Selective IgA deficiency and hyposplenism.
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Biomedical subjects
Publications and source records attributed to S H Lim.
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Thrombocytopenia in patients with lymphoproliferative disorders is usually multifactorial. In some patients, peripheral destruction of platelets by platelet autoantibodies may account in part for the thrombocytopenia. However, the diagnosis of autoimmune thrombocytopenic purpura in this group of patients can be difficult due to the splenomegaly and compromised bone marrows in some of these patients. The development of autoimmune thrombocytopenic purpura in these patients does not affect the eventual outcome of the underlying lymphoproliferative disorders. Unfortunately the current available therapy for this condition is unsatisfactory. Other innovative treatment modalities are therefore much needed.
House dust mite allergens constitute one of the most important allergens in house dust. In this study, the levels of two common dust mite allergens, Der p I and Der f I, in a general hospital in Singapore were evaluated. Our results showed that these allergens were detected in 42/74 (or 57%) of the dust samples. Der p I was found to be the predominant allergen detected (p < 0.001). The allergen levels were, however, low with only 1/74 having a Der p I concentration above 2 micrograms g-1 dust. None of the samples had Der f I concentrations above this level. Of the various niches studied (mattresses, pillows, sofas, carpets, blinds and floors), the blinds and floors had the lowest concentration of allergen (p < 0.05). These low levels in the hospital compared to homes were attributed to the vigorous cleaning schedule in the hospital, the use of plastic to encased mattresses and pillows, vinyl covered sofas and vinyl lined floors. These practices may be adopted in the home as a means to reduce mite allergen exposure.
Methicillin resistant Staphylococcus aureus (MRSA) is a major infection control problem in many countries. There have been many reports of outbreaks in neonatal nurseries including, in our part of the world, Australia, Hong Kong and Malaysia. A recent outbreak of MRSA in the neonatal intensive care unit in the Kandang Kerbau Hospital, Singapore, presented us with the opportunity to study the clinical characteristics of the outbreak and the effects of infection control measures. Neonates admitted to the neonatal intensive care unit were studied over a 20-month period. They were all screened for nasal colonisation on admission and weekly thereafter. Infections were documented. Over this period there were altogether 2,576 admissions of which 85 infants had nasal colonisation with MRSA (3.3%) and 28 developed infections (1%). Although the majority of infants colonised by MRSA suffered no ill effects, 3 had septicaemia and 2 had septicaemia with osteomyelitis. There were no deaths. Standard infection control measures with barrier nursing and the use of mupirocin nasal ointment were ineffective, and control was achieved only after strict cohorting together with the use of mupirocin was instituted. This was done without additional costs to the department and without additional nurses or doctors.
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1. The presence and partial characterization of immunoreactive ANP (irANP) in eggs were investigated using high performance liquid chromatography (HPLC), immunohistochemistry and Northern-blot hybridization in mammalian and nonmammalian vertebrates. 2. Serial dilution curves of egg extracts from frogs and freshwater teleostean fishes (silver crusian carp and loach) were parallel to the standard curve of atriopeptin III. Rat oocytes also contained irANP (25-30 pg/egg). 3. The HPLC profile of irANP showed two main peaks corresponding to low and high molecular weight of irANP. 4. ANP mRNA was detected in the fish eggs. With immunohistochemical analysis of the rat ovarian follicles, this ANP-like material was localized mainly at the oocytes. 5. We, therefore, suggest that the vertebrate oocytes synthesize ANP and that the presence of ANP in the oocytes may be linked with the cell differentiation.
Six patients with autoimmune thrombocytopenic purpura (three of whom had CLL/NHL and one previous Hodgkin's disease) refractory to conventional therapy were treated with an antilymphocyte monoclonal antibody directed at CDw52 (CAMPATH-1). We observed response in four of the five evaluable patients; in three patients the response has lasted more than 4-9 months. However, response did not occur in most cases until 4-6 weeks after the commencement of the antibody therapy, suggesting that the mechanism of action is probably that of immune modulation.
In all, 88 patients with haematological malignancies requiring Hickman catheters for intensive chemotherapy were randomized to receive either one single bolus intravenous injection of teicoplanin, 400 mg, or no teicoplanin immediately before insertion of a double-lumen Hickman catheter. Lower incidences of catheter-related Gram-positive sepsis were recorded in patients receiving prophylactic teicoplanin; exit site infection, tunnel infection and catheter-related Gram-positive septicaemia were all reduced. The benefit of prophylactic teicoplanin was observed particularly among patients who were already neutropenic at the time of catheterization. All Gram-positive organisms isolated from infected skin sites or from blood cultures taken from Hickman catheters were susceptible to teicoplanin. No adverse reaction was reported in any of the patients receiving prophylaxis. Prophylactic teicoplanin, therefore, may be used routinely for patients requiring insertion of Hickman catheters for intensive chemotherapy, to reduce the early incidence of catheter-related sepsis, particularly during the period of neutropenia following chemotherapy.
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Huntington's disease is an autosomal dominant neurodegenerative condition which is rare in Singapore. Five siblings with progressive chorea and dementia were treated at the Singapore General Hospital and followed up over a seven-year period. Family history revealed five deceased affected individuals, two living affected siblings and more than 35 "at risk" offspring spanning another two generations each with about a 50% probability of carrying the Huntington's disease gene. We believe this is the largest kindred with Huntington's disease in Singapore.
Eighty patients had Computed Tomography (CT) performed for evaluation of epileptic seizures. Abnormal scans were found in 37 of the 80 patients (46.3%). Focal CT abnormalities were seen in 26 of the 80 patients (32.5%). Tumors were present in four and arteriovenous malformation (AVM) in three. Simple partial motor seizures were most strongly correlated with abnormal scans (five, 45.4%). Nineteen out of 21 patients with focal electro-encephalographic (EEG) abnormalities had focal CT abnormality compared to one out of 15 of those with generalised abnormality. 88.9% of patients with hemiplegia had abnormal scans. Whilst focal EEG abnormalities and abnormal neurologic signs pointed to a higher likelihood of CT abnormality, two subjects who were shown to have vascular malformations had normal EEG and neurologic exams. Routine CT scanning for evaluation of patients with recurrent seizures is advocated.
Epilepsy surgery is now accepted as a treatment modality for medically intractable epilepsy. A careful and detailed evaluation of patients is required by a trained epilepsy team which includes neurosurgeons, neurologists, neuroradiologists, psychologists and psychiatrists. For intractable complex partial seizures of temporal lobe origin, epilepsy surgery offers an 80% success rate.
Atrial natriuretic peptide (ANP) has been reported to be locally synthesized in the ovary although its physiological roles are still unknown. To define the origin of ovarian ANP, we demonstrated the presence and release of immunoreactive (ir) ANP in pig granulosa cells and characterized its biochemical properties. Serial dilution curves made with the extracts of pig granulosa cells, their perfusates and follicular fluid were paralleled to the standard curve of ANP. The amount of irANP in the granulosa cell was 2 fg/cell. The total amount of irANP in granulosa cells significantly correlated with the levels of irANP in follicular fluid. Additionally, the total content of irANP in the follicle negatively correlated with the follicular size. On reverse phase HPLC, the major form of irANP in granulosa cells and follicular fluid was high molecular weight but that in perfusate was low molecular weight. In Northern blot analysis, ANP mRNA was detected in the pig granulosa cells. Immunohistochemistry showed ANP prohormone location in granulosa cells of rat ovary. These data strongly suggest that the granulosa cells synthesize and secrete ANP.
A system has been developed for the import in vitro of precursor proteins into Euglena chloroplasts, which have three envelope membranes. Preparation of functional chloroplasts with intact envelope membranes has been optimized. Import of the precursor (50 kDa) for the tetrapyrrole biosynthesis enzyme porphobilinogen deaminase (PBGD), and processing to the mature size (40 kDa), occurred at 25 degrees C in the light and the presence of ATP, with an estimated efficiency of 62%. Pretreatment of the chloroplasts with proteases abolished this import, suggesting the involvement of specific protein receptors. The presequence of PBGD was found to be cleaved by Escherichia coli leader peptidase to an intermediate form (46 kDa). A construct in which the first 30 residues of the presequence (presumed to be the region removed by leader peptidase) had been deleted was no longer imported. Neither prePBGD nor the truncated precursor were imported into pea chloroplasts, although both bound to the pea chloroplast envelope. Conversely, a chimeric construct, in which the mature PBGD protein was fused downstream of the transit peptide for pea ferredoxin-NADP reductase, was efficiently imported into pea chloroplasts and processed to the mature size. However, this was not imported into Euglena chloroplasts, although again it bound to them. These results provide preliminary evidence for the possibility of two functional domains within the Euglena PBGD presequence. The implications of these findings with respect to the evolution of Euglena chloroplasts are discussed.
A group of 13 patients with acute myeloid leukaemia of differing disease status were treated with continuous intravenous infusion of high-dose recombinant interleukin-2 (rIL-2). There was up-regulation of the cellular cytotoxic functions in all these patients following the rIL-2 therapy, with increase in the natural killer (NK) activity, lectin-dependent cellular cytotoxicity, induction of cytotoxicity-linked cytoplasmic serine esterase and lymphocyte activation. However, the clinical response to rIL-2 in these patients was disappointing, especially in patients treated in frank relapse. Although 1 patient treated in early second relapse achieved a third complete remission, the duration of the remission was brief and lasted only 6 months. Adverse reactions among these patients were common. Whether or not lymphokine-activated killer cells are needed to improve the response rate over rIL-2 alone in these patients deserves further investigation.
The advance of monoclonal antibody (MoAb) technology in recent years provides a further treatment modality for cancer therapy. In this review, we discussed the various strategies available for MoAb therapy. We also addressed the problems encountered so far in early clinical trials and suggested possible solutions. We finally reviewed some of the interesting clinical studies conducted so far on the use of MoAbs in patients with non-Hodgkin's lymphomas.
We administered high-dose mitoxantrone in combination with etoposide to 6 patients with relapsed Hodgkin's disease as the conditioning regimen for autologous bone marrow transplantation. This regimen was well tolerated and no significant cardiotoxicity was observed. Responses of the Hodgkin's disease to this therapy were favourable but short-lived. Serial measurements of the serum levels of mitoxantrone suggested an open 3-compartment model of drug distribution. The rapid early phase of drug distribution was followed by an intermediate phase and a slow terminal drug-elimination phase. However, mitoxantrone was still detected in the serum of all patients 7 days after the last dose of mitoxantrone and on the day of bone marrow re-infusion. The clinical significance of such findings is unclear but they may suggest a need for the use of other anthracycline-related cytotoxic agents for the conditioning in autologous bone marrow transplantation.