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Background: Whereas sublingual allergen immunotherapy (AIT) is routinely performed without any adjuvant or delivery system, there is a strong scientific rationale to better target the allergen(s) to oral dendritic cells known to support regulatory immune responses by using appropriate presentation platforms., Objective: To identify a safe presentation platform able to enhance allergen-specific tolerance induction., Methods: Virosomes with membrane-integrated contiguous overlapping peptides (COPs) of Bet v 1 and TLR4 or TLR2/TLR7 agonists were assessed for induction of Bet v 1-specific IgG1, IgG2a and IgE antibodies, hypersensitivity reactions and body temperature drop following subcutaneous injection in naive CD-1 mice. The most promising candidate, Bet v 1 COPs anchored to virosomes with membrane-incorporated TLR4 agonist (Vir.A-Bet v 1 COPs), was further evaluated by the sublingual route in a therapeutic setting in BALB/c mice with birch pollen-induced allergic asthma. Airway hyperresponsiveness, pro-inflammatory cells in bronchoalveolar lavages and polarization of Th cells in the lungs and spleen were then assessed., Results: Both types of adjuvanted virosomes coupled to Bet v 1 COPs triggered a boosted Th1 immunity. Given a more favourable safety profile, Vir.A-Bet v 1 COPs were further evaluated and shown to able to fully reverse asthma symptoms and lung inflammation in a sublingual therapeutic model of birch pollen allergy., Conclusions and Clinical Relevance: We report herein for the first time on the capacity of a novel and safe presentation platform, that is virosomes with membrane-integrated TLR4 agonist, to improve dramatically sublingual AIT efficacy in a murine model due to its intrinsic dual properties of targeting and stimulating to further promote anti-allergic immune responses. As such, our study paves the ground for further clinical development of this allergen presentation platform for patients suffering from respiratory allergies., (© 2020 John Wiley & Sons Ltd.)

Introduction: Interleukin-5 (IL-5) is the principal cytokine regulating eosinophil growth, differentiation, activation, and expression. It is a specific target of mepolizumab, an anti-IL-5 monoclonal antibody used in the treatment of severe eosinophilic asthma. This new drug can improve symptoms, reduce asthma exacerbations and steroid use. Few data are available on its efficacy for nasal symptoms., Objective: To describe the all-round clinical impact of mepolizumab in a real-life setting, evaluating the efficacy and safety of the drug in severe eosinophilic asthma patients., Population and Methods: We retrospectively collected the clinical and functional data on 27 patients (16 males) affected with severe eosinophilic asthma, diagnosed at the Siena Regional Referral Centre and monitored for 6 months. Clinical, immunological, and functional data at baseline and follow-up were entered in a database together with comorbidities, number of exacerbations, steroid treatment, multiple-flow exhaled nitric oxide, and validated questionnaires., Results: A significant reduction in asthma exacerbations was observed in all patients after 6 months of the biological therapy (p = 0.0009), and 4/6 patients discontinued chronic oral steroids. A significant improvement in ACT, FEV1, SNOT22, and alveolar nitric oxide was observed after 1 month of mepolizumab (p = 0.003, p = 0.007, p = 0.047, and p = 0.019, respectively) and maintained after 6 months of treatment. After 6 months, FeNO 50 was reduced as well (p = 0.030). Mepolizumab was very well tolerated, and no major side effects were observed., Conclusions: Our study suggests that mepolizumab is effective in improving control of asthma, lung function parameters, exhaled biomarkers, and nasal symptoms in patients with severe eosinophilic asthma., (© 2020 S. Karger AG, Basel.)

The relation of infectious agents to arthritis is an area of great interest to the rheumatologist. Septic arthritis of bacterial origin accounts for approximately 6.5% of all childhood arthritides. Septic arthritis usually results from haematogenous spread from a focus of infection elsewhere in the body, but also by direct extension of an infection from overlying soft tissues or bone or traumatic invasion of the joint. As a result, if a focus of underlying osteomyelitis breaks throught the metaphysis, it may enter the joint and result in septic arthritis. Systemic signs of illness are fever, severe bone pain, and tenderness with or without local swelling. A wide range of microorganism can cause septic arthritis in children; Staphylococcus aureus and nongroup A and B streptococci are most common overall. However, different organisms are more common at some ages and in certain circumstances. Kingella kingae is an emerging pathogen in young children under 4 years of age. The clinical presentation of K. kingae invasive infection is often subtle and may be associated to mild to moderate biologic inflammatory responses. Affected children often have few signs and symptoms of osteoarticular infections. Early MRI is useful in differentiating K kingae from Gram-positive cocci in osteoarticular infections. Cartilaginous involvement, modest soft tissue and bone reaction suggest K. kingae. It's very important to include K. kingae in differential diagnosis of osteoarticular infections in young children. We report an unusual case of osteomyelitis: clinical manifestations and MRI are suggestive for K kingae infection.

In this study the Author's analyze their experience (between September 1973 and December 2002) with 108 pulmonary resections for metastatic tumors to the lungs to evaluate prognostic factors and the impact on survival of extended metastasectomy. Overall mortality and major morbidity were 1.85% and 2.78%. The actuarial survivals at 5 and 10 years were respectively 46.6% and 39.9%. The best mean survivals are observed in patients with metastases from breast, colorectal, thyroid and urinary tract carcinomas, in cases with disease free interval > 12 months and in the patients who underwent sequentially surgery and chemotherapy. Patients with pulmonary metastases also potentially benefit from iterative pulmonary resection.

The aim of this preliminar report is to evaluate alfa and beta tubulins, components of cellular microtubules, alterated expression in sporadic colorectal cancer patients. The Authors considered 16 patients who underwent surgery for sporadic colorectal carcinoma with radical intent. Alfa and beta tubulins were evaluated in tumoral mucosa by immunohistochemistry. In 56.2% of the examined patients a low expression of alfa and beta tubulins was showed while the alteration of alfa tubulin was showed in 81.2% of the patients. This finding supports the hypothesis of Porter that alterations in microtubule structure might be part of the cellular response to DNA damage.

The Authors review the natural history of colorectal cancer from the point of view of molecular biology and genetics from aberrant crypts foci and familiar adenomatous polyposis to hereditary non polyposis colon cancer and sporadic colorectal cancer. They carry out international literature about basis knowledges, experimental trials and personal studies. Up to day traditional colorectal cancer surgical treatments and adjuvant or neoadjuvant pharmacological therapy cannot be modified, nevertheless "new drugs generation" known as signal transduction inhibitor could, in the future, prove to be an effective cancer treatment. The Authors highlight recent experimental clinical trials probably able to prevent sporadic colorectal cancer spreading and precursor evolution.

The surgical treatment of large bowel malignant tumors is now the most important therapeutic approach. The aim of our study was to evaluate a possible prognostic implication of ploidy and NM23 expression. The study includes 120 non selected patients who underwent surgery for colorectal cancer. The analysis of ploidy was obtained with cytometric test. The cases with only one gaff G0/G1 were considered as diploid. Patteras with more than one aneuploidic population were classified as multiploidic or poliploidic. While NM23 expression was evaluated with a double blind retrospective study by two separate equipe of authors in different centres. NM23 positivity degree was classified in 3 classes: absent or weak if < 10%; moderate if 10-50%; strong if > 50%. Forty-two patients (35%) were classified as diploidic; 30 patients (25%) as aneuploidic; 40 patients (33.2%) as multiploidic; in 8 cases (6.7%) the material was inadequate. Among the two groups who evaluated NM23 expression the group I a positivity: absent or weak in 32 cases (26.7%); moderate in 62 cases (51.7%); strong in 26 cases (21.6%); while the group II shows positivity: absent or weak in 30 cases (25%); moderate in 52 cases (43.3%); strong in 38 cases (31.7%). We cannot consider ploidy and the NM23 research as independent prognostic factor.

Neurogenic neoplasms represent approximately 20% of the space-occupying lesions in the mediastinum. They are primary tumors originating from structures belonging to the peripheral or sympathetic nervous system, they are most commonly diagnosed in subjects in the age range between 10 and 30 years. Benign forms are significantly more frequent than malignant forms, an observation that was confirmed by our own experience; whether these tumors have a predilection for the male or female sex cannot be concluded from the various case series studied to date. Surgical resection can be considered the treatment of choice on the basis of the long-term results, which are greatly satisfactory in benign tumors and encouraging in the malignant variants.

It's shown by literature and confirmed by Author's experience that, on account of the excellent results, prosthetic repair of inguinal hernia is more effective than "conventional" (Bassini, Mc Vay, Shouldice). Between January 1993 and December 2000 were observed 875 patients with inguinal hernia (814 monolateral, 61 bilateral); all patients underwent a Lichtenstein repair both in the primary version and in its variations (internal ring plastic, trasversalis plicate, plug repair). The patients were discharged from hospital within 24 hours after surgery in 90% of cases. No important intraoperative complications were observed; the patients restarting work varied from 3 to 15 days after the discharging in relation to patient anxiety, onset of complications and to the type of work. The complications observed were: urine retention (1.6%), superficial haematoma (1.3%), superficial infection (1%), wound suppuration (0.5%), serous effusion (0.7%), postsurgery pain (2.1%), scrotal edema (1.7%), persistent inguinal neuralgia (0.6), local hypoesthesia (4.3%), ischemical orchitis (0.1%), recurrence (0.2%). In conclusion Authors assert that "tension free" repair allows optimal results both for the surgery point (easiness of the technique, repeatability, less invasivity, scanty incident of recurrences, low frequency of postoperative complications) and in economic terms, allowing an early mobilization of the patients. A further improvement would be obtained with more care in surgical and patient management, with more excellent results.

A second thoracotomy in patients who have undergone previous chest surgery can be performed soon or immediately after the first operation and is usually aimed at resolving severe or even life-threatening postoperative complications. Late reoperations, on the other hand, are either performed to resolve complications of previous surgery or to remove second primary lung tumors (SPLCs) or metastases. The most exacting reoperation in this context is completion pneumonectomy, which is particularly indicated in the case of failure of the residual lobe to re-expand after primary surgery; it is also used for--rarely occurring--fistulas of the lobar bronchi and for new ipsilateral primary lung tumors. This type of surgery is technically complicated and has been associated, in our experience and that of others, with a certain mortality. Technically less difficult is a second ipsilateral thoracotomy for exploratory purposes or minor parenchymal resection, and the same is true of contralateral lobar or sublobar resections. Lastly, Abruzzini's operation, for fistulas of the primary bronchus, is relatively complicated but often leads to good results; we have performed 15 such operations with only one death occurring due to acute myocardial infarction.

A marked worldwide increase in the prevalence of pulmonary tuberculosis has occurred over the past 15 years. The reasons for this change include the worldwide epidemic of AIDS, poverty and the unprecedented extent of migration. We selected 47 patients with pulmonary tuberculosis or its sequelae for 51 surgical operations, with a high prevalence of subjects under 50 years of age (48.9%). There were three major non-fatal complications, and three minor complications. One patient died on postoperative day 1 as a result of unrelated causes. At present, surgery for tuberculosis of the lungs is mainly indicated when all medical treatments have proved ineffective or in circumstances where complete control of complications or disease sequelae is necessary, provided there is a correct indication and a flawless execution.

The basic assumption as rationale of this research was that DNA repair genes (MMR system) are at beginning of the genetic mutational cascade causing the induction of oncogenesis of sporadic colorectal cancers as well as their multiclonal heterogeneity. In a previous study the Authors randomly selected, from a series of 256 patients, 29 patients up to the age of 60 years who underwent surgery for colorectal carcinoma with radical intent. All selected cases were considered as sporadic cancers from a clinical point of view, since none of them fulfilled the Amsterdam criteria for HNPCC and familial adenomatous polyposis was included too. Mismatch repair gene proteins expression and, in particular, gene hMSH2 protein was investigated by immunohistochemistry analysis. In 12 cases (41.4%) hMSH2 exhibited strong expression in the tumoral cells as well as in the surrounding mucosa and at distant mucosa. In 14 cases (48.3%) loss of hMSH2 protein expression was observed in tumoral cells and low immunoreactivity was detected in peritumoral mucosa while strong hMSH2 expression was observed in distant mucosa. In a third small group of patients (10.3%) loss of hMSH2 protein expression was detected in tumoral, adjacent and at distance normal mucosa. After a five years follow up, 100% of twelve patients of first group are still alive vs 64.3% of fourteen patients of second group, while in the third group only one patient survives. These results support the hypothesis of an involvement of hMSH2 gene defect in development of a subset of sporadic colorectal cancer. For the patients with strong expression of hMSH2 in the tumoral cells as well as in the surrounding mucosa and at distant mucosa, this parameter could represent an independent criterion for a good prognostic value.

Environment, climate and habits of many saharan nomadic and partially nomadic tribes are similar: and diseases they suffer from are consequently similar. An outline is presented of two of these tribes, Tuaregs and Tubu, the most interesting because of their historical and anthropological features. The first are mainly settled in the mountain ranges of central Sahara (Tassili, Hoggar, Iforas and Air) and in the huge plain at the north of the Niger river. The Tubu people are originally from the Tibesti mountains, but are now spread farther afield and tend to be found in small number in other areas of Tchad and in oases of eastern Niger desert. The medical system that these tribes developed before the colonial presence is a mixture of logic and effective practical conduct with superstitious and ineffective spells. The use of natural drugs and the treatment of traumatic events are similar, but the hygienic customers are totally different.

Chest injuries have a high and steadily increasing incidence in western countries, but only some of the most common problems they create require an emergency thoracotomy or surgical video thoracoscopy. Flail chest, persistent pneumothorax, massive haemothorax, mediastinal emphysema, cardiac tamponade and intrathoracic foreign bodies can be identified as major surgical problems. Some of such patients (i.e. those with flail chest or foreign bodies) would be immediately candidates for major intervention. Other require fast but diagnostic procedures, because the choice of a therapy is dependent upon a precise identification of the damage. Injuries of trachea and primary bronchi, oesophagus, diaphragma, vena cava, great lung vessels, heart and aorta may represent important surgical emergencies; some leading rapidly to death. Fortunately, major surgical procedures are not really frequent in the management of thoracic traumas. Only 42 (3.5%) of nearly 2,000 patients with non-penetrating thoracic injuries had a thoracotomy or an surgical video thoracoscopy. The figure is far different for penetrating wounds; in fact 12 patients (41%) of 29 underwent mayor surgery.

The term "limit" applied to cancer surgery, denotes the ideological moment beyond which one cannot and should not propose any aggressive treatment. Such limits may concern the operability of a patient and may be represented by some general characteristics independent of the patient's current disease status (e.g. very old age, poor performance status, poor cardiac, respiratory, renal hepatic or mental conditions). They may concern the neoplastic involvement of the organ affected by the tumor: if undertaken, surgery should guarantee a reasonable duration of life, and a quality of life that makes it worth living. Other factors to be taken in consideration are the possibility the tumor spread to local or distant sites, as well as certain extreme conditions such as cancer, cachexia, liver/kidney failure, irreversible septic-toxic shock, ect. Moreover, there may be limits related to the structural conditions of the establishment where the operation is to be carried out (facilities, equipment, pharmacological supplies, medical and paramedical personnel) and to the social environment and the economic situation of the patient, in view of the assistance required following surgery. Lastly, a severe assessment of one's own fitness to perform any specific task should be part of the daily preparation of any surgeon.

Over the past 30 years, there has been considerable controversy regarding the role of segmental and wedge resections in the management of stage I (T1-T2N0M0) non-small-cell lung cancer. Recently, a prospective randomized trial (Lung Cancer Study Group, 1995) revealed unfavorable results after limited resection, which, in early stage lung cancer, remains a reasonable option for patients with compromised pulmonary reserve, especially those in whom a previous contralateral resection has been performed. The following report describes the role of limited resection in the management of patients with T1-T2N0 non-small-cell lung cancer and presents a retrospective review of our series of 125 limited resections out of 1356 resections performed for lung cancer. In particular, long term survival and the frequency of local/regional recurrence were noted in 92 cases operated on with a curative intent. 26.6% vs 12.5% local/regional recurrence rates were observed among patients undergoing limited resections for T2 and T1 lung cancer, respectively. The five year survival in the limited resection group was 13.5% for T1 and 60% for T2 vs 51% and 72% in the standard procedure group, respectively. The lobectomy results were superior to those of sublobar resection. The latter should be reserved for patients in poor general condition contraindicating a standard lobectomy.

Lung tumors invading the chest wall are classed as belonging to the T3 group and are considered potentially resectable. Their management, however, is controversial, and extrapleural resection, when possible, is preferred to en bloc resection which is regarded as a far more invasive and dangerous operation. Five year survival rates for completely resected cases range in the literature from 25 to 35%, but survival rates are much worse if lymph node metastases are present. These poor outcomes have prompted the development of combined surgical approaches: preoperative radiation therapy, with or without chemotherapy, has been used with an improvement in resectability rates, but only modest results in terms of median survival; in a number of case series, increased operative morbidity and mortality have been reported with this approach. The present report relates to 122 patients treated by en bloc (20 cases) or extrapleural (102 cases) resection, 31 of whom also received neoadjuvant treatment. The operative mortality was 4.6%. Median survival was 17 months after en bloc resection and 19 months after extrapleural resection. Though no statistically significant difference was found, extrapleural resection would appear to yield better results than the en bloc procedure.

Pneumonectomy for benign disease of the lung is a rather infrequent intervention. A retrospective study based on 1900 pulmonary resections performed in our institute up to 1998, identified a total of 15 patients submitted to pneumonectomy for non-neoplastic disease. Indications were chronic infections in 11 cases, congenital malformations in 2 cases, left primary bronchial stenosis caused by closed thoracic trauma one in case and gunshot wound in one case. Access to the lung was obtained in all cases by a classic postero-lateral thoracotomy: intra-pericardial ligature was required in five cases and in one patient an extrapleural pneumonectomy was performed. The intra-operative mortality was 20% and the average time of hospitalization 27 days. One patient, operated for pulmonary tuberculosis, developed a broncopleural fistula requiring a second operation. In conclusion, the use of pneumonectomy for non-neoplastic diseases presents serious problems and may be associated with major complications.

The incidence of second primary lung cancer (SPLC) seems to have increased in recent years. In our series that included more than 4000 patients with lung cancer and 1600 operations, we observed 26 cases of SPLC up until June 1999. We considered the standard criteria accepted by most authors for the selection. Characteristics of patients and tumors at the time of the first operation were compared with the statistical data of our general series. Age, sex, performance status and smoking were all considered, as well as cancer site, histology, stage and type of first surgical operation. No significant independent factor could be identified for the prediction of a new tumor at that time. A second operation was possible in 16 cases: two patients died in the postoperative period, two survived for 12 and 24 months, respectively, 12 are still alive 8-87 months after the new resection. The high rate of surgical cases (16/26 = 62%) and a good survival rate is clearly correlated with an early diagnosis of SPLC.

Perioperative morbidity in elderly patients has decreased in last years, with the advent of newer surgical, anaesthetic and monitoring techniques, but is still important when compared with that of younger patients. Complications in the post-operative show different frequencies and mainly depend: a) on age-related conditions of pulmonary, cardiovascular and renal functions, of C.N.S. and of nutritional status; b) on surgery and medication-related risk factors, inclusive of emergency, bedrest, analgesia and infusions, drugs and intensive care; c) on neoplastic or non-neoplastic disease, type of surgery and surgeon's experience. Appropriate surgical intervention, therefore, should not be deferred because the patient is elderly, but surgeon must look beyond measured indices to the qualities of vitality and motivation.

Background: The survival rate for surgically resected stage III N2 non-small cell lung cancer (NSCLC) patients is less than 10%., Methods: A phase II study of cisplatin, epirubicin, and VP-16 (PEV) was undertaken in an attempt to improve the curative potential of surgery. Forty-one patients with stage III N2 NSCLC received 3 cycles of pEV. Patients with either complete response (CR) or partial response (PR) underwent surgery and 3 additional courses of PEV., Results: The response rate in the whole patient population was 58%. Eighteen patients were resected; twelve resections were complete and 6 were incomplete. Toxicity was mild and consisted mainly of myelosuppression. Twenty-six patients have died, and the median survival of all 41 patients was 18.1 months, with a 3-year survival of 23%. The median survival for those patients who were resected was 27 months with a 3-year survival of 42%., Conclusions: PEV is an effective low toxic drug combination for limited NSCLC.

Objective: To assess the pharmacokinetics after i.v. administration of a recombinant human LH and to compare them to those of a reference hMG preparation containing urinary human LH., Design: Prospective, dose-escalating, cross-over study., Setting: Phase I clinical research environment., Patient(s): Twelve healthy pituitary down-regulated females., Intervention(s): Subjects received single i.v. doses of 300, 10,000, and 40,000 IU of recombinant human LH, followed by a single i.v. dose of 300 IU of hMG, all separated by 1 week., Main Outcome Measure(s): Pharmacokinetic parameters., Results: For both preparations, LH serum levels were well described by similar biexponential models. The pharmacokinetics of recombinant human LH were linear over the 300 to 40,000 IU range. After a rapid distribution phase with an initial half-life of 1 hour, both recombinant human LH and urinary human LH were eliminated with a terminal half-life of 10-12 hours. Total serum clearance was 1.7 L/h with < 4% and 30% of the dose being eliminated in the urine for recombinant human LH and urinary human LH, respectively. The volume of distribution at steady-state was approximately 10 L. Irrespective of the dose, recombinant human LH was well tolerated., Conclusion(s): The pharmacokinetics of recombinant human LH are linear with dose and similar to those of urinary human LH.

Objective: To assess the single-dose pharmacokinetics of a recombinant human LH preparation administered by the i.v., i.m., and s.c. route., Design: Prospective, randomized cross-over study., Setting: Phase I clinical research environment., Patient(s): Twelve healthy pituitary down-regulated females., Intervention(s): Subjects received single i.v., i.m., and s.c. doses of 10,000 IU of recombinant human LH, each separated by 1 week., Main Outcome Measure(s): Pharmacokinetic parameters., Result(s): After single i.v. administration, the pharmacokinetics were described by a two-compartment model, after i.m. or s.c. administration, by a one-compartment model with zero order absorption and a lag time. Using the immunoassay, after i.v. administration initial half-life was 1 hour and terminal half-life was 10 hours (half-life was prolonged after extravascular administration, suggesting rate-limiting absorption). Total serum clearance was 2.6 L/h, and steady, state volume of distribution was 14 L. Observed Cmax, after i.m. and s.c. administration, was 43 IU/L with median tmax of 9 hours (i.m.) and 5 hours (s.c.). Bioavailability was 0.54 (i.m.) and 0.56 (s.c.). The pharmacokinetics of LH are comparable using an in vitro bioassay., Conclusion(s): The terminal half-life of recombinant human LH is around 12 hours and is slightly prolonged after extravascular administration. The pharmacokinetics are similar after i.m. and s.c. injection, and one-half the administered dose is available systemically.

Objective: To assess the pharmacokinetics of a recombinant human LH preparation and its pharmacokinetic and pharmacodynamic interactions with recombinant human follicle-stimulating hormone (FSH)., Design: Prospective, randomized cross-over study., Setting: Phase I clinical research environment., Patient(s): Twelve healthy pituitary down-regulated females., Intervention(s): Subjects received 150 IU of s.c. recombinant human LH and FSH, either alone or in combination, followed by recombinant human LH and FSH once daily for 7 days., Main Outcome Measure(s): Pharmacokinetic parameters, ovarian follicle development., Result(s): No pharmacokinetic interaction between recombinant human LH and FSH was observed, with no significant difference in baseline-corrected maximal observed concentration over baseline, area under the concentration-time curve from t = 0 to t = 24 hours, or time to maximal concentration after single doses alone or in combination. After daily administration, the mean accumulation ratio was 1.6 for LH and 2.9 for FSH, with absorption and terminal phase half-life estimates of 4 and 11 hours for LH and 8 and 16 hours for FSH, respectively. Combined administration of FSH and LH for 7 days was effective in stimulating ovarian follicular development and steroidogenesis, with large interindividual variability related to ovarian sensitivity., Conclusion(s): A new recombinant human LH preparation has a low accumulation ratio at steady-state and no pharmacokinetic or pharmacodynamic interactions with recombinant human FSH.

The results of a series of 3,596 patients affected by lung cancer and submitted to multimodality treatment are reported. Long-term survival at 5 and 10 years of resected patients was related to cancer staging: 5 years after surgery 63% of treated patient died because of metastasis and only 12% because of local recurrence, while after 10 years metastases were observed in 40% and local recurrence almost in none.

Removal of foreign bodies from the tracheobronchial tree is generally possible by bronchoscopy. Seldom requested is a thoracotomy, to be considered an "ultima ratio" for cases with asphyxia, with an acute or chronic obstructive pulmonary infection, for cases-finally-of very little foreign body in a peripheral location. We collected in the past fifteen patients who had a thoracotomy for a tracheobronchial foreign body: extensive description is given of our most recent case.

An inflammatory pseudotumour of the lung was occasionally observed at radiology and is reported. Such lesions account for 1% of all lung tumours and are frequently asymptomatic; the findings on physical and laboratory examinations are usually nonspecific. Radiographic findings and invasive diagnostic procedures--including bronchoscopy and transthoracic fine needle biopsy--may be not sufficient for histological diagnosis. Surgery is then important for both diagnostic and therapeutic reasons; the treatment of choice is complete but non extensive excision. Radiotherapy should be considered in patients who had incomplete surgical resection or postoperative recurrences and in patients non resectable due to associated medical conditions.

The authors examined 23 precipitin-positive symptomatic patients with Farmer's Lung(FL) and compared them to different groups of exposed asymptomatic precipitin-positive(EAPP) and precipitin- negative(EAPN) farmers. The sera were tested using several techniques (i.e., immunodiffusion and ELISA for specific antibodies; polyethylene glycol [PEG] for circulating immune complexes [CIC]) in an attempt to find an in vitro test correlated with the disease which could also provide an insight into the pathogenic mechanisms of Farmer's Lung. Circulating immune complexes formed by IgG were significantly higher in Farmer's Lung patients than in EAPP subjects. In polyethlyene glycol precipitates from Farmer's Lung patients, specific antibodies found by ELISA correlated well with serum positivity, but they were not found in EAPP subjects. The possibility that the circulating immune complexes found were Ig aggregates was ruled out, as was the possibility that the antibodies found in the polyethylene glycol precipitate were also due to an unspecific link. The authors suggest that the circulating immune complexes of Farmer's Lung patients contain specific specific antibodies and that since their composition is different in EAPP subjects, these circulating immune complexes may play a role in the pathogenesis of the disease.

The method of guided-interview on selected questionnaires was employed for the assessment of quality of life in patients radically resected for lung cancer. A selection of thirty patients was done in a group of 151 long-term survivors non treated by adjuvant therapy. An assessment protocol and personal results were discussed.

A correlation between the personality profile and the clinical history in lung cancer patients was studied. Selection of cases included in the sample only surgical patients with a medium educational level and a tested capability to understand a specific questionnaire. One hundred and seventy patients were selected and the so-called C.R.I.C.S. (Clinical-Rated Inventory of Character Style) was applied. Score variations were recorded after curative resection as well as during relapse. Changes in the character profile pattern were found in all subjects who experienced the disease and its surgical treatment. These changes occurred either in "regression"-with an increase of schizoid, narcissistic or hysterical aspects-or in a "positive evolution", with a decrease of paranoid traits and into a depressive position. The two groups of responses demonstrated a similar percentage.

Up to 1994, we surgically treated for lung cancer, 1222 patients, selected from a total of 3157 observed cases. N.S.C.L.C. were 2891 and 899 of these were resected. Some neoadjuvant therapy has been applied in recent years to 170 patients: 83 of these were treated with CT (cisplatin, epirubicin and VP-16, in two cycles with a three week interval) and 41 had RT (30 Gy in daily fractions of 2); 16 patients had the two treatments in sequence. Radiation was mainly used for T problems, chemotherapy for management of N2; the sequence has so far been applied in selected cases. There have been 73 thoracotomies after a successful neoadjuvant, that is in more than 52% of the re-evaluated patients. Resection was possible in 32 of the RT-prepared patients, in 21 of the CT-prepared and in 8 who completed the double treatment: that means a resection was possible in 47% of cases. Because of the recent introduction of neoadjuvant therapy, late survival cannot be evaluated at present.

Objective: To assess and compare the pharmacokinetics of recombinant human FSH with those of a reference preparation of urinary human FSH., Design: Urinary human FSH and recombinant human FSH (Metrodin and Gonal-F; Laboratoires Serono, Aubonne, Switzerland) were administered in a balanced, random order, crossover sequence as a single i.v. dose of 150 or 300 IU separated by 1 week of washout to 12 pituitary down-regulated, healthy female volunteers. Serum FSH concentrations were measured by an immunoradiometric assay (IRMA) and by an in vitro rat granulosa cell aromatase bioassay. Urine FSH concentrations were measured by IRMA., Results: The mean concentration-time profiles after 150 IU of urinary human FSH and recombinant human FSH were superimposed, and the mean profile after 300 IU of recombinant human FSH was double that of the 150 IU dose. The data for both FSH preparations were well described by a biexponential equation. Total clearance of the preparations was comparable, judging from immunoassay and bioassay data (0.5 and 0.15 L/h, respectively). Based on the immunoassay, renal clearance of urinary human FSH was 0.1 L/h, whereas for recombinant human FSH it was slightly lower at 0.07 L/h, indicating that less than one fifth of the administered dose was excreted in the urine. Immunoassay showed that the two preparations were similar in terms of initial and terminal half-lives (2 and 17 hours, respectively). The volumes of distribution at steady state (11 L) were similar. The results of the in vitro bioassay confirmed this pharmacokinetic analysis. Just after i.v. administration, an initial decrease in the serum bioassay:immunoassay ratio was observed because of dilution of urinary human FSH or of recombinant human FSH in the residual endogenous FSH pool. Then the ratio increased progressively with time, suggesting either metabolic selection or activation of both types of injected human FSH toward forms with greater in vitro bioactivity. The bioassay:immunoassay ratio returned to baseline by day 7., Conclusion: The results obtained in this study indicate that the following [1] the pharmacokinetic characteristics of recombinant human FSH are similar to those of urinary human FSH; [2] the terminal half-life of human FSH is approximately 1 day; [3] after a single i.v. injection of human FSH a progressive increase in FSH bioassay: immunoassay ratio is observed; and [4] clinical use of recombinant human FSH could follow protocols and treatment regimens currently applied to urinary human FSH.

Objective: To assess the single-dose pharmacokinetics of a recombinant human FSH preparation (Gonal-F; Laboratoires Serono, Aubonne, Switzerland), administered by i.v., IM, and SC routes and its pharmacokinetics at steady state after multiple dosing by the SC route., Design: Twelve healthy down-regulated female volunteers received in random order three single doses of recombinant human FSH (150 IU, i.v., IM, and SC), with each administration separated by 1 week. The volunteers then received multiple recombinant human FSH doses by the SC route (150 IU one time per day) for 7 days. Follicle-stimulating hormone concentrations were measured by an immunoradiometric assay and an in vitro granulosa cell aromatase bioassay., Results: After a single administration, the pharmacokinetics of recombinant human FSH were well-described by a two-compartment model after i.v. administration and by a one-compartment model with first order absorption after IM or SC administration. The mean total clearance of FSH was approximately 0.6 L/h, and renal clearance accounted for one tenth of the total elimination after i.v. administration. The distribution half-life was close to 2 hours. The terminal half-life was nearly 1 day when estimated either by modeling the i.v. data set or from analysis of the terminal phase of the steady state pharmacokinetic curve or from the time taken to reach steady state after repeated SC administrations. After single IM and SC injection, two thirds of the administered dose was available systemically. The cumulation factor for repeated SC administration was approximately 3 when steady state was reached. The in vitro bioassay data confirmed these estimations. The temporal evolution of the bioassay:immunoassay ratio suggests either metabolic selection or activation of recombinant human FSH toward forms with greater in vitro bioactivity., Conclusion: The estimation of the elimination half-life of approximately 1 day indicates that the maximal effect of a given dose of recombinant human FSH administered daily cannot be observed until 3 to 4 days of repeated administration. This indicates that, on a pure pharmacokinetic basis, physicians should wait at least 4 days to assess the efficacy of a given dose of recombinant human FSH and that they should not modify dosage too frequently.

Twenty patients with stage IIIA-IIIB non-small-cell lung cancer were treated with cisplatin, epirubicin and VP-16 (PEV) neoadjuvant chemotherapy (CDDP, 70 mg/m2, i.v., d 1; EDX, 60 mg/m2, i.v., d 1; VP-16, 100 mg/m2, i.v., d 1-2-3; every 3 weeks). A partial response was obtained in 11 cases (55%), stable disease in 3 cases (15%), and progressive disease in 6 cases (30%). After chemotherapy, 8 (40%) patients, all achieving a partial response, were elegible for surgery: 5 (25%) had a complete resection (4 IIIA and 1 IIIB) and 3 (15%) an incomplete resection. The treatment was well tolerated. These data show that PEV is an active regimen for neoadjuvant chemotherapy in NSCLC and recommend this therapeutic approach for stage IIIA patients.

Over five hundred lung resections were considered, out of a series of 1570 cases of lung cancer. Histology of resected patients resulted squamous (348), adenocarcinoma (107), large cells (21) and small cells carcinoma (37). According to Mountain staging, 41% of patients were related to stage Ist, 12% to the IInd, 40.9% to the IIInd A: in such a group, a special class T3N0M0 was considered, due to the better follow-up observed in such cases. Lobectomies and minor resections were performed in 321 cases, pneumonectomies in 192. An analysis was done of differences in Histology, staging, early mortality, complications and late results after pneumonectomy which was traditional in 117 patients and required an intrapericardial section of great vessels in 68 cases: 16 patients had some pericardial resection, specific ECG disturbances, early mortality and recurrence within five years proved to be higher in the patients who had some pericardial operation: also as far as no connection was recognized with histology, the responsibility of such results can be attributed to the stage, that in those patients required a more aggressive operation.

Morbid obesity is a disease of modern society. Surgery is indicated when there is no endocrinopathy, medical treatment failed and Body Mass index (W/H2) is more than 40 (III degree obesity of Garrow). Many different methods were suggested in connection with the type of obesity, the associated diseases and the psychical state of the patient. Jejuno-ileal by-pass intend to produce a generic malabsorption syndrome. Personal experience is however good, possibly due to the blind loop jejunostomy that we always prepare as a conclusion of the operation and which gives an excellent support for the early post-operative time.

Cardiac herniation is a rare, highly lethal complication of intrapericardial pneumonectomy, demanding urgent treatment. The condition presents in the immediate or early postoperative period. Cardiovascular collapse is invariably present. Elevation of the jugular venous pressure and cyanosis in the drainage area of the superior vena cava are frequently noted. ECG may demonstrate the abnormal position and some ischemia of the heart. The effects of cardiac herniation are due to a combination of cardiac malposition, with subsequent torsion of the great vessels, obstruction to the outflow of blood from the heart and strangulation of the prolapsed ventricles by the borders of the pericardial defect. The diagnosis rests on an awareness of this condition, its clinical manifestations and radiological examination. Urgent reduction of the herniated heart gives the only possibility of survival. Prevention of possible recurrence must be considered.

Starting from one case of chylous ascites of their own observation, the authors attempt an etiological classification of this clinical entity, taking into account pertinent published material and the fact that in many instances chylous ascites is nothing more than a symptom. The authors then proceeds to a critical review of diagnostic and therapeutical resources; in that respect, they stress the extreme difficulties often encountered both in diagnosing the condition and in trying to correct it.

This report describes a new case of occupational asthma in a goldsmith. A 25-year-old female suffered attacks of urticaria and asthma at each exposure to the dust of cuttle-fish bone used to polish gold jewellery. A specific occupational bronchial provocation challenge showed a dual asthmatic response with a maximum fall in FEV1 of 26% of the baseline value after 6 hours. A prick-test with crude cuttle-fish bone dust in glycerin 10% also gave a positive response.