Association of the Kynurenine Pathway of Tryptophan Metabolism With Human Immunodeficiency Virus-Related Gut Microbiota Alterations and Visceral Adipose Tissue Accumulation.

BACKGROUND: The aim of the study was to investigate the association between human immunodeficiency virus (HIV)-related gut microbiota changes, alterations in the kynurenine (Kyn) pathway of tryptophan (Trp) metabolism, and visceral adipose tissue in the context of HIV infection. METHODS: Three hundred eighty-three people with HIV (PWH) were included from the Copenhagen comorbidity in HIV infection (COCOMO) study. Gut microbiota composition was analyzed by 16S ribosomal ribonucleic acid sequencing. Plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured by single-slice computed tomography (CT) scan (4th lumbar vertebra). RESULTS: The HIV-related gut microbiota alterations were associated with lower Trp (ß -.01; 95% confidence interval [CI], -0.03 to -0.00) and higher Kyn-to-Trp ratio (ß 0.03; 95% CI, 0.01-0.05), which in turn was associated with higher VAT-to-SAT ratio (ß 0.50; 95% CI, 0.10-0.90) and larger VAT area (ß 30.85; 95% CI, 4.43-57.28). In mediation analysis, the Kyn-to-Trp ratio mediated 10% (P = .023) of the association between the VAT-to-SAT ratio and HIV-related gut microbiota. CONCLUSIONS: Our data suggest HIV-related gut microbiota compositional changes and gut microbial translocation as potential drivers of high Kyn-to-Trp ratio in PWH. In turn, increased activity in the Kyn pathway of Trp metabolism was associated with larger visceral adipose tissue area. Taken together, our findings suggest a possible role for this pathway in the gut-adipose tissue axis in the context of HIV infection.

Hand eczema and stratum corneum ceramides.

BACKGROUND: Hand eczema (HE) is a multifactorial disease, comprising different aetiological conditions and different morphologies. There are two aetiologically distinct groups of HE recognised: exogenous, such as contact dermatitis (allergic and/or irritant HE) and endogenous, such as the classic hyperkeratotic HE. Differences in the skin barrier properties of these two conditions could theoretically be expected. AIM: To examine whether differences exist in the lipid profile and the susceptibility of the stratum corneum (SC) in patients with allergic/irritant HE and those with hyperkeratotic HE. METHODS: Using cyanoacrylate, SC samples were taken from 23 patients with allergic/irritant HE and 15 with hyperkeratotic HE for lipid analysis by high-performance thin-layer chromatography (HPTLC). Samples were also taken from adjacent, unaffected skin. Severity of HE was assessed by the Hand Eczema Severity Index (HECSI), and skin barrier susceptibility was assessed by measuring transepidermal water loss (TEWL) after a 24-hour patch test with sodium lauryl sulfate (SLS). RESULTS: No statistically significant difference was found between groups for the lipid analysis or for skin susceptibility to SLS. We found a significantly higher HECSI score for hyperkeratotic HE compared with irritant or allergic HE (P = 0.02). CONCLUSIONS: There appears to be no difference in skin barrier between allergic/irritant HE (exogenous eczema) and hyperkeratotic HE (endogenous eczema) with regard to SC lipids or susceptibility to SLS.

Ceramide profile in hypohidrotic ectodermal dysplasia.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disease. The clinical presentation includes lack of sweating ability, and an often widely spread dermatitis resembling atopic dermatitis (AD). In AD, the skin-barrier defect is partly ascribed to the altered lipid profile in the stratum corneum and partly to mutations of the filaggrin genes. To our knowledge, no data are available about the epidermal lipid profile of HED. AIM: To compare the ceramide profile for patients with HED and AD. METHODS: The ceramide profile and ceramide/cholesterol ratio were compared between patients with HED (n = 7) and patients with AD (n = 21), using cyanoacrylate to take biopsy samples from the stratum corneum. Lipids were extracted from the biopsies and analysed using high-performance thin-layer chromatography. RESULTS: The lipid profiles of HED and AD were similar in distribution, apart from ceramide 1, which was significantly higher in HED (P = 0.04). CONCLUSIONS: The increased ceramide 1 level found in HED compared with AD is known to play a role in the structure of the lipid bilayers. However, further studies are needed to identify the functional significance of these observations and thereby elucidate differences in the skin barrier between HED and AD.

Ethnicity and stratum corneum ceramides.

BACKGROUND: The barrier function of the skin is dependent on an optimal composition of the stratum corneum lipids, exemplified by the altered lipid profile in patients with atopic eczema (AE). Differences in the global prevalence of AE point to the environment as an important factor in AE. Studies on filaggrin point to a genetic aspect in AE. The influence of environment and genes needs to be explored. OBJECTIVES: To investigate possible differences in stratum corneum lipids between different healthy ethnicities living in the same environment. METHODS: Healthy participants without any major skin diseases were enrolled in the study. Twenty-five participants of Asian origin (Asians), 18 of African origin (Africans) and 28 of Danish origin (white-skinned), all students at universities in the Copenhagen area of Denmark, had the ceramide profile of their stratum corneum examined using the cyanoacrylate method and analysed using high-performance thin layer chromatography. RESULTS: For the ceramide/cholesterol ratio we found statistically significant differences between groups, with Asians having the highest ratio (P < 0·001 as compared with both white-skinned individuals and Africans), white-skinned individuals having intermediate values, and Africans having the lowest values. No statistically significant differences were found between any of the ceramide subgroups. CONCLUSIONS: We found different ceramide/cholesterol ratios in comparable groups of different ethnicity, pointing to unknown genetic differences.

Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema.

BACKGROUND: Prior to the discovery of filaggrin (FLG) mutations, evidence for an impaired skin barrier in atopic dermatitis (AD) has been documented, and changes in ceramide profile, altered skin pH and increased trans-epidermal water loss (TEWL) in patients with AD have been reported. Until now, no studies have analysed stratum corneum (SC) lipids combined with skin barrier parameters in subjects of known FLG genotype. METHODS: A cohort of 49 German individuals genotyped for the most common FLG mutations (R501X, 2282del4) had SC samples taken for lipid analysis by high-performance thin layer chromatography. In addition, TEWL, erythema, skin hydration and pH were measured. In 27 of the 49 individuals, a 24-h irritation patch test with sodium lauryl sulphate was performed. For the analysis, both the AD group and the control group were stratified by FLG mutation status (FLGmut/FLGwt). RESULTS: In the FLGmut AD group, significantly lower levels of ceramide 4 and significantly higher levels of ceramide 7 were observed when compared to both healthy control groups. However, ceramide 7 levels also significantly differed between FLGwt AD and FLGwt controls, as did ceramide 1 levels. No significant differences were observed for ceramide 2, 3, 5 and 6. FLGmut individuals had significantly higher skin pH values than individuals not carrying FLG mutations. Patients with AD with FLG mutations had significantly higher erythema compared to patients with AD without FLG mutations. CONCLUSION: Our results confirm previous observations of altered ceramide levels in AD, which however appear to show no clear relationship with FLG mutations.

Histopathological grading of soft tissue tumours. Prognostic significance in a prospective study of 278 consecutive cases.

A consecutive 10-year series of 278 soft tissue sarcomas was prospectively graded, using a system based on the number of mitoses and taking into account parameters such as cellularity, anaplasia, necrosis, and histogenetic type and subtype of tumour. Prognostic factors in relation to metastasis-free survival were studied by uni- and multivariate analysis. Fifty-seven (20.5 per cent) were low-grade tumours, 43 (15.5 per cent) were intermediate, and 178 (64 per cent) were high grade. High-grade tumours were divided into two groups; 80 (29 per cent) grade 3A (= 5-20 mitoses per 10 high power fields (HPF)) and 78 grade 3B (28 per cent) (= more than 20 mitoses/10 HPF); 10 HPF corresponds to 2.5 mm2. Twenty (7.2 per cent) high-grade tumours could not be further subdivided. Grading was found to be the prognostic factor associated with the strongest predictive value. Five-year survival in low-grade and intermediate tumours (95 and 86 percent, respectively) differed significantly (P less than 0.0001) from high grade (50 per cent) and (p = 0.0018) between grade 3A (64 per cent) and grade 3B (41 per cent). Other prognostic indicators of importance in high-grade tumours were age, local recurrence at presentation (primary operation outside the Centre), and localization (superficial vs. deep).

[Delayed diagnosis of epiphysiolysis capitis femoris]. / Forsinket diagnose af epiphysiolysis capitis femoris.

The prognosis in epiphysiolysis of the head of the femur (ECF) depends on immediate treatment in the earliest stage of the disease. The reasons for and the extent of delayed diagnosis of slipping of the epiphysis in the hip were analysed in 56 children (72 hips) with ECF. The median total delay was six months with a delay of one month due to the patient and delay of three months due to the doctor. Pain in the lower limbs not related to the hip, including pain in the knee, occurred in 1/3 of the patients and resulted in more extensive delays due to the doctor (median four months). Other reasons for delay due to the doctor were erroneous interpretation of the x-ray films (14 patients). The most characteristic clinical finding was limited internal rotation of the affected hip. Comparison with the literature revealed that delay in the diagnosis of ECF has not been reduced during the past 35 years. Clinical examination of the hips should be undertaken in any child who complains of pain in the knee or thigh. If internal rotation is limited, x-ray examination including Lauenstein's projection should be carried out or the child should be referred to a department of orthopaedic surgery on account of suspected hip disease.

Amputation of the little finger.

We review 17 patients who had 21 amputations of the little finger. Transmetacarpal amputations gave satisfactory results in older patients, but in young patients loss of breadth of the palm caused significant disability. Disarticulation through the metacarpophalangeal joint is recommended in younger patients.

The sequelae of Osgood-Schlatter's disease in adults.

Seven adults with the sequelae of Osgood-Schlatter's disease presented after experiencing symptoms for an average of eight years. In four cases a true joint had formed between an ossicle in the patellar ligament and a facet on the tibia. Surgical treatment produced good results in all of the patients. Treatment differs from that in children in whom the epiphyseal lines are open.

Benign cystic lesions of peripheral nerves.

A patient with multiple cystic changes of the sural nerve, and another with a tarsal tunnel syndrome caused by invasion of the median plantar nerve by a ganglion in the tarsal tunnel, are presented. It is believed that there are three different kinds of benign cystic involvement of the peripheral nerves, multiple cystic degeneration of the nerve itself, invasion of nerves from outside by a ganglion and formation of simple cysts within the nerve proper, presumably as a result of trauma.

The Chiari pelvic osteotomy. A long-term review of clinical and radiographic results.

We have reviewed a series of 94 Chiari pelvic osteotomies carried out from 1966 to 1982. In 83 hips the indication for surgery had been pain, and of these patients 73 (88%) had appreciable relief within one year of operation. The other 11 hips were all in children and were painless; in them the osteotomy had successfully stabilised progressive subluxation of the hip. At review after a mean follow-up of 10 years (range, 2 to 18 years) 68 previously painful hips were reassessed. Although function of the hips had deteriorated slowly with time, four of the seven cases with 18 years' follow-up had good function and only minor symptoms. A detailed analysis of the radiographic changes produced by the Chiari osteotomy was made, using computerised analysis of variance. The beneficial effects of the osteotomy resulted from complex changes, among which the provision of a stable fulcrum for the hip seemed to be the most important.

Hemophilic arthropathy of the upper limb.

Little has been written about the effects of hemophilic arthropathy on the function and radiography of the upper limb. Therefore, 14 moderate and 19 severe hemophiliacs between the ages of 10 and 57 years were examined clinically and radiographically. The extent of the arthropathic changes in the shoulders, elbows, wrists, and hands were classified according to the system proposed by the World Federation of Hemophilia. The severity of the arthropathy increased with the age of the patient and with the number of hemarthroses recorded, although the correlation between these parameters was variable. The elbow joints were the site of recognizable arthropathy in 87% of the cases, with a slight preponderance for the nondominant side. The glenohumeral and wrist joints were affected in a small proportion of patients, although symptoms were rarely experienced. Hemorrhages affecting the hands were uncommon and produced arthropathy infrequently.

[Septic arthritis of the finger joints. Treatment with immediate arthrodesis]. / Septische Arthritis von Fingergelenken. Behandlung mit sofortiger Arthrodese.

A consecutive series of 44 patients with septic arthritis of finger joints is presented. The patients were treated with antibiotics, incision, debridement and usually drainage. In 13 patients with destruction of the joint cartilage, an arthrodesis was made at the time of incision. The failure rate with conventional therapy was 42 per cent. The failure rate in the arthrodesis group, which represented all the severe cases, was 23 per cent. In septic arthritis of finger joints with destruction of the cartilage arthrodesis with Kirschner-wire and interosseous wiring is recommended at the time of primary incision.

Foot deformities associated with onycho-osteodysplasia. A familial study and a review of associated features.

A family, of which thirteen members suffered from hereditary onycho-osteodysplasia (HOOD), is presented. Four of the thirteen patients also had foot deformities, and it is postulated that this anomaly may be a true part of the HOOD syndrome, and not just an incidental finding.

Hansen-Street nailing of fractures of the femoral shaft. A study of 70 consecutive cases.

A series is presented of 70 consecutive cases of fractures of the femoral shaft fixed with the solid Hansen-Street nail. They were followed until the nail was removed and the patient fully recovered. There were no deep infections, but one pseudarthrosis. There were four cases of fat embolism. The mean time spent in hospital was 32 days, and the patients began to take full weight at an average of 14 weeks after the injury. It was concluded that Hansen-Street nailing is a safe procedure which does not demand advanced technical skills or equipment.

Sliding screw in the treatment of trochanteric and subtrochanteric fractures.

From spring 1979 all patients with trochanteric and subtrochanteric fractures treated at Aarhus County Hospital have been operated on with the sliding nail, and the patients' progress has been followed for 1 year. In this article the results from the 92 first operations are compared with the results from a controlled trial comparing Ender's nailing and McLaughlin's nail-plate fixation. The latter series originated from the same department but from 1976 until 1978. It was bound that the time of anaesthesia in the Ender, the McLaughlin and in the sliding-nail group wad 125, 131 and 145 minutes respectively. There was no significant difference in the occurrence of post-operative complications between the 3 groups. In the Ender group 56 per cent of the patients had technical complications compared with 23 per cent in the McLaughlin group. In the Ender group 14 per cent had second operations compared with only 3 per cent in the two other groups. The results at the 1-year follow-up examination were the best in the sliding-nail group. It was concluded that the use of the sliding nail carried great advantages compared with Ender nailing and McLaughlin nail plating.