Biomedical subjects
Publications and source records attributed to G Negri.
Ectopic prostatic tissue was found in the spleen in a 49-year-old white man who died of wide-spread malignant mesothelioma. The prostatic origin of the tissue was affirmed by positive immunohistochemical staining for prostatic specific antigen and prostatic acid phosphatase.
D-Lactic acidosis associated with encephalopathy is a clinical condition that occurs in patients with short bowel syndrome. We studied the fecal flora and the composition of fecal water of a child who developed this unusual disorder. Bacteriological studies showed that the patient's stool contained a marked predominance of gram-positive anaerobes. Two strains were identified, Lactobacillus plantarum and Lactobacillus salivarius, as the main bacteria isolated. Fecal water showed pH 4.8 and total lactic acid (sum of L- and D-lactic acids) was the principal organic anion found in the feces. We also incubated the patient's stool in a continuous culture with a view to determining the effect of the pH on the production of volatile fatty acids (VFA) and L- and D-lactic acids. The culture was maintained at pH 5.0, 5.5, 6.0, and 6.5 for four consecutive periods of four days each. We then studied the culture for a further four days at pH 5.0 once again. This study showed that with the progressive rise of the pH from 5.0 to 6.5 L- and D-lactic acids decreased and VFA production increased. D-Lactic acid formation was inhibited at pH 6.5, but when the culture was returned to pH 5.0, it increased to a high level again. These results suggest that the pH plays an important role in the ecological changes in the colonic bacteria that result in D-lactic acid production.
CONCLUSION: Anti-p53-autoantibodies (a-p53-aabs) may suppress the development of distant metastases, but not lymph node metastases. This could explain the significantly prolonged survival of patients with UICC stage III tumors who have a-p53-aabs compared to those without a-p53-aabs. BACKGROUND: Mutation within the tumor suppressor gene p53 leads to increased intracellular p53 protein levels and an increased antibody formation against this molecule. Altered p53 has been proposed to be associated with poor prognosis, and the present study investigated whether the detection of a humoral response to p53 gives evidence for a prognostic or diagnostic parameter in pancreatic disorders. METHODS: We screened 145 patients with pancreatic cancer and 95 patients with chronic pancreatitis for the development of a-p53-aab via ELISA and Western-blotting. p53 expression was examined by immunohistochemistry. RESULTS: We found that 41% of the tissues of patients suffering from pancreatic carcinoma overexpressed p53, and 15.9% of the patients suffering from pancreatic cancer developed a-p53-aab. In pancreatic cancer, we could exhibit a significant correlation between grading, p53-overexpression, survival, and antibody response against p53. A-p53-aabs were significantly more frequent in patients with stage III tumors (tumors with lymph node metastases, but not distant metastases, p < 0.02).
As the goals of palliative cancer treatments have not always been clearly specified, this paper describes how frequently the goals of palliative cancer treatment can be specified according to a given definition and how frequently those specified goals can be achieved. The clinical problems of 171 cancer patients were discussed in the Interdisciplinary Oncologic Conference (IOC) of the Cancer Centre University of Ulm (CCUU) and recommendations concerning further diagnostic treatments and/or therapy were provided. These recommendations had been documented and analysed retrospectively. The goals were classified as either cure or palliation or further investigation. If the goal was palliation, it was investigated whether or not the goal was specified as either alleviation of existing problems or prevention of impending problems. The achievement of the specified goals was assessed. Palliation was the goal of treatment in 119 (71%) of the 168 evaluable recommendations. In 83 of the 119 cases (70%), immediate treatment was recommended. The goal was specified in 57 (69%) of the 83 recommendations and could be realized in 24 of 57 specified cases (42%). Patients in this group survived longer (p < 0.01) than patients in whom the goals could not be achieved. Impending problems could be prevented more often (p = 0.001) in 14 out of 18 cases, while existing problems could be alleviated in only 10 out of 34 cases. It is concluded that specification of the goals of palliation is necessary because it is impossible to decide if a goal of treatment could be achieved or not unless the goal of treatment has been defined (as existing/impending problem). The prevention of impending problems could be investigated in prospectively controlled clinical trials.
INTRODUCTION: Langerhans cell histiocytosis, once called histiocytosis X, is a rare disease. Usually it can occur in children and is characterized by granulomas (eosinophilic granuloma and Hand-Schueller-Christian disease) or by a extensive involvement of various organs (Letterer-Siwe disease). The etiology remains uncertain and could be related to undefined immunologic disturbance. Lesions can involve bone marrow, skin, oral mucosa, retro-orbital tissue, central nervous system, lymph nodes, spleen, liver, lung, and gastroenteric tract. Surgery, radiotherapy and chemotherapy can be employed as treatment. Prognosis is different in relation to the extension of the disease. CASE REPORT: In our case (a 33 year old female) came to observation for swelling in temporal region. The patient underwent clinical and radiological examinations: the lesion involved the skull base in the right part of the sphenoid bone. CT and MRI showed a "clepsydra" lesion with wider extension to infratemporal fossa and to intracranial middle fossa and shrinking in the base of the skull; inside the lesion a lot of wider calcifications were present. A biopsy proved a diagnosis of Langerhans cell histiocytosis. No other localizations of disease were found. The patient was treated with chemotherapy followed by localized radiotherapy. Chemotherapy was performed with 3 cycles of etoposide 260 mg for 3 days every month. After this treatment a response of 25% was observed. Afterwards a radiotherapy with cobalt 60 was employed through two angled wedged fields for a total dose of 22 Gy and conventional fractionation. During the follow-up a slow, partial regression of the lesion with increase of the extension of the calcifications documented by CT and MRI was observed. After 5 years follow-up no progression of disease was observed. DISCUSSION: The usual treatment of Langerhans cell histiocytosis is surgery and eventually radiotherapy for localized disease and chemotherapy for extended disease. The prognosis is related to the number of involved organs: usually favorable with only one site of disease and unfavorable when more organs are involved. Other unfavorable prognostic factors are the age < 2 years, the presence of anemia, liver and spleen involvement and respiratory failure. In our case only one site of disease was evident and the clinical behavior has been quite favorable. The main peculiarities are the radiologic aspect and the slow, partial regression after the treatment; this fact could be related to the presence of wide calcifications inside the lesion. After 5 years follow-up it is possible to consider the absence of progression as a response to the treatment.
The aim of the present paper is to determine the effect of Paracetamol (P) acute intoxication in cholestatic rats. Four groups of animals were considered: controls, controls intoxicated with P, rats intoxicated with P and cholestatic rats. Hepatic biochemical tests and liver histology were performed in every group. It is concluded that cholestatic rats intoxicated with P showed less Liver damage than in control groups.
The recent developments in thoracic surgery have broadened the application spectrum of thoracoscopy. Video-assisted thoracoscopic lung resection is now available both to diagnose and to treat peripheral pulmonary nodules. A major factor limiting the success of thoracoscopic lung resection is the difficult localization of the pulmonary nodule. When lesions are very small and deep inside the lung, their preoperative detection may be difficult. This study was aimed at investigating the effectiveness of hookwires for CT-guided localization of peripheral pulmonary lesions requiring thoracoscopic resection. In 12 patients 12 nodules, previously detected with chest radiography, were localized with hookwires under CT guidance. Ten of 12 patients underwent thoracoscopic resection for diagnostic purposes, while the extant two patients underwent therapeutic wedge resection. In all patients prethoracoscopic hookwire positioning was successful. In 11 of 12 patients the lesion was accurately localized, while in the extant patient the wire tip was inserted deeper than the nodule. In 3 patients the wire was dislodged before surgery: in all of them a small hemorrhage developed on the visceral pleura and wedge resection was likewise possible. Four patients had a small pneumothorax which was not treated before surgery. In conclusion, percutaneous hookwire localization of peripheral lung lesions is an easy and efficacious technique and promotes thoracoscopy as a less invasive alternative to thoracotomy.
Luminal proteolytic activity (PA) of different colonic segments was ascertained in animals subjected to pancreatic duct ligation (PDL) and in control rats. The PDL rats revealed a significant PA reduction in the cecum, proximal colon (P < 0.01), and distal colon (P < 0.005). Proteolytic activity, trypsin, and chymotrypsin activity in control rats diminished progressively from the cecum to the distal colon. Conversely in PDL rats, we found maximal PA in distal colon. The conclusion is drawn that a significant proportion of colonic proteolytic activity can be attributed to pancreatic proteases with a maximal contribution at cecum level.
BACKGROUND: We have recently shown that in achalasia patients morphine has a striking inhibitory action on resting lower oesophageal sphincter (LOS) pressure, which is mediated by opioid receptors. The aim of this study was to investigate the effect of a peripheral opioid agonist, loperamide, administered at a dose of 16 mg, on resting LOS pressure in nine patients with untreated idiopathic achalasia. METHODS: All patients underwent two experiments after oral administration of placebo and loperamide, respectively, on separate days and in randomized order. At the end of the placebo experiment we also tested the effect of loperamide as compared with distilled water, both infused intraluminally at the level of the LOS. In the loperamide experiment, after a 60-min basal period, naloxone, 40 micrograms/kg, was injected intravenously, and recordings continued for a further 10 min. RESULTS: Loperamide administered orally decreased (p < 0.01) LOS pressure by 10 +/- 2 mmHg (37 +/- 7%) compared with placebo, and naloxone intravenously failed to block the effect. LOS pressure was not affected by infusion of either distilled water or loperamide at the level of the LOS. CONCLUSIONS: Our findings indicate that in patients with idiopathic achalasia oral administration of loperamide at a high dose markedly decreases resting LOS pressure. This may not occur through opioid receptor stimulation and requires intestinal absorption of the drug. The possible effect of combining a small dose of loperamide with the traditional achalasia drugs awaits further evaluation.
Seventy-three cases of paranasal sinus tumors observed between 1980 and 1991 were retrospectively analyzed. Our series consisted of 50 men and 23 women aged 43 to 83 years. Histology demonstrated 33 squamous cell carcinomas, 20 adenocarcinomas, 10 undifferentiated carcinomas, 3 mucoepidermoid carcinomas, 3 adenoid-cystic carcinomas, 2 osteosarcomas, 1 fibrosarcoma and 1 melanoma. All patients were untreated. The lesions from maxillary sinus consisted of 3 T2, 13 T3 and 39 T4 tumors; 50 cases were N0 and 5 N+. "Central" neoplasms consisted of 6 stage I, 7 stage II and 5 stage III lesions. All patients underwent irradiation (with 60Co) with two angled fields or three fields -2 opposing lateral and 1 anterior. Critical structures were shielded when possible and wedges were used to optimize dose distribution. Locoregional lymph nodes were treated in N+ cases only. Dose distribution was studied on CT images. All patients received a total dose of 54-72 Gy (mean: 61.4, median: 62 Gy) with 1.8-2 Gy/day fractions for 5 days/week. After irradiation 27/73 (30.8%) complete responses were observed. Local control at 6 months was obtained in 17/73 cases (23.3%) and it was correlated with the total dose. Actuarial survival rates at 3 and 5 years were 27.9% and 21.8%, respectively. At the multivariate analysis, the only significant variable was the stage; no correlations were found with sex, histology and site. During follow-up, lymph node metastases were observed in 4/66 initially N0 cases. Distant metastases were found in 10/73 patients (13.7%) and secondary lesions in 8/73 (11%). Severe complications were observed in 7/73 cases (9.6%).
We report on 2 phenotypic sisters, one with 46,XY; the other with 46,XX. The 2 girls had similar related internal malformations, including agonadism, hypoplasia of the right pulmonary artery, hypoplasia of the right lung, isolated dextrocardia with complex vitium cordis, and diaphragmatic hernia (only sib 1) or omphalocele (only sib 2). This combination of malformations did not fit into any of the previously described syndromes. For this syndrome we suggest the acronym PAGOD ([hypoplasia of the] pulmo, and pulmonary artery, agonadism, omphalocele/diaphragmatic defect, dextrocardia). The occurrence of a basically similar set of malformations in 2 unlike sex is interpreted as evidence for autosomal recessive inheritance. The different gonosomal status excludes the Y chromosome as a responsible factor. The peculiar finding of a 46,XX sex chromosome constitution combined with agonadism and an intact urogenitral tract emphasizes the concept of secondary regression of Wolffian and Müllerian structures. The associated malformations of mesodermal structures can be interpreted as midline defects. We suggest that, from the developmental field perspective, secondary regression of midline structures including the gonadal anlage explains the pathogenesis reasonably well.
Following the exclusion of the ventilation of a lung, perfusion is arrested as a consequence of the Von Euler and Liljestrand vasoconstrictive reflex. However it is as yet unknown how long this phenomenon takes to manifest itself in human beings. In order to verify whether hypoxic pulmonary vasoconstriction follows immediately on the arrest of ventilation or whether there is one some delay, in 21 candidates for pneumonectomy a bronchial block was provoked during fibrobronchoscopy and the hemogasanalytic modifications induced by the acute occlusion of the main bronchus have been studied. The analysis of the resulting data allows for the hypothesis that the exclusion of lung ventilation for 14 minutes is not sufficient to cause the complete manifestation of the hypoxic vasoconstrictive reflex.
Impairment of non-cholinergic innervation of the lower oesophageal sphincter has been suggested in idiopathic achalasia. As opioid nerves are present in the lower oesophageal sphincter and opioid peptides affect lower oesophageal sphincter motility, the effect of an opioid agonist, morphine (100 micrograms/kg iv), and an opioid blocker, naloxone (80 micrograms/kg iv), on lower oesophageal sphincter motor function was assessed in 10 healthy subjects and in 10 patients with untreated idiopathic achalasia on separate days and in randomised order. In addition, in six of the patients, naloxone 0.8 mg iv was injected 60 minutes after morphine and recordings continued for a further five minutes. Lower oesophageal sphincter pressure was monitored by a sleeve device. In the healthy subjects morphine decreased (p < 0.01) resting lower oesophageal sphincter pressure by 4 (1) mm Hg (23 (8)%). In the achalasia patients the effect was more marked, lower oesophageal sphincter pressure being reduced (p < 0.01) by 11 (2) mm Hg (46 (8)%). Naloxone reversed lower oesophageal sphincter pressure to basal. Both absolute and percentage decreases after morphine were significantly greater (p < 0.05) in the achalasia patients than in the healthy subjects. Swallow induced lower oesophageal sphincter relaxation was significantly decreased (p < 0.05) by morphine in the healthy subjects but not in the achalasia patients. Naloxone had no effect on resting lower oesophageal sphincter pressure or swallow induced relaxation in either healthy subjects or achalasia patients. In conclusion achalasia patients are hypersensitive to the effect of morphine on resting lower oesophageal sphincter pressure. This finding is unlikely to be the result of a denervation process involving opioid nerves.
The influence of right hemicolectomy (RH) on fecal nitrogen excretion was determined with selected protein levels up to 25%. The endogenous fecal N was determined by extrapolating protein intake to zero. Fecal N was higher in RH than in control rats at all protein levels used. However, the slope of regression curves describing fecal nitrogen excretion was greater for RH compared with the control group. The endogenous fecal nitrogen was not significantly different between the two groups of rats. The feces from rats fed with 25% of protein were partitioned into individual fractions by physical separation and a study was made of the distribution of nitrogen in the bacterial, soluble and fiber fractions of the stool. RH decreased the N excreted in the bacterial fraction by 33% (from 1.71 +/- 0.32 to 1.15 +/- 0.18 mmol/day) and increased the N excreted in the soluble fraction by 280% (from 1.60 +/- 0.30 to 6.08 +/- 1.16 mmol/day). These results show that the RH increased the fecal N excretion and that this N is mainly in the soluble fraction.
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In the present study 90 patients affected with pyriform sinus carcinomas are analyzed. They underwent irradiation alone from 1970 to 1986. All cases were staged according to TNM criteria (UICC 1982): 7 were T1, 16 T2, 40 T3, 27 T4, 36 N0, 18 N1, 3 N2, 33 N3. Radiotherapy was performed with 60Co. In all cases doses of 60-70 Gy were delivered to T and N1 and doses of 45-50 Gy to N0. Locoregional control obtained in 35 patients (38.9%): 6/7 T1 (85.7%), 9/16 T2 (56.2%), 15/40 T3 (37.5%), 5/27 T4 (18.5%) and 20/36 N0, 8/18 N1, 1/3 N2, 6/33 N3. The overall and NED 3-year survival rates are 23.3% (21/90) and 20.0% (18/90), respectively; at 5 and 10 years all patients alive are NED, with survival rates of 12.2% (11/90) and 9.8% (5/51) respectively. Locoregional failures were observed in 12/35 cases (34.3%); 91% of them occurred within the first two years of follow up (mean: 10 months). Distant metastases appeared in 26/90 patients (28.9%) and secondary tumors occurred in 10/90 cases (11.1%). Our experience confirms radiotherapy to be an effective alternative treatment to surgery in the early stages (I-II) of pyriform sinus carcinomas, but no more than only a palliative treatment in stage III-IV cancers.
The present study is the continuation of a previous programme performed by a mail or phone questionnaire. In this study 18 subjects with anorexia nervosa were submitted to a clinical semi-structured interview, and underwent a medical examination regarding eating habits and Rorschach tests. Clinical results seemed to be quite satisfactory (none died and 84% were greatly improved or had recovered clinically) whereas the psychopathologic aspects were less positive. The authors conclude that complete clinical evaluation can be considered the only safe approach for the understanding of the clinical course.
Deep venous thrombosis is very frequent after general surgery, and its major complication, pulmonary embolism, is today the most frequent cause of postoperative death. The reduction of this cause of mortality is mainly based on its prevention rather than its therapy. This purpose was achieved by using physical and pharmacological means. During the past 15 years, low-dose heparin has been one of the most important means in the prevention of deep venous thrombosis, associated with early mobilization of surgical patients, but its actual efficacy against fatal pulmonary embolism was never statistically proved. In the early 80s new heparins became available, and their first experimental and clinical use demonstrated a longer half-life, a higher anti-Xa activity, and a lower haemorrhagic risk. On the basis of these data, we started a study in order to assess efficacy and tolerance of the new low-molecular-weight heparin CY 216 in preventing fatal pulmonary and thromboembolic death in patients undergoing general surgery. The study was designed as a multicentre, double-blind, randomized, controlled clinical trial versus placebo. A total of 4,498 patients, aged over 40 years undergoing general surgery, with anaesthesia lasting at least 45 min, were consecutively enrolled in the 18 centres which took part in the trial. 2,247 accounted for the CY-216-treated group and 2,251 for the placebo group. The patients received either subcutaneous injections of 0.3 ml of CY 216, equivalent to 7,500 anti-Xa units, or of 0.3 ml of a saline solution supplied in an identical form. The first dose was administered 2 h before surgery, the second 12 h later, and then once daily for at least 7 days. A post-mortem examination was carried out in every patient who died. The trial began in February 1986 and ended in June 1988. Statistical analysis showed that the two groups of patients were well matched for age, sex, type of disease, site and duration of operations, as well as for the incidence of risk factors which could predispose to the thromboembolic disease. Twenty-six deaths were recorded and validated. Eight (0.36%) belonged to the CY 216 group and 18 (0.80%) to the placebo group. In the CY 216 group, pulmonary embolism was the direct cause of death in 2 patients (0.09%), while the remaining 6 deaths could not be ascribed either directly or indirectly to thrombosis. In the placebo group, pulmonary embolism was the cause of death in 4 cases (0.18%; p less than 0.05) and contributed to death in 4.(ABSTRACT TRUNCATED AT 400 WORDS)