The relationship between mucosal immunoresponse and clinical outcome in patients with recurrent upper respiratory tract infections treated with a mechanical bacterial lysate.

This open prospective study aims to evaluate whether a therapy with a polyvalent mechanical bacterial lysate (PMBL) could be associated to the enhancement of the locoregional immunoresponse in patients with recurrent upper respiratory tract infections. Forty patients (23 females and 17 males) were enrolled, 33 of whom concluded the study. The duration of the study was six months and each patient was visited five times. Twenty-six patients had an objective improvement in clinical and medical locoregional conditions, while in seven patients the treatment did not result in an objective amelioration. Twenty-five out of 27 patients with clinical response were characterized by an increase of specific antibodies against PMBL antigens in salivary fluids. Only two patients, with a non-significant clinical result, had a slight increase in the concentration of salivary specific IgA. The association between PMBLspecific immunoglobulin titers and clinical results was significant for IgG and IgA, but not significant for IgM. Th1 switch was detected only in patients with clinical amelioration, while the Th0 phenotype was observed in three responder and four non-responder patients. Weak Th2 polarization was also observed in one clinical responsive patient. The capacity of effectively opsonizing living bacteria was detected in samples derived from responder patients. These results suggest that PMBL treatment was able to trigger an efficient and well-targeted immune-response resulting in positive clinical outcome of the patients treated.

Transformation of elite white poplar (Populus alba L.) cv. ' Villafranca' and evaluation of herbicide resistance.

Transgenic white poplar plants (Populus alba L.) expressing the nptII gene and the bar gene from Streptomyces hygroscopicus have been produced using Agrobacterium tumefaciens-mediated gene transfer. Eleven kanamycin-resistant plant lines were obtained with a transformation frequency of 7%. Successful genetic transformation was confirmed by Southern and northern analyses. The level of resistance to the commercial preparation of phosphinothricin (Basta; Roussel-Hoechst Agrovet) was evaluated by in vitro and in vivo assays. Using in vitro selective conditions for phosphinothricin, only plantlets from four kanamycin-resistant independent lines remained green and continued to grow and root. After transfer to the growth chamber, all selected transgenic lines were shown to be completely resistant to the herbicide Basta with doses equivalent to 6 l ha-1 (normal field dosage) and were tolerant at concentration of 12 l ha-1. This is the first report describing the genetic transformation of a P. alba clonal cultivar of commercial interest with a gene of agronomic value.

[Bacterial and fungal colonization in indwelling total laryngectomy phonatory prostheses: identification of microbial agents, treatment protocol and prevention]. / Colonizzazione, batterica e micotica, di protesi fonatorie fisse in pazienti laringectomizzati: identificazione degli agenti microbici, protocollo terapeutico e preventivo.

Today, after the erygmophonic voice, the application of phonatory prostheses is the rehabilitation strategy of choice in patients who had undergone laryngectomy. This is because the surgical procedure is simple and because they are highly successful. The main cause of complications is infection or biofouling. The present study examined the results of cultures taken from phonatory prostheses in 15 laryngectomy patients. The dominating strains of the bacteria and fungi were tested to determine their sensitivity to various pharmacological treatments. By working up and applying a preventive and treatment protocol to reduce prosthetic infections, the average duration of these devices, and thus their functionality, has been increased by approximately 50% bringing it from 6 to 9 months.

[Chemotherapy of head and neck carcinomas]. / La chemioterapia nei carcinomi della testa e del collo.

In most cases head and neck tumors manifest themselves on a local-regional level giving rise to highly mutilating pathologies with psycho-social repercussions. Surgery and radiotherapy are effective treatments for limited neoplasms (stage I-II). On the other hand, after surgery and/or radiotherapy, the treatment of locally advanced tumors (stage III-IV) or local recurrences and/or distant metastases is still problematic. For this reason chemotherapy, initially used only as a palliative, is today associated with other treatments to achieve better results both in terms of survival and disease-free time spans. Hence chemotherapy must be considered part of any multimodal primary treatment for advanced squamous cell carcinoma of the head and neck. In fact, numerous clinical studies have clearly demonstrated that adjuvant or neoadjuvant chemotherapy has a highly relative affect on survival in locally advanced diseases and that the incidence of distant metastases is reduced. This is not, however, followed by a similar reduction in local recurrences which are often the cause of death in such patients. It would, on the other hand, appear that survival is improved with integrated radio-chemotherapy. Immunochemotherapy, which has not as yet provided significant clinical results in cases of advanced tumors and/or metastases, must still be evaluated in the treatment of locally limited neoplasms. Organ preservation, which proves feasible in the larynx, leads one to hope it can be applied in other head and neck sites. The future balance leans in favor of the multidisciplinary approach and multi-center studies must be performed so that an adequate number of cases can be gathered over a brief period. This will make it possible to answer those questions and, at times, illusions which accompany chemotherapy in the treatment of advanced head and neck tumors.

Combined craniofacial approach to facial tumours involving the anterior skull base.

The authors report their experience on six male patients and one female patient (age range: 58-76 years, median: 67) with facial tumours involving the anterior skull base, undergoing craniofacial resection between January 1992 and May 1994 at the Division of Surgical Oncology in the Tumor Institute, Genoa. Three patients had squamous carcinoma and adenocarcinoma of the nasal fossa; two patients had squamous carcinoma rT4NO and adenocarcinoma rT4NO1 of the maxillary sinus; one patient had squamous carcinoma of the eyelid, and another had squamous carcinoma of the internal chantus. Four patients had had previous radiotherapy, another underwent pre-operative chemoradiotherapy, and only two patients had not been treated before. A proper craniofacial tumour resection was performed in three patients; one patient had a left maxillectomy with ethmoidectomy and orbital exenteration; one patient underwent maxillectomy, resection of the medial and inferior wall of the orbit, ethmoidectomy, and orbital exenteration; one patient underwent maxillectomy, ethmoidectomy, and mucosectomy of the sphenoidal sinus, and one patient had total ethmoidectomy. As for reconstruction procedures of the anterior skull base, lyophilized dura with galeal pericranial flap was commonly used. A myocutaneous flap transposition (transverse rectus abdominis and latissimus dorsi myocutaneous flap) was used in two patients for the reconstruction of the resected tissues and bones of maxillary and orbital regions. Post-operative complications included intraoperative liquorrhea in one patient; one case of early and serious pneumocephalus; flap necrosis occurred following transposition of latissimus dorsi. Median hospital stay was 34 days. After a median follow-up of 18 months (range: 3 to 34 months) five of seven patients (71.4%) are alive and disease-free at 15, 17, 18, 30 and 34 months from surgery.

[Early stages of laryngeal cancer (I-II stage) and therapeutic options: case report and review of literature]. / Tumori della laringe I-II stadio; opzioni terapeutiche, presentazione di una casistica e revisione della letteratura.

Between 1987 and 1993, 36 patients with early squamous cell carcinoma of the larynx (I-II stage) were treated with radiotherapy, at the National Institute for Cancer Research of Genoa; 25 patients were stage I (5 T1N0 of supraglottic larynx, 15 T1aN0 and 5 T1bN0 of glottic larynx) and 11 patients stage II (7 T2N0 of supraglottic larynx and 4 T2N0 of glottic larynx); there were 32 males (89%) and 4 females (11%), ages ranging from 34 to 83 years (mean age 61 years). The radiotherapy was performed utilizing the X-ray of a 6 MV linear accelerator, with a daily conventional fractionation and a dose of 66-70 Gy/33-35 fr./7 weeks, with co-axial latero-lateral beams including cervical lymph-nodes, except for T1N0 glottic cancer. The median follow-up was 51 months (range 8-84 months). The local control rate of all the patients was 80.5% at 51 months. According to the stage and tumor subsite, it was 80% for stage I a-b of the glottic site, 60% for the stage I of supraglottic site, 91% for stage II of supraglottic and glottic site. Only 6 patients (18%) underwent the salvage surgery and in all the patients the illness was under control. The overall survival rate was 83.3% at 51 months (4 patients died of a second tumor (11%) and 2 from heart disease (5.5%)). The only complication we observed was a glottic edema. The analysis of our results demonstrates that radiotherapy seems to be more appropriate in the T1a-b glottic cancer. These results are in agreement with those obtained by other studies. On the contrary, the results obtained with radiotherapy, in the T2N0 glottic cancer, are not satisfactory, with regard to local control, as those obtained with surgery, but offers best functional results. In most T2N0 tumors, after the failure of radiotherapy, a reconstructive laryngectomy is still possible. We also obtained good results with the supraglottic lesions. The small number of cases we treated does not allow us to achieve final conclusions and other studies are necessary to confirm our results.

[Non-toxic nodular goiter: treatment and follow-up]. / Trattamento e follow-up del gozzo non tossico uni o multinodulare.

Between 1982 and 1993, 224 patients (196 females and 28 males) with benign lesion of the thyroid underwent surgery. This group included: 1) 210 pts with p multinodular goiter or solitary nodule with normal serum levels of T3, T4, FT3, FT4, TSH (Thyroid stimulating hormone; 2) 14 pts with a hyper-functioning goiter; 3) 12 pts with recurrent nodules following surgery which had been carried out in another hospital. In this study only those pts with solid cold (hypofunctioning) nodules which had not been treated previously were evaluated. The minimal follow-up was 18 months. It consisted of serologic studies (86 cases), ultrasonography (70 cases) and ultrasonography and scintigraphy (5 cases). We performed isthmusectomy in 2 cases, total lobectomy in 42 cases and subtotal thyroidectomy in 42 cases. Out of the 86 pts evaluated, 70 (81.3%) were treated with post-surgical hormone suppressive therapy (Levothyroxin 100 gamma daily). The endogenous thyroid stimulating hormone (TSH) was suppressed in 50 cases (71%), while 20 pts (28.5%) remained within the norm. Thyroid ultrasonography demonstrated recurrent nodules in 14 out of the 86 evaluated (16.2%). All these pts received thyroxine therapy. Among the 50 pts who had been treated with an adequate dose of thyroid hormone, 5 had recurrences (10%), as compared to 3 out of the 20 cases (15%) who had been administered thyroxine dosage not high enough to suppress THS and to 6 pts out of the 16 (33.5%) who had not been administered thyroid hormone. One out of the 20 pts (5%) who had undergone total lobectomy and post-surgical suppressive hormone therapy developed recurrence as compared to 6 out of the 24 pts (25%) who had under gone lobectomy and had been administered a hormone dosage which was not high enough to suppress TSH. Four out of the cases (13.3%) who had under gone subtotal thyroidectomy and post-surgical suppressive hormone therapy had recurrence as compared to 3 out of the 12 (25%) who had undergone subtotal thyroidectomy without TSH suppression. We conclude that treatment with thyroid hormone decreases the risk of benign recurrences only when undergone a long thyroxine therapy in doses high enough to suppress endogenous TSH.

Mandible reconstruction with metallic endoprosthesis following Commando's operation for advanced head and neck cancer. Personal experience.

Invasion of the mandible is found in 22% to 29% of advanced (Stage III-IV) head and neck cancers; only an aggressive surgical technique, such as Commando's operation with subsequent reconstruction of tissue defects, can give a chance of cure to these patients. The reconstruction is feasible both by means of microsurgical free-tissue transfers or with alloplastic materials and myocutaneous flaps. Between 1982 and 1991, 34 patients in Stage III (n = 6; 17.7%) and IV (n = 28; 82.3%) head and neck cancers underwent Commando's operation with different types of reconstruction in 30 patients: pectoralis myocutaneous flap (n = 9), osteo-myocutaneous flap with the underlying segment of the fifth rib (n = 2), myocutaneous flap plus prosthesis (n = 17), or prosthesis alone (n = 2). Two different prostheses were implanted: the linear A-O mandibular reconstruction plate (n = 13), and the Dumbach titanium cage (n = 6). In the group of patients in which the linear A-O mandibular reconstruction plate was used there were four cases of prosthesis dislodgement and major exposure and one case of prosthesis breakage while in patients who were given the Dumbach titanium cage there were four cases of major exposure. Prosthesis removal was required in five and two patients with linear A-O and Dumbach titanium cage prosthesis, respectively. Median survival was 14 months with 28% five-year survival. In our experience, metallic prostheses with a shape and arrangement that allow a distribution of traction forces on a wider surface, with screws drilled in nonaligned points of the mandible, seem to be more reliable as they reduce the risk of dislodgement and breakage.

[Cell kinetic analysis and treatment planning in epidermoid tumors of the head and neck]. / Test di cinetica cellulare e pianificazione dei trattamenti dei tumori epidermoidali del capo e del collo.

Cell kinetic parameters were evaluated using the method based on in vivo incorporation of Bromodeoxyuridine (BrdU) and flow cytometric (FCM) analysis in 30 human epidermoid head and neck tumors from oropharynx, oral cavity, rhinopharynx, larynx and lips. BrdU was injected four/six hours before the obtainment of multiple bioptic samples from the tumor tissues. The flow cytometric method was carried out on 70% ethanol fixed cell suspensions based on established protocol for the simultaneous evaluation of DNA content and BrdU uptake using anti-BrdU monoclonal antibodies. We have evaluated the following FCM parameters: DNA ploidy, the degree of DNA aneuploidy (DNA index), Labelling Index (LI), duration of s-phase (Ts) and tumor potential doubling time (Tpot). LI values ranged from 1.5 to 20% with a median value of 10%. The median LI of DNA diploid tumors was 5.4% compared to 14% in DNA aneuploid tumors. Ts values ranged from 8 to 11, the median value being 10 hours. Tpot values ranged from 2 days to 16 days, the median Tpot being 5 days. The large heterogeneity of all these parameters indicates that these tumors may have a different degree of biologic aggressiveness (9). Tpot values did not correlate with DNA ploidy nor with lymph node metastasis status. Tpot values did not correlate in a statistically significant manner with degree of differentiation although shorter Tpot were more frequently observed in moderate or poorly differentiated tumors. Our study shows that the FCM-BrdU technique in vivo is feasible in a clinical setting to evaluate the proliferative behaviour of head and neck tumors, before any specific therapeutic decision is taken after surgery is performed. It is likely that tumors with more aggressive biological behavior, as indicated by LI > 15%, DNA aneuploidy and Tpot < 5 days, may benefit from more aggressive therapies such as accelerated regimeus of radiotherapy and/or other multimodal therapies in respect to tumors with slow growth rate (LI < 15%), DNA diploidy and Tpot > 5 days. So far, however, it still remains to be demonstrated from randomized clinical trials if the knowledge of such individualized cell Kinetic parameters really can help to choose the most effective therapy for every individual patient.

Perilymphatic injections of recombinant interleukin-2 (rIL-2) partially correct the immunologic defects in patients with advanced head and neck squamous cell carcinoma.

Patients with advanced head and neck squamous cell carcinoma (HNSCC) are severely immunocompromised. In virtually all such patients who have been studied, reduced numbers of circulating CD3+ T-cell-receptor (TCR)alpha/beta+ T lymphocytes, a reduction of natural killer (NK) activity, and a poor induction of lymphokine-activated killer (LAK) cell activity (following in vitro treatment with recombinant interleukin-2 [rIL-2]) have been detected. Recently, however, it has been demonstrated that perilymphatic injections of low doses of rIL-2 may induce a local reduction of tumor masses in these patients. The present study, a cooperative pilot effort on the clinical effects of this route of administration, showed an activation of the lytic machinery in lymphocytes belonging to the T-cell lineage, as well as a potentiation of NK activity in the peripheral blood. These findings demonstrated that the severe immunodeficiency of HNSCC patients may be at least partially corrected by in vivo administration of rIL-2.

[Lipoma of the tongue. A clinical case report]. / Lipoma della lingua. Descrizione di un caso clinico.

Lipoma is a benign tumor of the adipose tissue. It is a common neoplasm but very rarely involves the tongue. Only 0.3% of all tumors involving the tongue are lipomas. A case of lipoma originating in the tongue is described. The tumor was removed and did not recur one year after excision.

Correlation between environmental parameters and leaf injury in Nicotiana tabacum L. cv. 'Bel-W 3'.

Tobacco plants (Nicotiana tabacum L. cv. 'Bel-W3') were exposed to ambient air for 25 weeks during the 1987 growing season next to an air pollution monitoring station in Brera (Milan, Italy). The research objective was to study the influence of selected environmental parameters on leaf damage in this plant, which is widely used as an ozone indicator. A multiple linear correlation model was estimated between leaf damage and available meteorological and air pollution data. Leaf injury was positively correlated with ozone integrated exposure and temperature, but negatively with vapour pressure deficit. A linear correlation model was used to estimate ozone integrated exposure from the leaf injury index.

Ozone biomonitoring in Northern Italy.

This report presents the results of an ozone monitoring experience performed with tobacco indicator plants (Nicotiana tabacum L. cv. 'Bel-W3'). These bioindicators were exposed to ambient air in 23 sites in Northern Italy from 27 April 1987 to 21 October 1987. Typical ozone-induced leaf necrosis was observed in every site. The percentage increase in injured leaf area was estimated weekly and a Leaf Injury Index (LII) was calculated. The weekly series of LIIs were statistically inspected for spatial and temporal relationships. Sample correlation coefficients were statistically significant for almost every possible pair of sites. The time series properties of ten series of LIIs with no missing data were analyzed using Box-Jenkins models. An autoregressive first order model, or AR(1), was selected to remove the autocorrelation from these series. Linear correlation coefficients between 'prewhitened' (i.e. from which autocorrelation had been removed) pairs of LII series were statistically significant. Hence synchronous variations in leaf necrosis could only be related to the regional diffusion of tropospheric ozone.

[Neoplasms of the major and minor salivary glands. The diagnostic and therapeutic approaches and case presentations]. / Neoplasie delle ghiandole salivari maggiori e minori. Approccio diagnostico, terapeutico e presentazione di una casistica.

Between January 1982 and December 1988, 37 patients with neoplasm of salivary glands have been treated in our Division of Surgical Oncology. The sites of tumors were: parotid 26, submandibular gland 4, minor salivary gland 7. The preoperative diagnostic procedures were: sialogram, ultrasonogram, fine needle aspiration. Malignant tumors were 16:5 adenoca., 4 metastases, 3 adenoid cystic, 2 mucoepidermoid, 1 acinic cells, 1 lymphoma. Twenty-one patients affected by neoplasms and 5 by malignant tumors were treated with surgery only. Nine patients affected by malignant tumors were treated with surgery and RT. Two patients were treated with RT only. The first therapeutic step is surgery; in order to control local evolution of tumor, postoperative irradiation is recommended. Possible indications of preoperative diagnostic procedures and the therapeutic choices are discussed.

Biochemical and ultrastructural effects of nitrite in rainbow trout: liver hypoxia as the root of the acute toxicity mechanism.

In Salmo gairdneri specimens exposed for 12, 24, 48, and 72 hr to nitrite (450 micrograms NO2-N) the main biochemical parameters of cerebral and hepatic hypoxia were studied. Observations on liver ultrastructure were also made to follow nitrite hepatotoxicity. Furthermore, some physiological alterations in liver mitochondria incubated in a medium containing a nitrite concentration similar to that found in the liver of in vivo exposed trout were studied. Results suggest that tissue hypoxia, due to the nitrite-induced high methemoglobinemia, is too low to be directly responsible for animal death. Nevertheless liver hypoxia is thought to be at the root of nitrite acute toxicity mechanism by producing suitable conditions for toxic potentialities. Thus irreversible and deadly damages arise in liver biochemistry and ultrastructure, particularly at the mitochondrial level.

Biochemical bases for environmental adaptation in goldfish (Carassius auratus L.): resistance to ammonia.

Goldfish specimens were exposed for 24-48 hr to 20, 40, 600, and 2500 micrograms N/liter unionized ammonia (UIA). This treatment causes, in the brain, increases in total ammonia, glutamine, lactate, and succinate and decreases in glutamate, glucidic stores, total NADH, and ATP. Most of these effects have already been reported in ammonia-treated trout. It is therefore suggested that the cerebral biochemical mechanisms of ammonia toxicity in these two species are fundamentally the same. The most important metabolic alterations, however, appear for UIA concentrations which are higher than those necessary to produce the same effects in trout, in accordance with the greater resistance of goldfish to ammonia. Some of the physiological-biochemical adaptations which are at the root of this phenomenon have been pointed out and discussed. In the liver of the ammonia-treated goldfish total ammonia, glutamine, glutamate, and succinate all increase, while lactate, glycine, and taurine decrease; liver glucidic stores remain unaltered. These results indicate a difference in the metabolic responses of goldfish and trout liver.

Lysosomal damage under nitrite intoxication in rainbow trout (Salmo gairdneri Rich.).

1. In Salmo gairdneri specimens exposed to 450 micrograms/l NO2-N (nearly 36 hr LC50) for various exposure times (12-72 hr) some parameters of liver lysosomal function were examined. 2. In vivo both total proteolytic activity and single protease activities were inhibited, the inhibition increasing with the lengthening of exposure time. In vitro no analogous effect was observed. 3. Lysosomal membranes showed an increased fragility correlated with the physiological conditions of treated animals. 4. Data were considered as the results of a nitrite mediated effect on functional and structural proteins.