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Hematopoietic stem cell transplantation remains the only curative treatment currently in use for patients with sickle cell disease (SCD). The first successful hematopoietic stem cell transplantation was performed in 1984. To date, approximately 1,200 transplants have been reported. Given the high prevalence of this disorder in Africa, and its emergence in the developed world through immigration, this number is relatively small. There are many reasons for this; primary among them are the availability of a donor, the risks associated with this complex procedure, and the cost and availability of resources in the developing world. Of these, it is fair to say that the risks associated with the procedure have steadily decreased to the point where, if currently performed in a center with experience using a matched sibling donor, overall survival is close to 100% and event-free survival is over 90%. While there is little controversy around offering hematopoietic stem cell transplantation to symptomatic SCD patients with a matched sibling donor, there is much debate surrounding the use of this modality in "less severe" patients. An overview of the current state of our understanding of the pathology and treatment of SCD is important to show that our current strategy is not having the desired impact on survival of homozygous SCD patients, and should be changed to significantly impact the small proportion of these patients who have matched siblings and could be cured, especially those without overt clinical manifestations. Both patient families and providers must be made to understand the progressive nature of SCD, and should be encouraged to screen full siblings of patients with homozygous SCD for their potential to be donors. Matched siblings should be referred to an experienced transplant center for evaluation and counseling. In this review, we will discuss the rationale for these opinions and make recommendations for patient selection.

In this issue, [Gelfand and Cleveland][1] comment ([1][2]) on our recent photo quiz ([2][3], [3][4]) about Weissella confusa bacteremia in a Crohn's disease patient. In particular, they raise the possibility that the bacteremia resulted from the patient's use of a probiotic supplement rather than

Surgical excision of cerebellar haemangioblastomas, once they become Symptomatic, is the standard treatment in patients with von Hippel-Lindau disease. This case report describes a von Hippel-Lindau disease patient with a rare recurrent symptomatic dural based cystic haemangioblastoma.

Various cutaneous lesions including granulomatous reactions may occur at sites of resolved herpes zoster infection. A 46-year-old man with Hodgkin's disease developed localized granuloma annulare lesions on herpes zoster scars 3 months after allogeneic peripheral stem cell transplantation. This is the first case of granuloma annulare localized on herpes zoster scars that developed following peripheral stem cell transplantation.

Universidade Estadual Paulista, Departamento de Microbiologia e Imunologia, Instituto de Biociencias de Botucatu

Parkinson's disease (PD) is characterized by motor disturbances such as tremor, slow movement and rigidity. Also, pain is a common symptom in patients with PD. The prevalence of pain is 40–75% in patients with PD. Physicians should pay attention to pain in patient with PD. We report a PD patient who suffered from fibromyalgia (FM). If the amount of pain is not maximal in the side more affected by parkinsonism and pain is not markedly relieved when the patient is in the “on” state, the pain may be due to FM.

This paper reports a case of S. constellatus chorioamnionitis in a pregnant Crohn's disease patient who was taking azathioprine. Chorioamnionitis is a major cause of perinatal morbidity. Azathioprine, an immunosuppressive antimetabolite, is widely used to treat inflammatory bowel disease. Streptococcus constellatus is a Gram-positive bacterium that has not previously been associated with chorioamnionitis. A high index of suspicion for chorioamnionitis and unusual pathogens should be maintained in the management of obstetric patients on immunosuppressive agents.

Item does not contain fulltext Inborn errors of metabolism are rare and laboratories performing diagnostic tests in this field must participate in external quality assurance (EQA) schemes to demonstrate their competence and also to maintain sufficient experience with patient material. EQA schemes for metabolite analyses are available (ERNDIM), but corresponding EQA schemes for enzyme analyses are nonexistent. In this paper we describe a pilot study on lysosomal enzyme testing by four centres in The Netherlands. Quantitative aspects of EQA were studied by interlaboratory comparison of activities of six lysosomal enzymes in a series of buffy coat samples. Interlaboratory variance was enormous. To reduce variance caused by methodological differences, participants reported enzyme activities relative to mean normal values. beta-D: -Galactosidase activities compared well between the participating laboratories (average interlaboratory CV 13%), but for other enzymes large differences were observed, e.g. sphingomyelinase (average CV 38%). Diagnostic proficiency was tested with cultured fibroblasts. In 45 out of a total of 48 tests (12 cell lines, 4 participants) the correct diagnosis was accomplished on the basis of merely biochemical investigations, i.e. without clinical data of the patients. In a survey using blood of a late-onset Pompe disease patient, less conclusive results were obtained. A stable enzyme source was developed for easy distribution. Most lysosomal enzymes were stable upon lyophilization of leukocyte homogenates and during subsequent storage of the freeze-dried material at room temperature, in particular when cryolyoprotectant was added. Shipment of such lyophilized samples is simple and cheap and ideal for an EQA scheme. Our study shows that an EQA programme for enzymatic testing of lysosomal storage diseases is necessary to accomplish reliable diagnostic procedures for lysosomal storage diseases. We recommend that EQA for lysosomal enzymes be implemented through ERNDIM.

Dear Sir, We appreciate the interest in our report1 and the comments from Drs. Katsano and Asproudis,2 which allow us to clarify some important issues regarding the probable association of adalimumab and retinopathy in a Crohn's disease patient. First, the characterization of the causality based on the method of estimating the probability of adverse drug reactions (ADR) developed by Naranjo et al.,3 an ADR can be considered as “probable” related to a drug if the overall score is between 5 and 8. In our case the ADR appeared after the suspected drug administration (+ 2 points), alternative causes for the ADR were not found (+ 2 points), and the ADR was confirmed by objective evidence (+ 1 point). Therefore, in our patient, the adverse effect (retinopathy) could be considered as “probably” related to …

Introduction. The goal of the Eurotransplant renal allocation scheme is to provide every patient on the waiting list with a reasonably balanced opportunity for a donor offer. New initiatives were taken in order to maximize donor usage while maintaining a successful transplant outcome. Methods. Two Eurotransplant projects were launched in order to accommodate changes in donor and recipient profiles. A re-addressing of the non-heart-beating donor pool was undertaken and an allocation scheme in which organs from donors aged >65 are allocated to recipients aged >65 [the Eurotransplant Senior Programme (ESP)] was introduced. Results. Especially in The Netherlands, an enormous increase in the number of non-heart-beating donor kidneys has been observed, however with a pace-keeping reduction in heart-beating donors. The organization-wide implementation of the ESP has been successful. The 3 year graft survival rates for these age-matched transplants were as good as the human leukocyte antigen (HLA)-matched transplants (64 vs 67%) (P=0.4). Conclusion. Within the framework of sound research, the utmost flexibility and creativity is needed to keep or even increase the number of renal transplants when faced with a quantitatively stagnating but qualitatively deteriorating donor pool. Both the non-heart-beating donor protocol and the ESP have proven to be quite successful in achieving this goal without compromising the outcome for the individual end-stage renal disease patient.

Although the molecular basis of sickle cell disease (SCD) is well established, the wide variability in clinical manifestations still puzzles haematologists and clinicians. Recently, SCD started to be considered by different groups as a chronic inflammatory condition, where the inflammatory tendency of each individual could drive more or less severe clinical features. Here we describe a haemoglobin SC disease patient (heterozygous to both HbS and HbC variants) that experienced several vaso-occlusive crises before underwent a successful kidney transplantation. Since then (16 years ago), she is on uninterruped immunosuppressive therapy, and do not experienced any severe vaso-occlusive crisis. Considering SCD associated morbidity as a result of exacerbated immune responses, we suggest that the immunosuppressive therapy directed to the kidney graft maintenance is actually also helping in the control of the chronic inflammatory responses associated to SCD.

A recent case report in the journal described a Gaucher’s disease patient, dangerously infected with salmonella that responded poorly to antibiotic treatment.1 However, use of enzyme replacement with glucosylceramide glucosidase lowered tissue levels of glucosylceramide (GlcCer), and produced a slow but dramatic improvement. The article points out that infection is an important aspect of the genetic disorder. I would like to mention important observations that explain this unfortunate complication and their significance for many patients with infections. Many research studies have shown that a wide variety of bacterial and viral infections involve binding of the organism to a glucosphingolipid in the cell surface. Patients …

Aging is progressing in our country and therefore, cerebral disease is becoming a serious problem. Aged and cerebral disease patient support is a useful research theme. Because drinking is closely related to cerebral disease, we assess the degree of decline of cognitive ability and memory ability caused by drinking with a recognition test using cerebral disease patients. From the decline of nonlanguage function and the influence on judgment ability, we could make the condition look like the early symptoms of vascular dementia. In the next experiment, we synthesised a face image based on pictures of a drinking subject's face, and examined the AU (action unit). We confirm the existence of an AU corresponding to each facial expression.

Pain in the thyroid gland is rarely present in Graves’ disease. We describe a 32-year-old female hyperthyroid Graves’ disease patient with an initial manifestation of painful goiter. On physical examination, the thyroid gland was diffusely enlarged and tender. The laboratory examinations showed high serum thyroid hormone and low thyrotropin values. Serum inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate, were elevated. Thyroid ultrasound revealed multiple focal hypoechoic areas. All these findings gave an initial impression of an acute inflammatory and destructive process in the thyroid gland. However, subsequent thyroid scintigraphy demonstrated a diffuse radioactive iodide uptake pattern with positive serum thyrotropin receptor antibodies. Fine-needle aspiration cytology showed only the presence of lymphocytes. She was diagnosed as having Graves’ disease and was treated with propylthiouracil, and prednisolone was given for neck pain. Within a few days, the thyroid tenderness dramatically improved, and the erythrocyte sedimentation rate progressively normalized. However, follow-up thyroid function tests still showed high serum thyroid hormone levels. The possible etiologies of a painful thyroid gland in Graves’ disease will be discussed.

Sickle cell disease affects 10% of tribal population of India. These patients have multiple orthopaedic complications like AVN (avascular necrosis) of femoral and humeral head, osteomyelitis, etc. One such patient having an atypical bilateral hip ankylosis has been reported. A 17 year female, known case of sickle cell disease, came to our hospital with complains of pain in bilateral hip since five years, both hips showed ankylosis and both knees showed flexion deformities. Ideal treatment for ankylosed hip in modern era is total hip replacement. However in sickle cell disease patients belonging to tribal population requiring squatting ability and having financial constraints, alternatives like RAO (resection angulation osteotomy) and arthrodesis for mobility as well as stability respectively should be considered inspite of inferior outcomes.

Background:Informing patients and families about the diagnosis of Alzheimer’s disease (AD) is a complex ethical and practical issue. This qualitative study explores the psychosocial impact of disclosing a diagnosis of AD on patients and family members.Methods:This study identified 14 patients and their accompanying family members undergoing a multidisciplinary assessment for dementia at an outpatient clinic for AD and related disorders. Of the group, three patients had probable AD and five had possible AD as per NINCDS-ADRDAcriteria. Six patients were not demented as per DSM IIIR criteria. Disclosure of diagnosis occurred, in a family conference, within six to eight weeks of the assessment. Data collection methods included observation of the assessment and the family conference as well as in-depth home interviews with family members and with each patient whenever feasible. The interviews were transcribed verbatim and coded for recurrent themes.Results:A total of 40 individuals across 14 families participated in this study. Only two families chose not to have the patient attend the family conference. The disclosure of a diagnosis of probable AD brought on an experience of relief in three families, marking the end of a lengthy period of confusion about the nature of memory problems. Patients diagnosed with possible AD and their families interpreted how indicative the diagnosis was of the presence of the disease with varying degrees of certainty depending on pre-assessment beliefs about the cause of memory problems. In the group diagnosed as not demented, four patients had complaints of forgetfulness likely related to minor depression. The disclosure of a diagnosis of no dementia did not produce the anticipated relief. Two patients continued to believe their memory problems were caused by the early onset of AD or some other “organic” problem.Interpretation:This study reveals that disclosure of the diagnosis of AD to patients and family members is generally beneficial but that there are variations in the understanding of the diagnostic information, particularly in instances where the assessment results are ambiguous.

The purpose of this chapter is to provide basic required information about the various anticopper drugs. I recommend that prior to initiating treatment of a Wilson’s disease patient, or taking over the therapy of a previously treated patient, that physicians read both this chapter and the following chapter on overview of management in order to become familiar with various aspects of anticopper treatment and management. They can then turn to the chapter on managing their specific type of patient (one of Chapters 6–9).

Human leukocyte antigen (HLA)-DQA1*0510 has been identified in a Spanish patient diagnosed with celiac disease. DQA1*0510 differs from DQA1*0505/09 by a point mutation at exon 2 producing an amino acid replacement at codon 77 (I>V).

Wilson's disease is an autosomal recessive disorder. More than 60 mutations of the Wilson's disease gene have been described so far. We have analysed 148 Polish Wilson's disease patients from 95 families for His1069Gln and Gly1267Lys mutations and correlated this finding with age and clinical form of the disease at presentation. To identify these mutations, single strand conformation polymorphism analysis was performed. In our group there were 94 patients with neurological presentation, 28 with hepatic presentation, whilst 26 were in a pre-clinical stage of the disease. His1069Gln mutation was present on 171 (57%) of the 296 studied chromosomes, and Gly1267Lys mutation was present on 27 chromosomes (9.1%). Most of our patients were homozygous or heterozygous for His1069Gln mutation (39.9% and 30.4%, respectively); 4% of the patients were homozygous for Gly1267Lys mutation and 5.4% had both of these described mutations on their chromosomes. His1069Gln and Gly1267Lys mutations occurred often in our Wilson's disease patient population but we did not find any relationship between investigated mutations and the clinical form of Wilson's disease or age of first symptoms.

Physiological evidence indicates that the resting tremor of Parkinson’s disease originates in oscillatory neural activity in the forebrain, but it is unknown whether that activity is globally synchronized or consists of parallel, independently oscillating circuits. In the present study, we used dual microelectrodes to record tremor-related neuronal activity from eight sites in the internal segment of the globus pallidus (GPi) from an awake Parkinson’s disease patient undergoing stereotaxic pallidotomy. We utilized spectral analysis to evaluate the temporal correlations between multiunit activity at spatially separated sites and between neural and limb electromyographic activity. We observed that some GPi neural pairs oscillated synchronously at the tremor frequency, whereas other neural pairs oscillated independently. Additionally, we found that GPi tremor-related activity at a given site could fluctuate between states of synchronization and independence with respect to upper limb tremor. Consistent with this finding, some paired recording sites within GPi showed periods of transient synchronization. These observations support the hypothesis of independent tremor-generating circuits whose coupling can fluctuate over time.

An excess accumulation and presence of metal ions may significantly alter a brain cell’s normal functions. There have been increasing efforts in recent years to measure and quantify the density and distribution of excessive accumulations of constituent elements (such as Fe, Zn, Cu, and Ca) in the brain, as well as the presence and distribution of contaminating elements (such as Al). This is particularly important in cases of neuropathological disorders such as Alzheimer’s disease, Parkinson’s disease and ALS. The aim of this paper was to measure the Al present in the temporal cortex of the brain of an Alzheimer’s disease patient. The specimens were taken from an unfixed autopsy brain which has been preserved for a period of 4 years in the deep freezer at −80 °C. Proton Induced X-ray Emission Spectroscopy was used for the measurement of Al concentration in this brain tissue. A tandem accelerator with 2 MeV of energy was also used. In order to increase the sensitivity of the signals in the low energy region...

Summary The concentrations of seven elements (Ca, Cu, Fe, Mg, P, S and Zn) in three autopsy livers (from two β-thalassemic patients and one Wilson's disease patient) were determined by ICP-AES technique. At autopsy the three livers were subdivided into a large number of samples for a detailed study of the distribution of Fe and Cu, the accumulation of which characterizes the two diseases. In the same samples Ca, Mg, P, S and Zn concentrations were also determined in order to study significant variations or anomalous trends that could help identify these diseases. Our results generally show a good coincidence with literature data within the limits of sample variability. Based on Factor Analysis as well as Regression Analysis there is evidence of a high correlation between Fe and P contents in β-thalassemia. The latter finding led us to propose tentatively an accumulation of Fe as a complex with P-containing molecules.

Clinically, the earlier acute vertiginous attacks in Menière's disease and the later deafness appear to constitute a continuum. It is therefore possible that effective treatment of the cause of the acute attacks might prevent the later auditory symptoms. This paper describes biochemical events preceding the acute attacks, and then points to a common factor in the acute and chronic states. If true, this occurrence supports use of intravenous calcium gluconate to abort or cut short an acute attack. Because of the complexities of the situation, it is probable that not every Menière's disease patient will respond to this treatment and a controlled widespread trial is necessary.

The End-Stage Renal Disease Program is underfunded and overregulated. Objective parameters of end points of care do not correlate to specific clinical practice patterns. We do not have consensus between payers, providers, and patients as to what the objectives of the End-Stage Renal Disease Program are or should be. This report will address the need for an integrated health care delivery system that would benefit the end-stage renal disease patient and the barriers to designing such a system. The quality improvement program of a five-unit dialysis system will be described. The deficiencies of the quality improvement program and the limitation of the facilities to improve outcome will be discussed, and constructive alternatives to achieve an integrated health care delivery system that promotes improvement in patient outcomes will be suggested.

Clinical management of the Alzheimer's disease patient in his or her home requires an array of services. Such services are often available from voluntary organizations, religious groups, for profit, not-for-profit, or governmental agencies. This article reviews the structure and range of those services that contribute much help to maintain the patient outside of the institution.

Elastosis perforans serpiginosa secondary to D-penicillamine treatment in a Wilson's disease patient

Axillary hidradenitis suppurativa successfully treated with infliximab in a Crohn's disease patient

The P1 potential (50 msec) of the middle latency auditory evoked potential was lacking in 12 of 31 (39%) patients with probable Alzheimer9s disease and seven of 12 (58%) demented patients with Parkinson9s disease. Component P1 was not present in one normal control subject and one nondemented Parkinson9s disease patient. Clinical and experimental evidence suggests that abnormalities of P1 in dementia may be due to cholinergic dysfunction.

Diagnosis of dementia needs to be complemented by precise determination of disease severity across the broad spectrum of disease progression. The Mini-Mental State Exam (MMS), the Activities-of-Daily-Living assessment (ADL) and the Clinical Dementia Rating scale (CDR) were modified for direct comparability and administred to 112 outpatients and 45 nursing home residents with a range of dementia severity from mild to profound. The scales showed the highest correlations for the probable Alzheimer's disease patient group (62) (Global Assessment of Dementia; GAD vs. ADL: r = 0.91; Extended Mini-Mental Assessment; EMA vs. GAD: r = 0.91; ADL vs. EMA: r = 0.86). For these patients, scores on the individual scales tended to be similar. Disparity among the three scores for individual cases was associated with the presence of comorbidities. The high correlations and correspondence among these scales demonstrate their reliability, validity, and utility in the assessment of dementia severity. The use of an average of these measures, with their increased precision, may give a more accurate indication of dementia severity over a broader range of impairment.