Imaging of skeletal metastases in myxoid liposarcoma.

Unlike other soft tissue sarcomas, myxoid/round cell liposarcoma (MRCL) has a tendency to spread to extrapulmonary sites but bone metastases are thought to be uncommon. In case reports, negative bone scintigraphy has been noted in patients with myxoid/round cell liposarcoma and bone metastases but the prevalence and optimal method of diagnosis of bone metastases in this common subtype of liposarcoma are unclear. In an attempt to answer these questions, data were obtained from a prospective database of patients with sarcoma, including MRCL, and the diagnostic imaging used was examined. A variety of imaging tools were used including plain X-rays, bone scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI). Eight patients (4.3%) developed skeletal metastases all of which were positive on MRI. Bone scintigraphy was negative in two out of four cases, CT was negative in six out of seven, and X-rays were negative in four. Radiography and CT measure mainly cortical bone involvement, whereas MRI examines bone marrow. When investigating patients with MRCL for bone pain, negative X-rays and bone scans do not rule out bone metastases. In our experience, MRI provides the most sensitive technique for the diagnosis of bone metastases in MRCL.

[Deferred consent for inclusion of patients unable to give their consent in studies in the field of emergency medicine]. / Uitgestelde toestemming voor inclusie van beslissingsonbekwame patiënten in studies van spoedeisende geneeskunde.

Respect for individual autonomy, expressed in the concept of informed consent, is a basic principle in research with humans. Many patients in intensive care are unable to give consent because of mental incapacity, and this can be further complicated in emergency research, in which the treatment or experiment needs to be initiated without delay. In those situations consent can be deferred. Randomization is done without prior consent, followed by patients' or relatives' consent at a later stage. Butwhat should one do with the data if the patient dies at an early stage after randomization before consent could be obtained? Should the data be used or not? Should the relatives be asked for consent for using the data? The Dutch Central Committee on Research involving Human Subjects (CCMO) states that asking for consent after the patient has died makes no sense, because with the death of the patient the research has ended. Relatives do not have the authority to give consent for the use of medical data after the patient has died. Data can be used anonymously in the final analysis of the trial. We propose a flowchart for this procedure.

A comparative proteinomic analysis of nipple aspiration fluid from healthy women and women with breast cancer.

This pilot study examines the feasibility of nipple aspiration to distinguish women with breast cancer from healthy women using surface-enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF/MS). Nipple aspiration fluid (NAF) was collected from each breast in 21 women newly diagnosed with unilateral breast cancer and 44 healthy women. No differences were found when proteomic profiles of NAF from the cancer-bearing breast and the contralateral non-cancerous breast were compared. In contrast, 9 protein peaks were significantly different between the cancer-bearing breast compared with healthy women and 10 peaks were significantly different between the contralateral healthy breast and healthy women (P<0.05). These data suggest that invasive breast cancer may result in a field change across both breasts and that proteomic profiling of NAF may have more value in breast cancer risk assessment than as a diagnostic or screening tool.

Treatment of cefuroxime-induced neurotoxicity with continuous venovenous haemofiltration.

A 61-year-old woman with decreased consciousness, myoclonus, tremors, nystagmus and bradypnoea, due to cefuroxime-induced neurotoxicity, was admitted to the intensive care unit. Continuous venovenous haemofiltration (CVVH) rapidly reduced plasma cefuroxime concentrations and improved neurological manifestations within the next few hours. Retrospective pharmacokinetic assessment showed a total cefuroxime clearance of 166 ml/min during the CVVH.

Microvascular alterations in adult conscious spontaneously hypertensive rats.

The dorsal skin flap technique was used to study skeletal muscle microcirculation in conscious 10-12-week-old spontaneously hypertensive rats and normotensive Wistar-Kyoto control rats. Videorecordings were made for off-line analysis of consecutive segments of the vascular bed. Resting diameters were significantly smaller in spontaneously hypertensive rats than in Wistar-Kyoto rats at the first-order (-28%) and second-order arteriolar (-21%) levels. Precapillary third-order and fourth-order arterioles of spontaneously hypertensive rats had normal diameters, whereas postcapillary small venule diameters were slightly larger in spontaneously hypertensive rats. Thirty percent and 41% of the spontaneously hypertensive rat and Wistar-Kyoto rat third-order arteriolar vessels and 63 and 45% of the fourth-order arteriolar vessels exhibited vasomotion. Vasomotion amplitude, but not frequency, was significantly higher in spontaneously hypertensive rats than in Wistar-Kyoto rats. It is concluded that, in the established phase of spontaneous hypertension in the rat, a decreased diameter of large arterioles is the major mechanism underlying the increased vascular resistance in cutaneous skeletal muscle.

A functional morphometric study of the cremaster muscle microcirculation in young spontaneously hypertensive rats.

Increased vascular resistance in spontaneous hypertension has been attributed to a reduced arteriolar lumen and a decrease in the number of arterioles and capillaries. In the present study, microvascular mechanisms for increased resistance were investigated in the cremaster muscle of 5-6-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) using intravital microscopy. Vessels were classified on the basis of their location in the network relative to their branching order and function (A1-A4). In each preparation, one vessel of each category was observed for its side-branches, using bright-field microscopy. By comparing the number of side-branches seen under control conditions and after maximal vasodilatation (10(-3) mol/l adenosine, topically) we assessed their functional reserve. Capillary density was investigated using incident fluorescence microscopy. Both under control conditions and after vasodilatation, mean arterial pressure and heart rate were increased in SHR (mean arterial pressure: SHR 103 +/- 4 mmHg, WKY 89 +/- 3 mmHg, P less than 0.05; heart rate: SHR 380 +/- 16 beats/min, WKY 343 +/- 12 beats/min, P less than 0.05). Arterioles (A1-A4) of SHR and WKY were equal in diameter (SHR: 75.8 +/- 3.2, 48.7 +/- 1.1, 21.4 +/- 0.9, 10.0 +/- 0.04 microns; WKY: 71.6 +/- 2.4, 48.9 +/- 1.1, 18.5 +/- 0.9, 9.8 +/- 0.3 microns; A1-A4, respectively). After adenosine, the relative increase in diameter was similar in both groups. The number of side-branches under control conditions was similar in A1 and A2 vessels. SHR had fewer A3 vessels per A2 and fewer A4 vessels per A3 (per unit length), indicating a diminished arteriolar reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Clearance of corneal crystals in nephropathic cystinosis by topical cysteamine 0.5%.

A 2-year-old girl with nephropathic cystinosis was successfully treated with topical cysteamine 0.5% to one eye. Clearance of crystals from the treated cornea was virtually complete after three months. The possibilities and limitations of this form of treatment are discussed.

Prediction of enophthalmos by computed tomography after 'blow out' orbital fracture.

In 11 patients with blow out fracture of the orbit, measurement of orbital volume using computed tomography (CT) more than 20 days after injury correlated well with enophthalmos measured from the same scans (r = 0.87, p < 0.001, SEE 0.63 mm), with a 1 cm3 increase in orbital volume causing 0.8 mm of enophthalmos. This confirms the cause of enophthalmos after blow out fracture to be increase in orbital volume rather than fat atrophy or fibrosis. In a further 25 patients scanned within 20 days of injury the degree of enophthalmos was less marked than would be predicted from the orbital volume measurement. This was probably because of the presence of oedema, haemorrhage, or both behind the globe which would prevent immediate development of enophthalmos. CT measurement of orbital volume within 20 days of injury may predict the final degree of enophthalmos and identify those patients at risk of late enophthalmos, allowing appropriate early surgical intervention.

Orbital volume measurement in the management of pure blowout fractures of the orbital floor.

With the recent advent of accurate orbital volume assessment by computed tomography, a retrospective analysis was made of 31 patients with 'pure' blowout fracture of the orbital floor, managed either surgically or conservatively, to determine whether orbital volume measurement could provide an additional parameter of use in the management of such fractures. There was a significant difference in orbital volume discrepancy between patients managed surgically or conservatively suggesting that this investigation may be of use in decision making on surgical intervention in patients with orbital blowout fractures.

Florid xanthelasmata (yellow lids) in orbital Wegener's granulomatosis.

AIMS: A new sign of florid xanthelasmata is described in four male patients with orbital manifestations of Wegener's granulomatosis. METHODS: The case notes of four patients with Wegener's granulomatosis, with orbital involvement accompanied by yellow lid lesions, are reviewed. RESULTS: All the patients had active Wegener's granulomatosis at the time the lid lesions were most florid. The lesions gradually resolved as the inflammatory disease was controlled with immunosuppressive agents. The lesions displayed marked asymmetry and predominantly involved the side with the most severe inflammation. Abnormalities of lipid metabolism were not identified and it is believed that the lesions developed in a susceptible anatomical region affected by a vasculitic process. CONCLUSION: A 'yellow lid' associated with orbital inflammation and is a strong pointer to the clinical diagnosis of Wegener's granulomatosis.

The microcirculation and essential hypertension.

Essential hypertension is characterized by a progressive increase of the mean arterial pressure paralleled by a concomitant increase in the total peripheral resistance. This elevated resistance is the consequence of (a) a decreased internal diameter, (b) an increased wall-to-lumen ratio or (c) a decreased number of small arteries or arterioles. A considerable part of the elevated vascular resistance is determined at the microcirculatory level. This paper reviews the studies performed to unravel the resistance-elevating mechanisms in the microvasculature of different tissues. Furthermore the possible role of the microcirculation in the pathogenesis of essential hypertension is discussed.

Microphthalmos with cyst in monozygous twins.

We present two cases of microphthalmos with cyst affecting monozygotic twins. The etiology and pathogenesis of this developmental anomaly are discussed. The diagnostic evaluation, differential diagnoses, and management options of this unique disorder are also considered.

The microcirculation and hypertension.

AIM: To review published evidence on the effects of arteriolar changes in primary and secondary hypertension. BACKGROUND: Pressure profile analyses have shown that the microcirculation is a major site of vascular resistance. With the recent refinement of intravital microscopy techniques detailed information has become available on mechanisms of the microvascular resistance increase in hypertension. Three mechanisms play an important role: (1) a decrease in arteriolar diameter; (2) arteriolar vessel wall hypertrophy; and (3) small arteriolar and capillary rarefaction. METHOD: The evidence was synthesized into a hypothesis on the role of the microcirculation in primary forms of hypertension. HYPOTHESIS: The hypothesis formulated contains two important elements in that (1) diminished outgrowth of the microvascular bed in different tissues is seen as an important early pathogenic mechanism; and (2) the decreases in arteriolar diameter and vessel wall hypertrophy are seen as adaptive mechanisms that maintain a constant wall stress. The three factors together maintain the increase in vascular resistance that is common to all established forms of primary hypertension.

Pharmacological evidence for rapid destruction of efferent renal nerves in rats by intrarenal infusion of 6-hydroxydopamine.

In a previous study we reported that intrarenal (i.r.) infusion of 1 mg 6-hydroxydopamine (6-OHDA) in rats resulted in selective efferent denervation of the infused kidney. Although the vasoconstrictor response to electrical stimulation of the posterior hypothalamus (PH) was already abolished 24 h after infusion, norepinephrine (NE) content of the kidney was reduced by only approximately 50% at that time. In the present study, the status of renal nerves 45 min after infusion of 6-OHDA by i.r. application of scorpion venom (SV), a NE releasing agent, was investigated. In saline pretreated rats, 10 micrograms SV i.r. caused a rapid increase (+355 +/- 80%) in vascular resistance in the injected kidney, whereas only minor changes were observed in resistances of the non-injected kidney, mesentery and hindquarters. Pretreatment of animals with phentolamine (1 mg/kg i.v.) largely abolished the vasoconstrictor response (+57 +/- 20%), confirming dependence of the effect of SV on release of NE from nerve terminals. Finally, pretreatment with 1 mg 6-OHDA i.r. also resulted in abolition of renal vasoconstriction following SV (+7 +/- 6%). The results indicate that as early as 45 min after i.r. infusion of 1 mg 6-OHDA in rats, efferent renal nerve endings are no longer functional.

Microcirculatory changes in cremaster muscle during early spontaneous hypertension in the rat.

The microcirculatory control of flow was studied in the cremaster muscle of 5- to 6-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using intravital microscopic techniques. Arterioles were classified according to a functional branching order from A1-A4 vessels. Capillary architecture was measured in a separate series of experiments. No significant differences were found in the WKY or SHR vessel diameters, with the exception of third-order arterioles, which were slightly, but significantly, larger in SHR. However, the number of A3 and A4 vessels as well as the capillary density was significantly lower in SHR than in WKY. The differences were even more pronounced during maximal vasodilation induced by local application of 10(-3) mol/l adenosine. The data show that rarefaction of small blood vessels rather than decreased arteriolar diameter is an early characteristic of spontaneous hypertension in the rat.

Moderate dose capecitabine in older patients with metastatic breast cancer: a standard option for first line treatment?

Single agent capecitabine is effective and well tolerated in metastatic breast cancer (MBC). We have retrospectively analysed capecitabine outcome as 1st, 2nd or 3rd line chemotherapy in 89 elderly patients ≥70 years with locally advanced or MBC treated in our Unit, 55 (62%) as 1st line and 34 (38%) as 2nd or 3rd line. Starting dose was 1000 mg/m(2) twice daily, days 1-14 every 3 weeks, but 36 (41%) started on a 25% dose reduction because of frailty and 12 (13%) reduced dose after the 1st or the 2nd cycle. Overall response rate (ORR) was 45% (95% CI: 35-55%). A further 19 (21%) achieved stable disease (SD) for ≥6 months. Median time to progression (TTP) and overall survival (OS) were 30 (95% CI: 23-37) and 61 (95% CI: 44-77) weeks, respectively. The ORR for 1st line treatment was 51% compared with 35% for 2nd and 3rd line treatment (p = 0.03). No significant difference in efficacy was seen between patients receiving the full versus reduced dose. Capecitabine was well tolerated, although 35% had treatment delays and 57% required dose reduction. Grade 3-4 toxicities were hand-foot syndrome in 11%, lethargy 9% and diarrhoea 2%. Capecitabine is an effective and well-tolerated drug in elderly patients with MBC including for 1st line treatment. Dose reduction is frequently required but does not appear to affect outcome.