Trafficking and homing of systemically administered stem cells: the need for appropriate analysis tools of radionuclide images.

AIM: Despite its enormous relevance, homing of hematopoietic stem cells (SCs) remains relatively uncertain due to the limitations of measuring small number of systemically administered cells in the different organs. Despite its high sensitivity, radionuclide detection has been relatively underutilized to this purpose since it cannot differentiate hematopietic SCs recruited by target tissues from those circulating in the blood pool. Our study aims to verify the potential of tracer kinetic approaches in estimating the recruitment of labeled SCs after their systemic administration. METHODS: Twenty-four Lewis rats underwent administration of 2 millions cells labeled with 37 MBq of 99mTc-exametazime. Animals were divided into 2 groups according to administered cells: hematopoietic SCs or cells obtained from a line of rat hepatoma. Cell injection was performed during a planar dynamic acquisition. Regions of interest were positioned to plot time activity curves on heart, lungs, liver and spleen. Blood cell clearance was evaluated according to common stochastic analysis approach. Either fraction of dose in each organ at the end of the experiment or computing the slope of regression line provided by Patlak or Logan graphical approach estimated cell recruitment. At the end of the study, animals were sacrificed and the number of cells retained in the same organs was estimated by in vitro counting. RESULTS: Cell number, documented by the dose fraction retained in each organ at imaging was consistently higher with respect to the "gold standard" in vitro counting in all experiments. An inverse correlation was observed between degree of overestimation and blood clearance of labeled cells (r=-0.56, P<0.05). Logan plot analysis consistently provided identifiable lines, whose slope values closely agreed with the "in vitro" estimation of hepatic and splenic cell recruitment. CONCLUSION: The simple evaluation of organ radioactivity concentration does not provide reliable estimates of local recruitment of systemically administered cells. Yet, the combined analysis of temporal trends of tracer (cell) tissue accumulation and blood clearance can provide quantitative estimations of cell homing in the different organs.

The rational use of fine needle aspiration biopsy (FNAB) in diagnosing thyroid nodules.

AIM: Fine needle aspiration biopsy (FNAB) plays a crucial role in the diagnosis of thyroid nodules and enables the number of surgical operations to be reduced. Theoretically, FNAB should be carried out on all nodules, though currently only those displaying certain characteristics are biopsied. Indeed, to perform FNAB on all nodules may be regarded as an excess of zeal. Therefore, it seems advisable that the endocrinologist should be able to confirm on the spot the necessity and utility of FNAB. METHODS: We evaluated on a sample of 263 consecutive requests (209 female, 57 male; age 56.7+/-13.7 years) for FNAB in 2004: 1) the appropriateness of the investigation, 2) expected efficacy, 3) practical efficacy, 4) efficiency. FNAB was performed under echo-guidance in accordance with the standard technique. In 50%, 36%, 6%, 3%, 2% and 1% of cases, the echographic diagnosis was of MNG, UNG, pseudo-nodular lesion in ATD, lymph-node, neck cyst, suspected parathyroid lesion and tumefaction of the salivary glands, respectively. A pre-FNAB clinical risk score was assigned to each case on the basis of clinical and echographic data, with a maximum possible score of 11. The results of FNAB were subdivided into 5 categories according to the criteria of the BTA (Thy1-Thy5). After FNAB, a decisional category was assigned, ranging from ''observation'' to ''surgery''; this was subsequently (7-18 months) compared with the management strategy adopted by the attending physician. Information was gathered by means of telephone enquiry. RESULTS: 1) Appropriateness: on the basis of clinical and echographic findings, FNAB was not judged appropriate in 24% of cases because of either the lack of confirmation of a significant target (34%) or a low pre-FNAB risk score (range 0-2) (66%). The decisional category was ''observation'' in 87% of cases and ''further investigation'' in 13%. 2) Expected efficacy: FNAB was performed in 76% of cases. The biopsies (3%) performed on swollen lymph-nodes and extra-thyroid neck tumefactions, in which biochemical evaluation was positive, proved to be diagnostic but not classifiable according to the BTA. In 82% of the remaining cases, the result was Thy2 (observation) or Thy 4-5 (surgery). Thy3 results (surgery) were rare (1%). Thy1 results (16%) were yielded by the aspiration of colloid cysts (29%), solid lesions (10%) characterised by means of PTH-FNAB and Tg-FNAB, nodules (9%) no longer detectable on repetition of FNAB, nodules (16%) in which FNAB was already a repetition of a non-diagnostic investigation (2003), and nodules (9%) in which the presence of normal thyrocytes, ''hot'' scintigraphic image and prior decision of the surgeon advised against repeating FNAB. Of the patients with Thy1 results, 26% refused to repeat FNAB. In all, 95% of FNAB supported by biochemical evaluation yielded results that usefully contributed to patient management. The correlation between pre-FNAB clinical risk and cytological score according to the BTA proved significant (P<0.001). No difference in diameter was recorded between nodules with adequate cytology (23.3+/-0.9 mm) and those with inadequate cytology (25.2+/-1.6 mm). 3) Practical efficacy: 75% of patients were reached by telephone. In most cases, observation was the most frequent clinical choice, after echography and/or FNAB. The decisional category assigned after FNAB correlated significantly (P<0.001) with the approach adopted by the attending physician. d) Efficiency: following FNAB, 11 patients were assigned to surgery. DTC was detected in 100% of these cases (1 follicular carcinoma, 1 insular carcinoma, 9 papillary carcinoma). The success of FNAB (9/11) in detecting lesions that proved malignant on histological examination (11/11) was significant (P<0.05). Of the 2 Thy 3 cases, 1 was follicular carcinoma and 1 was follicular adenoma with adjacent papillary carcinoma. The incidence of thyroid carcinomas in the population studied was 5.5%. CONCLUSIONS: 1) Together with clinical-biochemical evaluation, echo-guided FNAB re-mains the first-line diagnostic test in the management of thyroid nodules; 2) a pre-FNAB clinical risk score is useful in limiting the number of probably inappropriate investigations; 3) efficacy, in terms of cytology results that are useful for patient management after FNAB (and after biochemical evaluation, when indicated) is high, enabling patients to be stratified in classes with different subsequent pathways; 4) in the vast majority of cases, FNAB influences subsequent clinical decisions; 5) false negatives cannot be excluded, while false positives are practically nil; 6) further indications may be yielded by studies on larger populations, and new prospects may emerge from the application of other techniques associated to FNAB.

Safety and efficacy of administering 0.2 mg of recombinant human TSH for two consecutive days as an adjuvant to therapy with low radioiodine doses in elderly out-patients with large nontoxic multinodular goiter.

AIM: The aim of this study was to evaluate the efficacy of recombinant human TSH (rhTSH) as an adjuvant to radioiodine therapy for nontoxic multinodular goiter (MNG) in elderly subjects. METHODS: Twelve elderly out-patients with large MNG (group 1) were studied. The effect of adjuvant rhTSH administration (0.2 mg i.m. on 2 consecutive days) before low-dose (131)I was compared with that of radioiodine alone in 8 out-patients matched for age and MNG volume (group 2). The follow-up period was similar in both groups. RESULTS: The number and severity of side-effects during the first month of treatment were similar in both groups. On final examination, the number of patients symptomatic for goiter was significantly lower in group 1 than in group 2 (P=0.03). In group 1, TSH levels peaked at 40.3+/-9.5 mU/L on day 3, from the baseline value of 0.5+/-0.1 mU/L (P<0.001). In group 2, baseline TSH was 0.4+/-0.1 mU/L. Although a marked increase in f-T3, f-T4 and Tg (P<0.001) was noted in both groups during the first 2 weeks of treatment, peak values were much higher in group 1 than in group 2. On final examination, a slightly significant increase (P=0.01) in TSH levels from the baseline was noted in both groups (group 1: 1.2+/-0.2 mU/L; group 2: 1.4+/-0.3 mU/L). The percentage of patients who did not need therapies to control TSH secretion at the last examination was higher in group 1 (83%) than in group 2 (38%). Only in group 1, a significant reduction was noted in mean anterior-posterior lobar width (31+/-1.7 mm) from the baseline value (24.5+/-1.7 mm, P=0.04). Thyroid volume was reduced from 78.1+/-11.7 mL to 49.4+/-13.4 mL (P=0.001) in group 1 and from 89.8+/-25.2 mL to 67.1+/-20.5 mL (P=0.04) in group 2. Six months after (131)I therapy, slight changes in thyroid length and tracheal lumen were noted in both groups. CONCLUSIONS: This long-term controlled study demonstrates that 0.2 mg of rhTSH on 2 consecutive days increases the efficacy of ambulatory (131)I dosages in treating nontoxic MNG in elderly subjects. Adequate drug preparation generally prevents side-effects due to short-term but marked thyrotoxicosis that is aggravated by rhTSH administration. An increase in thyroid volume reduction seems to be the most important effect of rhTSH administered before (131)I.

A case-controlled study on the quality of life in a cohort of patients with history of differentiated thyroid carcinoma.

Although quality of life (QoL) has become an important aspect of cancer rehabilitation, psychometric studies on thyroid cancer patients are rare. We performed a case-controlled study on QoL in patients with differentiated thyroid carcinoma (DTC). QoL was evaluated in 61 patients with a history of DTC diagnosed from < 1 to 23 yr earlier. An undetectable thyroglobulin (Tg) level after recombinant human TSH (rhTSH) testing was considered the best predictor of cure. QoL was evaluated by means of a general psychiatric interview, the self-rating Kellner Symptoms Questionnaire (KSQ) and the Hamilton Depression Scale (HDS). QoL was also evaluated in a control group of subjects on L-T4 therapy with a non-toxic multinodular goiter diagnosed from < 1 to 25 yr earlier. DTC and control subjects were similar in age, male-female distribution and concomitant psychiatric therapies. Per-week dosage of L-T4 was higher in DTC patients than in controls (p < 0.01). In neither group of subjects was there any correlation between current TSH levels or interval from diagnosis and KSQ or HDS scores. Only in DTC patients was there a positive correlation between age and KSQ (p < 0.05) or HDS (p < 0.01) scores. There was a significant difference in overall KSQ scores between DTC (33.4 +/- 2.1) and control (24.5 +/- 1.9; p < 0.01) subjects. The subscales of KSQ showed a significant inter-group difference. HDS scores were higher in DTC subjects (35.8 +/- 1.0) than in controls (30.0 +/- 1.1; p < 0.01). HDS score was significantly (p = 0.02) higher in female than in male DTC patients. In patients with papillary carcinoma there was a positive correlation between the MACIS (metastases, age, completeness, invasiveness, size) score and KSQ (p = 0.01) or HDS (p < 0.01) scores. After rhTSH testing, detectable Tg levels were found in 13% of DTC patients. In Tg-positive patients, KSQ and HDS scores were not different from those of Tg-negative patients. After an 8-14 month period, a significant decrease in the KSQ scale somatization (p = 0.02) was found in a sub-set of 31 DTC patients. In conclusion, even in the age of rhTSH testing, DTC patients suffer an impairment of their QoL, as noted when short-term L-T4 withdrawal was the gold standard. Longitudinal evaluation seems to indicate a slight improvement in QoL when safe rhTSH testing is extensively used in the management of the disease.

Circulating nitric oxide is modulated by recombinant human TSH administration during monitoring of thyroid cancer remnant.

During the administration of recombinant human TSH (rhTSH) to monitor differentiated thyroid carcinoma, mild side effects, such as nausea and headaches, often occur. The origin of these is not clear. Since changes in TSH and thyroid hormones can modulate some endothelial-derived factors, we aimed at testing whether rhTSH administration induces changes in nitric oxide. We studied 25 patients (56.6+/-12.6 yr) who had undergone thyroidectomy followed by ablative radioiodine for papillary thyroid cancer and who were under follow-up. While L-thyroxine therapy continued, thyroglobulin (Tg), TSH, free-T3, free-T4 and nitrite-plus-nitrate (NOx) concentrations were evaluated before and after rhTSH administration (0.9 mg i.m. on 2 consecutive days). Mean TSH showed a huge increase from baseline (0.1+/-0.0 mIU/l) to day 3 (216.3+/-17.5 mIU/l, p<0.001), which was not accompanied by changes in thyroid hormones. Mean baseline NOx levels were 12.6+/-1.2 micromoles/l and showed a significant increase on day 3 (20.1+/-1.2 micromoles/l, p<0.05 vs day 0), followed by progressive reduction from day 6 (18.1+/-2.8 micromoles/l) to day 9 (10.6+/-1.3 micromoles/l, p<0.05 vs day 0). There was a significant (p=0.04) correlation between the percentage increase in TSH and the percentage increase in NOx. On the other hand, increase in TSH did not correlate with the percentage decrease in NOx from day 6 to day 9. No correlation was noted between the increase in TSH or NOx and the occurrence or severity of the symptoms. Our study shows that, during rhTSH testing, circulating nitric oxide increases. This endothelial-derived factor might, in turn, mediate the occurrence of vasomotor headache and nausea in some particularly susceptible patients.

Pharmacokinetics of an allergen and a monomeric allergoid for oromucosal immunotherapy in allergic volunteers.

BACKGROUND AND OBJECTIVE: Little is known about the pharmacokinetics of allergens for local immunotherapy. Thus, we studied the pharmacokinetics in allergic volunteers of a commercial allergenic vaccine in orosoluble tablets (LAIS(R), Lofarma S.p.A). METHODS: The carbamylated monomeric allergoid derived from Parietaria judaica major allergen (Par j 1), characterized by maintenance of the original molecular size, and the native allergen, were radiolabelled with 123I, then incorporated into the commercial soluble tablets and administered to allergic subjects. Early sequential and late static scintigraphic acquisitions were performed, and plasma radioactivity was measured at different time intervals. RESULTS: No difference in local pharmacokinetics was observed between the allergen and the allergoid: part of the tracer was retained in the mouth for at least 2 h after swallowing. No direct absorption through the oral mucosa could be detected, as plasma radioactivity increased only after swallowing and peaked at 2 h. However, the plasma peak attained with the allergoid in tablets was significantly higher with respect to the native allergen. Finally, some undegraded allergoid, but not the allergen, could be constantly detected in the bloodstream at plasma peak. CONCLUSIONS: The results showed a similar behaviour of the allergoid and the allergen in tablets as far as their local kinetics are concerned, whereas plasma peak was higher with the allergoid than with the allergen. Therefore we conclude that the chemical modification of the allergen may affect its pharmacokinetics, by making it less susceptible to enzymatic degradation.

Evaluation of effective renal plasma flow with I-127 ortho-iodohippurate and I-123 ortho-iodohippurate in rabbits.

RATIONALE AND OBJECTIVES: Radiolabeled ortho-iodohippurate is commonly employed for evaluating effective renal plasma flow (ERPF) by means of either in vivo scintigraphy and/or plasma clearance curves. A new method has recently been developed for measuring levels of stable iodine (iodine-127) in biologic samples, based on the detection of x-ray fluorescence photons. In this study, the authors assessed the potential of the new system to evaluate ERPF by using an iodinated contrast medium with adequate glomerular filtration and tubular secretion properties. MATERIALS AND METHODS: A commercial system was used to evaluate ERPF after intravenous injection of stable I-127 ortho-iodohippurate. The results were compared with the clearance values of I-123 ortho-iodohippurate, considered the reference standard. Seven rabbits under general anesthesia were given intravenous injections of I-123 ortho-iodohippurate and I-127 ortho-iodohippurate. The corresponding plasma curves were evaluated from 4 to 60 minutes to calculate ERPF as the dose/integral of plasma curve. RESULTS: The initial distribution volumes of I-123 ortho-iodohippurate (149.4 mL/kg +/- 12.1) and I-127 ortho-iodohippurate (148.8 mL/kg +/- 11.8) were virtually superimposable, thus confirming the chemical identity of the two compounds. The plasma clearance values for I-127 ortho-iodohippurate (11.15 mL/min kg(-1) +/- 1.44) were slightly (not significantly) higher than those for I-123 ortho-iodohippurate (10.49 mL/min kg(-1) +/- 1.41), perhaps because of a relative "mass" load effect of the iodinated medium. CONCLUSION: The results obtained in this study demonstrate the feasibility of the new system for evaluating ERPF, provided that a compound with adequate glomerular filtration and tubular secretion properties is employed.

Clinical experience with recombinant human thyrotrophin (rhTSH) in the management of patients with differentiated thyroid cancer.

The purpose of this work was to gain clinical experience with and to identify the optimal conditions for the use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC). The study involved 22 patients for a total of 27 administration cycles of rhTSH, for either diagnostic (in 19 instances) and/or therapeutic purposes (in 8 instances). There were 19 patients with papillary cancer (follicular variant in 4, columnar variant in 1) and 3 patients with follicular cancer (1 Hurtle cell variant). All patients had previously undergone total thyroidectomy and 1-5 cycles of 131I-therapy. Thyrogen was administered i.m. according to the suggested protocol: 0.9 mg i.m. on days 1 and 2, radioiodine on day 3. Peak serum TSH levels between 68-237 microIU/mL were observed after rhTSH administration; these were on average 65% higher, on a patient-by-patient basis, than peak serum TSH observed after conventional withdrawal of thyroxine treatment in 19 patients, while in 3 patients they were 28% lower, but still in the potent stimulation range (86-94 microIU/mL). There was general agreement between imaging results obtained under rhTSH stimulation and those obtained on prior occasions during thyroxine withdrawal, although radioiodine uptake was interpreted as less intense following Thyrogen administration. Of 18 patients undergoing rhTSH administration for diagnostic purposes, 11 patients had a negative radioiodine whole-body scan (WBS) and 7 had a positive WBS. Three of the WBS-negative patients were shown to be actually affected by tumor recurrence, respectively by PET with [18F]FDG (in 2 cases) and by post-131I therapy scan. Serum thyroglobulin (hTg) increased to abnormal levels following rhTSH stimulation in 3/7 of the WBS-positive patients as well as in 1/11 WBS-negative patients. In 3/7 WBS-positive as well as in 3/11 WBS-negative patients, serum hTg progressively rose under rhTSH stimulation, yet still remaining below 3 ng/mL. Post-131I therapy scans following Thyrogen administration showed good radioiodine uptake in 7/8 patients, the single unsuccessful case being most likely due to expansion of the iodine pool because of recent use of an iodinated contrast medium. The overall results show the feasibility and practical advantages of employing rhTSH stimulation in the general clinical setting rather than thyroxine withdrawal in the management of DTC patients. Caution should be raised on the interpretation of the serum hTg response to such potent but short-lived TSH stimulation.

[Pulmonary metabolism of beta-endorphin in asthmatic patients in asymptomatic periods and after bronchospasm induced by methacholine]. / Metabolismo polmonare delle beta-endorfine in soggetti asmatici asintomatici e dopo broncospasmo indotto con metacolina.

Blood concentration of endogenous beta-endorphines can change during the clinical evolution of chronic bronchopneumopathies. The authors assessed the beta-endorphine concentrations in the pulmonary arterial and systemic arterial blood in 8 asthmatic patients during a symptom-free period and after methacholine-induced bronchospasm. The beta-endorphine analysis was performed in duplicate dor each sample, by means of a RIA assay. There is not difference in the systemic arterial blood concentration of beta-endorphines between asthmatic patients and normal subjects. Furthermore, there is no change in the beta-endorphine blood concentration during the passage through the pulmonary tissue after methacoline-induced bronchospasm.

Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol.

The aim of this study was to assess the effect of a long-term course of high-dose i.v. pulses of calcitriol (CLT) on hyperparathyroid bone disease (HBD) and functional mass of parathyroid glands of chronically hemodialyzed uremic (CHU) patients. We prospectively studied nine CHU patients treated with CLT, 30 ng/kg/body wt, i.v., thrice weekly over a period of eight months. Plasma concentrations of intact parathyroid hormone (iPTH), bone GLA protein (bGLA) and bone isoenzyme of alkaline phosphatase (biALP) were sampled throughout. Transiliac bone biopsies were made before and after the start of CLT therapy. Double scanning scintigraphy of the neck with 201Tl-99Tc was made before, during and eight months after the start of the treatment. All patients but one, who later responded to higher than planned CLT doses, had significant decreases of plasma iPTH (F = 76; P < 0.0001; ANOVA). The mean pretreatment value of PTH was 966 +/- 160 (mean +/- SE) pg/ml and it had decreased significantly by the first week (T = 2.4, P < 0.04), and had fallen an average of 80% by the 35th week. Ionized plasma calcium concentration was 1.19 +/- .01 mmol/liter which rose significantly (F = 13.5; P < 0.0001) by the 14th week to maximal peak levels, averaging 1.34 +/- .02 mmol/liter. Changes in biALP were parallel to those of iPTH, while bGLA tended to increase immediately after the start of the therapy and to significantly decrease thereafter (T = 3.2; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in immune status due to anesthesia and surgical intervention. The role of thymopentin and interleukins]. / Modificazioni dello stato immunitario indotte dall'anestesia e dall'intervento chirurgico. Il ruolo della timopentina e delle interleuchine.

OBJECTIVE: Purpose of the study was clinical evaluation of thymopentin and interleukins in the changes of immunity due to anesthesia and surgical operation. DESIGN: After randomization the patients were divided into four groups according to starter type (thiopental or propofol) and immunological pre-treatment (tymopentin or saline of control group) administered for three days before and two days after operation. SETTING AND PATIENTS: The study was effected on 40 patients undergoing venous vascular surgery in operating rooms of Medical School of University of Genoa. MEASUREMENT: At pre-established times (basal, before and after induction, recovery and 72 postoperative hours) were measured some immunological data (plasmatic concentrations of red blood cells, white blood cells, lymphocyte cells, antibodies, complement analysis, interleukins 1 and 2). RESULTS: The results show a depression of immunity with hypoleucocistosis and hyperlymphocytosis due to surgical trauma or to anesthesia drugs. CONCLUSIONS: Pre-treatment with thymopentin no change perioperative immunity and the role of interleukins isn't clear; the immunological depression is the same in thiopental of propofol groups.

[The clinical evaluation of the hypocholesterolemic effects of an inhibitor of cholesterol synthesis: mevalonic acid]. / Valutazione clinica degli effetti ipocolesterolemizzanti di un inibitore della sintesi del colesterolo: l'acido mevalonico.

Twenty eight patients with heterozygous familial hypercholesterolemia were treated with mevalonic acid (an inhibitor of cholesterol synthesis) for 45 days. Patients received a daily dose of 750 to 1500 mg mevalonic acid depending on plasma cholesterol levels. Results showed a significant reduction in cholesterol values whereas no significant difference was observed in HDL cholesterol and triglyceride levels.

[Clinical evaluation of pre-surgical anxiety: changes in plasma levels of the anxiety peptide (diazepam binding inhibitor)]. / Valutazione clinica dell'ansia pre-intervento chirurgico: modificazioni dei livelli plasmatici del peptide dell'ansia (DBI).

The score scale of anxiety (STAI, Y, 1-2) and haematic levels of DBI (diazepam binding inhibitor) were used in 48 surgical patients for clinical evaluation of preoperative anxiety, before and after drugs for preoperative medication. After randomization, were clinically and statistically compared 6 groups according to premedicant drugs (diazepam 0.3 mg/kg; flunitrazepam 0.03 mg/kg; saline; prometazine 0.7 mg/kg); before and after preoperative medication were evaluated the anxiety relief with the score scale, haematic levels of DBI and haemodynamics (systolic and diastolic AP and HR). The results show that DBI can objectively measure the anxiety relief, that not are correlate haematic levels of DBI and score scale, that the best benzodiazepines are diazepam (0.3) and flunitrazepam (0.015) and that the prometazine might give anxiety relief for 5-HT antagonist action. Even if there are limits to study (scanty cases, are missing the range and the brain values of DBI and blood test of DBI is slow method) may be useful the use of score scale and haematic levels of DBI in clinical evaluation of preoperative anxiety relief.

Gastric chief cell mass in chronic gastritis. Count and relationships to parietal cell mass and functional indices.

The chief cell mass, expressed as the Zymogenous Index (number of cells per mm2 multiplied by the thickness of the glandular layer) was calculated in 42 subjects with chronic gastritis, and in 40 subjects with normal gastric mucosa, and was compared with the serum concentration of Pepsinogen I (PG I), with the parietal cell mass (expressed as Parietal Index: number of cells per mm2 multiplied by the thickness of the glandular layer), and with the acid output. The results showed that there are no significant variations in the chief cells in comparison with healthy controls in the case of superficial gastritis and follicular gastritis. Conversely, in the case of pre-atrophic and atrophic gastritis there is a significant reduction in the chief cell mass. The serum PG I increases significantly in the case of superficial gastritis as compared with healthy controls, while it is equivalent in the case of follicular gastritis, decreases non-significantly in pre-atrophic gastritis and is significantly reduced in the case of atrophic gastritis. The parietal cell mass shows a behavior equivalent to that of the chief cell mass, and the acid output decreases significantly in the case of pre-atrophic and atrophic gastritis, with no significant variations in the case of superficial and follicular gastritis. On comparing the behavior of the chief cell mass with that of the parietal cell mass, it was noticed that in the most severe stages of chronic gastritis there is a more pronounced reduction of the former than of the latter.

[Tumor markers. II. Their significance in the follow-up of patients after radical resection of lung neoplasms]. / Marcatori tumorali. II. Loro significato nel follow-up dei pazienti sottoposti a resezione radicale di neoplasie polmonari.

The clinical field in which tumor markers proved to be most useful is the monitoring of cancer patients. The present study was carried out in order to evaluate the role of tumor markers in the prognostic assessment, and pre-clinical identification of disease recurrence in patients with completely resectable non-small cell bronchial carcinoma. Tumor markers have been measured: a) pre-operatively, in 109 patients with resectable lung cancer and b) post-operatively, in 61 patients who underwent complete resections and were followed for at least one year after surgery. The carcinoembryonic antigen (CEA), the neuron specific enolase (NSE), the tissue polypeptide antigen (TPA), the carbohydrate antigen 19-9 (CA 19-9) and the carbohydrate antigen 50 (CA 50) have been determined in each patient. Long-term survival was significantly correlated with serum levels of the CEA, CA 50 and CA 19-9, while not with those of TPA and NSE. For pre-clinical detection of cancer recurrence, TPA and NSE were the most suitable indicators.

[Tumor markers. I. Their significance in the preoperative assessment of lung neoplasms]. / Marcatori tumorali. I. Loro significato nella valutazione pre-chirurgica delle neoplasie polmonari.

The present study has been carried out in order to evaluate the role of tumor markers in the presurgical assessment of patients with bronchial carcinoma. The carcinoembryonic antigen (CEA), the neuron specific enolase (NSE), the tissue polypeptide antigen (TPA), the carbohydrate antigen 19-9 (CA 19-9) and the carbohydrate antigen 50 (CA 50) have been preoperatively measured in 133 subjects with potentially resectable lung cancers, and in 75 healthy smokers. Sixty-one patients had squamous cell carcinoma, 55 adenocarcinoma and 17 small cell carcinoma. Lobectomy (or bilobectomy) was performed in 74 cases, pneumonectomy in 36 cases, exploratory thoracotomy in 15 cases and a palliative resection in 8 cases. When individual markers were considered, TPA showed the highest sensitivity (85%) and CA 19-9 the lowest sensitivity (11%). Specificity was uniformly superior to 90%. When marker associations were considered, the combined measurement of TPA and NSE gave the best results: both the sensitivity and specificity rates approached 90%. The application of the TPA-NSE association allowed detection of 94% of small cell carcinomas, 89% of adenocarcinomas and 85% of squamous cell carcinomas. A positive correlation was found between the complete resectability of lung cancer and serum levels of CEA, CA 50 and CA 19-9. By using the discriminant analysis, a statistical model yielding identification of about 74% of patients with tumors which were judged potentially resectable according to the pre-operative non-invasive diagnostic procedures and were found to be unresectable at thoracotomy, has been get available.

[Variations of vasoactive intestinal peptide (VIP) concentration in the lung of asthmatic patients]. / Variazioni del peptide intestinale vasoattivo (VIP) nel passaggio attraverso il polmone nella malattia asmatica.

The vasoactive intestinal peptide (VIP) concentrations in the pulmonary and systemic arterial blood were evaluated in 11 asthmatic patients in symptom-free period and during methacholin induced broncospasm. The basal venous and arterial mean values do not significantly differ. A significant difference was observed after bronchial challenge. This could be caused by an increased VIP pulmonary production as a defensive mechanism. No correlation was found between bronchial reactivity (as PD20-FEV1 Methacholin) and VIP concentrations.

Chief cell mass in normal gastric mucosa: relationship with serum pepsinogen I.

In the present study, a counting method for the evaluation of chief cell mass was proposed, based on the assessment of a zymogenous index (ZI) obtained by multiplying the number of cells/mm2 by the thickness of the glandular layer. Results obtained in 40 subjects with normal gastric mucosa did not show significant ZI differences between sexes. A statistically significant decrease in ZI was observed in patients above age 50, thus being directly related to the significant decrease in the thickness of the glandular parenchyma and in the number of chief cells/mm2 observed in this age group. The data obtained were in agreement with the pattern of change observed for serum pepsinogen I (PG I) whose values were related to the chief cell mass in connection with sex and age of the subjects.