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Introduction Chemotherapy-induced myelosuppression (CIM) is one of the most common dose-limiting complications of cancer treatment, and is associated with a range of debilitating symptoms that can significantly impact patients’ quality of life. The purpose of this study was to understand patients’ perspectives on how the side effects of CIM are managed in routine clinical practice. Methods An online survey was conducted of participants with breast, lung, or colorectal cancer who had received chemotherapy treatment within the past 12 months, and had experienced at least one episode of myelosuppression in the past year. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection. Results Of 301 participants who completed the online survey, 153 (51%) had breast cancer, 100 (33%) had lung cancer, and 48 (16%) had colorectal cancer. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Most participants (79%) reported having received treatment for CIM, and 64% of participants recalled chemotherapy dose modifications as a result of CIM. Although most participants believed their oncologist was aware of the side effects of CIM, and treated them quickly, 30% of participants felt their oncologists did not understand how uncomfortable they were due to the side effects of CIM. Overall, 88% of participants considered CIM to have a moderate or major impact on their lives. Conclusion The data highlight that despite the various methods used to address CIM, and the patient-focused approach of oncologists, the real-world impact of CIM on patients is substantial. Improving communication between patients and health care providers may help improve patients’ understanding of CIM, and foster shared decision-making in terms of treatment. Additional insights from patients should be obtained to further elucidate the totality of life burden associated with CIM., Plain Language Summary This study looked at people with cancer who received chemotherapy and developed a condition where their bone marrow activity was reduced, called myelosuppression. This meant they had fewer red blood cells that carry oxygen around the body, white blood cells that help fight infections, and platelets that help the blood to clot. The researchers wanted to understand how chemotherapy-induced myelosuppression affects peoples’ lives and their cancer treatment, and people’s experiences of treatment for myelosuppression. Overall, 301 people in the USA with breast, lung, or large bowel (colorectal) cancer completed an online survey. They had all received chemotherapy in the last year, and had myelosuppression at least once during their treatment. The survey showed that around 8 in 10 people (79%) had to be treated for myelosuppression, and around 7 in 10 people (73%) felt they received treatment for myelosuppression quickly. Chemotherapy was delayed, reduced, or stopped because of myelosuppression in around 6 in 10 people (64%). Around 3 in 10 people (30%) felt their oncologist did not understand the discomfort that myelosuppression caused them, and around 9 in 10 people (88%) felt that myelosuppression made their quality of life worse. The researchers concluded that because myelosuppression impacts peoples’ lives and their ability to keep receiving chemotherapy to treat their cancer, effective prevention and treatment for this condition are important. Better communication between people and their health care teams could help them to understand how people experience myelosuppression and make plans for treatment together.

It was hypothesized that activity exercise at professional levels could lead to an increase in metabolic levels and a decrease in performance parameters. These trends are explained by physical activity as a cellular stressor.We used an algorithm, Laboratory Index which evaluates salivary cortisol, CK and d-ROMs, collected previously from elite Italian soccer players, compared to InStat Index. The last one estimates analytically the athlete's performance in soccer pitch, applying the Heath Maps.A good agreement between the two Index was obtained, especially for two players, who showed an ideal combined trend.We would investigate the clinical and activity profile of soccer players with the aim of providing information for the development of training strategies. Also, the performances, during training and match time, are an objective evaluation of the athlete's physical preparation. As a consequence, the combination of two Index could be used for a new approach to the sports world.

Appendiceal mucocele represents specimen finding in 0.2-0.3% out of appendectomies. The rupture or perforation in peritoneal cavity might cause pseudomixoma peritonei (PMP), with multiple mucinous deposits in the abdominal cavity. We report a case of PMP caused by a perforated appendiceal cistoadeonoma.

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

A series of substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones was synthesized from amino alcohols or amino thiols and keto acids. A pharmacological model based on the results obtained with these compounds led to the synthesis and evaluation of a series of isoxazoles and other monocyclic compounds. These were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. The in vivo hypoglycemic efficacy and potency of these compounds were evaluated in a model of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), the ob/ob mouse. 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies.

Objective: Impaired quality of life (QOL) in patients with ulcerative colitis (UC) may be a prominent feature of the disease, and in some cases, may become an indication for surgical treatment. The objective of this study was to assess QOL in patients who underwent proctocolectomy with ileo-anal anastomosis with a J pouch for severe UC and to compare it with patients with UC of different severity who were under medical treatment. Methods: We used a validated, disease-specific research instrument (a 29 item, self-administered questionnaire) that examines the following four functions: intestinal (score 0–24) and systemic symptoms (0–21), and emotional (0–27) and Social Function (0–15). High scores indicate an impairment of the function examined and the sum of the four scores (maximal total score = 87) reflects the patient's QOL. We studied 29 operated patients (22 men, mean age 35 yr, mean time after intervention 3.8 yr) and compared their scores with those of 57 UC patients (39 men, mean age 36 yr) with different degrees of disease activity, and with those of 72 healthy controls (38 men, mean age 31 yr). Results: In UC, scores were significantly higher than in controls, increasing with the severity of the disease. Even patients in remission had higher scores than controls in the “systemic” (4.6 vs. 2.0) and emotional (5.6 vs. 2.5) functions. Patients who underwent surgical treatment had much better scores than patients with severe disease (total score 20.1 vs. 38.2), with values comparable to those of patients in remission or with mild disease activity. There was no significant gender difference, either for UC and ileo-anal anastomosis patients, or in healthy controls. Conclusion: In patients with UC, even in remission, there is a measurable impairment of QOL, which increases with the severity of disease. Operated patients have a QOL that is comparable to that of patients in remission or with mild disease, and proctocolectomy with ileo-anal anastomosis may restore an acceptable QOL in patients with moderate/severe UC.

In order to assess the suspected influence of indwelling lines on the measurement of cyclosporine (CSA) blood levels, we evaluated CSA concentrations in samples drawn simultaneously from both silicone catheter lumens and peripheral veins of eight bone marrow transplant recipients. Blood samples were obtained at 30 min or 6-12 h after discontinuation of intravenous CSA. CSA concentrations were determined in whole blood by specific monoclonal antibody assay. Mean CSA levels from the lumen used for CSA administration were significantly higher than those from samples drawn from the second lumen (i.e., not used for CSA infusion) or peripheral vein. This difference, obtained when the infusion had been interrupted for 30 min, was still the case 6-12 h after discontinuation of CSA infusion. No difference was found between samples obtained from the second lumen and peripheral vein. These observations suggest that CSA might be adsorbed or bound by the silicon catheter and, thus, CSA blood level measurements may be misleading. The second lumen of the catheter or a peripheral vein should be used for accurate monitoring of CSA concentrations.

479 families, each with a proband affected by homozygous β-thalassemia, were typed for HLA. 224 families with a total of 1020 members were typed for the HLA-A, B, C, DR and DQ loci and 255 families with 1046 family members, were typed for the HLA-A, B, and C loci. Altogether, 896 A, B, C, DR and DQ haplotypes and 1020 A, B and C haplotypes were defined. At the same time, 120 healthy unrelated individuals from the same population were typed and used as controls. The analysis of the results was carried out at antigen, allele, haplotype, genotype and sex ratio level with the aim of looking on the one hand, for the existence of heterogeneity between the probands, the unrelated individuals and the healthy siblings and, on the other, for the existence of any distortion whatsoever of the HLA segregation in either the probands or in the healthy siblings in respect of the expected values according to the Mendelian equilibrium. No significant differences were evident between the probands and the controls by the tests carried out at different levels of the HLA system. This leads us to exclude the existence of an association between β-thalassemia and HLA in the population studied. Moreover, the analysis of the transmission of the alleles, the haplotypes, the genotypes and the sex-ratio by parents to both affected and to healthy children did not show any clear evidence of segregation distortion in respect of the theoretical values.

Hereditary factors are suspected to contribute to the pathogenesis of sporadic primary glomerulonephritis, but their contribution is difficult to delineate in the general population. We studied the prevalence of primary glomerulonephritis in an isolated population from the extreme northern Valtrompia valley, Northern Italy. Investigation of medical records, community urinary screening program and molecular characterization of the population's ancestry were performed; genealogies of affected individuals were researched. Forty-three patients with primary glomerulonephritis were identified: 25 had biopsy-proven disease (11 immunoglobulin A (IgA) nephropathy; eight mesangial proliferative glomerulonephritis without IgA deposits; four focal segmental glomerular sclerosis; two membranous nephropathy), and 18 had clinical glomerulonephritis. All 43 patients originated from three mountain villages (Collio, San Colombano, and Bovegno). In contrast, we found only four cases of primary glomerulonephritis in two nearby villages (Pezzaze and Tavernole) that shared similar population histories and lifestyles, demonstrating heterogeneity of risk factors for glomerulonephritis ( P =3 × 10 −5 ). All 43 affected individuals could be traced back to common ancestors (XVI–XVII centuries), enabling the construction of three large pedigree including three parent–child affected pairs and five affected siblings pairs. Molecular data showed lower genetic diversity and increased inbreeding in the Valtrompia population compared to the control population. Molecular and genealogical evidence of limited set of founders and the absence of shared nephritogenic environmental factors suggest that our patients share a common genetic susceptibility to the development of primary glomerulonephritis. Further molecular study of our families will offer the possibility to shed light on the genetic background underlying these glomerular disorders.

Common etiopathogenic factors may explain the association of systemic sarcoidosis with inflammatory bowel disease.We report two cases of such an association: one of sarcoidosis that developed 2 years after proctocolectomy for ulcerative colitis and one of sarcoidosis and Crohn's colitis. Factors like increased cellular immunity or circulating immunocomplexes or autoantibodies may have a role. Exogenous agents or familiarity may also be involved.It is postulated that the association between sarcoidosis and inflammatory bowel disease (both ulcerative colitis and Crohn's disease) does not occur by chance alone and that the two conditions may share some genetic or immunologic alterations. The two diseases, however, follow an independent clinical course.

Conglomerates of food and mucus or phytobezoars composed of vegetable matter are sometimes found in the stomach in the general population. Reports of phytobezoars in uremic patients are, however, scarce. Here we describe 2 uremic patients in which esophagogastroduodenoscopy was performed due to dyspepsia associated with weight loss and in which stomach phytobezoars were discovered. Theoretically, uremic patients should be at risk for producing bezoars. In fact, these patients frequently present predisposing conditions such as autonomic neuropathy, diabetes mellitus and delayed gastric emptying. Gastric bezoars cause anorexia. Anorexia is a frequent symptom in dialysis patients and is associated with malnutrition. In these patients, malnutrition is strongly associated with mortality and is quite difficult to reverse. Similarly, phytobezoars cause chronic anorexia. We suggest that clinicians working in dialysis units should consider the possibility of a gastric bezoar when evaluating anorexic uremic patients.

Persistent symptoms of nausea, distress, and vomiting triggered by reminders of cancer treatment were examined among 273 Hodgkin's disease survivors, 1 to 20 years posttreatment. Prevalence rates were high for distress and nausea but low for vomiting. Retrospective report of anticipatory symptoms during treatment was the strongest predictor of persistent symptoms, suggesting that treatment-induced symptoms are less likely to persist if conditioning does not occur initially. Time since treatment was also a significant predictor, with patients more recently treated more likely to experience persistent symptoms. Thus, an explanatory model based on classical conditioning theory successfully predicted presence of persistent symptoms. Symptoms also were associated with ongoing psychological distress, suggesting that quality of life is diminished among survivors with persistent symptoms. Recommendations for prevention and treatment of symptoms are discussed.

The antiangiogenic, antitumoural and antimetastatic effects of two novel sulphonic derivatives of distamycin A, PNU145156E and PNU153429, were studied in a Kaposi's sarcoma-like tumour model obtained by injecting nude mice with cells releasing extracellular HIV-Tat protein, derived from a tumour which developed in a BK virus/tat transgenic mouse. Both PNU145156E and PNU153429 were administered intraperitoneally every fourth day for three weeks at doses of 100 or 50 mg/kg of body weight respectively, starting one day after injecting the tumour cells. Both drugs delayed tumour growth in nude mice, preventing neovascularization induced by the Tat protein. PNU153429 also significantly reduced the number and size of spontaneous tumour metastases. Both effects on tumour growth and metastases were augmented by treating simultaneously nude mice with 7.5 mg/kg of body weight of minocycline given per os daily for four weeks starting four days after injecting the tumour cells. Neither acute nor chronic toxic side-effects were observed during the life span of treated nude mice. Due to their antiangiogenic and anti-Tat effects, these drugs are promising for the treatment of Kaposi's sarcoma in AIDS patients.

Our aim was the assessment of frequency and evolution of osteopenia in patients with inflammatory bowel disease and identification of related factors.Bone mineral density (BMD) of the lumbar spine was measured in 54 patients with Crohn's disease (CD) and in 49 patients with ulcerative colitis (UC) and was repeated after a mean observation period of 21 (range, 8-50) months in 30 CD and 14 UC patients. Eighteen age-matched healthy subjects served as controls. Serum biochemistry (parathyroid hormone, osteocalcin, alkaline phosphatase, insulin-like growth factor 1, minerals, and markers of inflammation) was assessed at the time of the second BMD measurement.Reduced BMD values were found in 48% of CD, and in 38% of UC patients. Compared with control subjects, the mean BMD was significantly lower in CD (p0.003) and UC (p0.0001) patients. BMD was positively correlated with the body mass index (p0.05) and inversely correlated with the lifetime steroid dose (p0.03). After 21 months the BMD of CD patients was virtually unchanged, with an annual variation (%deltaBMD/yr) of -0.31 +/- 0.49, whether treated with steroids or not, whereas in UC patients the BMD decreased significantly (p0.02) with a %deltaBMD/yr of -2.47 +/- 0.82 (p0.02 vis CD). This decrease can be attributed to steroid treatment. No biochemical alterations were detected in patients with rapid bone loss, compared with those with stable BMD.Low bone density is frequent in both CD and UC, but apparently stable in CD. The evolution of BMD suggests that low bone density is associated with the pathogenesis of CD, whereas in UC it seems to be correlated with the side effects of corticosteroid treatment.

Preoperative chemotherapy and chemoradiation protocols are generally associated with high clinical response rates but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel and carboplatin plus concurrent, fractionated external-beam radiation, followed by organ-preserving or function-restorative surgery (when applicable to maximize locoregional tumor control). Operable patients staged by triple endoscopy received a percutaneous gastrostomy and vigorous dental and nutritional support during therapy. Paclitaxel 60 mg/m2 and carboplatin at an area under the concentration-time curve of 1 were administered weekly with radiation therapy 45 Gy, with repeat biopsy of the primary site at 5 weeks. Patients with a positive biopsy had definitive surgery within 4 to 5 weeks. Patients with a negative biopsy received 3 additional weeks of radiation therapy, to a total dose of 72 Gy plus paclitaxel and carboplatin. Forty-three patients were enrolled, including 33 men and 10 women ranging in age from 37 to 81 years. Fourteen patients had stage III disease, 19 patients had stage IVA disease, and 10 patients had stage IVB disease. Sites of disease included the floor of the mouth (n = 8), tongue (n = 8), oropharynx (n = 5), hypopharynx (n = 4), larynx (n = 12), palate-tonsil (n = 2), unknown primary (n = 3), and nasal cavity (n = 1). Of 38 patients evaluable for primary response (two patients had unknown primary tumor, two patients failed to complete the chemoradiation protocol, and one patient was evaluable for toxicity only), 18 patients had a complete clinical response and 20 patients had a partial response; the overall clinical response rate was 100%. A pathologic clinical response at the primary site occurred in 25 of these 38 patients (66%), who subsequently received completion radiation (67 to 72 Gy). After induction chemoradiation, 36 patients with N1-N3 nodes had neck dissection; seven had positive nodes (19%). Fourteen patients had residual cancer at the primary site at the time of the repeat biopsy. Sites of the lesions were the floor of the mouth/mandible (n = 4), nasal cavity/maxilla (n = 2), base of tongue (n = 2), and larynx (n = 6). All were resected with function-preserving reconstruction (two patients required total laryngectomy and one patient refused surgery). At a median follow-up of more than 16 months, progression-free and overall survival rates were 64% and 68%, respectively. Preoperative paclitaxel, carboplatin, and radiation was associated with a high clinical response rate at the primary site and a high level of organ preservation or functional restoration, if ablation was performed.

Radiotherapy or surgery alone for advanced head and neck cancer generally yields poor results. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, namely, blocking the cell cycle in the G2/M phase and inhibiting DNA repair. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel 60 mg/ml and carboplatin (area under the concentration-time curve of 1), each given as a single dose weekly with concurrent conventional fractionated external beam radiotherapy. Patients were stratified into two groups: operable and inoperable/unresectable. The operable and inoperable groups received 5 weeks (45 Gy) and 8 weeks (72 Gy) of chemoradiotherapy, respectively. Patients in the operable group were evaluated with repeat biopsies from the primary site after 5 weeks. Those with a positive biopsy underwent surgery; those with a negative biopsy received 3 additional weeks of chemoradiotherapy. Thirty-four patients were entered in the operable group (28 men and six women; 40 to 71 years of age; 12 stage III and 22 stage IV). Of 26 evaluable patients, 19 (73%) had a complete clinical response (95% confidence interval [CI], 52% to 88%) and six (23%) had a partial response (95% CI, 9% to 44%), for a total clinical response rate of 96% (95% CI, 80% to 100%). A pathologic complete response at the primary site (two had an unknown primary site) occurred in 17 of 24 (71%) patients (95% CI, 49% to 87%). Of 20 patients with N1-3 nodes who underwent neck dissection, 17 (85%) had pathologically negative lymph nodes. Seven patients with residual tumor at the primary site were resected (oral cavity, three; maxilla, one; base of tongue, one; and larynx, two). Grades 3 and 4 mucositis were seen in 19 (73%) patients; mucositis was the most common and significant morbidity. Accrual for the inoperable group continues. Concomitant paclitaxel, carboplatin, and external beam radiotherapy yielded excellent clinical responses, but produced significant grade 3/4 toxicity. In the operable group, the majority of responders had a complete pathologic response. These preliminary findings will be assessed in terms of response duration, organ preservation, and long-term survival.

In this paper the authors review the latest international literature regarding prostate tumour surgery, comparing surgery with the so-called "wait and see" approach. Together with hormone treatment, the latter method has been used by many researchers over the past few years given the low mortality caused by this tumour in spite of the increasing number of cases diagnosed. The wait-and-see approach is now rendered controversial by improved diagnostic methods and the widespread introduction of early diagnosis programmes. The authors report a number of studies on the use of "wait-and-see" in relation to radical prostatectomy and compare the results of the two techniques in terms of morbidity, mortality and survival. They go on to describe the various types of surgical technique used and their respective pros and cons as well as the complications typical of each technique. In conclusion, the authors discuss the indications for radical prostatectomy which, if performed in selected patients, appears to be a promising therapeutic approach in terms of disease-free survival and with a low operating mortality with complications that are not impossible to resolve using appropriate treatment.

Hand venous hypertension is a rare complication of Cimino-Brescia vascular access. The authors report their experience in a case of hand and forearm venous hypertension in a brachial arterio-venous fistula.

The role of free (F) and complexed serum PSA is now under investigation. In the present study, we evaluated the clinical significance of F-PSA and F/Total (T) PSA ratio in a preliminary series of samples from 88 patients with prostate cancer (PC), 113 with benign prostatic disease (BPD), and 98 with non-prostatic disease (NP). We used the F-PSA and third generation T-PSA (DPC, Los Angeles, USA) chemiluminescent enzyme immunometric assays with the IMMULITE automated system. At the 10 ng/ml cutoff for T-PSA levels, we obtained a sensitivity of 83% with a specificity of 100% in NP and 80% in BPD. The addition of the FIT ratio –rather than F-PSA levels – was useful to better discriminate PC and BPD in the cases erroneously classified by T-PSA alone: 44/68 samples (65%) were correctly diagnosed. Moreover, the FIT ratio was particularly effective in the critical T-PSA range between 4.1-9.9 ng/ml; 26/40 cases (65%) were correctly evaluated. In conclusion, the FIT ratio seems to be an interesting auxiliary test to T-PSA, to be reserved for selected cases where additional diagnostic information is necessary.

Pectus excavatum, a congenital depressive malformation of the sternum, is described since 1594 by Johannes Schenk and has successively been the subject of many studies because of its various inherent problems. The repercussions on the respiratory and cardiac dynamics caused by the compression on the mediastinal structures and by the reduction of the respiratory volume have only recently been valuated completely with the application of the latest techniques to diagnosis, cardiology and radiology. The aesthetic defect, often the first aspect to attract the attention of patient and doctor, has serious psychological implications, especially for what concerns the affective life and relationships in general. The surgical therapy consists in radical interventions with large sternocostal resections and repositioning of the sternum (turnover), or in interventions with a less invasive technique to correct only the aesthetic defect. In this study have been examined 7 cases of patients affected by pectus excavatum who were operated at the Institute of General Surgery IV and the Department of Plastic surgery of the University of Rome "La Sapienza" between 1983 and 1993. The patients were divided in two groups: a first group of 4 patients who underwent a sternal turnover, and a second group of 3 patients who were operated with conservative methods to correct the aesthetic defect. In both groups the results were good without any post-operatory complications. The experience gained during these years consents us to propose radical interventions for patients who have a severe malformation with evident physiopathological implications; this intervention is especially indicated if the patient is young, to prevent further disabling complications. Less invasive methods, on the other hand, should be applied to all other cases, considering the higher degree of tolerance of the intervention, the absence of postoperatory complications and the minor cost, thanks to a shorter hospital stay.

We suggest a Bayesian method in order to evaluate the disposition kinetics of the drug plasma concentrations after intravenous (i.v.) and/or after extravascular administration of the drug in the same subject pooled with information obtained taking into account previous pharmacokinetics of the drug. This approach was applied to the investigation of teicoplanin pharmacokinetics after 200 mg i.v. administration to 10 healthy subjects.

The Authors report their experience in the management of 30 patients undergone tension free hernioplasty according to Trabucco for inguinal hernia. Results and some modifications of the original technique are discussed.

The authors report their own experience about 156 cases of acute cholecystitis observed between January 1991 and October 1992. The most part of the patients were between 30 and 65 years old (84 cases observed). In 27 cases, for the positive evolution of the pathology, it was put on practice a non operative treatment. The other 129 cases were treated surgically. The patients with lithiasic cholecystitis were 148; those affected by non lithiasic cholecystitis were 5; and 3 of them presented an acute cholecystitis as a manifestation of a carcinoma. Between the various diagnostic methods, the echography, executed in emergency, is considered as an indispensable one, for having changed completely the diagnostic approach. It is discussed, particularly, the timing of surgery, an aspect able to influence considerably the therapeutic iter and its results. There are analysed the criteria for whom some authors are favourable to a medical treatment of the acute cholecystitis, postponing the operation, while other of them are favourable to an early surgical treatment. The authors' casuistry put in evidence 110 operations effectuated in emergency (12 hours), 19 operations after an 12-72 hours interval, no operations at a long distance (1-10 months). The results are to be considered satisfactory: 1 deceased (on 129 operated cases, 0.78%); 10 immediate complications (7.75%): 8 suppurations of the wound, 1 biliar fistula and 1 internal hemorrhage after video-laparoscopic operation; 2 late complications (1.55%): they were relapsing gallstones. The aim of this work is to offer a contribution to codification of the treatment of the acute cholecystitis, on the ground of the acquired experience.

Surgery and radiotherapy mainstays in the management of advanced head and neck cancer, although historically, only 20-30% of patients survive. Therefore, in an attempt to improve locoregional control and survival, a multimodal protocol using cisplatin as a radiosensitizer was implemented.Between 1984 and 1990, 68 patients with advanced head and neck cancer (Stages III and IV) were treated with a regimen consisting of an induction phase of 4500 cGy and two cycles of cisplatin followed by an eradicative phase of either radical surgery (Group A, 27 patients) or radical radiotherapy (Group B, 41 patients). The maintenance phase chemotherapy consisted of adjuvant 5-fluorouracil (5-FU) and cisplatin after completion of locoregional treatment. Of the 68 patients, 19 had Stage III disease, and 49 had Stage IV; 21 had no regional lymph node metastases (N0), and 47 had regional lymph node metastases (N+).The induction phase yielded a 26% (18 patients) complete response (CR) rate and a 57% (39 patients) partial response (PR) rate (response50%), yielding an overall response rate of 83%. Eleven patients (16%) had stable disease (ST) (i.e.,50% response). The 2-year survival rates by initial treatment response for patients who had a CR, a PR, and stable disease were 53%, 56%, and 36%, respectively; for Groups A and B, 63% and 45%, respectively; for Stages III and IV, 68% and 43%, respectively; and for N0 and N+, 69% and 43%, respectively. In Group A, 14 of 27 patients (52%) had no viable tumor in the surgical specimen (i.e. had pathologic complete tumor clearance [CTC]); this subgroup had a 5-year survival rate of 58%. Ten patients (37%) who had gross total resection of tumor with negative margins but had tumor present in the specimen had a 5-year survival of 22%. In Group B, the 5-year survival rate was 43% for 27 patients who achieved CR after completion of radical radiotherapy (total tumor dose, 6480-7020 cGy). The 5-year survival rate of the 14 patients who had a PR and stable disease after radical radiotherapy and 3 patients whose resection was incomplete was 0%. The overall 2- and 5-year survival rates for all patients were 53% and 32%, respectively. Of 21 patients in whom treatment failed, most (90%) had a locoregional recurrence: 13 local recurrences (62%), 5 regional (24%), and 1 locoregional (5%). Two patients (10%) experienced failure at distant sites (the lung). Major treatment-related morbidity developed in two patients.Although induction chemotherapy-radiotherapy produces a high clinical response rate, this does not translate into improved survival compared with historical controls. A subgroup that showed complete tumor clearance (CTC or pathologic complete response) at surgery had an apparent improved survival and merits further study. Patient selection did not appear to be a factor for the CTC group, because the majority of patients in this group had partial responses to induction therapy, nodal disease and advanced tumor stage, and tumor presence in unfavorable sites.

Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.

We have analyzed the reactivation of fetal hemoglobin (HbF) synthesis under rigorous in vitro conditions, ie, in mature erythroblasts generated by erythroid burst-forming units (BFU-E) stringently purified from normal adult peripheral blood and grown in fetal calf serum(FCS)-free semisolid or liquid phase culture. In clonogenetic dishes, graded amounts of c-kit ligand (KL) were added together with saturating levels of erythropoietin (Ep) and variable amounts of interleukin-3 and granulocyte-macrophage colony stimulating factor (IL-3/GM-CSF), ie, high or low level, or no IL-3/GM-CSF addition. In all conditions, KL induced a sharp, dose-dependent increase in the percentage of F cells and HbF content from nearly normal levels (10% and2.5%, respectively, at 0.1 and 1 ng/mL) up to 40% to 50% and 10% to 15% at 100 to 200 ng/mL. This increase was not associated with significant differences of burst number or stage of maturation at the time of analysis (as evaluated on the basis of percent mature erythroblasts and Hb content per cell). However, the KL-induced reactivation of HbF synthesis was strictly and directly correlated with a sharp increase of colony size, ie, cell number per burst. Addition of large amounts of IL-3 and GM-CSF (10 to 100 U and 1 to 10 ng/mL, respectively) significantly potentiated the KL-induced reactivation of HbF, as compared with low levels (0.1 U and 0.01 to 0.1 ng) or no addition of these growth factors: this increase was highly significant at low KL doses (ie, 1 to 10 ng/mL). Single-burst analysis showed that the KL-induced HbF reactivation occurs homogeneously in the erythroid colonies within each of these culture conditions. We have analyzed the effect of KL in liquid phase BFU-E culture treated with the IL-3/GM-CSF/Ep combination at sequential times until terminal erythroid maturation: KL causes a sharp increase in the percentage of F cells and HbF content in all stages of maturation, whereas the IL-3/GM-CSF/Ep combination alone has a markedly lower effect. These results suggest that KL plays a key role in the reactivation of HbF synthesis in adult life, whereas IL-3/GM-CSF potentiate this effect at low KL levels. The KL-induced HbF reactivation is seemingly related to an enhanced proliferation of erythroid progenitors in the erythropoietic differentiation pathway.

Respiratory events are between the most frequent postoperative complications. The preoperative conditions associated with postoperative respiratory failure were evaluated in a prospective study of 1182 patients from six Italian Surgical Units. Multiple regression logistic analysis was employed for statistical evaluation and a predictive prognostic score was derived. Only the presence of the following conditions was significant in affecting postoperative respiratory outcomes: preoperative respiratory and cardiac failure, hypotransferrinemia, prolonged surgical procedures (above the 2 hours) and peroperative bacterial contamination. Advanced age did not appear as a major risk factor. Studies on the predetermination of the pulmonary complications have been widely published. Historical risk factors include the presence of respiratory disease, smoking habits, obesity and thoracic or upper abdominal surgical procedures. Although the results of the present study need a prospective confirmation, the predictive scoring system proves to be a usefull tool that can be employed in most of the General Surgery Units.

Dose-effect curves for amphetamine on key-pecking behavior of pigeons maintained by two-component multiple schedules of shock postponement were determined. During the first experimental phase the response-shock interval (RS) was held constant and the shock-shock interval (SS) varied. Under these conditions, shock rate was greater during the component with the shorter SS. However, response rates were comparable in both components. Also, the magnitude of the response rate increments caused by appropriate doses of amphetamine during both schedule components were similar. During the second experimental phase, the SS was held constant and the RS varied. As a consequence, baseline response rate was considerably lower in the component with the longer RS than in the short RS component. Shock presentations were also less frequent during the former than during the latter component, but the differences in shock rate between the components were comparable or smaller than those observed during the first experimental phase. Under these conditions, the effects of amphetamine in the two schedules components were markedly different, lower response rates being considerably more increased than higher rates.

The pharmacokinetics of norfloxacin were studied in six healthy volunteers, and three patients each with moderate renal and hepatic damage. A new specific and sensitive high performance liquid chromatography method was set up to measure plasma and urine concentrations of norfloxacin. The mean urinary concentrations after a single oral dose of 400 mg norfloxacin exceeded many times the MIC and MBC values of most of the bacterial strains responsible for urinary tract infections. Results in the patients with hepatic and renal damage indicated slight and not statistically significant differences in comparison with healthy volunteers.

A case of hereditary xanthinuria in a 68-year-old man with congestive heart failure and alcoholic liver disease is presented. Urolithiasis and muscular symptoms were absent, and the metabolic error was revealed by hypouricemia, hypouricosuria and excess of xanthine and hypoxanthine excretion in urine. Xanthine oxidase (EC 1.2.3.2) activity in liver tissue was absent, confirming the diagnosis of xanthinuria.

Defibrotide is a new compound with antithrombotic and profibrinolytic activity. It increases the endogenous fibrinolytic activity by promoting the cellular activator of plasminogen from endothelial cells and by decreasing the concentration of its inhibitors. In this study we evaluated a total of 223 patients for a mean period of 43 days for the following vascular conditions: (a) superficial venous thrombosis; (b) prophylaxis against deep venous thrombosis; (c) peripheral vascular disease (ischaemic foot and intermittent claudication; (d) prophylaxis against TIAs in patients with carotid plaques determining embolization; (e) treatment of venous ulcerations determined by chronic venous incompetence; (f) patients with Raynaud's phenomenon and disease. The tolerability observed was good. No side effects were observed even in more prolonged treatments. The overall efficacy was good for all groups especially in comparison with other treatment already in use for these vascular conditions. In conclusion defibrotide is a particularly useful drug in these vascular diseases and can be used both for acute and chronic treatments.

We carried on an immunological in vitro study on conalbumin, an iron binding protein structurally similar to lactoferrin, a well know bacterial inhibitor of human milk. Conalbumin itself has been proved to have bacteriostatic activity against a broad spectrum of bacteria responsible for gastrointestinal infections. The activity of conalbumin on the in vitro response to PHA, PWM and Con A and on the E-rosette formation ability and does not induce blastic transformation of lymphocytes. However, conalbumin has been able to significantly increase the in vitro response of lymphocytes to PHA and PWM, suggesting an action on both T and B lymphocytes.

One hundred fifty-seven premenopausal women with metastatic breast cancer were prospectively randomized to treatment consisting of oophorectomy + vincristine, prednisone, cyclophosphamide, methotrexate, 5-fluorouracil (VPCMF) (Reg. I) or oophorectomy + cyclophosphamide (Reg. II) or oophorectomy followed by an observation period (Phase 1), followed by VPCMF (Phase 2) (Reg. III). Complete plus partial response rates were 72% on Reg. I, 65% on Reg. II, 18% on Reg. III, Phase 1 and 50% on Reg. III, Phase 2. Median duration of response for Reg. I was 17 months, for Reg. II 16 months, and for Phase 1 and Phase 2 of Reg. III, respectively, 5 months and 8 months. The response rate for patients treated with oophorectomy plus chemotherapy is significantly higher than the response rate achieved with oophorectomy alone as first treatment following the appearance of metastases in premenopausal women.

Four paediatrics patients affected by Chronic Mucocutaneous Candidiasis associated with hypoparathyroidism have been studied. In vivo and in vitro responses to Candida albicans antigens and to other common antigens (Dermatophytin T, Varidase), the percentage of T and B cells and the response to the selective polyclonal phytomitogens (PHA, ConA, PWM) have been investigated in order to quantitate and functionally characterize the B and T lymphocyte classes. The HLA A an B typing has been also performed. Our results show a remarkable and most likely primitive impairment of the T cells, unresponsive either to the C. albicans and the two other skin test antigens or to the selective polyclonal mitogens in vitro. The infectious disease (Mucocandidiasis) is most likely secondary to the T-cell failure. The association between the Mucocandidiasis, hypoparathyroidism and the T-cell deficiency is probably due to a common primitive disembryogenetic defect.

Results of the comparison between tobramicine and ceftriaxone (new long-acting 3rd generation cephalosporin) in the treatment of pediatric acute respiratory tract infections are referred. Treatment with ceftriaxone is judged more advantageous both for efficacy and for saving the number of administered doses.

An immunological in vitro study was carried out on conalbumin, an iron binding protein structurally similar to lactoferrin, which is a well-known bacterial inhibitor in human milk. Conalbumin itself has been proved to have bacteriostatic activity against a broad spectrum of bacteria responsible for gastrointestinal infections. The activity of conalbumin on the in vitro response to PHA, PWM and Con A and on the E-rosette formation ability of peripheral lymphocytes of 10 normal subjects was studied. The results showed that conalbumin did not affect the lymphocytes' E-rosette formation ability and did not induce blastic transformation of lymphocytes. However, conalbumin was able to produce a significant increase in the in vitro response of lymphocytes to PHA and PWM, suggesting an action on both T and B lymphocytes.

Five hundred and sixty-six patients with either Stage III or IV Hodgkin's disease were prospectively randomized to test whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine with procarbazine and prednisone. The combination of CCNU, vinblastine, procarbazine, and prednisone (CVPP) was shown to be a highly effective program with a complete response frequency of 69%. The use of CCNU as part of the induction program was also shown to be the most significant determinant of prolonged remissions (P = .025). Reduced vomiting and neurotoxicity, as well as the oral administration, were the chief advantages of the CVPP as compared with MOPP. These factors resulted in improved patient and physician compliance. The MVPP regimen was also shown to be a highly effective regimen with a complete response frequency of 73% in patients without prior exposure to chemotherapy. However, the induction regimens containing vinblastine were associated with a significantly higher frequency of fatal hematopoietic toxicities than the induction regimens containing vincristine (P = .05). This higher frequency was almost exclusively seen in the elderly or in patients previously treated with both chemotherapy and radiotherapy. At this time, the remission durations maintained by vinblastine with periodic reinforcement are longer when compared with vinblastine maintenance alone (P = .06), but there is no corresponding increase in survival.

The psychiatric histories of relatives of 17 boys admitted to an inpatient unit with "unsocialized aggressive" behavior and of 19 boys admitted with other problems were investigated by means of structured interviews. The interviews were rated blind and diagnoses made on the respondents and relatives described in the family histories using research criteria. Fathers and combined parents of the probands qualified for the diagnosis of antisocial personality disorder more often than the fathers and combined parents of control boys. Uncles of probands and combined uncles and aunts more often had a history of marked antisocial behavior than the corresponding relatives of controls. Siblings of the probands more often had a history of behavior problems as children or adolescents than the siblings of controls. The data suggest an association between unsocialized aggressive reaction in boys and antisocial personality disorder in their adult relatives. Such an association is an interesting contrast to the relationship between hyperactivity in children and alcoholism in their adult relatives.

A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR and high-dose MTX with citrovorum rescue) and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also rendomized: 1) to determine the effects of prophylactic whole brain irradiation; and 2) to establish the effects of maintenance chemotherapy. Survival, frequency of response and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (40% vs. 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs. 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic while brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival.

Conalbumin has been used as a prophylactic treatment in artificially fed babies to prevent enteritic infections. Conalbumin being a heterologous protein, it could have sensitizing properties. The trial here reported demonstrated that when conalbumin-treated milk was fed to 15 such babies for 60 days the values of total IgE, as determined by the radioimmunoassay method, remained within the normal range.

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkin's disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3-drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4-drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3-drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4-drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

The antiepileptic drug therapy of 1912 patients coming from various neurological clinics of Northern Italy has been evaluated in a collaborative survey. The following epidemiological data have been analysed: incidence of the various seizures types, according to the International Classification (Gastaut, 1969), in relation to the age; drug choice and therapeutic schedules in relation to the seizure type and to the age; number of drugs administered in various age and seizure groups; side effects in relation to type, number and plasma concentrations of the administered drugs. The analysis of the drug plasma level determinations, carried out either with gas-chromatographic methods or with the EMIT system, was effected in order to evaluate the number of patients who were under, in or over the suggested therapeutic ranges, the influence of age on drug disposition and the modifications of the drug plasma levels due to drug interactions.