Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay

An in vitro assay, which evaluates drug effect on ³H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activities were generally observed for DDP and CHIP, whereas CBDCA exhibited a lower, although not significantly different cytotoxicity on breast and ovarian cancers. The relative activities of Platinum analogues were analyzed on 239 two-way drug sensitivity comparisons. The overall agreement rates ranged from 80.2 to 83.9% for the different comparisons. High coresistance, from 61.1 to 93.8%, was observed for all the comparisons, regardless of the tumor type. Cosensitivity rates were poor for breast and ovarian cancers, from 0 to 37.5%, whereas for melanomas an association in sensitivity was observed in 80% of the cases.     

Assessment of split renal function with99mTc-aprotinin

The aim of this work is to correlate the net kidney uptake of^99mTc-aprotinin (TcA) in 103 subjects with separate effective renal plasma flow (ERPF) and some blood chemistry parameters at 90, 180, and 360 min postinjection both in the normal and diseased kidney. Correlations found with separate ERPFs are highly significant at any time (P < 0.001). However, although the slope of the regression line is steeper at 180 min,r tends to deteriorate slightly with time postinjection and a higher intercept on they axis: this pattern is more pronounced if diseased kidneys are considered separately. The following are probably related to the renal handling of TcA: (1) Early scans better reflect blood flow to the kidney, while later scans are more related to the metabolism/excretion tubular mechanisms; (2) correlations found with urea, creatinine, urea clearance, and creatinine clearance are highly significant at any time; (3) in 20 additional patients with diseased kidneys, renal uptake measurements done 360 min postinjection first with TcA and then with DMSA showed better correlations with ERPF employing TcA. Our results indicate that TcA is a feasible indicator of split renal function even at 90 min postinjection when a scan is easily carried out on an outpatient basis.This paper was in part presented at the European Nuclear Medicine Congress, August 14–17, 1984, Helsinki, Finland     

Uptake and intracellular distribution of idarubicin in secondary cultures of normal and neoplastic urothelium

This study analyzes the uptake and endocellular distribution of idarubicin (IDA) in normal and neoplastic urothelial secondary cultures in relation to the changes in concentration and time of exposure. The urothelial lines were isolated by Freshney's method from biopsy fragments taken from five patients with superficial bladder cancer. Pharmacological experiments were carried out on subcultures previously immunophenotypically characterized and did not exceed ten passages. The uptake and endocellular distribution of IDA was analyzed by densitometric image analysis on cells treated for 10, 20, 30 and 60 min and 2 h with scalar dosages from 10 ng/ml to 2430 ng/ml. Microscopic observations and densitometric analyzes revealed that in the cells treated with IDA, fluorescence was higher in the cytoplasm compared to the nucleus and increased with the change in dosage. Moreover, densitometric data showed that IDA uptake in the first 20 min was higher in the neoplastic cells, but after that period its behavior became heterogeneous at 30 and 60 min, while at 2 h there was an inversion of the trend. These results suggest that the in vitro cytotoxicity should be evaluated in order to verify whether the elevated uptake of IDA in the first 20 min of treatment is really correlated to a more elevated toxicity in the neoplastic cells with respect to the normal cells. This is presently under investigation.     

Total extrusion of the talus: A case report

Total extrusion of the talus without recovery of the bone is a very unusual injury. The authors present a case of a 25-year-old man who sustained an open total enucleation of the talus in a motorcycle accident. The talus was not recovered at the scene of the accident. An immediate tibiocalcaneal stabilization was performed by using an external fixator. In the postoperative period, a polymicrobic infection was observed and treated with parenteral antibiotics. Nine months after injury, the patient developed an infection of both the empty space and the distal third of the tibia. A wound debridement with tibial sequestrectomy and insertion of gentamicin-impregnated polymethylmethacrylate beads was performed. Three months later, after multiple negative bacteriologic examinations, a tibiocalcaneal arthrodesis with staples and autogenous bone graft was performed. Because of a pseudoarthrosis, the patient underwent a revision of the arthrodesis by retrograde tibiocalcaneal nailing, achieving clinical and radiographic success. The definitive treatment of total enucleation of the talus is still controversial because of its rarity and the high rate of complications, such as avascular necrosis, osteomyelitis, and ankle stiffness. In this case, without recovery of the talus, retrograde nailing afforded good stability by bypassing the bone defects.     

Treatment of Status Epilepticus in Adults: Guidelines of the Italian League Against Epilepsy

Summary:  Status epilepticus (SE) is a medical emergency which can lead to significant morbidity and mortality and requires prompt diagnosis and treatment. SE is differentiated into generalized or partial SE on the basis of its electro-clinical manifestations. The guidelines for the management of SE produced by the Italian League against Epilepsy also distinguish three different stages of SE (initial, established and refractory), based on time elapsed since the onset of the condition and responsiveness to previously administered drugs. Treatment should be started as soon as possible, particularly in generalized convulsive SE, and should include general support measures, drugs to suppress epileptic activity and, whenever possible, treatments aimed at relieving the underlying (causative) condition. Benzodiazepines are the first line antiepileptic agents, and i.v. lorazepam is generally preferred because it is associated with a lower risk of early relapses. If benzodiazepines fail to control seizures, i.v. phenytoin is usually indicated, though i.v. phenobarbital or i.v. valproate may also be considered. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. In refractory SE, general anesthesia may be required. Propofol and thiopental represent first line agents in this setting, after careful assessment of potential risks and benefits.     

Cancer risk in farmers: Results from a multi-site case-control study in north-eastern italy

The relationship between farming and cancer risk was investigated in an integrated series of case-control studies conducted from 1985 to 1991 in the Friuli Venezia Giulia region, north-east Italy. Patients with cancer of the oral cavity and pharynx, larynx, oesophagus, colon and rectum, pancreas, breast, thyroid gland, kidney and urinary tract, bladder, prostate, soft-tissue sarcomas, Hodgkin's diseases, non-Hodgkin's lymphomas and multiple myelomas, and controls admitted to hospital for acute, non-neoplastic conditions, were interviewed. For males, a significantly elevated relative risk was seen for oral cavity and pharynx. Farming, however, was associated with a significant protection against cancer of the colon and rectum and bladder. In females, only one significant association emerged, for multiple myeloma. A few significant interactions between cancer risk and year of birth (i.e., before 1930 or 1930 and after) were observed. The risk of cancer of the larynx was significantly elevated in younger male farmers but not in older ones. Our multi-site case-control study confirms that farmers have, for some cancer sites, a distinctive pattern. Excesses of cancer of the oral cavity and pharynx in farmers are characteristic of the present study area and, possibly, of similar European rural populations who have in common high levels of alcohol consumption and, at least in the past, unbalanced diets.     

Tension-free vaginal tape for the treatment of urodynamic stress incontinence with intrinsic sphincteric deficiency

The purpose of this study was to evaluate the outcome of tension-free vaginal tape (TVT) procedure in women with urodynamic stress incontinence diagnosed as having intrinsic sphincteric deficiency (ISD). The combination of a maximal urethral closure pressure <20 cm H₂O and a Valsalva leak point pressure <60 cm H₂O was considered as diagnostic of ISD. Subjects with detrusor overactivity on preoperative urodynamics were excluded. A total of 35 patients with both low closure pressure and leak point pressure were enrolled. Bladder perforation occurred in three (8.6%) cases. Postoperative urinary voiding difficulties occurred in nine (25.7%) women. Two patients underwent surgical detension of the tape, with complete resolution of urinary retention and no relapse of incontinence. Women with postoperative voiding dysfunction had a significantly lower detrusorial pressure at the peak flow on preoperative urodynamics compared to those who voided efficiently after TVT. The mean (range) follow-up time was 12.5 months (3–36). The objective cure rate for stress incontinence was 91.4%. Two of the three (66%) patients in whom the TVT procedure failed had a fixed urethra. De novo urge incontinence was found in five (14.3%) patients.     

Coronary flow characteristics after a Bentall procedure with or without sinuses of Valsalva.

OBJECTIVES: The sinuses of Valsalva are known to contribute to the normal function of the aortic valve. Little is known about their role in promoting coronary artery blood flow. The aim of this study was to compare coronary artery flow characteristics among patients undergoing a Bentall operation by means of a conventional cylindrical Dacron conduit or with a new conduit with pseudosinuses of Valsalva or in patients retaining their natural sinuses of Valsalva after aortic valve and supracoronary ascending aorta replacement. METHODS: One year after a Bentall procedure with a standard cylindrical Dacron conduit (7 patients, group A) or with the new conduit (7 patients, group B), or after aortic valve and ascending aortic replacement (control group, 7 patients, group C) coronary flow velocity reserve and diastolic to systolic time integral ratio at baseline and after maximal hyperemia (with 40 microg of adenosine) were assessed by using a 0.014-in. Doppler guidewire positioned in the middle portion of the left anterior descending coronary artery. All patients were in NYHA class I, sinus rhythm and free of coronary disease. RESULTS: Arterial blood pressures and heart rate were comparable among groups. Intracoronary Doppler measurements did not show any significant difference in coronary vascular reserve between the three groups (3.6+/-0.4 vs 3.1+/-0.7 vs 3.7+/-0.5, P = 0.2). A greater diastolic component at baseline was present in group B patients (5.5+/-1.9 vs 3.5+/-0.9 in group A and 3.7+/-0.9 in group C, P = 0.024). After maximal hyperemia the diastolic component increased slightly in group A patients (8%) while both in groups B and C significantly decreased (-15 and -20%, respectively) (P = 0.017). CONCLUSIONS: The presence of pseudosinuses of Valsalva does not influence coronary flow reserve. After maximal coronary vasodilation the increase in the systolic component of coronary flow is more evident in the presence of sinuses or pseudosinuses of Valsalva, thus suggesting that coronary flow pattern may be affected by the presence of sinuses.