A prospective study was undertaken in 16 patients with chronic renal failure on continuous ambulatory peritoneal dialysis, with 22 episodes of peritonitis treated with vancomycin, a known ototoxic agent. Twelve patients had one episode each, and four had recurrent peritonitis. Each treatment course consisted of two infusions of vancomycin (30 mg/kg body weight) in 2 L of peritoneal dialysate administered at 6-day intervals. Serum vancomycin analyzed by enzyme immunoassay showed a mean trough level of 11.00 microg/ml on day 6 and mean serum levels of 33.8 and 38.6 microg/ml about 12 hours after administration on days 1 and 7, respectively. Similar levels, well within the therapeutic range, were encountered with repeated vancomycin therapy for recurrent episodes of peritonitis, suggesting that no changes occurred in the pharmacokinetic profile of the drug. Pure-tone audiometry, electronystagmography, and clinical assessment performed during each course of treatment showed no evidence of ototoxicity even on repeated courses of vancomycin therapy. The results suggest that vancomycin therapy when given in appropriate concentrations as a single therapeutic agent is both effective and safe. We believe, however, that vancomycin administered in combination with an aminoglycoside may produce ototoxic effects that may be greatly aggravated, possibly because of synergism.
A prospective study was undertaken of 10 chronic renal failure patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) complicated by repeated bouts of peritonitis treated with gentamicin. Each 10-day treatment course consisted of a 120 mg loading dose, followed by 16 mg in 21 of peritoneal dialysate, given four times a day. Serum gentamicin analysed by enzyme immunoassay showed a mean level of 5.2 micrograms/ml, (range 3.7 to 6.6 mg/ml) four hours after the loading dose. Similar levels, well within the therapeutic range, were maintained on the 3rd, 5th, 7th and 9th days of intraperitoneal gentamicin therapy, suggesting no accumulation of gentamicin in the serum. Pure tone audiometry, electronystagmography and clinical assessment were performed during each course of treatment. Although no evidence of ototoxicity was found during the first two courses of gentamicin, but disequilibrium and bobbing oscillopsia were present during the third and fourth courses of gentamicin. These findings could be explained by cumulative injury to the vestibular apparatus caused by repeated therapeutic insults.
Cryptococcosis is a known opportunistic infection in immunosuppressed hosts. We report our experience of all cases presenting to our Department between December 1975 and September 1988. Eight post-renal transplant patients and three systemic lupus erythematosus (SLE) patients were affected. All were receiving treatment with steroids, in association with either azathioprine or cyclosporin. The diagnosis of cryptococcal meningitis was initially based on a positive cerebrospinal fluid (CSF) cryptococcal antigen, by latex agglutination test, and subsequently confirmed by cultures. Common clinical presentations, in descending order of frequency, included headaches, fever, mental confusion, epilepsy and papilloedema. Meningism was not a prominent feature. CT brain scans were obtained in eight patients and one showed a focal lesion and one showed cerebral atrophy. Four patients also had an abnormal chest X-ray (CXR) and one had disseminated cryptococcosis. Amphotericin and 5-fluorocytosine were the mainstay of therapy, although ketoconazole alone was subsequently used in three selected patients with cure. Four early deaths occurred in patients with delayed diagnosis and treatment, usually in association with other severe concurrent infections. We conclude that awareness of cryptococcosis is essential in immunocompromised hosts presenting with headache with, or without, mental confusion or fever.
The clinical outcome of bacteraemic patients is influenced by many factors. It is vital to know one's own local hospital epidemiological data so as to provide optimal care to the affected patients. This was a prospective, observational study carried out in the said patient population over a period of four months in the year 2005. One hundred and ninety one patients presented with bacteraemia over the study period. Fifty-two (27%) of the patients died. Mechanical ventilation, inappropriate empirical antibiotic usage, Chinese ethnicity and low serum albumin levels independently affected prognosis. These factors should alert physicians to those patients who require more intensive monitoring and care.
KEY WORDS:
Bacteraemia, Blood Culture Positive, Outcome, Risk factors, Kuala Lumpur, Malaysia
The usefulness of the direct immunofluorescent antibody technique--lupus band test--for the diagnosis of systemic lupus erythematosus (SLE) has been well established. The aims of the study were to determine the prevalence of the LBT at various sites of the skin in a cross section of patients with SLE and its correlation with disease activity. The LBT was demonstrated in 64% of skin lesions, 63% in non-lesional sun-exposed (NLSE) skin and 25% in non-lesional sun-protected (NLSP) skin. The prevalence of the LBT in lesional and NLSE groups was significantly different from the NLSP group (p = 0.03 and 0.005 respectively). There was a significant correlation between the presence of a positive LBT in NLSE skin with the presence of the LE cell phenomenon (p = 0.04) and anti - ds DNA antibody (0.02). In addition, there was a significant correlation between IgG LBT in the NLSE skin with serum hypocomplementaemia (p = 0.03) and anti - ds DNA antibody (p = 0.04). Other than these, no significant correlation was detected between the LBT from the 3 sites with overall clinical activity, renal disease, active skin lesions, or other laboratory indices of activity. These findings suggest that the LBT is mainly indicated as a diagnostic tool and has little role in assessing disease activity.
Study site: Wards and clinics of the General Hospital, Kuala Lumpur, Malaysia
Two-hundred and sixty-five patients with asymptomatic proteinuria and/or haematuria were studied at the Department of Medicine, Universiti Kebangsaan Malaysia and Department of Nephrology, General Hospital Kuala Lumpur. They represented 25.4% of all the renal biopsies performed during the period 1980-88. All the three races were affected with 71.3% occurring between the ages of 20-39 years and 41.1% were detected during routine medical examination. Excluding those patients with lupus nephritis, IgA nephropathy was the commonest histological diagnosis (51.7%). The presence of severe and advanced histological changes in a significant number of biopsies emphasises the need for more effective screening and early referral of this group of patients.
A total of 164 patients with IgA nephropathy were diagnosed at the Department of Medicine, Universiti Kebangsaan Malaysia and the Department of Nephrology, General Hospital, Kuala Lumpur between 1981-1988. This represented an incidence of 20.1% of all primary glomerulopathies seen in both units. The 3 major ethnic groups were equally affected with 59.7% occurring between the ages of 20-36 years. It was not uncommon in females. The high prevalence of hypertension, renal failure, heavy proteinuria at presentation and the increased chronicity index in the biopsy, suggest that IgA nephropathy is progressive disease leading to chronic renal failure.
Many studies have shown an association between human leucocyte antigens (HLA) and systemic lupus erythematosus (SLE) in the various study populations. Although SLE is not an uncommon disease in the Malaysian Archipelago, and appears to affect all three major racial groups equally (i.e. Southern Chinese, Malays and Southern Indians), very little information is available on the HLA profiles in the two latter groups. In phase I of our study of the HLA profiles in Malaysian SLE patients, the HLA phenotypes (class I: A, B, C; Class II: DR, DQ) of Malay patients with confirmed SLE and 91 normal Malay controls were determined using the microcytotoxicity assay. The strong association between DR (RR 3.28, P = 0.008) concurs with that reported among Chinese and Japanese populations. Moderate to strong associations with HLA-B 7 (RR 4.99, P = 0.02) and Cw 7 (RR 2.94, P = 0.003) were also found. We believe this is the first report of the association of HLA and SLE in the Malay population.
Angiotensin-converting enzyme (ACE) gene polymorphism, especially the deletion/deletion (DD) genotype, is associated with the disease progression of immunoglobulin A (IgA) nephropathy patients in various studies from both Asia Pacific and European populations. However, recent studies within the same populations were unable to reproduce the same results. Hence, we had studied the distribution of the DD genotype, the association between ACE gene polymorphism and the disease progression, and the factors (other than ACE gene polymorphism) which were involved in the disease progression of our local patients.
One hundred and two patients attending the systemic lupus erythematosus (SLE) clinic of the Department of Medicine, Universiti Kebangsaan Malaysia, were studied retrospectively to determine their survival rates and causes of death. There were 21 deaths. The 1, 5, and 10 year survival rates were 93%, 86% and 70% respectively. There was a bimodal pattern of mortality with more patients dying in the first 2 years or after 5 years of disease. Infection was the direct cause of death in 52% and contributed to a further 19% of deaths. Patients with lupus nephritis had a higher relative risk (RR) of death (RR = 4.34, p < 0.02) although there was no significant increase in risk with any particular histological type on biopsy. Cerebral lupus (RR = 3.08, p < 0.001) and methylprednisolone treatment (RR = 6.24, p < 0.001) were also associated with increased risk of death. Increased awareness of infection and earlier use of antibiotic therapy may improve survival of patients suffering from SLE.
Study site: SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
To determine the incidence, types and risk factors for infection in systemic lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we retrospectively reviewed the medical records of 102 patients with definite SLE attending a specialist clinic. Details of major infections (pneumonia or severe infection requiring intravenous therapy) and minor infections, and their time of onset in relation to immunosuppressive therapy and disease flares were recorded. There were 77 major and 163 minor infections during 564 patient-years of follow-up. In the month following a course of pulse methylprednisolone, the incidence of major infection was 20 times higher and the incidence of minor infection was 10 times higher than at other periods (p < 0.0001). In the month after disease flare, the incidence of major infection was 10 times higher and the incidence of minor infection six times higher than at other times (p < 0.0001). After allowing for methylprednisolone therapy and disease flares, there was no increase in the rate of infections during treatment with azathioprine, oral or intravenous cyclophosphamide. There was no effect of renal involvement on infection rate.
A 20-year-old girl first notice bilateral ocular muscle weakness in 2001. Two months later, she developed acute muscle paralysis and respiratory failure which required ventilation. Serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation test was positive and consistent with myasthenia gravis (MG). CT scan thorax revealed thymic enlargement and she underwent a video assisted thymectomy (VATS). However, over the next three years, despite maximal doses of various immunosuppressive agents with plasmapheresis and intravenous immunoglobulin, she was admitted with recurrent myasthenic crisis without any obvious precipitant. She was then commenced on mycophenolate mofetil and together with regular plasmapheresis, cyclosporine and prednisolone, her symptoms have finally improved and brought under control.
The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.
Study site: SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
An analysis of the clinical and serological features of 12 male and 122 female patients with SLE was done to determine whether sex related differences exist. We found a lower incidence of mucocutaneous symptoms and arthritis but an increased incidence of discoid lesions, pleuritis and pericarditis in males at disease onset. During the disease course, there was a lower incidence of arthritis, a similar prevalence of mucocutaneous symptoms but an increased incidence of pleuritis in males with a trend towards renal involvement. These findings were however not statistically significant except for the higher incidence of thrombosis among males. Serologically, both groups showed similar frequencies of autoantibodies and hypocomplementaemia. Although the study was small, it was shown that several sex-related differences in the clinical and serological features exist in Malaysian SLE patients.
Study site: SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
BACKGROUND: Studies have shown that certain genes within the major histocompatibility complex predispose to systemic lupus erythematosus (SLE) and may influence clinical and autoantibody expression. Thus, we studied the frequency of HLA-DR, -DQA, -DQB and -DPB alleles in ethnic Malays with SLE to determine the role of these genes in determining disease susceptibility and their association with clinical and immunological manifestations.
METHODS: Fifty-six Malay SLE patients were enrolled into the study. Demographic, clinical and immunological findings were obtained from medical records. HLA-DR, DQ and DP typing were done using modified PCR-RELP. Controls were from ethnically-matched healthy individuals.
RESULTS: We found a strongly significant association of the DR2 and DQB1 *0501 and DQB1*0601 (pcorr = 0.03, rr = 3.83, pcorr = 0.0036, rr = 4.56 and pcorr = 0.0048 and rr = 6.0, respectively). There was also a weak increase of DQB1*0.201 and DPB1*0.0901 with a weak decrease of DQA1*0601 and DQB1*0503 and *0301 which were not significant after corrections for multiple comparisons were made. There was a significant positive association of DR2 and DQB1*0501 with renal involvement and DR8 with alopecia. A nonsignificant increase of DQB1*0503 in patients with photosensitivity was noted. Significant autoantibody associations were also found: DQB1*0601 with anti-Sm/RNP, DR2 with antiSSA (Ro)/SSB (La), and DR2, DQB1*0501 and *0601 with antibodies to ds DNA. There was no specific DR, DQ or DP associations with age of disease onset (below 30 years or those at or above 30 years).
CONCLUSION: Our data suggests the role of the HLA class II genes in conferring SLE susceptibility and in clinical and autoantibody expression.
Study site: SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Age has been suggested to modify systemic lupus erythematosus expression. In this study we have attempted to study 13 patients with late onset (40 years and above) and 90 with early onset disease (below 40 years) to determine whether age-related differences in disease expression exist and whether the genetic make-up influences the age of disease onset. We found that patients with late onset disease initially presented with pericarditis (31% vs 3%, P<0.005) and a lower incidence of malar rash (31% vs 57%, p<0.05). During the disease course, there was a lower incidence of mucocutaneous symptoms especially malar rash (p<0.005) and psychosis (p<0.05) in the late onset group. Serological parameters were similar in both groups. There was a prevalence of HLA-DQA1*0103 in Chinese patients with late onset disease (pcorr=0.004). These findings suggest that a subgroup of late onset patients may experience milder disease and that the risk conferred by the HLA-DQA1*0103 may be significant among these patients.
Microalbuminuria is the earliest indicator of diabetic kidney disease and generalised vascular endothelial dysfunction. The Microalbuminuria Prevalence (MAP) Study was carried out to assess the prevalence of macroalbuminuria, microalbuminuria and normoalbuminuria in Asian hypertensive patients with type 2 diabetes on usual care. This paper presents a subanalysis of data from patients in Malaysia. In 733 analysed patients, the prevalence of macroalbuminuria and microalbuminuria was 15.7% and 39.7%, respectively. The high prevalence of diabetic nephropathy in these high-risk patients is a cause for concern, and the Malaysian Health Care system should be prepared for a pandemic of end-stage renal disease due to diabetic nephropathy.
Study site: six medical centres in Kuala Lumpur, Kota Bharu,
Kuching and Kota Kinabalu
Nocardiosis is an increasingly recognised opportunistic infection in immunologically incompetent hosts but diagnosis is often delayed. Between December 1975 to October 1988, our two Nephrology Units have encountered five cases of nocardiosis occurring in two post-renal transplant patients, two patients with systemic lupus erythematous (SLE) and one patient with mesangiocapillary glomerulo--nephritis. All were on immunosuppressants at the time. The first three patients presented with predominant pulmonary disease and were cured by combined trimethoprim-sulphamethoxazole (cotrimoxazole) and doxycycline therapy. The patient with limited skin involvement responded to cotrimoxazole alone. However, the last patient with lymphocutaneous disease initially responded to cotrimoxazole (+ chloramphenicol) but developed acute-on-chronic renal failure and relapsed with dose reduction of cotrimoxazole. Alternative treatment with amikacin and doxycycline was instituted with good response. We shall review potential clues that may suggest the diagnosis of nocardiosis and discuss other effective antimicrobial agents.