Automatic Identification of the Repolarization Endpoint by Computing the Dominant T-wave on a Reduced Number of Leads.

Electrocardiographic (ECG) T-wave endpoint (Tend) identification suffers lack of reliability due to the presence of noise and variability among leads. Tend identification can be improved by using global repolarization waveforms obtained by combining several leads. The dominant T-wave (DTW) is a global repolarization waveform that proved to improve Tend identification when computed using the 15 (I to III, aVr, aVl, aVf, V1 to V6, X, Y, Z) leads usually available in clinics, of which only 8 (I, II, V1 to V6) are independent. The aim of the present study was to evaluate if the 8 independent leads are sufficient to obtain a DTW which allows a reliable Tend identification. To this aim Tend measures automatically identified from 15-dependent-lead DTWs of 46 control healthy subjects (CHS) and 103 acute myocardial infarction patients (AMIP) were compared with those obtained from 8-independent-lead DTWs. Results indicate that Tend distributions have not statistically different median values (CHS: 340 ms vs. 340 ms, respectively; AMIP: 325 ms vs. 320 ms, respectively), besides being strongly correlated (CHS: ρ=0.97, AMIP: 0.88; P<10(-27)). Thus, measuring Tend from the 15-dependent-lead DTWs is statistically equivalent to measuring Tend from the 8-independent-lead DTWs. In conclusion, for the clinical purpose of automatic Tend identification from DTW, the 8 independent leads can be used without a statistically significant loss of accuracy but with a significant decrement of computational effort. The lead dependence of 7 out of 15 leads does not introduce a significant bias in the Tend determination from 15 dependent lead DTWs.

The surface electromyographic evaluation of the Functional Reach in elderly subjects.

This study proposes a comprehensive assessment of myoelectric activity of the main muscles involved in the Functional Reach (FR) test, in 24 elderly subjects. A specific protocol for the surface electromyography (sEMG) signal acquisition during FR-test was developed. Results show that anterior muscles activate following a caudo-cranial order. Tibialis Anterior (TA) is the first to be activated (-18.0±16.3% of the FR-period), together with Rectus Femoris (-10.4±17.9%). Then, Rectus Abdominis (19.7±24.7%) and Sternocleidomastoideus (19.9±15.6%) activate after the FR-start. Hamstrings, Soleus, and L4-level Erectores Spinae (posterior muscles) activate after the FR-start in this order (11.4±16.8%, 17.7±16.6%, and 35.2±29.0%, respectively) and remain active until the movement end. The analysis of the kinematic strategies adopted by subjects revealed an association between TA-activation patterns and two kinematic strategies (hip/mixed strategy), quantified by an increase (p<0.05) of TA-activity duration in subjects adopting the hip strategy (89.9±34.5) vs. subjects adopting the mixed strategy (27.0±16.8). This suggests that TA sEMG activity could be able to discriminate among kinematic strategies, providing different information on balance control. Thus, the present analysis represents the first attempt to quantify the sEMG activity during FR-test in elderly subjects, providing an early contribution in building a reference frame for balance assessment in clinical context.

A markerless system based on smartphones and webcam for the measure of step length, width and duration on treadmill.

BACKGROUND AND OBJECTIVE: A markerless low cost prototype has been developed for the determination of some spatio-temporal parameters of human gait: step-length, step-width and cadence have been considered. Only a smartphone and a high-definition webcam have been used. METHODS: The signals obtained by the accelerometer embedded in the smartphone are used to recognize the heel strike events, while the feet positions are calculated through image processing of the webcam stream. Step length and width are computed during gait trials on a treadmill at various speeds (3, 4 and 5 km/h). RESULTS: Six subjects have been tested for a total of 504 steps. Results were compared with those obtained by a stereo-photogrammetric system (Elite, BTS Engineering). The maximum average errors were 3.7 cm (5.36%) for the right step length and 1.63 cm (15.16%) for the right step width at 5 km/h. The maximum average error for step duration was 0.02 s (1.69%) at 5 km/h for the right steps. CONCLUSION: The system is characterized by a very high level of automation that allows its use by non-expert users in non-structured environments. A low cost system able to automatically provide a reliable and repeatable evaluation of some gait events and parameters during treadmill walking, is relevant also from a clinical point of view because it allows the analysis of hundreds of steps and consequently an analysis of their variability.

Muscle activation patterns related to diabetic neuropathy in elderly subjects: A Functional Reach Test study.

BACKGROUND: This study was designed to assess, in healthy elderly, non-neuropathic and neuropathic diabetic subjects, the activation patterns of the main muscles involved in the Functional Reach Test, a well-recognized method to identify elderly subjects at risk of balance impairments. METHODS: Surface electromyographic analysis of Sternocleidomastoideus, Rectus Abdominis, Erectores Spinae at L4 level, Rectus Femoris, Hamstrings, Tibialis Anterior and Soleus was performed in 10 healthy, 10 diabetic non-neuropathic and 10 diabetic neuropathic subjects. FINDINGS: Results showed that in every group the first motor is Tibialis Anterior, that is recruited before the start of the test. An earlier activation of Tibialis Anterior (P<0.05) was detected in diabetic neuropathic (ON at -24% of the test period), compared with healthy (-11%) and diabetic non-neuropathic (-13%) groups. A significant earlier activation of Sternocleidomastoideus and Rectus Abdominis was found in diabetic neuropathic group, only with respect to healthy subjects. No significant difference was found in Rectus Femoris, Soleus, Hamstrings an Erectores Spinae onset among the three groups. INTERPRETATION: Results suggest a trend of diabetic neuropathic patients in earlier anticipation of the activation of the anterior body-muscles. In particular, the earlier onset of Tibialis Anterior is likely to be performed to adjust the movement timing and to compensate for the delay in the recruitment of the motor units. This anticipation might be involved in the altered postural control with increased balance impairment detected in diabetic neuropathic patients, and thereby it might also be proposed as an index of neuropathy, evidenced in a simple and non-invasive manner.

Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer.

PURPOSE: Evidences have shown that neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with cancer. We wanted to test the prognostic significance of NLR in prostatic cancer of patients who are candidate to radical prostatectomy. METHODS: We have considered 731 patients. Complete demographic data including age, tumor stage, Gleason score, complete blood count and serum biochemical profile were collected. Pre-treatment percentage of neutrophils and NLR were considered, and correlated with patients data and recurrence free survival. RESULTS: 389 patients were evaluated, mean age 65 years, mean follow-up 51.5 months, mean recurrence free survival 51.3 months. Total neutrophil count does not correlate with biochemical recurrence and disease free survival. Patients with a value higher of 60% of neutrophils are more likely to have a recurrence. Patients with a total lymphocyte count <1,500 have a higher rate of relapse. NLR was not correlated with baseline total PSA, with Gleason score and with pathological stage; patients with a NLR >3 has a higher incidence of recurrence. In multivariate analysis including age, total PSA and NLR, NLR is the most important factor able to predict recurrence. There are some limitations to this study; first, this is a retrospective study, and the total number of patients analyzed is relatively small. CONCLUSIONS: Our study suggests that pre-treatment NLR may be associated with disease free survival in patients with prostate cancer, and could be introduced in clinical practice. NLR has the advantage of low economic cost and wide availability.

The segmented-beat modulation method for ECG estimation.

Electrocardiographic (ECG) tracings corrupted by noise with frequency components in the ECG frequency band, may result useless unless appropriately processed. The estimation of the clean ECG from such recordings, however, is quite challenging; being linear filtering inappropriate. In the common situations in which the R peaks are detectable, template-based techniques have been proposed to estimate the ECG by a template-beat concatenation. However, such techniques have the major limit of not being able to reproduce physiological heart-rate and morphological variability. Thus, the aim of the present study was to propose the segmented-beat modulation method (SBMM) as the technique that overcomes such limit. The SBMM is an improved template-based technique that provides good-quality estimations of ECG tracings characterized by some heart-rate and morphological variability. It segments the template ECG beat into QRS and TUP segments and then, before concatenation, it applies a modulation/demodulation process to the TUP-segment so that the estimated-beat duration and morphology adjust to those of the corresponding original-beat. To test its performance, the SBMM was applied to 19 ECG tracings from normal subjects. There were no errors in estimating the R peak location, and the errors in the QRS and TUP segments were low (≤65 µV and ≤30 µV, respectively), with the former ones being significantly higher than the latter ones. Eventually, TUP errors tended to increase with increasing heart-rate variability (correlation coefficient: 0.59, P<;10(-2)). In conclusion, the new SBMM proved to be a useful tool for providing good-quality ECG estimations of tracings characterized by heart-rate and morphological variability.

A stereophotogrammetric-based method to assess spatio-temporal gait parameters on healthy and Parkinsonian subjects.

Generally, the study of gait requires the detection of successive heel contacts and toe-off instants. Traditional gait analysis methods obtain these gait events using dynamometric platforms together with stereophotogrammetric data. Usually, are kept valid only those walking trials where the subjects step on each platform by only one foot. For subjects suffering from walking impairments it is very difficult or sometimes impossible to walk naturally and step properly on the dynamometric platforms. The aim of the present study is to propose a new method to identify, in an automatic manner, the initial contact (IC) and the toe-off (TO) time instants using only stereophotogrammetric data and a classic gait analysis protocol. The assessment of spatio-temporal gait variables during natural walking is also performed. The study consisted in analyzing healthy and Parkinsonian elderly subjects. The reliability of the proposed stereophotogrammetric-based method was tested by direct comparison with the IC and TO instants determined by the dynamometric platform data. The absence of any statistically significant differences between the values estimated by the two different modalities, highlights the reliability of the proposed method in the assessment of these two gait events. Results underline, as expected, the reduction of walking velocity in pathological patients during free ambulation. The present study proposes this method as a valid alternative to the traditional technique that use dynamometric platforms to identify main gait events, for subjects unable to walk naturally and to step properly on the platforms.

Assessment of the activation patterns of the muscles involved in the FR test in diabetic neuropathic patients.

This study was designed to assess, in elderly neuropathic diabetic (DN) patients, the activation patterns of the main muscles involved in the Functional Reach (FR) Test, a well-recognized method to identify elderly subjects at risk of recurrent falls. Surface electromyographic (sEMG) analysis of Sternocleidomastoideus (Scm), Rectus Abdominis (RAbd), Erectores Spinae at L4 level (L4), Rectus Femoris (RF), Hamstrings (Ham), Tibialis Anterior (TA) and Soleus (Sol) was performed to this aim. Results in DN patients are compared with a control group (CH) of healthy age-matched subjects. In DN patients, TA is identified as the first muscle to be recruited (ON at -34% of the FR-period) before the movement start, in order to initiate the body forward displacement. RF is the first muscle to be recruited after TA and, togheter with RAbd, showed a progressive earlier onset from CH group. Sol and Ham (ON after the FR-start), followed by L4, act mainly as tonic muscles, opposing the movement and preventing falls. Compared to the CH group, the DN subjects show an anticipatory recruitment (-34%±6%) of TA, showing a statistically significant difference (p<;0.05) in comparison to CH group, together with the Scm activation. Results suggest a trend of DN patients in anticipating the activation of the anterior muscles of the body. This is likely due to an attempt to compensate the neuropathy-related proprioception dysfunction and to adjust the movement timing. In conclusion, the present study shows that sEMG is a suitable tool to deepen the interpretation of the FR-test execution and proposes the earlier start of TA as a possible element to identify the presence of neuropathy in diabetic subjects.

Evaluation of gender-related differences in co-contraction activity of shank muscles during gait.

This study aims to investigate the possible differences between genders in co-contractions of tibialis anterior (TA) and gastrocnemius lateralis (GL), during walking at self-selected speed. To this purpose, the statistical gait analysis (SGA) was performed on seven female (F-group) and seven male (M-group) adults. SGA is a recently developed methodology for the characterization of gait, by averaging spatiotemporal and electromyographic parameters over hundreds of strides per subject. Co-contractions were assessed as the overlapping periods between TA and GL activity. Results showed that four co-contraction intervals are present during gait cycle in both groups. No relevant differences between genders were detected in onset-offset time instants of co-activations or in their temporal length. On the contrary, significant differences were observed in the number of strides where each co-contraction happens (i.e. the occurrence frequency). All the four co-contraction intervals result significantly (p<;0.05) more recurrent in females compared to males. This outcome suggests a larger presence of co-contraction activity in females walking, related to a female tendency for a more complex muscular strategy during gait. These findings could be useful to better understand gender differences in walking mechanisms and to develop separated normal walking reference frames for males and females.

Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma.

BACKGROUND: Everolimus is a mammalian target of rapamycin inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the outcome of patients treated with everolimus for mRCC. METHODS: Ninety-seven patients with mRCC were treated with everolimus till April 2013 in our institutions. Patients were stratified in two groups with NLR >3 (Group A) vs <3 (Group B). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Gender, age, Motzer prognostic group, PFS on first-line therapy, neutrophilia and NLR were included in the Cox analysis to investigate their prognostic relevance. RESULTS: Median OS and PFS were 10.6 and 5.3 months, respectively. Median OS was 12.2 months in Group A and 24.4 months in Group B (P=0.001). Median PFS was 3.4 months in Group A and 9.9 months in Group B (P<0.001). At multivariate analysis, only Motzer prognostic group and NLR were independent prognostic factors for OS and PFS. CONCLUSION: Pre-treatment NLR is an independent prognostic factor for patients with mRCC treated with second- or third-line everolimus. This should be investigated and validated in prospective studies.

Pazopanib and sunitinib trigger autophagic and non-autophagic death of bladder tumour cells.

BACKGROUND: Tyrosine kinase inhibitors (TKI) such as sunitinib and pazopanib display their efficacy in a variety of solid tumours. However, their use in therapy is limited by the lack of evidence about the ability to induce cell death in cancer cells. Our aim was to evaluate cytotoxic effects induced by sunitinib and pazopanib in 5637 and J82 bladder cancer cell lines. METHODS: Cell viability was tested by MTT assay. Autophagy was evaluated by western blot using anti-LC3 and anti-p62 antibodies, acridine orange staining and FACS analysis. Oxygen radical generation and necrosis were determined by FACS analysis using DCFDA and PI staining. Cathepsin B activation was evaluated by western blot and fluorogenic Z-Arg-Arg-AMC peptide. Finally, gene expression was performed using RT-PCR Profiler array. RESULTS: We found that sunitinib treatment for 24 h triggers incomplete autophagy, impairs cathepsin B activation and stimulates a lysosomal-dependent necrosis. By contrast, treatment for 48 h with pazopanib induces cathepsin B activation and autophagic cell death, markedly reversed by CA074-Me and 3-MA, cathepsin B and autophagic inhibitors, respectively. Finally, pazopanib upregulates the α-glucosidase and downregulates the TP73 mRNA expression. CONCLUSION: Our results showing distinct cell death mechanisms activated by different TKIs, provide the biological basis for novel molecularly targeted approaches.

VEGF and VEGFR polymorphisms affect clinical outcome in advanced renal cell carcinoma patients receiving first-line sunitinib.

BACKGROUND: Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients. METHODS: A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS. CONCLUSIONS: In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.

Twice-daily dosing of temozolomide in combination with fotemustine for the treatment of patients with refractory glioblastoma.

Alkylating agents, such as temozolomide (TMZ) and fotemustine (FTM) are widely used in recurrent glioblastoma (GBM) regimes. Several strategies have been proposed to prevent resistance to these agents, by combining or sequencing them. We report the results of a pilot study of patients with refractory GBM receiving a regime of twice-daily dosing of temozolomide administered on day 1, (with an initial oral dose of 200 mg/m(2) and a second oral dose of 75 mg/m(2) 12 h later), followed by fotemustine in a single i.v. infusion at 75 mg/m(2) on day 2, repeated every four weeks. Enrolment was stopped at 15 patients due to lack of effectiveness of this schedule for patients with GBM. Toxicity was mild, with no grade 4 side effects reported. Results indicate that our temozolomide -FTM combined schedule is not effective, although well tolerated, in non responsive patients with GBM. Further strategies are required to improve the outcome of these patients.

Stroke unit: a cardio-cerebral approach.

Stroke units are special units where stroke patients receive, simultaneously, medical and physical treatment. Compared to general neurological and medical wards, stroke units show a significant reduction of short- and long-time mortality, and an improvement of long-term quality of life. Nevertheless, mortality in these units is still high (1-year mortality approximately 32%; 5-year mortality degrees 60%), and consequently, new approaches are needed to control stroke parameters during the acute phase, with the goal to reduce mortality rates. The philosophy of our stroke unit in Fermo (Italy), is to establish a strong association between heart and brain care by approaching each stroke patient as a cardiocerebral patient. In particular, we perform 12-lead Holter ECG monitoring, to prevent the vicious cycle affecting correct cerebral and cardiac functions, and to react to cardiac complications, mostly arrhythmias, that can worsen cerebral damage. Holter ECG monitoring allows a fast physiotherapeutic approach, a better evaluation of metabolic parameters, and collectively, a better global evaluation of the patient during the acute phase of disease. In two years of activity, 80 patients that were admitted to our stroke unit during 1998, and treated as cardio-cerebral patients, were followed-up. This combined treatment decreased the 1-year mortality rate by about 30%, in comparison with the 22% mortality rate reported in the literature. These results confirm the validity of stroke units, as well as of our approach based on cardio-cerebral control of each stroke patient.

Beat-to-Beat repolarization variability in LQTS patients with the SCN5A sodium channel gene mutation.

Current techniques evaluating beat-to-beat variability of repolarization rely on accurate determination of T wave endpoints. This study proposes a T wave endpoint-independent method to quantify repolarization variability in a standard 12-lead ECG using a wavelet transformation. Our method was used to identify repolarization variability in long QT syndrome patients (LQTS) with the SCN5A sodium channel gene mutation. Using wavelet transformations based on the second Gaussian derivative, we evaluated repolarization variability in 11 LQTS patients with the mutation, 13 noncarrier family members, and 28 unrelated healthy subjects. Time-domain repolarization variability parameters (SDRTo, SDRTm) and wavelet parameters describing temporal (beat-to-beat) variability of repolarization in time (TVT) and in amplitude (TVA) were analyzed. Reproducibility of wavelet parameters and relationship of wavelet-based variability with heart rate and preceding RR interval were investigated. The wavelet-based method quantified beat-to-beat variability of the entire repolarization segment (regardless of QT interval identification) providing insight into variability in repolarization morphology. Our method showed that SCN5A carriers have significantly increased repolarization variability in amplitude (23% +/14% vs 8 +/- 4%, P < 0.001) and in time (14 +/- 17 ms vs 3 +/-2 ms, P < 0.004) compared to noncarriers. Variability of repolarization amplitude was found to be heart rate dependent with variability decreasing with increasing heart rate. Relative error describing reproducibility of TVA and TVT was < or = 5% and < or =10%, respectively. Our method quantifies repolarization variability in amplitude and in time without the need to identify T or U wave endpoints. Wavelet-detected repolarization variability contributes to phenotypic identification of SCN5A carriers, with more pronounced beat-to-beat variability in repolarization amplitude than in time.

Time-domain analysis of beat-to-beat variability of repolarization morphology in patients with ischemic cardiomyopathy.

There is growing evidence that beat-to-beat changes in ventricular repolarization contribute to increased vulnerability to ventricular arrhythmias. Beat-to-beat repolarization variability is usually measured in the electrocardiogram (ECG) by tracking consecutive QT or RT intervals. However, these measurements strongly depend on the accurate identification of T-wave endpoints, and they do not reflect changes in repolarization morphology. In this article, we propose a new computerized time-domain method to measure beat-to-beat variability of repolarization morphology without the need to identify T-wave endpoints. The repolarization correlation index (RCI) is computed for each beat to determine the difference between the morphology of repolarization within a heart-rate dependent repolarization window compared to a template (median) repolarization morphology. The repolarization variability index (RVI) describes the mean value of repolarization correlation in a studied ECG recording. To validate our method, we analyzed repolarization variability in 128-beat segments from Holter ECG recordings of 42 ischemic cardiomyopathy (ICM) patients compared to 36 healthy subjects. The ICM patients had significantly higher values of RVI than healthy subjects (in lead X: 0.045 +/- 0.035 vs. 0.024 +/- 0.010, respectively; P < .001); 18 (43%) ICM patients had RVI values above the 97.5th percentile of healthy subjects (>0.044). No significant correlation was found between the RVI values and the magnitude of heart rate, heart rate variability, QTc interval duration, or ejection fraction in studied ICM patients. In conclusion, our time-domain method, based on computation of repolarization correlation indices for consecutive beats, provides a new approach to quantify beat-to-beat variability of repolarization morphology without the need to identify T-wave endpoints.

ECG features of microvolt T-wave alternans in coronary artery disease and long QT syndrome patients.

UNLABELLED: T-wave alternans (TWA) is a marker of myocardial electrical instability. We compared ECG features of microvolt TWA in coronary artery disease (CAD) and long QT syndrome (LQTS) patients. METHOD: The study populations consisted of 43 CAD and 39 LQTS patients. TWA was detected in resting Holter recordings using the new correlation method (CM). After preprocessing to adjust for RR variability and respiratory modulation, CM was used to quantify TWA amplitude (A(CM)), duration (N(CM)), and magnitude (MAG(CM); defined as the product of A(CM) and N(CM)). RESULTS: TWA was detected in 19 (44%) CAD and 17 (44%) LQTS patients. TWA was associated with longer RR intervals (P = 0.006) and had larger magnitudes (P = 0.067) in LQTS than CAD patients. The TWA was identified as transient (nonstationary) in 15 of 19 (79%) TWA-positive CAD patients, and in 8 of 17 (47%) TWA-positive LQTS patients (P = 0.047). CONCLUSIONS: The frequency of TWA detected with CM is similar in LQTS and CAD patients. TWA is larger in LQTS than in CAD patients, whereas TWA is more frequently transient (nonstationary) in LAD than LQTS patients. In LQTS patients, but not in CAD patients, a longer RR is associated with TWA, indicating different electrophysiologic mechanisms in the two pathologies.

Bipolar Electrodes in the Treatment of Ectopic Pregnancy

During operative laparoscopy in the management of the ectopic pregnancy, conservative treatment consisting of linear salpingotomy and extraction of trophoblast must be carried out systematically. Until recently, tubal incision was performed with monopolar delivery systems. Bipolar electrosurgery has been used for many years, but is limited to coagulation. We applied bipolar technology in the conservative treatment of ectopic pregnancy. The instrument we used for the salpingotomy consisted of disposable Bilap needle or hook electrodes with shaft diameter of 5 mm and working length 33 cm. The trophoblast was extracted with a hydrodissection pump provided with 10- or 5-mm probes without irrigation holes. The electrodes were connected to an electrosurgical generator with maximum cutting power of 70 W. This system offers cutting in bipolar applications that are designed to eliminate current passing through tissues other than those selected. The conductive electrodes are closely spaced, reducing the energy requirements and power delivered to the surrounding tissue. The operative procedure was performed in 12 women. We had no persistent trophoblastic proliferation, and no patient required additional treatment.

ACTH 1-17 effects in oncology.

Since November 1981, 90 cancer patients treated with cytotoxic chemotherapy (CMF, FAC, FAM) have been studied to evaluate whether the administration of Synchrodyn 1-17, 100 micrograms i.m. a day for 15 consecutive days, could reduce some side effects caused by the cytotoxic drugs. Nausea, vomiting and weakness which are the most frequent side effects generally found to be very upsetting to patients, were less pronounced in the treated patients than in patients treated with a placebo. The performance status was not modified by the treatment. Skin pigmentation was noted in the majority of cases and it appeared to be related to the sustained treatment with high dosages of the peptide. Some side effects were observed in the treated patients such as sodium retention and hypertension, hyperglycemia. Successively we have begun to study the circadian rhythm of the cortisol, which often changes during the advanced stages of the illness and which chemotherapy does not seem to alter.