Disseminated Nocardia brasiliensis infection: an unusual complication of immunosuppressive treatment for childhood dermatomyositis

The use of steroids combined with cytotoxic drugs has increased in the last decade. The concomitant increase of opportunistic infections has contributed significantly to morbidity and mortality of patients treated with immunosuppressive agents. We describe a child with dermatomyositis who developed disseminated Nocardia brasiliensis infection while receiving steroids and methotrexate. Infectious etiology was established by gram stain. The patient was treated successfully. Disseminated Nocardia brasiliensis infection is rare with a high reported mortality. Diagnosis may be delayed secondary to insidious onset, similarity of clinical manifestations to other pathogens and slow growth in routine culture media. Nocardia should be considered early in the evaluation of infection in patients treated with immunosuppressive agents.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Are general practitioner hospitals cost-saving? Evidence from a rural area of Norway

OBJECTIVE: We aimed to determine whether general practitioner GP hospitals, compared with alternative modes of health care, are cost- saving. METHODS: Based on a study of admissions (n = 415) to fifteen GP hospitals in the Finnmark county of Norway during 8 weeks in 1992, a full 1-year patient throughput in GP hospitals was estimated. The alternative modes of care (general hospital, nursing home or home care) were based on assessments by the GPs handling the individual patients. The funds transferred to finance GP hospitals were taken as the cost of GP hospitals, while the cost of alternative care was based on municipality and hospital accounts, and standard charges for patient transport. RESULTS: The estimated total annual operating cost of GP hospitals was 32.2 million NOK (10 NOK = 1 Pound) while the cost of alternative care was in total 35.9 million NOK. Sensitivity analyses, under a range of assumptions, indicate that GP care in hospitals incurs the lowest costs to society. CONCLUSION: GP hospitals are likely to provide health care at lower costs than alternative modes of care.      

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.     

The long-term course of Lyme arthritis in children

BACKGROUND AND METHODS. The natural history of Lyme disease is not completely known. We studied the long-term course of Lyme arthritis in 46 children in whom the onset of the disease occurred between 1976 and 1979 and who received no antibiotic therapy for at least the first four years of the illness. RESULTS. Of the 46 children (age range, 2 to 15 years), 33 (72 percent) initially had erythema migrans, 7 (15 percent) had influenza-like symptoms, and 6 (13 percent) had migratory joint pain. These manifestations were followed by brief attacks of arthritis, particularly affecting the knee. The percentage of children with recurrent episodes of arthritis declined each year. By year 4, only 10 children still had a mean of two episodes of arthritis per year; the duration of arthritis was generally longer in older children (P less than 0.05). During the sixth year of illness, two children (4 percent) had keratitis, and more than 10 years after the onset of disease, a subtle encephalopathy developed in two other children. Of the 39 children whom we were able to contact in 1988-1989, 12 (31 percent) still had occasional brief episodes of joint pain and 1 (3 percent) had marked fatigue. All 46 children had positive IgG antibody responses to Borrelia burgdorferi throughout the illness and on long-term follow-up. As compared with those who became asymptomatic, the children with recurrent symptoms more often had IgM responses to the spirochete and had significantly higher IgG titers (P less than 0.05). CONCLUSIONS. The course of initially untreated Lyme disease in children may include acute infection followed by attacks of arthritis and then by keratitis, subtle joint pain, or chronic encephalopathy.     

Alloresponses to HLA-DP Detected in the Primary MLR: Correlation with a Single Amino Acid Difference

The one-way mixed lymphocyte reaction (MLR-1) response was measured in both directions in 50 HLA-A, B, DR and DQ identical pairs and the role of DP studied in MLR stimulation. DR, DQ and DP typing was performed at the allele level by the polymerase chain reaction-sequence specific oligotyping (PCR-SSO) technique. The group consisted of 19 potential bone marrow transplant recipients and 34 matched unrelated donors. When more than one matched donor was available for a patient, donor/donor MLR-1 was also studied. DP identity was observed in 3 out of 50 pairs (6%), however due to homozygosity no incompatibility was present in the stimulating cells in 21 out of 100 cases (21%). There was a significant difference in the range of relative responses (RR) between zero DPB1 mismatches and one (p = 0.002) and two (p = 0.02) DPB1 mismatches: 52.4% of cases in the zero DPB1 mismatch group had RR < 1.0% compared with 31.6% and 27.3% in the one and two DPB1 mismatches. Stimulation by DPB1*0201 and 0301 gave the highest RR (12.9 ± 22.5 and 17.5 ± 17.0, respectively) while stimulation with DPB1*0401 and 0402 resulted in low levels of T cell response (1.3 ± 8.2 and 0.6 ± 11.5, respectively). When the responses were restricted to DPB1*0401 homozygotes to standardise for responder type similar results were obtained (DPB1*0201 v DPB1*0402 p = 0.008). The protein products of the DPB1*0201 and 0402 alleles differ by a single amino acid at position 69 (DPB1*0402—Lysine, DPB1*0201—glutamic acid). A further analysis was performed therefore scoring responders and stimulators as glutamic acid positive (E+) or negative (E−). There was a highly significant increase in the response to E+ stimulators compared with E− stimulators (p = 0.004). There was also a significant difference in the distribution of relative responses between the E+ stimulator group and the subgroups of E− responders/E− stimulators (p = 0.012) and E+ responders/E− stimulators (p = 0.009). However the amino acid difference at position 69 does not explain all responses due to DP in the MLR-1 as evidenced by the strong responses observed in cases where DPB1*0301 (lysine pos.) was the only difference on the stimulator cells. The results indicate that not all DP incompatibilities elicit a measurable T cell MLR response, but where a response does occur residue 69 in the first domain of DP appears to be pivotal. These results may have implications with respect to GVHD in bone marrow transplantation.     

Intestinal permeability in kwashiorkor

Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS: To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN: A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS: The initial geometric mean L-R ratios (x100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are < 5, so the high ratios in controls indicate tropical enteropathy syndrome. Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreased L-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only L-rhamnose absorption. Despite, clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION: Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation.