. We had to pay attention for airway management and hormone supplementation. Anesthesia was induced with sevoflurane and nitrous oxide in oxygen. Tracheal intubation was facilitated with vecuronium bromide. We had no difficulty in airway management. Since this patient could not release enough endogenous cortisol in response to the stress of surgery, we supplemented hydrocortisone after anesthesia induction. Urine output and serum electrolyte concentrations were carefully monitored during surgery because of the impaired ADH response. We encountered no complications in the anesthetic management of this patient.     

Gaucher disease: four families with previously undescribed mutations

A large-scale sequencing project requires a tool to control the quality of the input data because a sizable number of trace data may be of low quality. If these data are allowed to enter the sequence assembly pipeline, harm will be done. Hence, it is important to detect such data as soon as possible. MTT (Move-Track-Trim) is a software package analyzing the quality of the lanes. It subjects each lane to a series of tests, and if a lane does not pass all tests, it is flagged as a "bad" lane. The use has a chance to examine both the "good" and the "bad" lanes and reclassify a "bad" lane as "good," or vice versa. Alternatively, the user may decide to retrack the gel or get rid of some lanes altogether. As a by-product of the analysis, MTT performs other useful functions. It trims the lanes and compresses the lane files and moves them to the directories where assembly is carried out. It also generates some useful statistics describing the quality of the gel.     

Anesthetic management of a Paget's disease patient complicated with Parkinson disease

Paget's disease is a metabolic disorder of unknown etiology characterized by excessively rapid remolding of bone. We report a case of Paget's disease complicated with Parkinson syndrome. A 69-year-old female patient was scheduled for ventriculo-peritoneostomy due to hydrocephalus. Her manifestations included disability to walk, slight deafness and muscular rigidity of limbs, without symptom of intracranial hypertension. After induction of anesthesia with thiopental and vecuronium, tracheal intubation with Macintosh laryngoscope was attempted but failed because mouth opening was restricted to only 3 cm. Again with Bullard laryngoscope, she was successfully intubated. During neurosurgical operation, the anesthesia was maintained with low concentration of isoflurane (under 0.3%), nitrous oxide and oxygen. The surgery was completed without adverse events such as disorder of autonomic nervous system. However 6-days after operation, ventilatory arrest occurred due to bronchial obstruction with sputum. Immediately, re-intubation was performed without any sequela and tracheostomy was also performed. In conclusion, as reported previously, intubation and postoperative pulmonary dysfunction should be carefully taken care of, and Bullard laryngoscope was useful for this patient.     

An autopsy case of fetal Gaucher disease

The freeze-dried powder of Lumbricus rubellus earthworm was administered orally to rats and its fibrinolytic and antithrombotic effects were investigated. The fibrinolytic activity of plasma was determined by measuring the plasmin activity of the euglobulin fraction and was increased to two-folds of the control at a dose of 0.5 g/kg/day and five times with 1 g/kg/day after 4-day administration. The antithrombotic effect was studied in an arterio-venous shunt model of rats. The thrombus weight decreased significantly from 43.2 mg to 32.4 mg at a dose of 0.5 g/kg/day after 8-day treatment. The level of fibrinogen/fibrin degradation product (FDP) in serum was elevated in a dose-dependent manner during the treatment period. On the 8th day after administration, the FDP value was increased to 7.7 micrograms/ml compared with the control value of 3.3 micrograms/ml. These results support that earthworm powder is valuable for the prevention and/or treatment of thrombotic conditions.     

Enzymatic and molecular diagnosis of Gaucher disease

Advances in the knowledge of the molecular genetics of Gaucher disease has made diagnosis more certain. Carrier detection in kindreds in which the responsible mutation has been defined is completely reliable now. Coupled with enzymatic assays, the diagnostic capabilities are greater than before. Use of these methods provides important information to individuals at risk and allows them to make critical decisions. The new, simplified methods reviewed in this article permit the molecular diagnosis of the disease and carrier stage of large numbers of samples within 1 week.     

Regression of skeletal changes in type 1 Gaucher disease with enzyme replacement therapy

A 9-year-old patient presented with an acute onset of pain of the right femur showing destructive changes with periosteal elevation mimicking osteomyelitis. Technetium-99m sulfur colloid (99mTc SC) marrow scan revealed lack of uptake in the right femoral head and the entire shaft of the right femur. Eight months following enzyme replacement therapy, radiography showed almost complete reconstitution of the femoral shaft, and 99mTc SC marrow scan uptake returned to normal.     

Pulmonary disease in the immunocompromised child

Adhesion receptors that are known to initiate contact (tethering) between blood-borne leukocytes and their endothelial counterreceptors are frequently concentrated on the microvilli of leukocytes. Other adhesion molecules are displayed either randomly or preferentially on the planar cell body. To determine whether ultrastructural distribution plays a role during tethering in vivo, we used pre-B cell transfectants expressing L- or E-selectin ectodomains linked to transmembrane/intracellular domains that mediated different surface distribution patterns. We analyzed the frequency and velocity of transfectant rolling in high endothelial venules of peripheral lymph nodes using an intravital microscopy model. Ectodomains on microvilli conferred a higher efficiency at initiating rolling than random distribution which, in turn, was more efficient than preferential expression on the cell body. The role of microvillous presentation was less accentuated in venules below 20 micrometers in diameter than in larger venules. In the narrow venules, tethering of cells with cell body expression may have been aided by forced margination through collision with erythrocytes. L-selectin transfected cells rolled 10-fold faster than E-selectin transfectants. Interestingly, rolling velocity histograms of cell lines expressing equivalent copy numbers of the same ectodomain were always similar, irrespective of the topographic distribution. Our data indicate that the distribution of adhesion receptors has a dramatic impact on contact initiation between leukocytes and endothelial cells, but does not play a role once rolling has been established.     

Clinical and molecular characteristics of Japanese Gaucher disease

Clinical signs and symptoms of Gaucher disease are more severe in Japanese than in Jewish and other non-Japanese patients. A higher percentage of bone crises and splenectomy was demonstrated by Japanese patients, and there were five fatalities among patients with type 1 Gaucher disease. Additionally, neonatal Gaucher disease, clinically characterized by hydrops foetalis, was observed. Japanese patients with type 2 and type 3 disease also demonstrate clinical heterogeneity. About 100 alleles of patients with Japanese Gaucher disease were examined for genotype determination with the PCR and SSCP methods. About 18 different mutations, including several novel mutations in Japanese patients, were identified. The most common mutations in Japanese patients were 1448C(L444P), accounting for 41 (41%) of alleles. The second most prevalent mutation was 754A(F2131), accounting for 14 (14%) of alleles. Other alleles identified included the 1324C, IVS2 and other mutations. Unidentified alleles comprised 16% of the total number of alleles studied. To date, neither the 1226G (N370S) nor the 84GG mutation has been identified in the Japanese population, although these mutations account for about 70% and 10% of the mutations in Jewish and other non-Japanese populations, respectively. The phenotype-genotype correlation in Japanese patients is more complex compared with that of the Jewish population. In Japanese patients, the 1448C mutation, in either heteroallelic or homoallelic forms, exhibits both neurological and non-neurological phenotypes. Japanese patients with the 754A mutation also exhibit both neuronopathic and non-neuronopathic disease. On the other hand, patients with the D409H mutation show only type 3 neurological disease, and those with the 1447-1466 del 20 ins TG mutation have the severe, neonatal neurological form of Gaucher disease. The 1503T allele was present only in patients with type 1 non-neurological disease. However, since this correlation was observed only in young patients, we do not as yet know the final phenotypic outcome of this mutation. Probably, Japanese patients with Gaucher disease have few mutations that exhibit non-neurological signs and symptoms.     

Clinical and molecular aspects of Gaucher disease in New Zealand

AIM: To report on the clinical and molecular aspects of Gaucher disease in New Zealand. METHODS: Patients known to have Gaucher disease were contacted and clinical information was recorded by questionnaire. Blood samples from affected individuals and their families provided DNA material for mutation analysis of disease causing alleles. Patients were assayed for beta-glucocerebrosidase, the enzyme deficiency which causes Gaucher disease. RESULTS: Twelve of 14 patients and 10 carriers were confirmed by DNA analysis. One asymptomatic individual was diagnosed. Four known mutations (N370S, 1444p, R463c and RecNcIl) and one unknown mutation were found from the 34 disease producing alleles that were identified. Of these, the L444P and N370S alleles were the most common. Most patients exhibited a clinical disorder typical of type 1 Gaucher disease. Two recent patients with severe neuropathic Gaucher disease had died in childhood. All patients showed a deficiency in beta-glucocerebrosidase. CONCLUSION: Gaucher disease in New Zealand is represented in a small number of non Jewish individuals with varying severity. Identifiable mutations and clinical symptoms aid in expanding the Australasian picture of this well studied disease. Enzyme replacement therapy for these patients has recently commenced in New Zealand.     

Therapeutic considerations for work with persons with HIV disease.

Although a growing literature base is developing addressing the role that mental health professionals can or may play in assisting individuals with HIV disease, the literature is in need of an organization which provides a framework from which professionals can conceptualize their work. As such, this article reviews the psychotherapeutic literature on HIV/AIDS, by placing it in the framework of E. Kubler-Ross's (1969, 1987) stages of Denial, Anger, Bargaining, Depression, and Acceptance of the terminal illness. A process model that details the emotional course that many HIV-infected individuals encounter is described, summarizing the therapeutic tasks relevant for each stage and the treatment recommendations previously reported in the literature. (PsycINFO Database Record (c) 2010 APA, all rights reserved)