Chronic inflammation predicts long-term mortality in patients with Raynaud's phenomenon.

BACKGROUND: Subclinical chronic inflammation could be the driving force behind the recently revealed association between abnormal nailfold capillaries as well as autoantibodies and long-term mortality in patients with incipient Raynaud's phenomenon. Whether laboratory markers that reflect a chronic inflammatory process are directly related to mortality in Raynaud's phenomenon is not known. METHODS: In total, 2958 patients with incipient Raynaud's phenomenon without previously known connective tissue disease (CTD) were enrolled. At their initial presentation, laboratory tests for C-reactive protein (CRP), leucocytes, fibrinogen and the haemoglobin concentration were obtained. In addition, nailfold capillaries and antinuclear antibodies (ANA) were assessed. Patients' mortality was recorded through a median follow-up period of 9.3 years. RESULTS: Baseline CRP, fibrinogen and haemoglobin concentration were associated with long-term mortality in an individual analysis of patients with incipient Raynaud's phenomenon. In a multivariable model including patients' age, nailfold capillaries and ANA, a low haemoglobin concentration remained independently related to future mortality. Amongst potential predictors for mortality in patients with Raynaud's phenomenon, a low haemoglobin concentration was most strongly related to patients' mortality risk. CONCLUSION: In Raynaud's phenomenon, laboratory markers that can be attributed to a chronic inflammatory state independently yield prognostic information in addition to the presence of abnormal nailfold capillaries and ANA. Amongst all prognostic markers, the haemoglobin concentration is most strongly related to patients' mortality in Raynaud's phenomenon.

Associations of nailfold capillary abnormalities and immunological markers in early Raynaud's phenomenon.

OBJECTIVES: Nailfold capillaroscopy (NC) and laboratory tests for antinuclear antibodies (ANA) are routinely used in parallel for detection of emerging connective tissue disease (CTD) in patients with Raynaud's phenomenon (RP). The aim of this study was to assess the associations between distinct nailfold capillary abnormalities and concomitant autoantibodies in patients with incipient RP without previously known CTD. METHOD: Patients with incipient RP without previously known CTD were included in this retrospective analysis. We analysed the association of particular capillary abnormalities (reduced density, avascular fields, dilations, giant capillaries, haemorrhages, tortuosity, ramifications, oedema) with ANA and ANA subsets (anti-Scl-70, anti-CENP-B, anti-U1-RNP, anti-dsDNA, anti-SSA(Ro), anti-SSB(La), anti-Sm, and anti-Jo-1 antibodies). We also developed a score that allows the estimation of each patient's individual probability for the presence of an ANA titre ≥ 1:160. RESULTS: The final analysis comprised 2971 patients. Avascular fields, giant capillaries, reduced capillary density, and capillary oedema were closely related to an ANA titre ≥ 1:160. Both giant capillaries and avascular fields were associated with anti-Scl-70 and anti-CENP-B antibodies. Only a weak association was found between giant capillaries and anti-U1-RNP antibodies. Each patient's individual probability for the presence of an ANA titre ≥ 1:160 can be represented by a sum score comprising giant capillaries, reduced density, avascular fields, ramifications, and oedema as well as patients' sex and age. CONCLUSION: In patients with incipient RP, anti-Scl-70 and anti-CENP-B antibodies are related most specifically to distinct capillary alterations. Although a sum score can represent the patient's probability for elevated ANA titres, NC cannot substitute for immunological tests in patients with incipient RP.

Microvascular autoregulation in children and adolescents with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Deterioration of microvascular function may have an early onset in individuals with type 1 diabetes mellitus. We hypothesised that microvascular autoregulation is impaired in children with type 1 diabetes and can be detected non-invasively by postocclusive reactive hyperaemia (PORH). METHODS: Microvascular autoregulation was assessed in 58 children with type 1 diabetes and 58 age- and sex-matched healthy controls by PORH using laser Doppler fluxmetry. Baseline perfusion, biological zero (defined as a 'no flow' laser Doppler signal during suprasystolic occlusion), peak perfusion following occlusion, time to peak and recovery time (time until baseline perfusion is resumed) were recorded and compared between the groups. RESULTS: Peak perfusion was higher in children with type 1 diabetes than in healthy controls (1.7 ± 0.93 AU [arbitrary units] vs 1.29 ± 0.46 AU; p = 0.004), and biological zero was lower in children with type 1 diabetes vs controls (0.14 ± 0.04 AU vs 0.19 ± 0.04 AU; p < 0.0001). No differences were seen between the groups in baseline perfusion, time to peak during PORH and recovery time following PORH. CONCLUSIONS/INTERPRETATION: PORH reveals impaired microvascular autoregulation in children with type 1 diabetes. The higher peak perfusion might reflect a decline in the vasoconstrictive ability of arteriolar smooth muscle cells upstream of capillary beds in children with type 1 diabetes.

Effect of nimodipine on ocular blood flow and colour contrast sensitivity in patients with normal tension glaucoma.

AIM: To investigate the effects of oral nimodipine on ocular haemodynamic parameters and colour contrast sensitivity in patients with normal tension glaucoma (NTG). DESIGN: The study was performed in a randomised, placebo controlled, double masked, crossover design. PARTICIPANTS: Nimodipine (60 mg) or placebo was administered to 14 consecutive NTG patients. METHODS: The effects or oral nimodipine or placebo on ocular and systemic haemodynamic parameters and colour contrast sensitivity along the tritan axis were studied two hours after administration. Optic nerve head blood flow (ONHBF) and choroidal blood flow (CHBF) were assessed with laser Doppler flowmetry. Ocular fundus pulsation amplitude (FPA) was measured with laser interferometry. Colour contrast sensitivity (CCS) was determined along the tritan colour axis. MAIN OUTCOME MEASURES: ONHBF, CHBF, FPA, intraocular pressure and CCS were assessed in patients with NTG. RESULTS: Mean ocular FPA increased by 14% (SD 14%) (p = 0.0008), ONHBF by 18% (SD 16%) (p = 0.0031), and CHBF by 12% (SD 14%) (p<0.001) after administration of nimodipine. Nimodipine also decreased the threshold of colour contrast sensitivity along the tritan colour axis (-14% (SD 12%); p = 0.048). However, individual changes in FPA, ONHBF, or CHBF were not correlated with changes in threshold of CCS along the tritan colour axis. CONCLUSIONS: The results indicate that nimodipine increases ONH and choroidal blood flow in NTG patients and improves CCS. The latter effect does not, however, seem to be a direct consequence of the blood flow improvement.

Neointimal proliferation within carotid stents is more pronounced in diabetic patients with initial poor glycaemic state.

AIMS/HYPOTHESIS: We studied the influence of initial hyperglycaemia on neointimal proliferation within carotid Wallstents. METHODS: A total of 112 patients were followed by duplex sonography after carotid stenting for 24 months. Patients were assigned to three groups: non-diabetic subjects (group A) and diabetic patients, who were assigned according to their baseline HbA(1)c values, to group B1(HbA(1)c6.5%). RESULTS: At baseline the groups did not differ with respect to other vascular risk factors and residual stenosis on angiograms. The maximal thickness of the layer between the stent and the perfused lumen was measured at the duplex follow-ups. At 3 months the typical ultrasonic structure of the neointima was clearly discernible. From this point on, group B2 differed significantly ( p<0.001) compared with B1 and A with respect to the maximal thickness of neointima and the time course of its ingrowth: group A vs B1 vs B2 was 0.51+/-0.39 vs 0.52+/-0.33 vs 0.56+/-0.35 at 3 months, 0.91+/-0.27 vs 0.90+/-0.38 vs 1.14+/-0.48 at 6 months, 1.02+/-0.24 vs 0.97+/-0.34 vs 1.21+/-0.44 at 12 months and 1.09+/-0.23 vs 1.10+/-0.31 vs 1.23+/-0.37 at 24 months. CONCLUSION/INTERPRETATION: Initial hyperglycaemia seems to be a predictor of more pronounced neointimal proliferation after carotid stenting independent of diabetes. As intimal hyperplasia is known to be responsible for stent restenosis, strict optimisation of the hyperglycaemic state should be aimed at before elective carotid artery stenting.

Influence of lipoprotein(a) on restenosis after femoropopliteal percutaneous transluminal angioplasty in Type 2 diabetic patients.

OBJECTIVE: The influence of vascular morphology and metabolic parameters including lipoprotein(a) (Lp(a)) on restenosis after peripheral angioplasty has been compared in Type 2 diabetes (DM) vs. non-diabetic patients (ND). RESEARCH DESIGN AND METHODS: The clinical course and risk profile of 132 (54 DM vs. 78 ND) patients with peripheral arterial occlusive disease (PAD) were observed prospectively following femoropopliteal angioplasty (PTA). Clinical examination, oscillometry, ankle brachial blood pressure index (ABI) and the toe systolic blood pressure index (TSPI) were used during follow-up. Duplex sonography and reangiography were also used to verify suspected restenosis or reocclusion. RESULTS: At the time of intervention patients with DM had a lower median Lp(a) of 9 vs. 15 mg/dl (P < 0.01) in patients without diabetes. Recurrence within 1 year after PTA occurred in 25 diabetic (= 46%, Lp(a) 12 mg/dl) and 30 non-diabetic (= 38%, Lp(a) 48 mg/dl) patients. DM patients with 1 year's patency had a median Lp(a) of 7 vs. 11 mg/dl in non-diabetic patients (P < 0.05). However, 12 months after angioplasty Lp(a) correlated negatively with the ABI (r = -0.44, P < 0.01) in diabetic and in non-diabetic patients (r = -0.20, P < 0.05). The probability of recurrence after PTA continuously increased with higher levels of Lp(a) in each subgroup of patients. CONCLUSIONS: Our data indicate that Lp(a) is generally lower in those with peripheral arterial occlusive disease and Type 2 diabetes than in non-diabetic individuals. The increased risk for restenosis with rising levels of Lp(a) is set at a lower Lp(a) in diabetes and may be more harmful for diabetic patients.

Microcirculation is similar in ischemic and venous ulcers.

Microcirculation of 15 ischemic and 15 venous ulcers, their scars, and intact surrounding skin were examined in order to demonstrate their similarities in the development and healing process. Subpapillary and nutritive perfusion of four areas were investigated by a laser Doppler perfusion imager (arbitrary units) and capillary microscopy (capillaries/mm2): one ulcer area without granulation tissue (no wound healing) and one with granulation tissue (ulcer healing); one skin area adjacent to the ulcer (1-8 mm) (scar developed from ulcer areas) and one distant (12-25 mm; intact skin). Areas without granulation tissue in ischemic and venous ulcers were similar, demonstrating a lack of capillaries (0.13 +/- 0.52; 0.93 +/- 2.09) and low laser Doppler flux (0.81 +/- 0.69; 1.47 +/- 1.17; P > 0.05 for each). In granulation tissue of both ulcers there was a tendency to a higher capillary density (0.67 +/- 1.40; 5.60 +/- 2.32; P < 0.0001 for venous ulcers) and a higher laser Doppler flux (1.15 +/- 0.67; 4.04 +/- 1.62; P < 0.0001 for venous ulcers) than in areas without granulation tissue. In scars of ischemic and venous ulcers capillary density (8.18 +/- 8.84; 13.60 +/- 5.45) and laser Doppler flux (1.72 +/- 1.00; 1.94 +/- 1.45) were similar (P > 0.05). In skin distant from ischemic ulcers very high capillary density (24.63 +/- 1.89) was associated with low laser Doppler flux (0.99 +/- 0.59); distant from venous ulcer capillary density was moderate (10.47 +/- 3.42) while laser Doppler flux was high (3.77 +/- 1.62; P < 0.0001 between both groups). The development and healing process of ischemic and venous ulcers is similar. Nutritive and subpapillary perfusion are involved in ulcer healing. In intact skin surrounding ischemic and venous ulcers, microcirculation is different due to the underlying pathophysiology.

Carotid artery stenting: effect of learning curve and intermediate-term morphological outcome.

PURPOSE: To assess the impact of learning on the rate of success and complications of carotid stenting in a single-center, one-operator series and prospectively follow a patient cohort with regard to restenosis. METHODS: In 303 patients (mean age 70 +/- 8.8 years), 320 internal carotid arteries (ICA) were treated with carotid stenting for stenoses > or = 70%. Four groups of 80 consecutive interventions were compared with regard to primary technical success and periprocedural complications. Stent patency in follow-up was assessed using duplex scanning. RESULTS: Stenting was successful in 298 (93%) arteries. The combined neurological complications (transient ischemic attacks and all strokes) and 30-day death rate was 8.2% (n = 25), but the all stroke and 30-day death rate was 3.0% (n = 9). A significant reduction in the frequency of neurological complications after the initial 80 interventions was observed (p = 0.03), but technical success was not appreciably improved with increasing experience thereafter. Over a median 12 months (interquartile range 6 to 24), cumulative patency rates were 91%, 90%, and 91% at 6, 12, and 36 months, respectively. CONCLUSIONS: Elective carotid stenting can be performed with excellent technical success, an acceptable frequency of periprocedural complications, and good intermediate-term patency. However, our findings suggest that a larger number of interventions should be performed to overcome the negative effects of the initial learning phase.

Low level laser treatment of primary and secondary Raynaud's phenomenon.

BACKGROUND: Patients who had been treated with low level laser (LLL) for their digital ulcers reported an impressive improvement of their symptoms of episodic digital ischaemia. Therefore this pilot study was performed to evaluate the efficacy of LLL as a new non-drug non-invasive treatment for patients with primary and secondary Raynaud's phenomenon (RP). PATIENTS AND METHODS: Forty patients (29 female, 11 male, mean age 51 years) with active primary (28%) and secondary (72%) Raynaud's phenomenon received 10 sessions of LLL distant irradiation during winter months. Assessment of subjective and objective parameters was performed at baseline, one week after the last session and three months later. Variations of subjective parameters as number of daily acute episodes and severity of discomfort were assessed by a coloured visual analogue scale. A standardised cold challenge test using computed thermography of continuous temperature recordings by means of infrared telethermography was used to assess the digital blood flow. RESULTS: A significant improvement was noticed clinically and thermographically after 6 weeks and 3 months, respectively (p < 0.0001). CONCLUSIONS: These data suggest that LLL treatment has a good short and medium term effectiveness in patients with Raynaud's phenomenon.

Microcirculation in chronic venous insufficiency.

In this review, the anatomy and physiology of the venous system and its pathophysiology are described. Theories regarding the possible causes of disturbances in venous microangiopathy are summarized. The theories concern the deoxygenation of red blood cells, arteriovenous shunts, fibrin cuffs, and the trapping of growth factors and/or white blood cells. Furthermore, microlymphatic, neurologic and hemorheologic disturbances in venous disease are outlined. Findings in venous microangiopathy obtained from histology, capillary microscopy, microlymphography, laser Doppler fluxmetry and transcutaneous oxygen partial pressure are detailed. Finally, the recently discovered pattern of perfusion in microcirculation within and around venous ulcers is discussed.

Transient swallow syncope during periods of hypoxia in a 67-year-old patient after self-extubation.

OBJECTIVE: To describe the case of an adult patient with swallow syncope after bypass surgery, possibly related to hypoxia. DESIGN: Case report. SETTING: University hospital, medical-cardiologic intensive care unit. PATIENT: A 67-yr-old patient after second aortocoronary bypass operation for unstable angina. MAIN RESULTS: After the patient managed to extubate himself, he was in a borderline respiratory condition with an oxygen mask. When drinking for the first time after extubation, asystole was observed coincidentally with interruption of oxygen insufflation. During the next days, similar events occurred during food ingestion or when drinking liquids after a fall of oxygen saturation. The bradyarrhythmia was readily reversible on administration of atropine and ventricular backup pacing via temporary pacing wires. After normalization of gas exchange, no more episodes of swallowing-associated asystole were observed and the patient was discharged without a permanent pacemaker. There was no esophageal or gastrointestinal disease. Pre- and postoperative PR and QRS durations were normal. CONCLUSION: Extrinsic and transient mechanisms, rather than intrinsic conduction system disease, seem to have been operative in this case. It is suggested that hypoxia reinforced the vagal pharyngocardiac reflex as described in pediatric patients.

Impact of different therapeutic alternatives in treatment of severe limb ischemia: experiences on 190 consecutive patients at a department of medical angiology.

BACKGROUND: Different therapies in consecutive patients (1987-1992) with chronic critical limb ischemia at a department of medical angiology, their short- and long-term outcome were investigated. PATIENTS AND METHODS: 190 patients (112 males, 78 females; age: 67 +/- 12 years); 78 in grade II, 112 in grade III according to Rutherford's classification. Therapeutic regimen: 1. vascular recanalisation by percutaneous transluminal angioplasty [PTA], local or systemic lysis; 2. surgical vascular reconstruction in case of impossibility or failure of catheter procedures; 3. prostanoids and/or antibiotics; 4. local wound treatment including amputations. RESULTS: Vascular recanalisation was attempted in 156/190 (82.1%): PTA in 116/190, surgical vascular reconstruction in 50/190, local in 24/190 and systemic lysis in 8/190 patients. Prostanoids were applied in 89/190 and antibiotics in 73/190 patients. At the time of dismissal 164/190 (86.3%) patients were clinically improved; 11/190 (5.8%) unchanged, 13/190 (6.8%) had undergone major amputations and 2/190 (1.1%) had died. After 2.6 +/- 2.2 years 77 of the 141 patients, who were still alive, were reexamined. Among these 77 patients 84.4% were in grade 0 or 1, 15.6% in chronic critical limb ischemia. Furthermore 13.0% had been amputated since dismissal. Forty-nine of 190 (25.8%) patients had died 3.2 +/- 1.9 years after dismissal from hospital. CONCLUSION: Catheter techniques, mostly PTA, is possible in the majority of patients with chronic critical limb ischemia. Cooperation with vascular surgeons in case of technical impossibility or failure of catheter recanalisation is mandatory. Such a regimen yields satisfactory short- and long-term results and a low rate of complications.

Microcirculation in venous ulcers and the surrounding skin: findings with capillary microscopy and a laser Doppler imager.

BACKGROUND: To obtain more information about microcirculatory disturbances in venous ulcers, we studied their laser Doppler flux images and capillary densities. MATERIALS AND METHODS: On photographs of venous ulcers and the adjacent skin of 17 patients, four regions of interest were marked: one non-granulation tissue area (NGTA) within the venous ulcer, one granulation tissue area (GTA) within the ulcer, one adjacent skin area (ASA) and one distant skin area (DSA). Within these four regions the average laser Doppler area fluxes and capillary densities were determined for each patient using a laser Doppler imager and capillary microscopy respectively. RESULTS: The laser Doppler area flux (mean +/- SD in AU) was significantly lower in NGTA (1.39 +/- 1.12) than in GTA (4.06 +/- 1. 52) or DSA (3.86 +/- 1.54) (P < 0.00001). In addition, the ASA flux (1.95 +/- 1.39) was significantly lower than the GTA or DSA flux (P < 0.0001). Capillary density (capillaries per mm2) in NGTA (0.82 +/- 1.98) was significantly lower than that in GTA (6.00 +/- 2.55), ASA (13.88 +/- 5.16) or DSA (10.29 +/- 3.41) (P < 0.0001). In addition, the capillary density of ASA was significantly higher than that of GTA or DSA (P < 0.05). CONCLUSION: The four areas showed the following characteristics: NGTA, low laser Doppler area flux and lowest capillary density (possible sign of ulcer area without healing tendency); GTA, high laser Doppler area flux and second lowest capillary density (possible sign of wound healing); ASA, low laser Doppler area flux and highest capillary density (possible sign of healing process nearly completed; scar); DSA, high laser Doppler area flux and second highest number of capillaries (sign of microcirculation of chronic venous disorder).

IV milrinone for cardiac output increase and maintenance: comparison in nonhyperdynamic SIRS/sepsis and congestive heart failure.

OBJECTIVE: To characterize the effect of the phosphodiesterase inhibitor (PDEI) milrinone in adult patients with a non-hyperdynamic condition during the course of the systemic inflammatory response syndrome (SIRS) or sepsis when compared with patients with congestive heart failure (CHF). PDEIs are potent inhibitors of cytokine production and expression. We hypothesized that there might be an outstanding beneficial effect of PDEIs in the setting of SIRS/sepsis. DESIGN: Prospective, open labeled, protocol-driven pilot study. PATIENTS: Nine patients with a nonhyperdynamic hemodynamic condition during SIRS/sepsis (group 1) and seven patients with CHF (group 2) requiring inotropic support. All patients were having heart disease. All patients had a combination of various catecholamines at the time of inclusion in the study and had received fluid resuscitation to an extent that left ventricular stroke work index (LVSWI) did not increase further. INTERVENTION: Milrinone infusion at a rate of 0.5 microg/kg per min in addition to preexisting catecholamine therapy. MEASUREMENTS AND RESULTS: Measurements of cardiac index (CI; thermodilution) and calculation of vascular resistance and LVSWI was done every 8 h for at least 40 h during milrinone infusion. CI and LVSWI significantly increased in both groups (p < 0.001 and p = 0.006, respectively). There were no significant differences between groups in these parameters (p > 0.11 and p > 0.13, respectively). The LVSWI increase occurred while there was a decrease in pulmonary capillary wedge pressure, suggesting a true and comparable improvement in cardiac function relatively independent of loading conditions. Preexisting catecholamines had to be increased in both groups (NS). Milrinone had to be discontinued in one patient due to hypotension. CONCLUSION: Milrinone administration is feasible in selected patients with a non-hyperdynamic condition during SIRS/sepsis and with preexisting heart disease. Under the conditions of this study, milrinone was no better in terms of CI and LVSWI maintenance in septic cardiac dysfunction when compared with CHF. These results do not necessarily extend to other cohorts with no preexisting heart disease.

Laser Doppler imaging and capillary microscopy in ischemic ulcers.

The local distribution of laser Doppler flux (mainly thermoregulatory perfusion) and capillary density (nutritive circulation) within 25 ischemic leg ulcers and their adjacent skin were investigated. For this purpose the technique of laser Doppler imaging and capillary microscopy were applied. In each ulcer a non granulation tissue area (NGTA), a granulation tissue area (GTA) and in adjacent skin a skin area (SA) were defined. In these areas the average laser Doppler area flux (arbitrary units, AU) and the number of capillaries/mm2 were determined for each patient. The mean+/-S.D. of laser Doppler area fluxes were: NGTA 1.30+/-1.93, GTA 2.13+/-1.53 and SA 1.21+/-0.77 AU, respectively. The differences between GTA and NGTA or SA was statistically significant (p < 0.001, each) The mean+/-S.D. of capillary densities were as follows: NGTA: 0.56+/-2.06, GTA 6.76+/-8.39 and SA 16.80+/-7.38 capillaries/mm2, respectively. The following differences were statistically significant: NGTA versus GTA (p < 0.01) and SA versus NGTA or GTA (p < 0.001, each). In conclusion following characteristics of the three areas can be described: In NGTA low laser Doppler area flux is combined with very low capillary density (ulcer area without healing). In GTA the highest laser Doppler area flux of all three areas and an intermediate capillary density (wound healing) is found. In SA an intermediate laser Doppler area flux is associated with the highest capillary density of all three areas with the healing process nearly completed and no granulation tissue.

Reproducibility of laser Doppler imager flux measurements within ischemic or venous ulcers and adjacent skin.

BACKGROUND/AIMS: The laser Doppler imager (LDI) is a device that maps the local distribution of the laser Doppler flux of tissues. To facilitate the interpretation of LDI measurements, we investigated their reproducibility. METHODS: We measured 10 arterial ulcers, 10 venous ulcers and their adjacent skin by the use of a LDI. The means were calculated of individual coefficients of variation ± standard error of mean (meanCV ±SEM) of measurements on the same day, on 5 different days and at specific time points (0, 30, 60, 90 and 120 min) during the application of PGE, on 2 different days. RESULTS: The meanCV ±SEM of measurements on the same day were 9.3±0.9% (ulcer), 9.8±0.9% (skin), and on 5 different days they were 21.9±1.9% (ulcer) and 28.6±2.4% (skin). Ulcer measurements on 5 different days were significantly more reproducible than skin measurements, if differences were calculated for all 20 patients or for the 10 patients with venous ulcers separately (P<0.05). During the application of PGE, for 120 min, meanCV ±SEM ranged from 19.2±4.0% to 26.9±5.0% (ulcer) and from 20.5±4.1% to 29.5+3.9% (skin). CV of skin measurements of all 20 patients at 0 min were significantly lower than those after 120 min of PGE(1) -application (P<0.05). CONCLUSION: Our results show an excellent reproducibility of LDI measurements on a single day. The reproducibility of measurements on 5 different days or during the application of PGE1 over a period of 120 min was poorer. Because of the poorer reproducibility, more patients are needed to study long-term or drug effects.

Lupus anticoagulants: strong association with the major histocompatibility complex class II and platelet antibodies.

A relationship between the presence of platelet autoantibodies and major histocompatibilty complex class II alleles was determined in 27 patients with lupus anticoagulants. Twenty-two patients had a primary antiphospholipid syndrome' and five patients had lupus erythematosus (SLE). Platelet antibodies against the platelet glycoproteins (GP) IIb/IIIa were detectable in 20 patients. Anti-GPIb/IX or -GPIV antibodies were detectable only in patients with anti-GPIIb/IIIa antibodies. An increased frequency of HLA-DQB1*06 was demonstrable in the total patient population. The association between the lupus anticoagulants and HLA-DQB1*06 was even stronger if patients also had detectable platelet antibodies. This association was also seen if patients with a history of thromboembolic disease were considered separately. However, within the patient population there was no difference between frequencies of HLA alleles detectable platelet antibodies.

Documented sudden onset of pseudothrombocytopenia.

A 66-year-old male patient was hospitalized for severe heart failure. Within 3 days after admission his platelet count dropped from 148 x 10(9)/l to 3 x 10(9)/l. Pseudothrombocytopenia was diagnosed based on the platelet count of 3 x 10(9)/l in K3-EDTA anticoagulated blood as opposed to 110 x 10(9)/l in sodium citrate. Platelet reactive antibodies were not detectable. To the best of our knowledge, this is the first report of a documented onset of pseudothrombocytopenia.

Specificities of platelet autoantibodies in patients with lupus anticoagulants in primary antiphospholipid syndrome.

We have studied target platelet antigens in 22 patients with lupus anticoagulants and a primary antiphospholipid syndrome in order to determine whether any specificities of platelet autoantibodies are correlated with thromboembolism, and if these antibodies cross-react with phospholipids, which would suggest their role in the development of thromboembolic disease. Platelet counts were median 203 x 10(9)/l, range 100-298 x 10(9)/l. Platelet antibodies were found in six thrombocytopenic patients and in further nine patients. All these 15 patients had antibodies against GPIIb/ IIIa, five patients against GPIb/IX, and six patients against GPIV. Anti-GPIb/IX and -GPIV occurred only in combination with anti-GPIIb/IIIa antibodies. There was no correlation between the presence of detectable platelet antibodies or any of their glycoprotein specificity and thrombocytopenia or the history of a thromboembolic disease. Eluates from platelets contained only GPIIb/IIIa reactivities, but neither anti-GPIb/IX nor anti-GPIV. None of the eluates contained lupus anticoagulant activity. In one case, the platelet eluates contained anti-GPIIb/IIIa and anticardiolipin IgG antibodies. These results suggest that in patients with a primary antiphospholipid syndrome the presence of platelet autoantibodies neither indicate a risk for thromboembolic disorder nor have lupus anticoagulant activity.

[Diagnosis and therapy of Cushing syndrome]. / Diagnostik und Therapie des Cushing-Syndroms.

Current diagnostic and therapeutic options in Cushing's syndrome have been retrospectively evaluated on the basis of 40 case histories of the years 1980 to 1994. After biochemical diagnosis, several radiological methods such as 131J-cholesterol-scintigraphy and, in 1 case, selective petrosal sinus blood sampling were employed. Out of 25 patients with central Cushing's syndrome 18 were cured by transsphenoidal pituitary surgery, in 1 case in combination with "Gamma-Knife" therapy. One patient was primarily treated by bilateral adrenalectomy, 5 as second intervention following unsuccessful pituitary surgery. One patient is not fully cured at present. Adrenal cortisol-producing adenomas were successfully treated by unilateral, subtotal or bilateral adrenalectomy in 9, 1 and 2 patients, respectively. Another patient with bilateral adrenal adenomas was treated medically following unilateral adrenalectomy. One patient with a cortisol-producing adrenal carcinoma died shortly after operation. One patient with an ACTH-producing pancreatic islet cell tumor died 1 year after initial remission. Adrenalectomy is the logical therapy in adrenal cortisol-producing adenomas. Improved diagnostic and surgical techniques have reduced bilateral adrenalectomy in patients with central Cushing's syndrome to rare cases in which transsphenoidal surgery (71% success rate) is the therapy of choice.