Aim of the present study was to compare the effect of timolol and carteolol monotherapy on retinal blood flow hemodynamic parameters and contrast sensitivity in POAG patients in order to evaluate the possible neuroprotective effects of ISA activity. Three homogeneous groups were considered. The first group (22 POAG eyes) underwent timolol monotherapy; the second group (18 POAG eyes) underwent carteolol monotherapy; the last group (20 healthy eyes) was the control group. All patients underwent a complete ophthalmological examination, hemodynamic evaluation with HRF and contrast sensitivity measurement with MAV. Contrast sensitivity in both POAG groups was significantly lower for all spatial frequencies (p < 0.01). In the carteolol group contrast sensitivity was higher than timolol group at 0.5 VA (p < 0.01). Hemodynamic parameters (flow and volume) were statistically higher in the carteolol group than in the timolol group. The results show a positive effect of carteolol on functional (contrast sensitivity) and hemodynamic parameters most likely due to the ISA activity of this molecule.

The diagnosis of primary open-angle glaucoma (POAG) is based on the coexistence of an intraocular pressure (IOP) increase, perimetric alterations and morphological alterations to the optic nerve head and the retinal nerve fibre layer. Studies published in the literature (Sommer 1979; Pederson & Anderson 1980; Caprioli 1989; Tuulonen & Airaksinen 1991; Zeyen & Caprioli 1993; Caprioli 1996) have pointed out that the anatomical changes to the optic disk and the retinal nerve fibre layer may precede the perimetric deficits by years. From when the pharmacological treatment of ocular hypertension in its initial stages showed it could slow down or even block the progression of the disease (Mao 1991; Chauhan and Drance 1992; Migdal 1994), it has been imperative to make the diagnosis of glaucoma in its initial phase. To do this, in addition to the perimetric examination, there are now the interesting prospectives of the methods using computed digital analysis of the optic nerve head and the retinal nerve fibre layer, among which the Heidelberg retina tomograph (HRT) is one that furnishes a detailed, reproducible and above all objective evaluation. This work was undertaken to evaluate the changes in the morphology of the optic nerve head and retinal fibre layer as well as in the visual field in eyes with ocular hypertension or POAG in its initial phase. Our research was conducted on 17 patients (24 eyes) with a mean age of 62.0 ± 10.7 years in our out-patient glaucoma centre at the eye clinic of the University of Turin who were found to have IOP values >22 mmHg. All the patients had a complete oculistic check and morphological examination of the optic disk and the retinal nerve fibre layer by the Heidelberg retina tomograph (HRT software 2.01) with a visual field of 15° × 15°. Three series of images were recorded for each eye. For analysis purposes, a topographic image created by the computer representing the mean of the three images obtained was used and, onto this, an expert examiner drew the contour line of the internal edge of the Elschnig scleral ring. A computed visual field examination by the perimeter OCTOPUS 2000 (program G1, central 30°, Peritrend analysis) was also made. All the patients had had at least 2 previous examinations with values of RF < 15%. The inclusion and exclusion criteria for enrolment in the study were as follows. Inclusion: IOP values >22 mmHg without therapy; visual acuity values ≥8/10; transparent dioptric means; MD < 6 dB; good collaboration at the HRT examination; good collaboration at the perimetric examination (RF < 15%). Exclusion: congenital malformation of the ocular apparatus; opacity of the dioptric means; presence of elevated refractive defects (>±3D for myopia and hypermetropia and >±1.5D for astigmatism); previous vascular and/or neurological pathologies of the retinal vessels and/or the optic nerve; impossibility of lending a suitable collaboration in the perimetric and morphological examinations; heavy smoking (>15 cigarettes/day); heavy drinking (>60 g/day alcohol). In 7 (29.16%) of the 24 eyes enrolled, there were no visual field alterations at base time. Mean IOP base values were 25.15 ± 3.21 mmHg. All the patients were prescribed a local antiglaucoma therapy. After a mean follow-up period of 426.6 ± 161.2 days during which the patients were given routine checks which always showed good tonometric control (IOP < 20 mmHg), the optic disk morphological and perimetric examinations were repeated. With regard to the HRT, those parameters were analysed that, on the basis of the data in the literature and our personal experience, were known to be of greater sensitivity and specificity: CA, C/D ratio, RA, RV, CSM, mRNFLt and RNFLcsa. As to the perimetric indices, we considered the mean defect (MD) and the defect corrected variance (CLV). In addition, an analysis by sector was made for both the morphological and the functional data, dividing the disk into 4 quadrants (0–90°, 90–180°, 180–270°, 270–360°). First, we analysed the data overall by Student's t-test in order to find out if the HRT parameter values were subject to significant modifications between the first and second examinations, independently of the follow-up time between them. Then, for the disk HRT parameters overall, the anova was calculated for corrected repeated measurements for the 2 subgroups of eyes with: subgroup 1 – mean follow-up between 161 and 450 days; subgroup 2 – mean follow-up between 451 and 755 days. The statistically significant threshold was fixed at 5% (P < 0.05). Also evaluated was the correlation between the anatomic and the functional data relating to the optic disk totally and to the 4 quadrants by Pearson's r test. In all the eyes, an increase of the mean defect over base time was observed (MD from 2.5 ± 1.8 dB to 4.0 ± 1.4 dB; +37.5%) and also of the defect corrected variance (CLV from 2.8 ± 1.7 dB to 4.49 ± 4.49 dB; +37.63%). The data obtained were statistically significant (P < 0.05). In particular, a functional damage (MD > 2 dB) was found in 7 eyes with hypertension. In so far as sector analysis was concerned, the superior temporal proved to have the most functional deficit (MD from 3.1 ± 1.9 dB to 4.3 ± 2.0 dB, +27.90%; P < 0.05). Base time HRT parameters are exhibited in Table 1. At follow-up end, there was a tendency to RNFL thinning and optic disk morphology changes towards glaucoma, also confirmed by sector analysis. The anova analysis results for repeated measurements (F) showed the variations to be not statistically significant (Table 2). There were good correlations at base time between MD and CA (r: 0.32), C/D ratio (r: 0.31) and CSM (r: 0.53). Data relating to the 4 quadrants showed a good correlation between MD and all the HRT parameters considered in the TS sector. So far as the CLV was concerned, there was a good correlation for all the parameters with the exception of CA and C/D ratio. At follow-up end, there was found an increase in the values of the perimetric indices, in particular the MD which was statistically significant. In 7 eyes which had normal visual field at base time there were found glaucoma-type changes. The optic disk and nerve fibre layer morphology had not changed significantly. The evolution of the functional damage might very possibly be a late consequence of the morphological changes already present at base time even in the ocular hypertensive eyes. That no significant changes were found in the HRT parameters might be due to the good tonometric compensation obtained through the local therapy. Further data to confirm or belie these hypotheses may be had by continuing to monitor these patients.

The activity of the combination of intravenous docetaxel 75 mg/m2 plus cisplatin 100 mg/m2 administered every 3 weeks for 3 cycles then every 6 weeks was investigated in 51 chemotherapy naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The population was 92% male, with a median age of 54 years and median performance status of 1; 80% of patients had metastatic disease, including 37% with bone involvement. All patients received prophylactic premedication (ondansetron, dexamethasone plus cetirizine) and standard hyperhydration. With a median of 4 treatment cycles (range 1–9), 14 of 42 evaluable patients responded (overall response rate 33.3%, 95% CI 19.6–49.6%); the median response duration was 7.3 months, median survival 8.4 months, and 1-year survival rate 35%. The most common adverse event was neutropenia, occurring in two-thirds of patients. Neurosensory effects were cumulative but generally mild. No treatment-related deaths occurred. This combination of docetaxel/cisplatin showed activity in advanced NSCLC. While it was not clearly superior to single-agent docetaxel, due to differences in prognostic factors among the patients in open trials, a randomised study would be needed to demonstrate definitively whether cisplatin adds to the activity of docetaxel or not.

The goal of nursing care in this protocol is to improve the patients’ (pts) quality of life during this treatment and to reduce the time of treatment in D.H.

From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). Nine patients had stage IIIB disease and 23 had stage IV disease. The first four dose levels of paclitaxel were 135, 175, 200, and 225 mg/m2 given with a fixed cisplatin dose of 100 mg/m2; at level 5, paclitaxel 225 mg/m2 was again given, and the cisplatin dose was increased to 120 mg/m2. Cycles were given every 3 weeks. Paclitaxel was administered as a 3-hour infusion followed by cisplatin, with standard premedication and hyperhydration. The maximum tolerated dose for the first cycle was not reached. Grades 3 and 4 neutropenia occurred in 24% and 16% of cycles (two cases with fever), respectively. Grades 2 and 3 peripheral axonal neurotoxicity occurred in two and 16 patients, respectively; the neurotoxicity appeared to be dose dependent and cumulative after a median total paclitaxel dose of 1,300 mg/m2. Of the 29 patients evaluable for efficacy, 11 (38%) had a partial response; efficacy was superior at paclitaxel doses of at least 200 mg/m2, with eight (47%) of 17 evaluable patients responding at these levels. In conclusion, at these doses of paclitaxel and cisplatin, the dose-limiting neurologic toxicity is dose dependent and cumulative after a total paclitaxel dose of approximately 1,300 mg/m2. This combination is highly active, with a total objective response rate of 38% and an objective response rate of 47% at paclitaxel doses of 200 mg/m2 or higher. Further evaluation is warranted.

Docetaxel is a tubulin polymerizing agent that shows activity as a single agent in advanced NSCLC. Its combination with cisplatin has been investigated in different phase II trials. In this study, we used a treatment schedule consisting of docetaxel 75mg/m2 and cisplatin 100mg/m2 every 3 weeks during 3 cycles and then every 6 weeks, with a standard premedication: dexamethasone, antihistaminic, antiemetic and hyperhydration. Evaluation of activity was performed every 6 weeks. Eligible patients (pts) had histologically proven locally advanced or metastatic NSCLC, measurable tumor, no previous chemotherapy, KPS≥60, age≤75, normal hematological, hepatic and renal functions, no brain or leptomeningeal involvement and signed informed consent. Fifty-one patients have been included: 3 were not eligible, the characteristics of the 48 remaining pts are: 44 males, 4 females; mean age: 54 years (range 34–75); stage IIIB: 13%, stage IV: 87%; they received a mean of 4 cycles (range 1–6). Among these 48 pts, 1 CR and 13 PR (29%) were observed, including 9 PR continned today by an independent panel, lasting from 15+ to 31+ weeks. Main toxicities (G 3–4) were: febrile neutropenia: 5 pts, documented sepsis: 5 patients. No toxic death was reported. As a result of using routine premedication, previously reported side effects were considerably lessened Based on this preliminary analysis combination of docetaxel 75mg/m2 and cisplatin 100mg/m2, indicates an interesting result which should deserve other investigations of this drug combination.

STUDY A lipid emulsion containing 10 percent medium-chain triglycerides (MCT) and 10 percent long-chain triglycerides (LCT) was infused at a rate of 1 ml/kg/h (3.3 mg/kg/min) for 2 h, in 12 patients (2 males, 10 females; mean age, 54 +/- 3 (SEM) years; range, 34 to 67 years) 24 h after open-heart surgery (mitral valve replacement). METHODS Hemodynamic factors (pulmonary and radial artery indwelling catheters), oxygen and carbon dioxide partial pressures, oxygen saturation, oxygen delivery and consumption, and intrapulmonary shunt fraction were obtained before, during, and after lipid infusion (for 2 h), at 30-s intervals, along with some metabolic indexes (triglycerides, free fatty acids, glucose, insulin, lactate, acetoacetate). RESULTS No statistically significant changes in heart rate, cardiac index, systemic and pulmonary pressures and resistances, central venous and pulmonary capillary pressures, or arterial oxygen partial pressure were observed during infusion. Arterial carbon dioxide partial pressure values were constantly reduced throughout and after the end of lipid infusion, as compared with baseline values, while oxygen consumption was increased significantly without any change in oxygen delivery. No adverse effects on intrapulmonary shunt fraction were observed. Statistically significant increases of triglycerides, free fatty acids, acetoacetate and insulin (peak values at end of the lipid infusion) were found in comparison with baseline values. Plasma glucose increased significantly during lipid infusion and remained higher than baseline values until the end of the study. Lactate levels were unchanged except for a slight decrease at the end of the study, without any derangement of acid-base equilibrium. Neither arrhythmias nor adverse clinical reactions were observed as a consequence of lipid infusion. CONCLUSIONS Fat emulsions containing both MCT and LCT, when given at 3.3 mg/kg/min for 120 min following valvular heart surgery, do not exert negative cardiopulmonary effects, and could represent a source of rapidly metabolized substrates.

OBJECTIVE--To investigate the activity of fleroxacin in acute uncomplicated infections with N. gonorrhoeae in comparison with conventional penicillin G plus probenecid treatment. DESIGN--Multicentre open label randomised parallel group study. SUBJECTS--Male patients aged 18 years or over from university departments of urology, epidemiology and dermatology and a clinic for sexually transmitted diseases. INTERVENTIONS--Two hundred and sixty male patients were randomly assigned to treatment with either a single oral dose of fleroxacin 400 mg (130 patients) or a single intramuscular dose of penicillin G (2.4 or 5.0 mega units) plus a single oral dose of probenecid 1 gram (130 patients). Efficacy and safety assessments were undertaken at follow-up (3-14 days after treatment). Efficacy was assessed as bacteriological outcome of treatment. Safety was assessed by evaluation of adverse events, laboratory abnormalities and changes in vital signs. RESULTS--Two hundred and twenty four patients (114 in the fleroxacin group and 110 in the penicillin plus probenecid group) were evaluated for efficacy. Bacteriological cures were achieved in 100% of patients in the fleroxacin group and 97% of patients in the penicillin plus probenecid group. There was no statistically significant difference between the two groups in this respect (Fisher exact test, p = 0.25). Clinical cures were achieved in 100% of patients receiving fleroxacin and 95% of patients receiving penicillin plus probenecid. Safety analyses were undertaken on 255 patients (126 in the fleroxacin group and 129 in the penicillin plus probenecid group). No adverse events were reported for either treatment group, and no clinically relevant laboratory abnormalities were apparent. Thus, there appeared to be no difference in the efficacy or safety of these two treatments when used to treat acute, uncomplicated urethral gonorrhoea in males. CONCLUSIONS--In this study fleroxacin proved to be highly effective therapy for uncomplicated gonococcal urethritis in males and may provide a favourable alternative to standard treatment.

This study compares the effects of cardiopulmonary bypass with different flows and pressures on intracellular energy metabolism, acid-base equilibrium, and muscle water compartments in two groups of patients undergoing coronary artery bypass grafting. Eighteen patients (16 men and two women aged 54 +/- 7 years, New York Heart Association class I-II) undergoing low flow (flow rate 1.5 L/min/m2 at 26 degrees C), low pressure (mean arterial pressure 40 to 60 mm Hg) cardiopulmonary bypass, as well as 10 age-matched and sex-matched patients undergoing normal flow (flow rate 2.2 L/min/m2 at 26 degrees C), normal pressure (mean arterial pressure 60 to 80 mm Hg) bypass were studied. Intracellular acid-base equilibrium (intracellular pH and intracellular bicarbonate), cell energetics (adenosine triphosphate, diphosphate, and monophosphate, phosphocreatine, and lactate), and muscle water compartments were evaluated in specimens of the quadriceps femoris muscle obtained by needle biopsy before and at the end of cardiopulmonary bypass. In both the low flow-low pressure and normal flow-normal pressure groups, adenosine triphosphate levels were unchanged at the end of bypass, whereas phosphocreatine concentration was decreased; muscle total water and extracellular water increased without variations of intracellular water; muscle and plasma lactate increased as intracellular bicarbonate decreased; intracellular pH values remained unchanged. The present study suggests the following: (1) Cardiopulmonary bypass is associated with the overall preservation of intracellular compartment metabolism in skeletal muscle (about 40% of body cell mass) of patients undergoing coronary bypass grafting, even though low phosphocreatine values and increased plasma and muscle lactate values found at the end of bypass could be an expression of cell functional reserve exhaustion; (2) the effects of cardiopulmonary bypass on cell metabolism are comparable, regardless of the flows and pressures used.

The main parameters of muscle acid-base, water and energy metabolism were studied in ten patients undergoing low-flux (1.5 l/min/m2), low-pressure (40 to 60 mmHg) hypothermic (26 degrees C) cardiopulmonary bypass (CPB) for aortocoronary grafting; absolute gas exchange and haemodynamic data were also measured throughout the entire CPB period. At the end of CPB a substantial preservation of water and energy metabolic indexes was found; a condition of extracellular metabolic acidosis was apparently sustained by muscle cell anaerobic glycolysis enhancement with a consequent increase of both muscle and plasma lactate content. Subnormal cell phosphocreatine levels as well as reduced bicarbonate buffer stores and decreased intracellular pH, were detected. Direct limiting effects of hypothermia on tissue O2 delivery and muscle oxidative metabolism as well as vasoconstriction and arteriovenous shunting associated with CPB procedures are likely to be involved in the above mentioned alterations of cell metabolism.

The activity of calcium, phospholipid-dependent protein kinase (PKc), which is thought to play an important role in cell proliferation, has been measured in the particulate and soluble fractions of cultured cells, under different proliferative conditions. Our results indicate that proliferating cells display higher PKc activity than quiescent cells. Furthermore, in both normal and transformed cells, PKc is preferentially associated with the particulate fraction when the cells are proliferating, while in mitotically quiescent cells the majority of the enzyme activity is found in the soluble fraction. These data suggest tha PKc activity and subcellular distribution undergo spontaneous changes according to the proliferative state of the cells.

In eight patients undergoing open heart surgery for elective myocardial revascularization, extra-intracellular acid-base and water metabolism parameters were studied before and after cardiopulmonary bypass procedures. All patients presented a different degree of metabolic acidosis related to plasma lactate increase. Intracellular acid-base indexes did not change significantly, though all but one patient showed an intracellular buffers consumption. Both total muscle and extracellular water increased, while intracellular water did not change. It was concluded that low flux-low pressure perfusion CPB was related to a substantial preservation of cell integrity.