Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients.

The proven antiangiogenic activity of zoledronic acid, a third-generation bisphosphonate widely used in bone metastatic cancer patients, led us to investigate if the vascular endothelial growth factor (VEGF)-related zoledronic acid modifications are correlated with survival advantages in advanced breast cancer patients. Forty-two consecutive breast cancer patients with scintigraphic and radiographic evidence of bone metastases were treated with a single infusion of 4 mg zoledronic acid before anticancer chemotherapy. The patients were prospectively evaluated for circulating levels of VEGF and interferon-gamma (IFN-gamma) just before and at 1, 2, 7, and 21 days after zoledronic acid infusion. Afterward, clinical outcome was prospectively monitored. The basal serum VEGF median levels were significantly decreased at each time point, but the major reduction was recorded 21 days after the infusion. In particular, 25 patients of 42 (59.5%) experienced a reduction of at least 25% in the VEGF circulating levels. In contrast, no statistically significant modifications of the IFN-gamma serum levels were recorded. We stratified patients on the basis of this VEGF reduction 21 days after the infusion. No differences in patient features were recorded between those with or without the VEGF reduction. The analysis of survival showed that patients with a reduction in the VEGF circulating levels had a longer time to first skeletal-related event (p = 0.0002), time to bone progression disease (p = 0.0024), and time to performance status worsening (p = 0.0352) than those without the VEGF reduction. No statistically significant differences were recorded in terms of overall survival and time to visceral progression. This study confirms that zoledronic acid could have an in vivo antiangiogenic property and that the VEGF modifications may represent a surrogate marker able to predict time to first skeletal-related event, time to bone progression disease, and time to worsening of performance status.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Is there an abnormal fasting duodenogastric reflux in nonulcer dyspepsia?

A quantitatively and/or qualitatively abnormal duodenogastric reflux (DGR) could be involved in the pathogenesis of nonulcer dyspepsia (NUD). The aims of this prospective study were to look for (1) a pathological DGR profile during fasting and (2) an eventual correlation between DGR profile and clinical symptoms. Twenty-six NUD patients were investigated. Seven other operated patients with a surgical procedure facilitating DGR episodes and 27 healthy volunteers served as control groups. A clinical score was determined for each patient from a standardized questionnaire. Gastric aspiration was performed for 6 hr in fasting subjects. The aspirates were pooled into 17 samples. In each sample the concentration and the output of total bile acids was determined. If the concentration was larger than 30 mol/liter in pooled samples, the concentrations of free bile acids and the distribution of the conjugated bile acids was determined. The percentage of aliquots with a total bile acid concentration larger than 50 mol/liter (without upper limit), and the percentage with a concentration larger than 2500 mol/liter was also obtained. No significant difference was demonstrated between the healthy volunteers and NUD patients, whatever the parameter considered. However, there was a significant increase in each of the quantitative parameters for the group of operated patients in comparison with the NUD patient group. No significant correlation was found between the clinical score and the DGR profile in NUD patients. Apparently, DGR episodes do not play a primary role in the pathogenesis of NUD.Part of this work was presented at the 4th European Symposium on Gastrointestinal Motility, Krakow, Poland. September 22–24, 1988.Hepatogastroenterology, 35:178, 1988 (abstract).     

Refluent testicular autotransplantation by Domini's method

Autotransplantation presently constitutes the best option for the surgical treatment of non-palpable retained intra-abdominal testes. Silber first proposed this technique in 1978; it is not suitable in children under 3 years of age because of the small caliber of the testicular artery. In 1986 Dòmini, mindful of the problem of arterial vascularisation, carried out refluent testicular autotransplantation (RTAT), where a natural anastomosis between the testicular and deferential arteries is used. Venous drainage is guaranteed by performing a microsurgical anastomosis between the internal spermatic and inferior epigastric veins.At our institution this technique has been employed since 1990, replacing staged orchidopexy. We report a 2-year experience (1990–1992) in seven children who underwent RTAT and discuss the results obtained and the technique used.     

Postzygotic instability of the myotonic dystrophy p[AGC]n repeat supported by larger expansions in muscle and reduced amplifications in sperm

We have analysed the [AGC] expansion in leucocytes, muscle and sperm from 17 individuals affected by myotonic dystrophy (DM). Skeletal muscle showed a larger repeat number than leucocytes in the same patient. A similar degree of expansion was detected in differently affected muscles of a single patient. The germline mutation ( 350 repeats) was expanded in somatic cells of the progeny in all patients examined. Our results provide evidence of an early postzygotic instability of the [AGC] repeat in DM.     

Value of culture of pus via percutaneous drainage under sonographic guidance in diagnosis and therapy of pyogenic liver abscess

Pyogenic hepatic abscess is often a serious disease, whose rates of cure are proportional to the timeliness of treatment and the correct use of antibiotics. The final choice of antibiotics should be guided by the results of a culture. Local cultures of pus are more often positive than blood cultures It is essential to plan an effective treatment regimen when dealing with immunocompromised patients. Our results, regarding 85 patients with pyogenic liver abscess, 19 of which were immunocompromised, seen at our Department from 1980 to 1992, indicate that planning the therapy on the base of blood culture alone means a 78% risk of inappropriate treatment.     

Carbon dioxide analysers: accuracy,alarm limits and effects of interfering gases

Six mainstream and twelve sidestream infrared carbon dioxide (CO₂) analysers were tested for accuracy of the CO₂ display value, alarm activation and the effects of nitrous oxide (N₂O), oxygen (O₂) and water vapour according to the ISO Draft International Standard (DIS) #9918. Mainstream analysers (M-type): Novametrix Capnogard 1265; Hewlett Packard HP M1166A (CO₂module HP M1016A); Datascope Passport; Marquette Tramscope 12; Nellcor Ultra Cap N-6000; Heilige Vicom-sm SMU 611/612 ETC. Sidestream analysers: Brüel &; Kjaer Type 1304; Datex Capnomac II; Marquette MGA-AS; Datascope Multinex; Ohmeda 4700 OxiCap (all type S1: respiratory cycles not demanded); Biochem BCI 9000; Bruker BCI 9100; Dräger Capnodig and PM 8020; Criticare Poet II; Heilige Vicom-sm SMU 611/612 A-GAS (all type S2: respiratory cycles demanded). The investigations were performed with premixed test gases (2.5, 5, 10 vol%, error ?1% rel.). Humidification (37° C) of gases were generated by a Dräger Aquapor. Respiratory cycles were simulated by manually activated valves. All monitors complied with the tolerated accuracy bias in CO₂ reading (≤ 12% or 4 mmHg of actual test gas value) for wet and dry test gases at all concentrations, except that the Marquette MGA-AS exceeded this accuracy limit with wet gases at 5 and 10 vol% CO₂. Water condensed in the metal airway adapter of the HP M1166A at 37° C gas temperature but not at 3(P C. The Servomex 2500 (nonclinical reference monitor), Passport (M-type), Multinex (S1-type) and Poet II (S2-type) showed the least bias for dry and wet gases. Nitrous oxide and O₂ had practically no effect on the Capnodig and the errors in the others were max. 3.4 mmHg, still within the tolerated bias in the DIS (same as above). The difference between the display reading at alarm activation and the set point was in all monitors (except in the Capnodig: bias 1.75 mmHg at 5 vol% CO₂) below the tolerated limit of the DIS (difference ≤ 0.2 vol%). The authors conclude that the tested monitors are safe for clinical use (except those failing the DIS limits). The accuracy of the CO₂-reading (average of mean absolute bias) is better in the M-type than in the S1- or S2- type analysers although no statistical (nor clinical) significant differences could be detected. Most manufacturers work with stricter limits than those proposed by the DIS.     

Hemodynamic effects of medical antishock trousers during mechanical ventilation

Purpose

To compare the hemodynamic effects of medical antishock trousers (MAST) inflation in mechanically ventilated patients with normal and poor left ventricular function.

Methods

Twelve patients requiring respiratory support were divided into two groups according to baseline transesophageal echocardiography (TEE) measurements: normal left ventricular dimensions and fractional area of contraction (FAC=61 ± 5%) (n=7) and dilated cardiomyopathy with reduced FAC (21 ± 1%) (n=5). All patients were studied when two successive levels of load (mild load by inflation of the leg compartment of MAST at 50 cmH₂O and high load by adding the abdominal compartment of MAST inflated at 30 cmH₂O) were applied. Global left ventricular systolic function was assessed on the TEE transgastric short-axis view. End-systolic wall stress (ESWS) was used as an indicator of left ventricular afterload.

Results

Total respiratory, lung and chest wall compliances were reduced by 48%, 51% and 27% respectively at the high load level (P < 0.05). Whereas no hemodynamic changes occurred at mild load, the high load level produced an increase in left ventricular afterload as evidenced by concomitant increases in diastolic arterial blood pressure (66 ± 6 to 79 ± 6 mmHg,P < 0.05) and ESWS (69 ± 12 to 74 ± 12 Kdyn·cm^?2·m^?2,P < 0.05). In patients with dilated cardiomyopathy, this increase in afterload impaired the left ventricular systolic function and end-systolic area increased (19.0 ± 2.5 to 21.4 ± 2.9 cm²·m^?2,P < 0.05) while FAC decreased (22 ± 2 to 16 ± 2%,P < 0.05). Left ventricular end-diastolic area remained unchanged during the study in both groups.

Conclusion

MAST inflation impairs respiratory mechanics and global left ventricular systolic function in cardiac patients without changes in left ventricular preload.