Strain Elastography for Prediction of Malignancy in Soft Tissue Tumours--Preliminary Results.

PURPOSE: To evaluate the ability of strain elastography to predict malignancy in patients with soft tissue tumors, and to compare three evaluation methods of strain elastography: strain ratios, strain histograms and visual scoring. MATERIALS AND METHODS: 60 patients with 61 tumors were analyzed in the study. All patients were referred due to suspicion of malignant soft tissue tumors after diagnostic imaging (contrast-enhanced MRI, CT or PET-CT). Ultrasound-guided biopsy was preceded by the recording of strain elastography video clips, which were evaluated in consensus between three investigators. Strain ratio, strain histogram analysis and visual scoring using a five-point visual scale were compared with the final pathology from either biopsy or resection of the tumors. RESULTS: The difference between the mean strain ratio for malignant and benign tumors was significant (p = 0.043). The mean strain ratios for malignant and benign tumors were 1.94 (95% CI [0.37; 10.21]) and 1.35 (95% CI [0.32; 5.63]), respectively. There were no significant differences for strain histograms or visual scoring. Liposarcomas had lower mean strain ratio, strain histogram values, and visual scoring than other malignant tumors. When analyzing a subgroup of patients without fat-containing tumors (n = 46), based on appearance on MRI or CT, the difference between the mean strain ratios for malignant and benign tumors increased (p = 0.014). CONCLUSION: The mean strain ratios of malignant tumors were significantly higher than the mean strain ratios of benign tumors. There was no significant difference for strain histograms and visual scoring. Strain ratios may be used as an adjunct in soft tissue tumor diagnosis, possibly minimizing the number of biopsies.

Radiation recall dermatitis: A review of the literature.

PURPOSE/OBJECTIVES: Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon. MATERIALS/METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration. RESULTS: One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0-63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2-132 weeks), 5 days (range, 2-56 days), and 14 days (range, 7-49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04). CONCLUSIONS: RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.

Flow-mediated vasodilation and dietary intake of n-3 polyunsaturated acids in healthy subjects.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major marine n-3 polyunsaturated fatty acids (PUFA), have been proposed to decrease the risk of atherosclerosis and coronary heart disease. An early event during atherogenesis is endothelial dysfunction. We studied the correlation between fish consumption, serum phospholipid (sPL) levels of DHA and EPA and flow-mediated vasodilation (FMD), a measure of endothelial function. Furthermore, subjects were classified according to whether they did (Fish+, n = 19) or did not (Fish-, n = 21) follow the Danish recommendations, consuming at least 300 g fish/week. Neither the fish intake, sPL EPA nor sPL DHA significantly correlated with FMD, -0.20 (p = 0.23), -0.23 (p = 0.15) and -0.06 (p = 0.72), respectively. Also, when comparing the Fish+ and the Fish- group we did not find any significant differences in FMD (p = 0.33). In conclusion, our results did not show any correlation between intake and sPL levels of marine n-3 PUFA and FMD in healthy subjects.

Prediction of survival after surgery due to skeletal metastases in the extremities.

AIMS: The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton. METHODS: We included a historical cohort of 130 consecutive patients (mean age 64 years, 30 to 85; 76 females/54 males) who underwent joint arthroplasty surgery (140 procedures) owing to MBD in the appendicular skeleton during the period between January 2003 and December 2008. Primary cancer, pre-operative haemoglobin, fracture versus impending fracture, Karnofsky score, visceral metastases, multiple bony metastases and American Society of Anaesthesiologist's score were included into a series of logistic regression models. The outcome was the survival status at three, six and 12 months respectively. Results were internally validated based on 1000 cross-validations and reported as time-dependent area under the receiver-operating characteristic curves (AUC) for predictions of outcome. RESULTS: The predictive scores obtained showed AUC values of 79.1% (95% confidence intervals (CI) 65.6 to 89.6), 80.9% (95% CI 70.3 to 90.84) and 85.1% (95% CI 73.5 to 93.9) at three, six and 12 months. DISCUSSION: In conclusion, we have presented and internally validated a model for predicting survival after surgery owing to MBD in the appendicular skeleton. The model is the first, to our knowledge, built solely on material from patients who only had surgery in the appendicular skeleton. TAKE HOME MESSAGE: Applying this prognostic model will help determine whether the patients' anticipated survival makes it reasonable to subject them to extensive reconstructive surgery for which there may be an extended period of rehabilitation. Cite this article: Bone Joint J 2016;98-B:271-7.

Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies.

OBJECTIVES: Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. MATERIALS AND METHODS: We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer's solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. RESULTS: The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). CONCLUSIONS: This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials.Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427-435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1.

Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial.

OBJECTIVES: We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. MATERIALS AND METHODS: We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. RESULTS: C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (sd) 0.8) and BMP-7 (50.6 ng/mg, sd 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. CONCLUSION: Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation.Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500-511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1.

Human neutrophils are selectively activated by independent ligation of the subunits of the CD11b/CD18 integrin.

The yeast cell wall preparation zymosan is a particulate stimulus for human neutrophils (PMNs). Unopsonised zymosan particles bind to the PMN CD11b/CD18 integrin and are phagocytosed, leading to activation of the 5-lipoxygenase pathway and release of the lipid chemotaxin leukotriene B4 (LTB4). Specific monoclonal antibodies (mAbs) to CD11b and to CD18 were used in the present study to evaluate the contribution of each chain to these processes. All four anti-CD18 mAbs but none of five anti-CD11b mAbs dose-dependently blocked PMN phagocytosis of zymosan. Nevertheless, all anti-CD11b mAbs and all anti-CD18 mAbs significantly inhibited zymosan-stimulated LTB4 release in a dose-dependent manner. In addition, there was a dose-dependent stimulation of LTB4 release resulting from the specific ligation and cross-linking of either chain of the integrin heterodimer. Thus zymosan-stimulated LTB4 release is initiated by signals from both chains of the CD11b/CD18 integrin, whereas only CD18 is essential for phagocytosis.

CD11b/CD18-dependent stimulation of leukotriene B4 synthesis by human neutrophils (PMN) is synergistically enhanced by tumour necrosis factor alpha and low dose diacylglycerol.

Unopsonised zymosan particles bind to the CD11b/CD18 integrin on human neutrophils (PMN) and are phagocytosed. Binding stimulates the release of leukotriene (LT) B4. The present study examined the effect on this interaction of two agents that 'prime' PMN for augmented responses to a variety of agonists. The cell permeable diacyl glycerol, 1,2-dioctanoyl-glycerol (DiC8) and TNF alpha each increased CD11b/CD18 expression on PMN [maximal at 10-9 M TNF alpha or 10-8 M DiC8]. There was a decrease, however, in CD11b/CD18 expression above 10-8 M DiC8, which was not observed at high concentrations of TNF alpha. Pre-treatment with either DiC8 or TNF alpha dose-dependently augmented the zymosan-stimulated release of LTB4 from PMN. DiC8 and TNF alpha in combination, however, synergistically increased LTB4 release. In contrast, at concentrations above 10-8 M DiC8, whether in the presence or absence of TNF alpha, LTB4 release was inhibited and this was ameliorated by protein kinase C inhibitors. The response to neither TNF alpha nor DiC8 (below 10-8 M) was kinase inhibitor sensitive. Doses of DAG, which activate protein kinase C, inhibit CD11b/CD18-dependent responses by down-regulating receptor expression. In contrast, the mechanisms of TNF alpha and low dose DAG 'priming' are not clear but are independent of PKC activation. The synergy between these two priming agents, however, suggests independent, complementary signalling pathways that provide a novel, potentially important mechanism for the control of PMN CD11b/CD18 integrin-dependent activation.

Human neutrophil secondary granule exocytosis is independent of protein kinase activation and is modified by calmodulin activity.

Exocytosis of the secondary (2 degree) lysosomal granule is an important process in the activation of human neutrophils. Stored enzymes such as collagenase and gelatinase are released, and adhesion molecules from the granule membrane are inserted in the plasma membrane. This exocytosis is independent of azurophil granule release and respiratory burst activation. We investigated, using kinase and phosphatase inhibitors and activators of adenylate cyclase, common intracellular signalling mechanisms involved in exocytosis (vitamin B12 binding protein release) stimulated by different agonists. Exocytosis in response to tumour necrosis factor alpha (TNF alpha), phorbol myristate acetate (PMA) and the chemotactic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) was inhibited by the calmodulin antagonist N-(6-amino hexyl)-5-chloro-1-naphthalene sulphonamide (W7). Neither staurosporine, H7 nor genistein was inhibitory. In contrast, the same doses of W7 synergistically enhanced the exocytosis stimulated by the tyrosine phosphatase inhibitor sodium orthovanadate, while kinase inhibition by staurosporine or genistein dose-dependently inhibited the vanadate response. Furthermore, adenylate cyclase activation with prostaglandin E2 or dibutyryl cyclic AMP, inhibited exocytosis in response to TNF alpha and FMLP, while having no effect on the release induced by vanadate or PMA. Thus, 2 degree granule exocytosis stimulated by receptor-bound ligands is calmodulin-dependent, and is independent of protein kinase activity. In contrast, exocytosis in response to tyrosine phosphatase inhibition is antagonised by calmodulin, since the response to vanadate was enhanced synergistically by W7. Thus, depending on the initial stimulus, calmodulin may promote or inhibit 2 degree granule exocytosis by human PMN.

Muscarinic agonist receptor subtypes in aging rat brain.

Whole brain homogenates from rats aged 6 months (young) and 24 months (old) showed a decline with age of the pre-synaptic cholinergic marker, choline acetyltransferase, and also of total specific binding sites for the muscarinic antagonist L(-)quinuclidinyl benzilate (L-QNB). However, neither the proportion nor the inhibition constants of high and low affinity muscarinic agonist binding sites (defined by displacement of L-QNB binding with carbachol) changed with age. These findings may be relevant to the central cholinergic deficit reported to be associated with cognitive impairment in aging man.

Loss of bone mineral of the hip assessed by DEXA following tibial shaft fractures.

We measured prospectively early changes (0-6 months) in bone mineral of the hip, the lumbar spine, and the tibia following tibial shaft fractures (n = 12), and in a cross-sectional study we evaluated the maximal amount of bone loss possible at the hip and tibia following long-term (average 3 years) impaired limb function as a consequence of complicated tibial shaft fractures [delayed union or nonunion (n = 7), chronic osteomyelitis (n = 5), decreased limb length (n = 1), or bone defect (n = 1)]. Bone mineral measurements were performed by dual energy X-ray absorptiometry. Following tibial shaft fractures, a significant decrease in bone mineral density (BMD) was seen at the hip reaching 7% [confidence limits (CL): -10.2%; -3.5%] and 14% (CL: -19.6; -7.8%) after 6 months for the femoral neck and greater trochanter, respectively. In the proximal tibia, bone mineral content (BMC) decreased and was 19% (CL: -27.4%; -9.9%) below the initial value after 6 months. BMD of the lumbar spine remained unchanged. In the cross-sectional study, BMC in the tibia of the injured legs was 43% (CL: -53.2%; -31.9%) below the value in the healthy contralateral legs, and BMD in the femoral neck and greater trochanter, respectively, was 22% (CL: -27.4%; -17.6%) and 24% (CL: -36.3%; -12.1%) below the values in the healthy contralateral legs. With respect to the expected age-related decay of bone mineral after peak bone mass, the loss of bone mineral of the hip and tibia associated with tibial shaft fractures may be considered of clinical importance with increased risk of sustaining a fragility fracture of the lower extremity later in life; and the complicated fractures may even represent a present risk of fracture.

The effect of methylprednisolone on monocyte eicosanoid production in patients with multiple sclerosis.

The in vitro effect of methylprednisolone on prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and thromboxane B2 (TXB2) synthesis by adherent monocytes was examined using samples of peripheral blood from 15 patients with multiple sclerosis and 18 normal controls. Eicosanoid production by monocytes was reduced in patients compared with controls and there was a dose-dependent inhibitory effect of methylprednisolone on eicosanoid production in both groups. In vitro production of PGE2 and TXB2 but not LTB4 was reduced in patients with multiple sclerosis following intravenous treatment with methylprednisolone compared with pretreatment samples. In a separate cohort of 20 patients with multiple sclerosis and 15 controls, the in vitro inhibition of PGE2 release by methylprednisolone was not associated with reduced pokeweed-mitogen-stimulated immunoglobulin G synthesis by peripheral blood mononuclear cells. These results suggest that methylprednisolone inhibits monocyte-macrophage function, but this effect is not specific to patients with multiple sclerosis.

Late changes in bone mineral density of the proximal tibia following total or partial medial meniscectomy. A randomized study.

The adaptive bone remodeling in the proximal tibia following medial meniscectomy was measured quantitatively by dual photon absorptiometry. Thirty-three patients who had undergone a meniscectomy (randomized to either total [n=19] or partial [n=14] meniscectomy) performed by open joint surgery approximately 12 years earlier were included in the study. Bone mineral density was measured in the previously injured legs and in the healthy contralateral legs in areas located medially and laterally in the cortical bone of the subchondral plates and below in the trabecular bone of the medial and lateral tibial condyles. The distribution of bone mineral within the proximal tibia showed a characteristic and significant pattern. In the trabecular bone of the healthy contralateral knees, bone mineral density was 15% higher in the medial tibial condyles compared with the values laterally; a total or partial meniscectomy increased this difference to 25%. With regard to the cortical bone of the subchondral plates, the bone mineral density in the healthy knees was 24.8-29.4% higher medially than laterally, whereas after total and partial meniscectomy the differences were, respectively, 37.7 and 41.4%. No significant differences in the distribution of bone mineral density, at either cortical or trabecular measuring sites, were found between totally and partially meniscectomized knees.

Differential alterations in striatal acetylcholine function in rats during 12 months' continuous administration of haloperidol, sulpiride, or clozapine.

Rats were treated continuously for 12 months with therapeutically equivalent doses of either haloperidol (1.4-1.6 mg/kg/day), sulpiride (102-109 mg/kg/day), or clozapine (24-27 mg/kg/day). After treatment for 3 and 12 months with haloperidol or clozapine but not sulpiride, striatal acetylcholine levels were increased. Striatal choline acetyltransferase activity was not altered by any drug treatment. Vmax for striatal acetylcholinesterase activity during the course of 12 months' treatment with haloperidol or clozapine, but not with sulpiride, tended to increase; Km was not altered by any drug treatment. Bmax for specific striatal [3H]quinuclidinyl benzilate binding was not altered by haloperidol or sulpiride treatment but was transiently elevated after 6 months of clozapine treatment, thereafter returning to control levels. Kd was not altered by any drug treatment. These findings indicate that alterations in striatal acetylcholine content caused by chronic treatment with some but not all neuroleptics are due to changes in cholinergic neuronal activity rather than neurotransmitter synthesis or destruction. The effects of haloperidol but not those of clozapine may be related to the emergence of functional striatal dopamine receptor supersensitivity. Since haloperidol (which is associated with a high prevalence of tardive dyskinesias) but not clozapine (which is not) had similar effects on striatal cholinergic function, the latter may not be related to the emergence of tardive dyskinesias during chronic therapy.

Influence of pre-operative bone mineral content of the proximal tibia on revision rate after uncemented knee arthroplasty.

Between 1986 and 1991, 106 patients (127 knees) underwent uncemented knee arthroplasty for osteoarthritis. There were 106 total knee arthroplasties and 21 medial unicompartmental knee arthroplasties. The arthroplasties were evaluated for aseptic loosening during the year 2000. For total arthroplasty we used 77 porous-coated anatomic prostheses and 29 press-fit condylar prostheses. The mean bone mineral content of the proximal tibia, measured the day before surgery using dual-photon absorptiometry was 5.48 g/cm for the porous-coated anatomic prostheses which were revised for aseptic loosening (n = 9). This was significantly higher (p = 0.02) than the mean of 4.33 g/cm for those which were not revised. Values for the two revised press-fit condylar knees (4.78 and 4.93 g/cm) were above the mean value (4.23 g/cm) for those which were not revised. We found no statistically significant (p = 0.38) difference between the bone mineral content of the 12 revised and nine unrevised unicompartmental arthroplasties. Low trabecular bone quality, measured as the pre-operative bone mineral content of the proximal tibia, was not a predictor for later revision surgery following uncemented total knee or unicompartmental knee arthroplasty.

Body composition and muscle strength in women scheduled for a knee or hip replacement. A comparative study of two groups of osteoarthritic women.

It is unclear whether patients with knee osteoarthritis (OA) and hip OA differ regarding soft tissue composition and bone mineral density (BMD). A total of 42 women waiting for a replacement of the hip (n = 20) or the knee (n = 22) due to OA were examined. Fat mass (FM), percent body fat (%fat), lean mass (LM) and BMD were measured by dual energy X-ray absorptiometry (DEXA). Knee extensor and flexor strength was measured by an isokinetic dynamometer. No significant differences in age, height, disease duration, Lequesne score or pain scores were found between the groups. Comparing the radiographic changes of the knees with those of the hips, changes were most severe in the joints which were to be replaced. Body weight, body mass index, total and regional FM, and %fat were more than 15% higher in patients waiting for a knee replacement (p < 0.001). Also lean mass tended to be higher in the knee patients. Differences in BMD did not remain statistically significant after correction for body weight. Muscle strength was similar in the two groups but was reduced by 20% in the legs in which the joint was to be replaced compared to the contralateral legs. However, the mean difference in lean mass between the two legs was only 3% (p < 0.05). The scores for pain felt during strength testing were significantly higher for the involved legs than for the contralateral legs. In conclusion, fat mass values were considerably higher in patients scheduled for a knee replacement. Impaired strength performance in OA may be more strongly associated with pain than with reduced muscle mass.

[External hip protectors against hip fractures. A randomized study in a nursing home]. / Virkningen af eksterne hoftebeskyttere mod hoftebrud. En randomiseret plejehjemsundersøgelse.

Most hip fractures seem to be related to trauma near the hip, so a controlled trial was conducted to investigate the effect of external hip protectors on the prevention of such fractures in residents of a nursing home. Ten of 28 wards of the nursing home were randomized to receive external hip protectors; thus 167 women and 80 men were given protectors and 277 women and 141 men no protectors. A fall register was set up for two treatment wards (45 residents) and two control wards (76 residents). There were eight hip and 15 non-hip fractures in the hip protector group and 31 hip and 27 non-hip fractures in the control group. The relative risk of hip fractures among women and men in the intervention group was 0.44 (95% CL 0.21-0.94). None of the 8 residents in the intervention group who had a hip fracture was wearing the device at the time of the fracture. 154 falls were registered and 20% of these falls produced a direct impact to the hip. In 25 falls direct impact to the hip was sustained at a time when hip protectors were not being worn, and six fractures were produced. The study indicates that external hip protectors can prevent hip fractures in nursing-home residents.

[Bone scintigraphy in patients with hip joint prostheses. Use of bone scintigraphy in hip pain after total hip replacement]. / Knogleskintigrafi ved hofteledsprotese. Anvendelse af knogleskintigrafi ved hoftesmerter efter proteseindsaettelse.

A retrospective investigation was undertaken to assess the value of bone scintigraphy with 99mtechnetium methylene-diphosphonate in patients referred with hip pain after total hip replacement. The material comprized 68 patients with a total of 68 prostheses. This review revealed that 10/25 of the patients with pathological scintigrams and 6/28 of the patients with normal scintigrams were submitted to replacement of the prostheses. In the way in which it was carried out and interpreted in this department, scintigraphy was of limited value in selection of the patients who required replacement of the prostheses.

Micro-albuminuria and the organ-damage concept in antihypertensive therapy for patients with insulin-dependent diabetes mellitus.

OBJECT OF TREATMENT: Antihypertensive treatment in hypertensive patients with insulin-dependent diabetes mellitus is intended to prevent long-term complications, particularly diabetic nephropathy. DIABETIC HYPERTENSIVES WITH ABNORMAL ALBUMINURIA: Antihypertensive therapy, particularly with angiotensin converting enzyme (ACE) inhibitors, typically produces a permanent reduction in the decline of the glomerular filtration rate (GFR) in diabetic patients with abnormal albuminuria. The rate of decline in the GFR during antihypertensive treatment is a well accepted end-point in diabetic renal disease. DIABETIC HYPERTENSIVES WITHOUT ABNORMAL ALBUMINURIA: In insulin-dependent diabetic patients with essential hypertension but with normal urinary albumin excretion there is no reduction in the GFR. Longitudinal studies have shown a fall in the GFR only in the presence of significantly increased urinary albumin excretion. ABNORMAL ALBUMINURIA AS A MARKER OF INCIPIENT NEPHROPATHY: Micro-albuminuria and proteinuria may be pathogenetic factors in the development of nephropathy, leading eventually to end-stage renal failure in diabetic patients. Measurements of micro-albuminuria and proteinuria, in addition to blood pressure recordings, might therefore be used as indications for initiating antihypertensive treatment. NEED TO MONITOR PATIENTS FOR ABNORMAL ALBUMINURIA: Transglomerular macromolecular traffic may produce mesangial damage, with subsequent glomerulopathy and diabetic nephropathy. Thus, close monitoring for micro-albuminuria and proteinuria is desirable in the management of diabetic hypertensive patients.