Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation.

BACKGROUND: The cytokine interleukin-4 (IL-4) is secreted mainly by activated T lymphocytes and characterizes the T-helper 2 (Th2) sub-type. In transplantation Th2 cells are believed to induce graft tolerance. Previous studies revealed that patients with a relatively high frequency of IL-4 producing helper T lymphocytes (HTL) before heart transplantation (HTX) had no or less rejection episodes compared with patients with a low frequency of IL-4 producing HTL. Three single nucleotide polymorphisms (SNPs) have been identified in the promoter region of the IL-4 gene, which influence promoter strength. We investigated whether there was a correlation between SNP genotypes in the IL-4 promoter and heart failure, and rejection after HTX. METHODS: Seventy HTX patients, 61 donors, and 36 controls were genotyped for the 3 SNPs by sequencing. RESULTS: Of the SNPs at -285 and -81, only the C and A alleles, respectively, were found in this study. Both alleles were found for the -590 SNP. No relation between patient genotype of the SNP at -590 and heart failure and rejection was found. However, incidence of rejection was significantly lower in patients that received a donor heart with the T-positive genotype compared with patients that received a heart from a T-negative donor. Patients who had the T-negative genotype and received a heart from a T-positive donor, suffered significantly less from rejection than T-negative patients that received a T-negative donor heart. This was not significant in the T-positive patient group. CONCLUSIONS: This indicates that IL-4 production within the donor heart and by cells from the donor is important for reducing incidence of episodes of rejection.     

The Outerbridge-Kashiwaghi procedure in elbow arthroscopy

We evaluated the results of the arthroscopic Outerbridge-Kashiwaghi procedure in a retrospective review of 20 elbows in 19 patients with a mean followup of 2 years (range : 6 months - 4 years). Range of motion improved from 94 degrees (range: 15 degrees-140 degrees) to 123 degrees (range: 110 degrees-140 degrees). Visual analogue scales for pain improved from 5.8 (range: 2 -8) to 1.8 (range: 0-8). The Mayo Performance Index increased from 54 (range: 15-85) to 88 (range: 45-100). The results were good to excellent in 16 elbows, fair in two and poor in two. Seventeen patients were better (85%), 3patients remained unchanged (15%). In elbows with severe arthritis, pain relief was minimal. The arthroscopic Outerbridge-Kashiwaghi procedure appeared in this study as a good surgical option in mild to moderate elbow arthritis, with significant pain relief and increased elbow mobility and function.     

Risk factors for recurrence of diabetic foot ulcers: prospective follow‐up analysis in the Eurodiale subgroup

Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of and risk factors for DFU recurrence after healing during a 3‐year follow‐up period. At our site, 93 Eurodiale‐enrolled patients had a healed DFU. Among these, 14 were not alive; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study, we assessed demographic factors (age, sex and distance from hospital); diabetes‐related factors [duration, and glycated haemoglobin (HbA1c) levels]; comorbidities (obesity, renal failure, smoking and alcohol abuse) and DFU‐related factors [peripheral arterial disease, ulcer infection, C‐reactive protein (CRP) and; foot deformities]. During the 3‐year follow‐up period, a DFU had recurred in 42 patients (57·5%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location [odds ratio (OR) 8·62, 95% confidence interval (CI) 2·2–33·2]; presence of osteomyelitis (OR 5·17, 95% CI 1·4–18·7); HbA1c > 7·5% ([DCCT], OR 4·07, 95% CI 1·1–15·6) and CRP > 5 mg/l (OR 4·27, 95% CI 1·2–15·7). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3‐year follow‐up period, despite intensive foot care. The findings at diagnosis of the initial DFU were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) and define those at high risk for recurrence, but may be amenable to targeted interventions.     

Laser treatment for further depigmentation in vitiligo

Background In patients with vitiligo, sometimes the greatest part of the skin has already lost its melanocytes. The remaining pigmented patches can be removed by using strong bleaching creams, but many adverse events have been reported with this treatment. Anew depigmentation therapy could be treatment with a Ruby laser. Methods Before treatment, the patients filled out a questionnaire about their vitiligo history. Eight patients with remaining pigmentation of the arms, hands, and face were treated once with a Ruby laser. Patients were monitored for developing repigmentation during the 9 months after treatment. Results In patients with a positive Koebner phenomenon, a permanent state of depigmentation was reached after laser therapy. None of the treated patients showed severe side-effects. Conclusions Ruby laser treatment can be an effective, fast, and safe method for removing cosmetically disturbing remnants of normal pigmentation in vitiligo patients with a positive Koebner phenomenon.     

Management of vitiligo. Results of a questionnaire among dermatologists in The Netherlands

BACKGROUND: Several therapeutic options are available for the treatment of vitiligo. Concern exists that there is no uniform approach towards the management of vitiligo among Dutch dermatologists. METHODS: A written survey concerning the management of vitiligo was sent to 332 dermatologists in The Netherlands. RESULTS: The response rate was 86%. "Giving information and reassurance concerning the nature of disease" was regarded by most dermatologists (68%) as being the most important goal in the management of vitiligo. Only 16% of the dermatologists aimed for active treatment in vitiligo. The reported therapy choices in children resembled those of adults, except that slightly more dermatologists did not prescribe active therapy in children. Nine different therapeutic modalities were mentioned as first choice therapies. Topical corticosteroids were indicated by most dermatologists as first choice therapy (241 out of 266, i.e. 91%); however, only 2% indicated that 50% or more of the patients achieved a successful treatment; 66% found that less than 25% of the patients were successfully treated with topical corticosteroids. Only 15% of the respondents reported that 50% or more of the patients were treated successfully with narrow-band UVB. The observed response profile to broad-band UVB therapy was found to be comparable with that of narrow-band UVB. The classical therapy with oral psoralen plus UVA (PUVA) was prescribed as first choice therapy by only 12% (32 out of 266) of the dermatologists. Only 6% of these respondents observed that 50% or more of the patients achieved successful therapy using oral PUVA. The recommended maximum treatment duration for topical corticosteroids, oral PUVA, and UVB therapy was found to vary from 3 to 12 months. CONCLUSIONS: Most dermatologists in The Netherlands do not offer active treatment in vitiligo, probably because the estimated effectiveness of (nonsurgical) repigmentation therapy is low. In cases where treatment is prescribed, there appears to be no consensus on the choice of therapies and treatment strategies. The development of practice guidelines may be helpful in reducing inappropriate care and improving treatment outcome.     

Steady state and instantaneous pressure-flow relationships: characterisation of the canine abdominal periphery

This study was performed to characterise a vascular bed in terms of pressure-flow relationships. Steady state and instantaneous relationships were obtained in the flow perfused isolated femoral beds of six mongrel dogs. The steady state pressure-flow relations were obtained by applying a series of stepwise changes of flow in random order. The relations were found to be straight and to have a zero-flow pressure intercept (P0). The slope of this relation is the differential resistance (Rd). On each steady state flow level a ramp-flow was superimposed. The pressure response was measured between 1.5 and 5 s after the start of the ramp-flow, to exclude compliance effects and (auto) regulatory effects, respectively. In this way instantaneous pressure-flow relations were obtained, the slope of this relation is the instantaneous resistance (Ri). The instantaneous resistance expresses the true physical resistance value at a working point of the steady state pressure-flow relation before the bed has performed its (auto)regulatory adaptation after a change in flow. Instantaneous resistance therefore characterises the vascular state that exists at that particular working point. After this particular vascular state has been modified by (auto)-regulation the steady state pressure-flow relation is reached again. Instantaneous resistance increases with increasing flow thereby approximating the value of the differential resistance. At the same flow a vasodilator decreases and a vasoconstrictor increases instantaneous resistance. The gain (G) of the system, that characterises the (auto)regulatory capability, was calculated as G = 1--Ri/Rd and was found to decrease with increasing flow. The (partial) reflection of travelling waves depends on both the characteristic impedance (Zc) and the instantaneous resistance rather than on differential or peripheral resistance. Furthermore it is the product of the instantaneous resistance (Ri) and vascular compliance (C) that determines the time constant of a vascular bed.     

Reduced parenchymal cerebral blood flow is associated with greater progression of brain atrophy: The SMART-MR study

Global cerebral hypoperfusion may be involved in the aetiology of brain atrophy; however, long-term longitudinal studies on this relationship are lacking. We examined whether reduced cerebral blood flow was associated with greater progression of brain atrophy. Data of 1165 patients (61 ± 10 years) from the SMART-MR study, a prospective cohort study of patients with arterial disease, were used of whom 689 participated after 4 years and 297 again after 12 years. Attrition was substantial. Total brain volume and total cerebral blood flow were obtained from magnetic resonance imaging scans and expressed as brain parenchymal fraction (BPF) and parenchymal cerebral blood flow (pCBF). Mean decrease in BPF per year was 0.22% total intracranial volume (95% CI: –0.23 to –0.21). Mean decrease in pCBF per year was 0.24 ml/min per 100 ml brain volume (95% CI: –0.29 to –0.20). Using linear mixed models, lower pCBF at baseline was associated with a greater decrease in BPF over time (p = 0.01). Lower baseline BPF, however, was not associated with a greater decrease in pCBF (p = 0.43). These findings indicate that reduced cerebral blood flow is associated with greater progression of brain atrophy and provide further support for a role of cerebral blood flow in the process of neurodegeneration.