Holocene evolution of Portus Pisanus, the lost harbour of Pisa.

The ancient harbour of Pisa, Portus Pisanus, was one of Italy's most influential seaports for many centuries. Nonetheless, very little is known about its oldest harbour and the relationships between environmental evolution and the main stages of harbour history. The port complex that ensured Pisa's position as an economic and maritime power progressively shifted westwards by coastal progradation, before the maritime port of Livorno was built in the late 16th century AD. The lost port is, however, described in the early 5th century AD as being "a large, naturally sheltered embayment" that hosted merchant vessels, suggesting an important maritime structure with significant artificial infrastructure to reach the city. Despite its importance, the geographical location of the harbour complex remains controversial and its environmental evolution is unclear. To fill this knowledge gap and furnish accurate palaeoenvironmental information on Portus Pisanus, we used bio- and geosciences. Based on stratigraphic data, the area's relative sea-level history, and long-term environmental dynamics, we established that at ~200 BC, a naturally protected lagoon developed and hosted Portus Pisanus until the 5th century AD. The decline of the protected lagoon started at ~1350 AD and culminated ~1500 AD, after which time the basin was a coastal lake.

DOSE MEASUREMENTS TO THE LENS IN NUCLEAR MEDICINE AND IN FLUOROSCOPY-GUIDED INTERVENTIONAL PROCEDURES: ANALYSIS OF THE RESULTS AND ASSESSMENT OF THE EFFECTIVENESS OF PROTECTIVE EYEWEAR ANTI-X.

The new limit of 20 mSv to the lens raises the need for further assessment of the equivalent dose to the lens for nuclear medicine and interventional radiology operators. (a) A measurement campaign was performed in nuclear medicine, (b) a routine monitoring was organised in interventional procedures and (c) the effectiveness of protective eyewear was assessed. In nuclear medicine, for photon fields, the adequacy of Hp(0.07) of dosemeter worn on the trunk is confirmed; with (90)Y, the annual values of Hp(3) measured in therapeutic session are <5 mSv. In interventional procedures, routine monitoring of the dose to the lens must be maintained where the values of Hp(0.07) dosemeter worn on the trunk are higher than one-third of the new limits. The measures carried out have shown that the attenuation factor mean of the protective glasses is equal to ∼4 (range 1.7-11.4).

Quantitative evaluation on [9°Y] DOTATOC PET and SPECT imaging by phantom acquisitions and clinical applications in locoregional and systemic treatments.

AIM: The aim of this paper was to compare [9°Y]-PET and SPECT imaging quantification for dosimetric applications in targeted radionuclide therapy. METHODS: Imaging studies were carried out by SPECT-CT and PET equipment performing phantom tests first. [9°Y]-SPECT and PET scans were compared in terms of sensitivity, minimum detectable activity concentration, recovery coefficients (RCs) and system spatial resolution (FWHM). Quantitative evaluations by PET and SPECT acquisitions were then assessed in patients who received therapeutic activity of [9°Y]-DOTATOC directly injected into the surgical cavity by locoregional route in glioma treatment and by systemic route in neuroendocrine tumour patients who underwent intravenous infusion. Finally 3D-dose distributions by SPECT and PET images were obtained. RESULTS: Sensitivity was proven to be about fivefold higher for SPECT than for PET. To obtain a good-quality PET imaging, the minimum detectable activity concentration was determined to be equal to 1 MBq/mL compared with 0.05 MBq/mL that was sufficient to assess adequate SPECT imaging. RCs were 100% for volume ≥ 25.5 mL for PET and ≥ 110 mL for SPECT. FWHM was 7 mm for PET and 19 mm for SPECT scans. With regard to locoregional therapy, excellent imaging was obtained with both PET and SPECT. On the contrary, systemic administration did not permit us to obtain suitable PET imaging. PET and SPECT images were affected by considerable noise, whose influence is much more important in the quantitative evaluation of dose volume histograms rather than in the visual interpretation of images. CONCLUSION: [9°Y]-activity quantification is feasible by SPECT and PET imaging. For clinical applications, SPECT-CT is the best technique for visualizing the radiopharmaceuticals following systemic infusion, while both SPECT and PET scans are effective in analyzing locoregional distribution. Nevertheless PET study demonstrates the best spatial definition.

Individual monitoring in nuclear medicine therapeutic procedures using extremity dosemeters LiF(Mg, Cu, P).

Unsealed beta-gamma-emitting sources are used (15 GBq (90)Y each session) in nuclear medicine therapeutic procedures. Inside the manipulation cell and while giving the injection to the patient, the skin exposure is very high; electron radiation field is not homogeneous and thus the exposure of the extremities is not uniform. Particular individual monitoring is adopted: single thermoluminescence dosemeter, wrapped in polyethylene film and placed on an adhesive tape, is positioned on the tip of the fingers; 6-10 dosemeters are assigned to each operator per session. The energy and angle response is studied for X-ray spectra, (90)Sr/Y and (204)Tl--a unique mean calibration factor is calculated in order to estimate H(p)(0.07). Performance of dosemeter is analysed according to ISO 62387-1(2007) and the combined uncertainty (calculated using the Monte Carlo method) results lie in the order of 11 %. This method reveals the critical step of manipulation and administration and ensures that dose limits are not exceeded.

SPECT/CT 90Y-Bremsstrahlung images for dosimetry during therapy.

BACKGROUND: the characteristics of (90)Y, suitable for therapy, are denoted by the lack of γ-emission. Alternative methods, using analogues labelled with (111)In or (86)Y, are generally applied to image (90)Y-conjugates, with some inevitable drawbacks. New generation SPECT/CT image systems offer improved Bremsstrahlung images. The intent of this brief communication is to show that high quality (90)Y-Bremsstrahlung SPECT-CT images can be obtained, allowing the biodistribution of pure ß-emitter therapeutical agents to be evaluated, also during the course of therapy. METHODS: the hybrid system Siemens Symbia-T2 was used for the acquisition of images of a patient given 1.7 GBq of (90)Y-DOTATATE. The following parameters were set for SPECT: 80 (50%) and 120 (30%) keV energy windows; medium energy collimators; 128 × 128 matrix, 64 projections (40s/step). Low-dose CT was acquired (80 mAs) for attenuation correction. Images were reconstructed with the OSEM 3D-Fast algorithm. RESULTS: post-therapy SPECT-CT (90)Y-Bremsstrahlung images of a patient undergoing receptor peptide radionuclide therapy are presented. (90)Y-Bremsstrahlung images obtained are suitable for tumour and normal organ dosimetry, providing detailed information on biodistribution, comparable to (111)In-diagnostic images. CONCLUSIONS: the improved Bremsstrahlung images means that the diagnostic examinations can be used for patient recruitment and that dosimetry evaluation can be restricted only to treated patients. This could avoid the need for a different radionuclide or isotope to mimic therapy. The clinical impact might be notable, as dosimetry and toxicity information are essential in radionuclide therapy, especially in patients with risk factors.

2,2'-bipyridine lariat calixcrowns: a new class of encapsulating ligands forming highly luminescent Eu3+ and Tb3+ complexes

A new class of calix[4]arene crown ethers with one or two bipyridines appended to the polyether ring (lariat calixcrowns) have been designed and synthesized; the luminescence properties of their Eu3+ and Tb3+ complexes have been studied in acetonitrile. In this solvent, long lifetimes for the metal emitting states and high metal-luminescence intensities obtained upon ligand excitation have been observed in both Eu3+ and Tb3+ complexes. The association constants in methanol have been determined for some of the complexes studied.

Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with 90Y: a phase I study.

A Phase I radioimmunotherapy trial was conducted in which radioconjugated monoclonal antibody (MAb) was directly infused into the tumor or postoperative tumoral bed in patients with high-grade malignant glioma. BC-4, a murine MAb that recognizes tenascin, was used in these studies. The MAb was labeled with 90Y, a pure beta emitter with maximum energy of 2.284 MeV, which can penetrate into tissue up to 0.5-0.7 cm. Stable 90Y-labeled MAb conjugates were prepared using the chelator p-isothiocyanatobenzyl derivative of diethylenetriaminepentaacetic acid (ITC-Bz-DTPA), obtaining >95% labeling efficiency and conserving the antibodies' immunoreactivity (>85%). Twenty patients, 2 with anaplastic astrocytoma and 18 with glioblastoma, were included in the study. All of the patients had been treated previously with conventional therapies (surgery, external radiotherapy, and chemotherapy) and presented with progressive disease not amenable to further treatment. A dose-escalation study was performed using doses ranging from 5-30 mCi (185-1110 MBq) of 90Y-labeled MAb BC-4. The protein dose of MAb was always 1 mg. Three patients were treated at the 5, 10, 15, and 20 mCi levels, and the 25- and 30-mCi doses were each administered to 4 patients. Systemic toxicity was completely absent in all of the patients. The maximum tolerated dose to the brain was 25 mCi (925 MBq). The average dose to the tumor was 3200 cGy/mCi. Doses to the liver, bone marrow, and kidneys were below 10 cGy/mCi in all of the cases. Biodistribution studies demonstrated that the 90Y-labeled MAb accreted exclusively in the neoplastic area without any diffusion into the normal brain or other normal organs. No clinical responses were recorded because of the very advanced stage of disease at the time of radioimmunotherapy.

Noninvasive localization of human atherosclerotic lesions with indium 111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells.

BACKGROUND: Targeting exclusive antigens in atherosclerotic plaques with antibodies may provide a noninvasive means to detect rapidly proliferative atherosclerotic lesions. 111In-labeled negative charge-modified Z2D3 F(ab')2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques. METHODS: The safety, biodistribution, accumulation, and elimination of Z2D3 were assessed in 11 patients who were candidates for carotid endarterectomy. The presence of atheromas in these patients was confirmed by angiography and Doppler ultrasound. Z2D3 (250 microg) labeled with 5 mCi of 111In was administered by slow intravenous injection. Planar and single photon emission computed tomography (SPECT) images were obtained 4, 24, 48, and 72 hours later. Carotid endarterectomy was performed and the surgical specimens were imaged, weighed, gamma-counted, and analyzed by immunostaining. RESULTS: Uptake of Z2D3 at the site of the carotid plaques was observed in the planar and SPECT views at 4 hours in all subjects. In addition, antibody uptake was noted in the contralateral vessel in 5 subjects. SPECT images identified the atherosclerotic plaques with focal uptake. The antibody uptake corresponded with the angiographic location of the disease. Immunohistochemical studies of the endarterectomy specimens confirmed the localization of Z2D3 into the plaque areas containing smooth muscle cells. Adverse drug reactions were not observed. CONCLUSION: This study demonstrates the feasibility of targeting atherosclerotic lesions with negative charge-modified antibody. It also proposes the possibility of selective identification of various components of atherosclerotic plaque, which may contribute to determining strategies of intervention in future.

[43 cases of primary empty sella syndrome: a case series]. / Quarantatre casi di "empty sella syndrome" primitiva: contributo casistico.

Primary empty sella syndrome (ESS) is an anatomo-radiological picture characterized by the presence of an arachnoid herniation filled with liquor that compresses the pituitary against the sellar wall. ESS occurs particularly in obese, hypertensive, cephalalgic women. It is often asymptomatic but may be associated with ophthalmologic, neurologic and non-characterizing endocrine disorders. We report here 43 cases of primary ESS observed and assessed in our Departments of Internal Medicine from June 1983 to May 1993. The following endocrinological diagnostic procedures were carried out: hormonal (RIA) basal profile: FT3, FT4, TSH, PRL, ACTH, FSH, LH, 8.00 a.m. and p.m., blood cortisol, aldo, PRA, DHEA-S, FTe, E2, P, PTH, CT, and calcemia and phosphoremia; provocative tests: TRH, GnRH, etc.; inhibition tests: high dose dexamethasone. Clinical, neurologic (skull radiographs, sellar stratigraphy, computed tomography scan and magnetic resonance), and ophthalmologic (fundus, visual fields) assessments were also made. Our findings fit with the data in the literature concerning common symptoms of ESS, associated endocrinopathies and other illness. We found obesity (62.7%), oligo-amenorrhea (16.6%), galactorrhea (14.6%), hyperPRL (11.6%), hypopituitarism (9.3%), hypogonadism (4.6%), diabetes insipidus (2.3%), (micro-)polycystic ovary syndrome (19%), hyperACTH (2.3%). In 9.3% of the cases, endocrinopathy referred to pituitary adenomas. Moreover, we noted a high frequency of psychological disorders, to our knowledge not previously reported in the literature, including anxiety or dysthymic disorders with altered behavior (chiefly oral compulsion). We also make the hypothesis that obesity (occurring in 62.7% of our patients) and hypertension (62.7%) may be related to hypothalamic alterations.

[Twelve year observation of the eyes after lensectomy]. / Dwunastoletnie obserwacje oczu po lensektomii.

The authors presented long-term results of surgery of congenital, residual, traumatic and post-inflammatory cataracts. Lensectomy through pars plana was performed in all eyes. Examination after 12-year follow-up was performed in 186 eyes, i.e.-69.4% of the total number of 268 eyes which underwent surgery. The most frequent complication was glaucoma (33.3%), which passed without any symptoms and was diagnosed accidentally, in the majority of cases in the period over 3 years after surgery. Other complications were rare; They included retinal detachment in 0.5% of the eyes. Visual acuity was 5/50 and less in 52.7% of the eyes; only in 10% it was 5/10 and better. The conclusion is that all patients after cataract surgery should be examined for glaucoma.

Glioblastoma therapy by direct intralesional administration of I-131 radioiodine labeled antitenascin antibodies.

Thirty patients with recurrent glioblastomas (29 brain, 1 spinal cord) received intralesional radioimmunotherapy aiming to control the progression of the tumor after surgery and radiotherapy. The BC-2 and/or BC-4 murine MAbs (Sorin-Biomedica, Saluggia, Italy) were utilized. They strongly react against tenascin (TN), which is an extracellular antigen expressed in large amounts by the stroma of glioblastoma but not by normal brain. The MAbs were labeled with I-131 and were injected directly into the tumor mass to maximize the antibody concentration in the tumor and to irradiate the neoplastic cells. The dose consisted, on average, of 3 mg antibody and 1100 MBq I-131. In most cases the radioimmunotherapy (RIT) applications were repeated two, three, or four times. No systemic adverse reactions were recorded. The brain tolerance to direct antibodies injection was quite good. The antibody concentration in the tumor was high and the MAb residence time in neoplastic tumor was prolonged. Consequently the mean radiation dose to the tumor was high: > 25,000 cGy/cycle. Of 23 evaluable patients, we recorded 7 tumor stabilization (lasting, on mean, 9.1 mo), 4 partial remission (10 mo), and 4 complete remission (18 mo). The overall response rate was 34.7%.

[A multicenter study for the evaluation of the diagnostic efficiency of mammography and echography in nonpalpable breast neoplasms]. / Studio multicentrico per la valutazione dell'efficacia diagnostica della mammografia e dell'ecografia nelle neoplasie mammarie non palpabili.

The Breast Section of the Italian Society of Radiology set up a cooperative study which included 17 Departments of Radiology and Breast Diagnosis in order to evaluate the diagnostic accuracy of US versus mammography in nonpalpable breast lesions. From January 1, 1989 to december 31, 1990, 400 nonpalpable breast lesions (142 benign lesions, 59 in situ and 199 infiltrating carcinomas) were detected by mammography and/or US; they had questionable/suspicious findings which called for further investigation by means of cytology and/or histology. US proved much less sensitive in non-palpable carcinomas than mammography (49.2% vs 93.8%), also in younger women, and failed to detect 50% of the benign/malignant nonpalpable lesions identified by mammography. US sensitivity was directly related to lesion diameter and probe frequency: 38.7% in infiltrating carcinomas < or = 5 mm vs 56.8% in those > 10 mm; 12% in the patients examined with a 5-MHz probe vs 57.7% in those examined with a > or = 7.5-MHz probe. Furthermore, the most significant US patterns of nonpalpable lesion were irregular contours, posterior attenuation and irregular internal echoes, while an irregular skin line and Cooper ligaments had no significant relation with carcinoma. Thus, breast US cannot be used as a screening test on asymptomatic patients not even on young women with radiologically dense breasts. On the contrary, US performed with high-frequency probes is useful in the assessment of nonpalpable lesions identified by mammography, and allows, in many cases, US-guided cytology and preoperative localization.

[Heterosexual transmission of HIV and a control organization model consisting of female subjects at the USL no. 36 Drug Control Service of Lugo]. / Esperienza di trasmissione per via eterosessuale dell'HIV e modello organizzativo di controllo dei soggetti di sesso femminile presso il settore tossicodipendenze dell'USL n. 36 di Lugo.

Human immunodeficiency virus-HIV heterosexual transmission is going to become the main problem in controlling the spread of HIV; our experience confirms the increased risk when genital lesions are present. These data advise to attend gynaecologic control of female drug addicts, often affected by sexually transmitted diseases, in order to realize primary and secondary HIV spreading prevention.

Asymptomatic patients with HIV infection. Keeping them well.

Primary care physicians need to be prepared to counsel and manage patients with human immunodeficiency virus (HIV) infection. Asymptomatic seropositive patients should be seen quarterly, and T4 lymphocyte counts should be followed. Other serologic markers that may detect disease progression are p24 antigen and beta 2 microglobulin. Abnormalities in the levels of these markers may influence the decision to initiate early antiretroviral therapy. Therapeutic regimens are now available for delaying progression of HIV disease and for preventing Pneumocystis carinii pneumonia, the most common opportunistic infection to develop in patients with HIV infection. Whether antiretroviral therapy should be initiated in all asymptomatic HIV-positive patients remains to be seen. Physicians can do their part by educating themselves about HIV infection so they can provide competent, nonjudgmental care to patients and by supporting legislation to protect the rights of HIV-infected persons.

Black hairy tongue.

Black hairy tongue is a benign disorder characterized by hypertrophy of the filiform papillae of the tongue. A brownish-black discoloration of the papillae occurs. The etiology is unclear, but the disorder has been associated with numerous predisposing conditions. Although black hairy tongue is usually cured by removal of these factors, a variety of measures, particularly brushing of the tongue, may aid in resolution.

Zinc and thymic hormone-dependent immunity in normal ageing and in patients with senile dementia of the Alzheimer type.

Plasma zinc levels were measured in young controls, aged controls, patients with dementia of the Alzheimer type and patients with non-Alzheimer type dementia. Zinc levels decreased with age; however, no difference was found between patients with dementia and age-matched controls. Plasma levels of active or inactive thymulin, a nonapeptide produced and released by the thymus gland, were also determined in young controls, aged controls, patients with dementia of the Alzheimer type and patients with non-Alzheimer type dementia. Basal levels of active thymulin were decreased in aged controls and in patients with dementia. In vitro reactivation of thymulin after zinc addition to plasma samples was decreased in aged controls. A further impairment of thymulin reactivation was present in patients with dementia. A significant age-dependent decrease in lymphocyte proliferation after mitogen stimulation was found; however, no difference was present between aged controls and patients with dementia of the Alzheimer type. Interleukin-2-induced cell activation and its effect on mitogen-induced proliferation were also measured; once again only an age-associated decrease was found. The endocrine function of the thymus of patients with dementia appears to be more compromised than that from aged controls.

Aerosolized pentamidine in HIV. Promising new treatment for Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia is the most common life-threatening disease diagnosed in patients infected with the human immunodeficiency virus (HIV). Patients treated for their initial episode are at risk for recurrence of the disease. HIV-positive patients with low T4 lymphocyte counts are also at risk. Conventional treatment regimens with parenteral pentamidine isethionate (Pentam 300) or trimethoprim-sulfamethoxazole have a 50% to 60% incidence of serious adverse effects and a 20% to 40% rate of failure. Aerosolized pentamidine represents a promising new therapy for HIV-infected patients. Major adverse reactions have not been reported with its use. The Food and Drug Administration's (FDA's) recent approval of aerosolized pentamidine may also have a positive effect on healthcare costs by preventing episodes of P carinii pneumonia. In addition, FDA approval may result in reimbursement of patients for this new therapy by more insurance companies.

Klebsiella pneumoniae bacteremia in the community hospital.

The purpose of this study was to elicit the circumstances of occurrence and organism sensitivities of Klebsiella pneumoniae bacteremia in the community hospital, since data on this illness from the community hospital are rare. All records of documented Klebsiella pneumoniae bacteremia (46 cases) at Alachua General Hospital, Gainesville, Florida, over the period July 14, 1982, through July 27, 1985, were reviewed in detail. Fifty-nine percent (27 organisms) were nosocomial, whereas 41% (19 organisms) were community acquired. The most common predisposing disorders in these patients were, in decreasing order, malignancy; following gastrointestinal or biliary surgery; biliary tract obstruction; diabetes; and unknown. Twenty-two percent (10) of the patients died from bacteremia. The majority of organisms tested were sensitive to mezlocillin, cephalothin, cefoxitin, tetracycline, tobramycin, gentamicin, co-trimoxazole and ceftizoxime. Therapy was considered to be appropriate in 89% (41) of the patients and inappropriate in 10.9% (5) of the patients. Contrary to previous thought, Klebsiella pneumoniae bacteremia is a relatively common problem in the community hospital and may be community acquired as well as nosocomial. There are many characteristics of this disease in the community that are different from those reported in studies on Klebsiella pneumoniae bacteremia from large referral centers.

Locoregional immunotherapy of human ovarian cancer: preliminary results.

Ten patients with advanced ovarian carcinoma (5 in FIGO stage III and 5 in stage IV), following the failure of repeated chemotherapy courses, were submitted to i.p. radioimmunotherapy (RIT). Several antibodies (HMFG1, HMFG2, H17E2, B72.3) were employed. The antibody choice was made on the basis both of immunohistochemistry and immunoscintigraphy results. The mean dose administered in each single course was 17 mg, 3 patients underwent two treatments and 2 patients were injected three times. The isotope employed was 131I (mean dose 92 mCi). The early or late untoward effects were negligible. All patients developed anti-mouse antibodies (HAMA) which reduced, during the further RIT, the MoAbs' effective half-life. The estimated radiation dose delivered to the tumour ranged from 2910 to 11,000 cGy. Both wholebody and liver radiation burden resulted in tolerable limits while the thyroid irradiation was high. In 3 patients the RIT result was ineffective; in 2 cases a temporary ascitis staunch was obtained. In 2 cases the tumour growth was slower than expected and in 3 patients instrumental evidence of partial tumour reduction, still lasting after 4-11 months, was observed.