Gemcitabine plus irinotecan as first-line weekly therapy in locally advanced and/or metastatic pancreatic cancer.

Single-agent gemcitabine has been established as standard treatment for advanced pancreatic cancer since clinical studies have shown an improvement in overall survival and significant clinical benefit when compared to the best supportive care despite low overall objective response. Several phase II studies have tested other single agents and different gemcitabine-based regimens in pancreatic cancer, but both response and survival rates have remained low. Irinotecan, a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer, has also demonstrated improved response rate in patients with pancreatic cancer. Our purpose was to determine the activity and toxicity of this regimen in patients with unresectable or metastatic pancreatic cancer. Patients with histologically confirmed pancreatic adenocarcinoma received gemcitabine 1000 mg/m2 plus irinotecan 100 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle for 6-8 months. From February 2004 to April 2006, 33 patients were entered into this study, 32 of whom were evaluable for treatment response, toxicity, median time to progression, and median survival. Characteristics included a median age of 63 years (range 41-79), 21 males (64%), and 12 females (36%). One patient discontinued treatment due to adverse effects. The total number of cycles administered was 188 and the median number of cycles for patients was 5.6 (range 2-7). Thirty-two patients were assessable for toxicity and response. Grade 3 hematological toxicity occurred in 9% of patients and was primarily neutropenia. No grade >2 gastrointestinal toxicities or death due to treatment were observed. The most frequent nonhematological adverse event was fatigue. Ten patients responded to treatment with two complete responses (6.3%) and eight partial responses (25.0%), for an overall response rate of 31.3%; 11 patients achieved stable disease (34.3%). The median time to tumor progression and the median survival were 9.2 (95% CI: 6.0-12.4) and 11.8 (95% CI: 7.7-15.9) months, respectively, with a 2-year survival of 22%. On the basis of this trial, the combination of gemcitabine plus irinotecan, administered in a weekly schedule and at this dose, is well tolerated and offers encouraging activity in the treatment of advanced and/or metastatic pancreatic cancer.

Lymphangiogenesis in Crohn's disease: an immunohistochemical study using monoclonal antibody D2-40.

Crohn's disease (CD) is a chronic inflammatory bowel disorder of unknown etiology. An involvement of the intestinal lymphatic system has been suggested. Recently, monoclonal antibodies have become available to distinguish lymphatic vessels from blood vessels. The aim of the study was to examine the distribution of lymphatic vessels in ileal and colic walls of patients affected by CD and compare it with healthy controls and other inflammatory bowel diseases. Twenty-eight cases of CD, 13 cases of other inflammatory bowel diseases, and 10 normal ileal and colic walls were studied. Immunohistochemical staining was performed using the monoclonal antibody D2-40. Quantification of lymphatic vessels was performed by identifying four fields with high density of lymphatics and then counting the number of lymphatic vessels at high resolution. Lymphatic diameter was also evaluated by using an ocular micrometer. Lymphatic vessels showed the highest density in CD specimens. The median number of lymphatics was significantly higher both in ileal and colic samples of CD than the other inflammatory diseases as well as normal controls. Moreover, in patients with CD, diffuse lymphangiectasia was also observed. The present data suggest that lymphangiogenesis and lymphangiectasia probably play a role in the pathogenesis of CD.

Effect of chlorhexidine digluconate on different cell types: a molecular and ultrastructural investigation.

Although several studies have shown that chlorhexidine digluconate (CHX) has bactericidal activity against periodontal pathogens and exerts toxic effects on periodontal tissues, few have been directed to evaluate the mechanisms underlying its adverse effects on these tissues. Therefore, the aim of the present study was to investigate the in vitro cytotoxicity of CHX on cells that could represent common targets for its action in the surgical procedures for the treatment of periodontitis and peri-implantitis and to elucidate its mechanisms of action. Osteoblastic, endothelial and fibroblastic cell lines were exposed to various concentrations of CHX for different times and assayed for cell viability and cell death. Also analysis of mitochondrial membrane potential, intracellular Ca2+ mobilization and reactive oxygen species (ROS) generation were done in parallel, to correlate CHX-induced cell damage with alterations in key parameters of cell homeostasis. CHX affected cell viability in a dose and time-dependent manners, particularly in osteoblasts. Its toxic effect consisted in the induction of apoptotic and autophagic/necrotic cell deaths and involved disturbance of mitochondrial function, intracellular Ca2+ increase and oxidative stress. These data suggest that CHX is highly cytotoxic in vitro and invite to a more cautioned use of the antiseptic in the oral surgical procedures.

Immediate transmucosal implant placement in molar extraction sites: a 12-month prospective multicenter cohort study.

AIM: To assess the clinical and radiographic outcomes of immediate transmucosal placement of implants into molar extraction sockets. STUDY DESIGN: Twelve-month multicenter prospective cohort study. MATERIAL AND METHODS: Following molar extraction, tapered implants with an endosseous diameter of 4.8 mm and a shoulder diameter of 6.5 mm were immediately placed into the sockets. Molars with evidence of acute periapical pathology were excluded. After implant placement and achievement of primary stability, flaps were repositioned and sutured allowing a non-submerged, transmucosal healing. Peri-implant marginal defects were treated according to the principles of guided bone regeneration (GBR) by means of deproteinized bovine bone mineral particles in conjunction with a bioresrobable collagen membrane. Standardized radiographs were obtained at baseline and 12 months thereafter. Changes in depth and width of the distance from the implant shoulder (IS) and from the alveolar crest (AC) to the bottom of the defect (BD) were assessed. RESULTS: Eighty-two patients (42 males and 40 females) were enrolled and followed for 12 months. They contributed with 82 tapered implants. Extraction sites displayed sufficient residual bone volume to allow primary stability of all implants. Sixty-four percent of the implants were placed in the areas of 36 and 46. GBR was used in conjunction with the placement of all implants. No post-surgical complications were observed. All implants healed uneventfully yielding a survival rate of 100% and healthy soft tissue conditions after 12 months. Radiographically, statistically significant changes (P<0.0001) in mesial and distal crestal bone levels were observed from baseline to the 12-month follow-up. CONCLUSIONS: The findings of this 12-month prospective cohort study showed that immediate transmucosal implant placement represented a predictable treatment option for the replacement of mandibular and maxillary molars lost due to reasons other than periodontitis including vertical root fractures, endodontic failures and caries.

Selection of patients for myocardial perfusion scintigraphy based on fuzzy sets theory applied to clinical-epidemiological data and treadmill test results.

Coronary artery disease (CAD) is a worldwide leading cause of death. The standard method for evaluating critical partial occlusions is coronary arteriography, a catheterization technique which is invasive, time consuming, and costly. There are noninvasive approaches for the early detection of CAD. The basis for the noninvasive diagnosis of CAD has been laid in a sequential analysis of the risk factors, and the results of the treadmill test and myocardial perfusion scintigraphy (MPS). Many investigators have demonstrated that the diagnostic applications of MPS are appropriate for patients who have an intermediate likelihood of disease. Although this information is useful, it is only partially utilized in clinical practice due to the difficulty to properly classify the patients. Since the seminal work of Lotfi Zadeh, fuzzy logic has been applied in numerous areas. In the present study, we proposed and tested a model to select patients for MPS based on fuzzy sets theory. A group of 1053 patients was used to develop the model and another group of 1045 patients was used to test it. Receiver operating characteristic curves were used to compare the performance of the fuzzy model against expert physician opinions, and showed that the performance of the fuzzy model was equal or superior to that of the physicians. Therefore, we conclude that the fuzzy model could be a useful tool to assist the general practitioner in the selection of patients for MPS.

Counting of platelet derived growth factor and transforming growth factor-beta in platelet-rich-plasma used in jaw bone regeneration.

AIM: Growth factors (GFs) as platelet derived growth factor (PDGF) and transforming growth factor (TGF-beta), found in platelet beta-granules also present in platelet-rich-plasma (PRP), accelerate bone revascularization and regeneration and for this reason they have been employed successfully in dental and maxillofacial surgery. Platelet concentrate is commonly used for this purpose as long as platelet release reaction and the consequent GFs loss are avoided. To reduce this phenomenon we set up an easy and fast procedure for preparing a satisfying clotted PRP by adding CaCl2 only (no exogenous thrombin). METHODS: ELISA essay has been used to measure PDGF and TGF-beta in plasma, platelets and serum and platelet GMP-140, with the cytofluorometric technique in order to quantify the degranulation entity. RESULTS: In the 13 examined patients receiving clotted PRP to enhance bone regeneration in post-extractive alveolar sockets, PRP showed no sign of platelet activation (degranulation) and short recalcification times (8-12 min). The autologous clotted PRPs specimen have been evaluated in laboratory in terms of GFs percent: 76% of initial GFs content could be recovered in clotted PRP. This result confirms the absence of platelet degranulation in our procedure. CONCLUSIONS: Significant clinical results in alveolar bone regeneration are reached only with a high percentage of GFs inserted in bone matrix, avoiding early platelet degranulation.

A double-blind comparison of nimesulide and ketoprofen in dental surgery.

The efficacy and tolerability of nimesulide were compared with those of ketoprofen when administered rectally in a double-blind investigation of 46 patients scheduled for dental surgery. Nimesulide was more effective and more rapid than ketoprofen in ameliorating the painful inflammatory symptoms (pain at rest and upon mastication) and signs (swelling and hyperaemia) associated with the operation. These effects were accompanied by improved quality of sleep and recovery of masticatory and swallowing function, which was superior for nimesulide-treated patients.

Short course therapy with cefitbuten versus azithromycin in pediatric streptococcal pharyngitis.

OBJECTIVE: To compare the safety and efficacy of a short course (5 days) of ceftibuten vs. azithromycin for 3 days for treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis in children. METHODS: A multicenter, open label, prospective, randomized trial in which patients > or =3 to < or =16 years of age with proven GABHS pharyngitis were randomized to receive either once daily ceftibuten for 5 days or azithromycin for 3 days. Patients were evaluated for clinical outcomes and/or for adverse events at days 6 to 8, 13 to 15 and 33 to 35 posttherapy. Microbiologic assessments (pharyngeal cultures) were conducted at baseline and at each follow-up visit. RESULTS: A total of 132 patients in the ceftibuten arm and 116 in the azithromycin arm were enrolled in the safety analysis, whereas 126 and 101, respectively, were enrolled for ceftibuten and azithromycin efficacy evaluation. Clinical success (cure or marked amelioration) at days 6 to 8 was recorded in 98 and 94% in the 2 groups, respectively. In the bacteriologic efficacy analysis at 6 to 8 days, the GABHS strain was eradicated in 76% of the patients treated with ceftibuten and in 76% of those receiving azithromycin. At 33 to 35 days, 84% of the patients in the ceftibuten arm and 71% in the azithromycin arm were GABHS-negative, and bacteriologic relapse was observed in 4 and 7% of the ceftibuten and azithromycin cases, respectively. Both treatments were well-tolerated by all patients. CONCLUSIONS: Ceftibuten and azithromycin allow simple treatment schedules (i.e. once daily administration, short duration of treatment). The somewhat higher eradication rate recorded after ceftibuten administration is consistent with the overall superior bactericidal activity of beta-lactams compared with macrolides vs. GABHS in vitro.

A morphologic study of nodular lung carcinomas and their possible pathogenesis from a cluster of non-obstructive bronchiectasis.

A very simple procedure has enabled us to show that nodular lung carcinomas correspond, to a high degree, to neoplasias arising in a cluster of bronchiectasis of the non-obstructive type. This pathogenesis explains their peculiar features: the round shape with a sharp borderline on the surrounding lung, the frequent cavitation, the prevailing histologic type of epidermoid carcinomas. At present, when thin-section CT allows discovery of bronchiectasis with no need for bronchography, this interpretation suggests the possibility of carrying out a prevention program which should consist of identifying the high-risk group of patients with bronchiectasis, 'sputum producers' and smokers, in which an early diagnosis of nodular lung carcinoma might be realized by periodical diagnostic cytology.

Clinical and pharmacological evaluation of a modified cefotaxime bid regimen versus traditional tid in pediatric lower respiratory tract infections.

It is generally accepted that the treatment of community-acquired pneumonia, either in adults or in pediatric patients, is mainly empirical. Thus, the treatment selection must fulfill both the epidemiological requirements, according to the most frequently described pathogens, and the pharmacological criteria to ensure adequate and prolonged drug concentrations at the infection site, to reach clinical efficacy. Cefotaxime has proven to be effective in this indication when traditionally administered three times daily and, more recently, twice daily, as a result of a re-evaluation of its pharmacokinetic/pharmacodynamic features. To gain further evidence using this updated dosing schedule, 258 pediatric patients with lower respiratory tract infections were treated with cefotaxime 100 mg/kg/day, administered as a twice daily or three times daily regimen. In the cefotaxime 50 mg/kg twice-daily group (n = 130), a complete resolution of clinical signs and symptoms were observed in 88.5% of patients. Similarly, in the cefotaxime 33.3 mg/kg group (n = 128), 93.6% of patients had a complete resolution of clinical signs and symptoms. Both drug schedules were well tolerated. Pharmacokinetic parameters determined for the two cefotaxime dosing schedules showed comparability. The serum half-life of desacetylcefotaxime was marginally longer than for cefotaxime in both dosage groups (1.64 and 1.36 h for desacetylcefotaxime versus 1.2 and 0.85 h for cefotaxime after 50 mg/kg or 33.3 mg/kg doses, respectively). Results from this study support the use of twice-daily cefotaxime administration for the treatment of lower respiratory tract infections in pediatric patients.

Management of upper respiratory tract infections in primary care in Italy: a national survey.

This prospective study, carried out in Italy during the winter of 1998 by the means of questionnaires, was designed to investigate the diagnostic and therapeutic approach of the Italian general practitioners (GPs) to the management of acute upper respiratory tract infections (URTIs) in adult outpatients. A total of 354 GPs were questioned about ten adult patients each who had visited the surgery with an URTI requiring an antibiotic prescription. Our data showed there was a tendency to prescribe antibiotics only on the basis of clinical diagnosis, microbiological investigations being required very rarely. Orally administered antibiotics were preferred and compliance with the number of daily doses strongly influenced the antibiotic prescription. In patients affected by more severe infections, injectable antibiotics were frequently prescribed.

Intra-arterial hepatic chemotherapy with 5-fluorouracil and 5-methyltetrahydrofolate in the treatment of unresectable liver metastases from colorectal cancer.

Treatment of patients with hepatic metastases from colorectal cancer using hepatic artery fluorodeoxyuridine (FUDR) has been reported to induce high remission rates but also a high incidence of limiting hepatobiliary toxicity. In an attempt to obviate the limiting FUDR toxic effects, a phase I-II study was undertaken to establish the efficacy and tolerability of intra-hepatic 5-fluorouracil (5-FU) when given in combination with 5-methyltetrahydrofolate. Patients with colorectal liver metastases (n = 17) received escalating doses of 5-FU as a 1 h infusion with a fixed dose (100 mg/m2) of intra-hepatic 5-methyltetrahydrofolate (4 h infusion) once a week. Dose limiting toxicity was hepatic and gastrointestinal (diarrhea) and occurred at doses > or = 350 mg/m2 5-FU. Other adverse effects included nausea/vomiting and cutaneous toxicity. One patient achieved a complete response and 2 a partial response (mean duration = 9 months) while 11 had stable disease. Patients with complete or partial responses had a mean survival of 17 months, while patients with stable disease survived 13 months and those with disease progression 5.5 months on average. These results suggest that this is a well tolerated regimen although with efficacy at the lower level of the range observed with fluoropyrimidines.

The influence of new technologies on laparoscopic adrenalectomy: our personal experience with 91 patients.

BACKGROUND: Laparoscopic adrenalectomy has proved to be the technique of choice for managing benign pathologies of the adrenals and isolated adrenal metastases, especially those arising from lung tumor, but the procedure should not be performed for primitive adrenal carcinoma. The Authors wanted to test the advantages of the Harmonic Scalpel in laparoscopic adrenalectomy. METHODS: From April 1995 to April 2001, the authors investigated their series of laparoscopic adrenalectomies performed at the Careggi General Hospital, Division of General and Vascular Surgery, Florence, Italy. This study enrolled 91 patients with various adrenal pathologies. The transperitoneal approach was used, with the patient in a lateral position, as suggested by Gagner. Special care was taken to improve the surgical approach to the adrenals by the use of new technological devices such as the Harmonic Scalpel. The operative time required by the surgical procedure was computed by dividing the study into three periods: 1995-1997, 1998-1999, 2000-2001. The first period was necessary to complete the learning curve. In the second period, a steady state in surgical time was reached. During the third period, the Harmonic Scalpel was introduced. The differences between the three periods were tested using a nonparametric analysis (Mann-Whitney U test or Kruskal-Wallis test) as appropriate. A two-tailed p value of 0.05 or less was considered statistically significant. The authors investigated the cost of the operation performed in each of the two groups using, respectively, the conventional laparoscopic device (1998-1999) and the Harmonic Scalpel (2000-2001). The following expenses were considered: Harmonic Scalpel impulse generator and disposable shears, operating room cost per hour, and endoclip applier. RESULTS: The 91 laparoscopic adrenalectomies were performed with these indications: 31 incidentalomas (26 adenomas and 5 cysts), 25 cases of Conn's disease, 18 cases of Cushing's disease, 9 pheochromocytomas, 2 myelolipomas, 5 metastases (from lung, kidney, and breast) and 1 primitive carcinoma diagnosed preoperatively. Considering the whole series (1995-2001), there was a significant trend of reduction in operative time (p = 0.0001). Moreover looking at the first period (1995-1997), in which the learning curve was completed, the mean surgical time was 148 min, as compared with 125 mm. For the second period (1998-1999) (p = 0.0002). This represents a significant reduction in operative time. The authors noted a further reduction in the operative time when surgery was performed with the Harmonic Scalpel (2000-2001) (92 min; p = 0.001). The reduction in operative time attributable to the Harmonic Scalpel was confirmed also by a multivariate analysis of covariance general linear models procedure (GLM), which accounts for several confounders: age, gender, site and size of tumors, and histology (p = 0.0001). The rate was 3.3% for morbidity, 1.1% for mortality, and 2.2% for conversion. There was no difference in complications between patients treated with conventional devices and those treated with the Harmonic Scalpel. CONCLUSIONS: The laparoscopic approach has proved to be an extremely reliable procedure for benign pathologies and isolated metastases. There may yet be doubts about its use for the treatment of adrenal carcinomas preoperatively diagnosed. When surgery is performed using Harmonic Scalpel, operative time is significantly reduced and surgery is easier and less expensive. Infact use of the Harmonic Scalpel allowed the cost per operation to be reduced $70. Moreover, if surgery is performed using the nondisposable clip applier, the expenses are reduced $105.

Efficacy and tolerability of brodimoprim in pediatric infections.

Brodimoprim is a long acting broad spectrum antibacterial agent. It is a new selective inhibitor of bacterial dihydrofolate reductase, structurally related to trimethoprim. The aim of the present study was to investigate the efficacy and tolerability of brodimoprim (10 mg/kg on the first day, 5 mg/kg/die onward) in the treatment of upper respiratory tract infections in children (age range: 2-14 years). This open group comparative study was performed either in 68 children affected by bacterial pharyngotonsillitis (37 treated with brodimoprim, 31 with erythromycin 560 mg/kg/8 hours) or in 50 patients affected by otitis media (25 treated with brodimoprim, 25 with amoxicillin/clavulanic acid 50 mg/kg/12 hours) or in 52 patients affected by acute sinusitis (25 treated with brodimoprim, 27 with amoxicillin/clavulanic acid 50 mg/kg/12 hours). All patients were clinically evaluated before admission, during the trial and 48 hours after the last dose of antibiotic. At the same time blood and secretion samples were collected for hematology/biochemistry and microbiological assays. A total of 170 subjects were treated and 141 patients demonstrated a clinical recovery/improvement following the treatment period, with approximately the same recovery rate (83%) among the groups. The bacteriological response was evaluated in 169 subjects. Eradication of pathogens was documented in 27 subjects treated with brodimoprim and 28 with erythromycin in the pharyngotonsillitis group, in 22 subjects treated with brodimoprim and 16 with amoxicillin/clavulanic acid in the otitis group and in 17 subjects treated with brodimoprim and 20 with amoxicillin/clavulanic acid in the sinusitis group. The overall eradication in brodimoprim treated patients was 77% in comparison with 76% of eradication obtained in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical signs of pneumonia in children: association with and prediction of diagnosis by fuzzy sets theory.

The present study compares the performance of stochastic and fuzzy models for the analysis of the relationship between clinical signs and diagnosis. Data obtained for 153 children concerning diagnosis (pneumonia, other non-pneumonia diseases, absence of disease) and seven clinical signs were divided into two samples, one for analysis and other for validation. The former was used to derive relations by multi-discriminant analysis (MDA) and by fuzzy max-min compositions (fuzzy), and the latter was used to assess the predictions drawn from each type of relation. MDA and fuzzy were closely similar in terms of prediction, with correct allocation of 75.7 to 78.3% of patients in the validation sample, and displaying only a single instance of disagreement: a patient with low level of toxemia was mistaken as not diseased by MDA and correctly taken as somehow ill by fuzzy. Concerning relations, each method provided different information, each revealing different aspects of the relations between clinical signs and diagnoses. Both methods agreed on pointing X-ray, dyspnea, and auscultation as better related with pneumonia, but only fuzzy was able to detect relations of heart rate, body temperature, toxemia and respiratory rate with pneumonia. Moreover, only fuzzy was able to detect a relationship between heart rate and absence of disease, which allowed the detection of six malnourished children whose diagnoses as healthy are, indeed, disputable. The conclusion is that even though fuzzy sets theory might not improve prediction, it certainly does enhance clinical knowledge since it detects relationships not visible to stochastic models.

Rigid internal fixation of the jaws in an adult patient with facio-scapulo-humeral muscular dystrophy: report of a case.

This study shows the advantages of rigid internal fixation in the surgical management of a facial deformity in a 29-year-old patient with facio-scapulo-humeral dystrophy (FSHD). After presurgical orthodontic treatment, surgery consisted of a Le Fort I maxillary osteotomy, with 5 mm of anterior movement, and fixation with miniplates. After mandibular sagittal split set-back osteotomy, internal fixation was applied on each side using two bicortical screws; no postoperative intermaxillary fixation was utilized. At the 2-year follow-up, the patient was satisfied with the surgical results; lip competence and occlusion were good. The advantages of using internal rigid fixation are: immediate osseous stability which does not require intermaxillary fixation, improved perioperative airway management (no preoperative tracheostomy) and earlier functional recovery.

[Long-term central venous access. Experience with 173 cases]. / Accessi venosi centrali a lungo termine. Esperienza relativa a 173 casi.

BACKGROUND: Utility of long term central venous accesses. METHODS: Personal experience in 173 long term central venous accesses (a.v.c.) performed from January 1990 to December 1997 in 172 patients mostly affected by neoplastic disease is reported. The device used was totally implantable in 102 cases (59%): 82 Port (80.3%), 20 Chrono-infusors (20.7%); in 71 cases (41%) an external tunnellized catheter (c.v.c.). Percutaneous way with Seldinger procedure was performed in 168 cases (97.3%), left subclavian vein was preferred in 118 cases (68.2%). RESULTS: The overall complications in this series were about 7.4%: early 4% (5 accidental arterial punctures, 2 pneumothoraxes), late 3.4% (1 subcutaneous pocket infection, 3 cutaneous necrosis, 1 venous catheter dislocation and 1 migration). No significative differences in terms of complications were reported between totally implantable devices and external tunnellized catheter. CONCLUSIONS: The reasons of a low rate of complications in our series are to be found in the perfect aseptic condition of the operating room, the positioning of the a.v.c. under constant fluoroscopic control and a good management during the postoperative care of the a.v.c. The indications and the economic aspect for each kind of device used (c.v.c. or totally implantable a.v.c.) are then discussed and the conclusion drawn that for short term therapy, up to six months, (hematologic patients of this series) the external tunnellized catheter should be advisable, while for long term therapy administration (solid tumors and parenteral nutrition) totally implanted device should be recommended.

[Acute rheumatic fever: a report]. / Segnalazioni di malattia reumatica.

Acute rheumatic fever (ARF) is still an important disease of the pediatric and adult age. The increased number of cases described in the literature in the last 10 years brought us to evaluate the ARF cases diagnosed in a Pediatric Teaching Hospital in the period 1988-1997. Most of the children with ARF presented with joint involvement even if patients with cardiac disease or chorea minor were numerous. About 50% of our patients with ARF did not refer a history of a febrile tonsillopharyngitis in the 15-60 days before the presentation of ARF. The remaining patients have had a preceding pharyngitis not adequately treated. In none of the subjects a throat swab positive for group A beta hemolytic streptococci was available. These results confirm the importance of the correct diagnosis and treatment of streptococcal pharyngitis but suggest that ARF can develop without any outstanding clinical evidence of streptococcal infection.

[New developments in Crohn's disease: unravelling the mystery of its etiopathogenesis and its reinstatement as a surgically treatable condition. Part 3: The rational principles of surgical therapy]. / Novità per la malattia di Crohn: la soluzione dei suoi misteri dottrinali ed il suo recupero come malattia di competenza chirurgica. Nota 3. I principi razionali della terapia chirurgica.

The diagnosis of Crohn's disease makes surgery mandatory in any form of the disease, because it is ingravescent, spreads in the bowel, and is unresponsive to any type of pharmacological treatment; it invariably involves major consequences and often leads to serious complications such as perforation and cancer in the long term. The operation has to be performed promptly, because the commonest complications, such as obstruction and perforation, may occur at any stage of the disease, including the initial phase. Moreover, it is advisable to prevent the spread of the disease to the colon and jejunum, which occurs in increasing percentages of patients and is related to duration of the disease. As a rule, surgery has to take the form of a resection of the diseased bowel, which includes not only the lesions already in progress, but also those which may be expected to develop. Therefore, since the disease is segmentary, the resection, too, has to be segmentary, even when part of the diseased segment is apparently sound. Inadequate resection is often followed by dehiscence of the anastomosis and sooner or later by an inevitable recurrence. Three types of resection are performed for Crohn's disease depending on whether it manifests as ileitis, ileitis plus right colitis, or ileitis plus right and left colitis. Ileitis requires an ileocolic resection. Because the resection has to be segmentary and the proximal limit of the segment, i.e. of the lesions, cannot be determined at external examination of the intestine, the surgeon has to perform an approximate, temporary resection and examine the resected specimen, open along its entire length, before constructing the anastomosis. The borderline between the diseased and intact ileum, where convinient valves, appear with their thin, delicate outline, can be identified exactly in the mucosal surface. The resection has a "safety margin" of 10 cm. Section of the ascending colon can be performed wherever the surgeon prefers. The ileitis plus right colitis forms require resection of the ileum according to the procedure described and of the right colon, even when the lesions are confined to the caecum. Section and anastomosis must be performed in the initial tract of the transverse colon. The ileitis plus right and left colitis forms call for total colectomy in addition to resection of the ileum, even when the lesions are confined to the transverse colon. The operation is completed with an ileorectal anastomosis constructed on the lower portion of the intraperitoneal rectum (drained by the hypogastric collectors).

[New developments in Crohn's disease: solution of doctrinal mysteries and reinstatement as a surgically treatable disease. 1. The process is not a form of enteritis but lymphedema contaminated by intestinal contents]. / Novità per la malattia di Crohn: la soluzione dei suoi misteri dottrinali ed il suo recupero come malattia di competenza chirurgica. Nota 1. Il processo crohniano non è quello di un'enterite, ma di un linfedema inquinato dal contenuto intestinale.

INTRODUCTION: It is unanimously acknowledged that the aetiopathogenesis of Crohn's disease (CD) is still a mystery despite the fact that almost 70 years have elapsed since it nosological identification. Another mystery and major problem of CD of the bowel is its histopathology, which has yet to be clarified; consequently, we do not know what kind of disease it is, that is to say, which process, among the ones known to us, it actually corresponds to. MATERIAL AND METHODS: The present paper presents the results of a new histopathological interpretation of the disease on the basis of 100 surgical cases of Crohn's ileitis and ileocolitis. RESULTS AND CONCLUSIONS: The disease is not a form of enteritis, but a lymphoedema of the intestinal wall, caused by a congenital lack of patency of the mesenteric lymphatic collectors, giving rise to stasis of lymph in the lymphatic network of the corresponding bowel segment and consequently to hypertension which dilates the lymph vessels in the intestinal wall. The lymph, which cannot be reabsorbed by the veins, because the venous wall denies entry to protein macromolecules, accumulates in the interstitial space with the result that the intestinal wall thickens considerably. Since the process takes place in the intestine perfused by a continuous flow of septic matter, the process is complicated by the development of lymphocytic lymphangitis, which occurs throughout almost the entire lymphatic network, obstructing the dilated lumen, limiting the dispersion of lymph and preventing gross spread of the intestinal contents into the dilated lymphatic vessels. The lymphocytic lymphangitis causes "transparietal phlogosis", which is rightly regarded as a characteristic of the disease, but is wrongly interpreted by those who have studied it. This transparietal phlogosis is neither excessive nor disproportionate to its task of obstructing the intestinal contents; it is transparietal because the lymphatic network where it takes places is itself transparietal. The reactive lymphocytic lymphangitis prevents the gross spread of the intestinal contents into the dilated lymphatic network, as stated above, but cannot prevent the limited uptake of dissolvable toxic bacterial substances (FMLP, PG-PS, LPS) conjugated in immuno-complexes. The immuno-complexes developing in the lymphatic network undergo lymph- and blood-borne spread, causing; obstructive lymphangitis in branches of the mesenteric lymphatic collectors which are still patent, increasing the degree of lymphatic obstruction and thus the extent of the intestinal lesions; general complications of so-called "metastatic Crohn's disease", which were once interpreted as autoimmune processes, but actually correspond to forms of vasculitis which may be localised in any of the organs or apparatuses of the body, sometimes proving extremely serious. Lymph dispersion in the intestinal lumen, causes not only diarrhoea, but often also lymphocytopenia and hypoproteinaemia, and therefore an immunodepression syndrome, which in the long term may give rise to intestinal and extraintestinal cancer.