Biomedical subjects
Publications and source records attributed to L Gallo.
A report on confirmed cases of desmoplastic fibroma in a 30-month-old male and a nine-year-old male, both of which responded well to surgical therapy and neither of which has shown signs of recurrence. A 10-year clinical and radiographic follow-up is included.
The effects of zidovudine on the platelet count were studied in 152 patients with HIV-related thrombocytopenia of severe grade (platelet count < 50 x 10(9)/l) and moderate grade (platelet count < 100 and > 50 x 10(9)/l). In both groups of patients there was a significant increase in the mean platelet count from the baseline value, after 2 weeks (from 21 x 10(9)/l to 48 x 10(9)/l and from 75 x 10(9)/l to 97 x 10(9)/l) and 3 months of therapy (to 59 x 10(9)/l and to 144 x 10(9)/l). Sixty-five and 39 patients were followed up for 12 and 18 months, respectively, and the mean platelet values after 12 and 18 months of therapy were still significantly increased, compared to the respective mean baseline values, in both groups of patients. Clinical progression of the disease was observed in 23 treated patients, none of them showing concomitant reductions of the platelet number. An increase in the mean CD4+ cell count after 3 months of therapy was followed by a progressive decline in the 65 patients with a 12-month follow-up, while no significant changes of the p24 antigenemia rates were observed after 1 year of therapy in 53 patients evaluated. The long-term effects of zidovudine on the platelet count, but not on other parameters of clinical outcome, might be explained by the involvement of specific mechanisms in the pathogenesis of this kind of thrombocytopenia and of its response to zidovudine.
148 patients with advanced untreated colorectal cancer were randomised to receive a weekly bolus of 5-fluorouracil (5-FU) 600 mg/m2 alone, with or without leucovorin (LV) 500 mg/m2. 5-FU plus LV produced a higher response rate than 5-FU alone: 23% (5 complete response, 11 partial response) vs. 8% (2 complete response, 4 partial response) (P = 0.03) out of 70 and 72 evaluable patients, respectively. Median survival was 11 months in both groups and median time to progression was not significantly different (P = 0.08). The combined regimen was more toxic than 5-FU alone, as evidenced by (a) a higher percentage of grade 3-4 diarrhoea, 19.5% vs. 8.5% (P = 0.045) and conjunctivitis, 26.5% vs. 5.6% (P = 0.0025); (b) the recording of one toxic death in the combined arm; and (c) the reduction of the median dose intensity of 5-FU actually delivered during the first 2 months of treatment. We conclude that 5-FU plus LV at a price of a higher toxicity is more active than 5-FU alone without improving survival and progression-free survival.
15 untreated patients with advanced measurable colorectal cancer along with other 29 patients in progression after failing first line chemotherapy with fluoropyrimidines received 5-fluorouracil (5FU) 500 mg/m2 given as a weekly bolus at mid-infusion of leucovorin (LV), 500 mg/m2 administered intravenously over 2 h and interferon alpha 2b (IFN) 3 x 10(6) U given intramuscularly every other day. All patients had their previous chemotherapy at least 4 weeks prior to 5FU-LV-IFN. 5 patients discontinued the three drug regimen due to toxicity (intense weakness, fever and influenza-like symptoms in 4 patients; diarrhoea in 1 patient) however no grade IV toxicity was observed. IFN administration was reduced to twice/weekly in 5 patients due to influenza-like symptoms. 1 complete response and 5 partial responses were observed (13.6% response rate); the complete response was obtained in a patient resistant to 5FU: the response rate was only twice as much in untreated patients (3/15 patients, 20%) compared with that in patients previously treated with fluoropyrimidines (3/29 patients, 10.3%). Therefore, modulation of 5FU with LV plus IFN at the doses and schedules employed in this study may rarely overcome clinical resistance to the fluoropyrimidine and the addition of IFN does not appear to enhance the activity of 5FU plus LV.
OBJECTIVE: We attempted to determine the prevalence of cervical dysplasia in human immunodeficiency virus-infected women in ambulatory care settings and to correlate Papanicolaou smears with demographic and clinical variables. STUDY DESIGN: Papanicolaou smears of 135 women attending three ambulatory care clinics were reviewed. Chart review identified demographic and clinical variables, including CD4 count. Prevalence of abnormal smears was compared with baseline community rates. Demographic and clinical variables were correlated with Papanicolaou results with the chi 2 test. RESULTS: Fivefold to eightfold increased rates of abnormal smears in human immunodeficiency virus-infected women were observed. Prevalence of abnormal smears increased from 21% in women with CD4 counts greater than 600/mm3 to 45% in women with CD4 counts less than 400/mm3. Age, ethnicity, or mode of human immunodeficiency virus transmission was not significantly correlated with Papanicolaou smear findings. CONCLUSION: Increased rates of abnormal Papanicolaou smears and significant correlation with CD4 counts were observed in human immunodeficiency virus-infected women at ambulatory care sites. We recommend comprehensive gynecologic care, including semiannual Papanicolaou smears, for all human immunodeficiency virus-infected women.
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We studied paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from 18 inactive multiple sclerosis (MS) patients and 10 with non-inflammatory neurological diseases. By means of a dual-colour cytofluorimetric micromethod we were able to count 1500 cells on average in each CSF sample. We found a significant reduction of CD45RA+ and CD4+CD45RA+ cells in the CSF of MS patients. Similarly, CD45RA+ and CD4+CD45RA+ CSF/PB ratios were lower compared with controls. The reduction of suppressor-inducer T-cells did not correlate with CD8+ cell levels in the CSF. The CD4+ subset ratio (CD4+CD45RA-/CD4+CD45RA+) was significantly increased in the CSF of MS patients. Our data suggest that the reduction of CD4+CD45RA+ cells in the PB is not due to a segregation of such cells in the CSF. Conversely, CSF changes reflect changes in the PB similar to these found for other T-cell subsets.
One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.
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A patient suffering from hemifacial microsomia with mandibular anodontia on the affected side is described. The various surgical and growth-guidance prosthetic measures employed to influence facial development and to correct deformities present evidence that the problems of such patients, even when severe, may be helped. Proper diagnosis and staging of the contributing elements of care are essential components of the treatment plan.
Fourteen normal subjects were submitted to isometric exercise (IE), dynamic exercise (DE) and a combination of the two (IE + DE). The main purpose of the present study was to use IE as a means of evaluating the mechanism of the heart rate (HR) increase induced by DE. To this end, the magnitude of the IE (handgrip) was standardized so as to cause an elevation of HR almost exclusively by vagal withdrawal: IE was performed using a dynamometer strain-gauge system with a linear response at 75% of maximum voluntary contraction (MVC) for 10 s, repeated at 1 min intervals. The change in HR evoked by IE under control conditions was compared with that evoked during DE, and during the corresponding recovery period. DE was performed by the legs, with the subject in the seated position for 4 min, at workloads of 55 and 105 watts, separated by a rest period. In the combined protocol, IE was performed at the beginning of DE, as well as at 1, 2 and 3 min during DE, and at 0, 1, 2, 3 and 5 min during recovery period. The following results were obtained: (1) IE associated with DE always induced smaller increase in heart rate than IE alone, and this effect was more marked at 105 than at 55 W; this finding suggested a workload-dependent vagal withdrawal at the very beginning of DE that was sustained until the end of effort.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The relative contribution of the sympathetic and parasympathetic components of the autonomic nervous system to the regulation of the chronotropic response to dynamic exercise was evaluated indirectly in nine patients with thyrotoxicosis and in seven normal volunteers. All subjects were women, with equivalent ages in both groups. Six of the nine patients with hyperthyroidism were reevaluated after clinical compensation of the disease with propylthiouracil. 2. Heart rate responses were evaluated during discontinuous dynamic effort maintained for 4 min on a bicycle ergometer at levels of 5, 15, 25 and 50 W, and also of 75 W in normal individuals. The study was also performed under conditions of sympathetic pharmacological blockade with propranolol (0.2 mg/kg body weight). 3. Even though the magnitude of the total increase in heart rate evoked by each level of dynamic exercise was equivalent in normal and hyperthyroid patients, the tachycardiac response occurring at the beginning of the exercise, which depends on a predominantly vagal mechanism, was substantially different from that observed after 30 s of effort, when sympathetic contribution becomes more important. The hyperthyroid patients showed considerably lower increases in heart rate than the normal individuals during the initial 30 s of effort, with the opposite occurring from this moment onward. 4. In the hyperthyroid patients, beta-adrenergic blockage depressed tachycardia after 30 s of effort at the 15 and 50 W levels, whereas in normal individuals this effect was only manifested at 50 and 75 W. 5. The patients who obtained clinical compensation showed a pattern of chronotropic response which tended to be close to that shown by normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The heart rate response to immersion of the face in water, as an isolated manoeuvre or in combination with apnoea, was studied in eight normal volunteers to establish the conditions under which it could be used as a standardized, simple, non-invasive and reproducible test of parasympathetic activity. 2. The following procedures were evaluated: (a) 10 s apnoea in air at different lung volumes; (b) facial immersion in water for 2 min at various temperatures (5, 15 and 25 degrees C), with respiration maintained through a closed circuit; (c) combination of immersion and apnoea at different lung volumes. Three volunteers were re-evaluated after pharmacological blockade with atropine sulphate (0.04 mg/kg body weight). 3. The results showed that: (a) apnoea in air triggered lung volume-dependent heart rate responses; (b) facial immersion in water induced transient bradycardia which was maximum between 20 and 30 s of immersion; (c) there was no appreciable difference in the bradycardia evoked by immersion at different temperatures; (d) the combination of immersion and apnoea caused heterogeneous heart rate responses with no potentiation of bradycardia in relation to each manoeuvre as performed separately; (e) atropine did not reduce the magnitude of bradycardia induced by immersion in two of the subjects studied. 4. The variability of responses observed in the present study was probably due to the multiple receptors and afferent pathways that are simultaneously excited during these manoeuvres. As a consequence, the autonomic efferent response will depend on the unpredictable net effect of interaction of these mechanisms. This is a limiting factor for the standardization of this test as a simple and reproducible method for the assessment of parasympathetic activity. 5. Furthermore, the results obtained under pharmacological blockade indicate that the vagal efferent mechanism is not the only factor responsible for the bradycardia caused by facial immersion without apnoea.
From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.
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The usefulness of tumor marker assay in pleural effusions for differential diagnosis is still debated. From the observation of common antigens on tissue polypeptide antigen (TPA) and keratins 8, 18 and 19 and vimentin, all substances contained in normal and neoplastic mesothelium, we felt it opportune to evaluate the use of TPA assay in 105 pleural effusions (46 benign and 59 malignant). The values were much higher than those found in blood. In hydrothorax the median value was 454 U/l (range, 59-1923), in exudative effusions 846 U/l (range, 258-4485), in metastatic pleural effusions 1277 U/l (range, 58-32352) and in mesotheliomas 7705 (range, 759-16000). The maximum value found in nonmalignant effusions was 4485 U/l; this value was taken as a cutoff level, so only 29.9% of the tumors were positive to the test. Our results showed this assay to be not very important for a differential diagnosis of malignant and nonmalignant pleural effusions. Nevertheless, the different TPA patterns in mesotheliomas (66.6% positive) and metastatic pleural effusions (15.9%) suggest that further studies are warranted.