Circular External Fixation as a New Offloading Standard of Treatment in Charcot Neuro-Osteoarthropathy Complicated by Midfoot Osteomyelitis: A Pilot, Prospective Case-Control Study.

After surgical treatment of Charcot neuro-osteoarthropathy (CNO) complicated by plantar ulcer and midtarsal osteomyelitis, offloading is mandatory to protect the surgical site. Total contact casting is, to date, the standard-of-care to offload the foot during the postoperative period. We have compared the application of external circular fixator, to the standard of care, with regard to surgical wound healing and time to healing. During the time period from January 2020 to December 2021, 71 consecutive patients admitted to our unit with diabetes and CNO complicated by plantar ulceration and midtarsal osteomyelitis were enrolled in our study. All patients were classified as stage 2, according to the Frykberg & Sanders classification. Wifi wound stage was W2 I0 FI2 in 43 of 71 patients (60.6%) and W2 I2 FI2 in 28 of 71 patients (39.4%). In cases where critical limb ischemia occurred, we performed an endovascular procedure to obtain patency in at least one of the tibial arteries. Localization of osteomyelitis was carried out with magnetic resonance imaging studies, and the degree of deformity was assessed using plain X-ray or computed tomography. A localized ostectomy through the ulceration was carried out with a fasciocutaneous flap to cover the surgical site. In 36 patients, an external circular fixator was applied intraoperatively (exfix+ group); the remaining 35 patients received fiberglass cast in the postoperative period (exfix- group). Complete healing of the surgical site was achieved in 36 of 36 patients in the exfix+ arm and in 22 of 35 in the exfix- arm (P < .02). Time to healing was 68 ± 28 days in exfix+ and 102 ± 88 days in exfix- (P = .05). Circular external frames should be considered as an effective offloading device that enhances the healing rate and reduces time to healing after surgical treatment of midfoot osteomyelitis in subjects affected by CNO.

Postpartum screening for type 2 diabetes mellitus in women with gestational diabetes: Is it really performed?

AIMS: This study evaluates the adherence to postpartum type 2 diabetes mellitus (T2DM) screening in women with previous gestational diabetes (GDM) and identifies elements associated with poor attendance. METHODS: We retrospectively collected data from 650 consecutive women with GDM between 2016 and 2018, who should had 75 g-OGTT, 4-12 weeks after delivery. Impaired glucose regulation (IGR) was defined according with ADA criteria. RESULTS: Only 41% of women had postpartum OGTT. Of these, 1.9% received T2DM diagnosis, with IGR prevalence of 18%. After introducing a recommendation letter, adherence to screening increased (47% in 2017 and 43% in 2018 vs. 32% in 2016). Screening procedure was less common in women with: no-family history of T2DM (38% vs. 46%; p < 0.05), age <35 (33% vs. 47%; p < 0.01), lower level of education (32% no-high-school-diploma vs. 35% high-school-diploma vs. 49% university-degree; p < 0.01) and unstable employment (35% vs. 44%; p < 0.05). At multivariate logistic regression analysis, age <35 years (OR 1.61; 95%CI: 1.14-2.28) and lowest educational level (OR 1.64; 95% CI: 1.13-2.37, compared to University degree) were independently associated with non-adherence. CONCLUSION: Only 41% of women had postpartum T2DM screening. Women with lower attendance are those with age <35 years or low educational level. Further strategies are needed to implement postpartum test.

Peritonectomy and hyperthermic intraperitoneal chemotherapy: cost analysis and sustainability.

BACKGROUND: Malignancies of the peritoneum remain a challenge in any hospital that accepts to manage them, due not only to difficulties associated with the complexity of the procedures involved but also the costs, which - in Italy and other countries that use a diagnosis-related group (DRG) system - are not adequately reimbursed. MATERIAL AND METHODS: We analyzed data relative to 24 patients operated on between September 2010 and May 2013 with special regard to operating room expenditure, ICU stay, duration of hospitalization, and DRG reimbursement. The total costs per patient included clinical, operating room, procedure, pathology, imaging, ward care, allied healthcare, pharmaceutical, and ICU costs. RESULTS: Postoperative hospital stay, drugs and materials, and operating room occupancy were the main factors affecting the expenditure for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We had a median hospitalization of 14 days, median ICU stay of 2.4 days, and median operating room occupancy of 585 min. The median expenditure for each case was € 21,744; the median reimbursement by the national health system € 8,375. CONCLUSIONS: In a DRG reimbursement system, the economic effort in the management of patients undergoing peritonectomy procedures may not be counterbalanced by adequate reimbursement. Joint efforts between medical and administration parties are mandatory to develop appropriate treatment protocols and keep down the costs.

False serum calcitonin high levels using a non-competitive two-site IRMA.

Dual site antibody-base immunoassays are commonly used in clinical laboratories to quantify the CT serum concentrations as a specific and sensitive marker of medullary thyroid carcinoma (MTC). Heterophile antibodies can interfere with these assays, however, and cause erroneous results. In order to avoid this interference, immobilized and conjugated antibodies from two different animal species or immunoreactive antibody fragments, as well as the addition of non-immune globulins, are generally included among the assay reagents. We describe the case of a 73-year-old man affected by a multinodular goiter, who showed high basal CT plasma levels as measured by a monoclonal antibody based IRMA. The finding of negative results for the presence of MTC at fine needle aspiration (FNA) and the mild increase observed in plasma CT during a pentagastrin (Pg) stimulation test, suggested that the high CT levels might depend on a cross-reaction with heterophilic antibodies. In fact, after the addition of the heterophilic blocking tube (HBT) to each specimen, the CT levels markedly decreased by more than 80% (average decrease+/-SE= 87.6+/-2.668%). Such a decrease strongly suggests that in our case the routinely used F(ab')2 fragments were unable to eliminate all of the interference and that the elevated serum CT levels might have been caused by human heterophilic antibodies. In conclusion, these results indicate a novel cause of CT false positivity, suggesting that high serum CT levels, when combined with a slight increase during Pg stimulation, should be critically interpreted in view of the possible presence of heterophilic antibodies in the specimens.

Intraoperative parathormone measurement in patients with multiple endocrine neoplasia type I syndrome and hyperparathyroidism.

Total or subtotal parathyroidectomy is considered the treatment of choice for multiple endocrine neoplasia type I (MEN-I)-associated primary hyperparathyroidism (HPT). However, persistent or recurrent HPT is frequently observed. The development of a rapid two-site immunoradiometric assay (IRMA) method for measuring intact parathormone (PTH) has provided a valuable tool for recognizing possible surgical failures. Our experience includes 16 MEN-I patients (10 females, 6 males) of mean age 35.5 years operated on between 1990 and 1996. Total parathyroidectomy (TPTX) with autotransplantation of parathyroid tissue was the standard treatment. Blood samples for PTH measurement were drawn at the induction of anesthesia (basal value), 10 and 20 minutes after the removal of each gland, and 60 minutes after TPTX. Rapid PTH measurement, which required only 15 minutes of incubation at 37 degrees C, showed a highly significant correlation (p < 0.0001) with the standard method. Circulating PTH levels exhibited a stepwise decrease during TPTX, reaching a mean value of 22.3% of the baseline 20 minutes after removal of the last gland. Two patients showed a prompt decrease of PTH after removal of the single enlarged gland, featuring the kinetics observed in the adenomas. One of these two patients was successfully treated with more conservative surgery. None of the patients showed persistence or recurrence of HPT. In our experience, intraoperative measurement of PTH seems to be a valuable adjunct in both the diagnosis of multiglandular involvement and the prediction of surgical treatment in patients with primary parathyroid hyperplasia.

[The role of echo-endoscopy in the staging of squamous-cell carcinoma of the esophagus. The correlation between the surgical and anatomicopathological findings]. / Ruolo dell'ecoendoscopia nella stadiazione del carcinoma squamoso dell'esofago. Correlazione con i reperti operatori ed anatomopatologici.

BACKGROUND: Endoscopic ultrasonography (EUS) is a relatively new diagnostic method to assess the extent and the depth of infiltration of esophageal carcinoma. METHODS: From October 1990, 100 patients affected by esophageal squamous cell carcinoma underwent preoperative evaluation with endoscopic ultrasonography, 85 of whom were operated on. The first 23 patients underwent endosonography with an Olympus GF-EUM2 with a 7.5 MHz echo-probe; the remaining 77 patients underwent EUS with an Olympus GF-EUM3 with a 7.5-12 MHz echo-probe. RESULTS: In 33 cases (33%), the procedure was not completed because of the impossibility of passing through the neoplastic stenosis. The depth of infiltration was correctly defined by EUS in 73 of 85 patients (86%) compared with 47% of Computed Tomography (CT) (p < 0.05). Overestimation occurred in 6 patients (7%), whereas underestimation occurred in 6 cases (7%). Lymph-node involvement was correctly classified by EUS in 50 of 57 patients (88%) compared with 39% of CT. CONCLUSIONS: EUS provides a high degree of accuracy in assessing both T and N parameters in staging esophageal cancer. The major problem of the method is still the frequent impossibility of passing through a neoplastic stenosis.

Excessive vasoconstriction after stress by the aging kidney: inadequate prostaglandin modulation of increased endothelin activity.

The adaptive capacity of the aging kidney to stimulation of the sympathetic nervous system, as induced by a 30-minute mental stress (MS), was assessed in 8 elderly healthy women (68 to 82 years of age) and compared with that of 8 younger women (24 to 40 years of age). The study encompassed 4 consecutive 30-minute periods (baseline, mental stress, recovery 1, and recovery 2). In the elderly subjects, baseline effective renal plasma flow (ERPF)(iodine 131-labeled hippurate clearance) was lower and glomerular filtration rate (GFR)(iodine 125-labeled iothalamate clearance) was proportionally less reduced than in the younger group; the filtration fraction (FF) was higher. The elderly group excreted more endothelin 1 (ET-1) (P < .05), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1alpha (6-keto PGF1alpha)(P < .001 for both)(radioimmunoassay). Mental stress induced similar increases in blood pressure, heart rate, and plasma catecholamines in the 2 age groups, limited to the stimulation period. In the elderly group, mental stress caused a prolonged decrease in ERPF that reached its maximum 60 minutes after mental stress (-33%, P < .05), while GFR remained constant during the whole experiment, so that FF increased. In the younger subjects, renal hemodynamic changes were limited to the mental stress period. ET-1 increased during mental stress and the first recovery period in the elderly group (+50% and +25%, P < .05) as it did in the younger group, but the elderly group differed from the younger in that vasodilating prostaglandins increased only during mental stress. In conclusion, the aging kidney reacts to adrenergic stimulation with more-pronounced and -prolonged vasoconstriction that is probably caused by a defect in prostaglandin modulation of endothelin activity. Autoregulation of GFR is maintained at the expense of increased intraglomerular pressure.

Renal adaptation to stress: a possible role of endothelin release and prostaglandin modulation in the human subject.

The aim of this study was to define the neurohumoral response associated with the renal hemodynamic perturbations induced by mental stress acting as an adrenergic stimulus. In 8 healthy women, the effects of mental stress were studied during four consecutive 30-minute periods (baseline, mental stress, recovery I, recovery II). Mental stress induced sympathetic activation as evidenced by increases in blood pressure, heart rate, and plasma norepinephrine level. Effective renal plasma flow (iodine 131-labeled hippurate clearance) decreased only during mental stress (-22%, p < 0.05 vs baseline); glomerular filtration rate (iodine 125-labeled iotalamate clearance) remained constant during the entire experiment; the filtration fraction increased significantly during mental stress and recovery I (+30% and +22%, respectively, p < 0.02 for both). Complex neuroendocrine responses were associated with the hemodynamic changes. Urinary excretion of endothelin-1 and 6-keto-PGF(1alpha) increased during mental stress (+53%, p < 0.01, and +20%, p < 0.01, respectively) and recovery I (+49% and +29%, respectively, p < 0.01 for both). Urinary cyclic guanosine monophosphate rose only during mental stress (+77%, p < 0.05), whereas excretion of PGE2 showed a stepwise increase throughout recovery I and II (+292%, p < 0.01, and +360%, p < 0.001, respectively). In conclusion, the present experiments demonstrate that renal hemodynamic response induced by mental stress is a complex reaction in which endothelin-1, prostaglandins, and presumably nitric oxide take part.

Serum biochemical markers of bone turnover in healthy infants and children.

Serum osteocalcin (OC), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D [1,25(OH)2D] were measured in 241 normal infants and children (134 males and 107 females aged 1.9 months-14 years, 1.8 months-12 years, respectively). Regarding the analysis of data for children above 2 yrs, we chose data with the following normalization: data/body surface x standard body surface, to eliminate biological variations not exclusively related to chronological age. The increase in serum OC occurred at the expected age of growth spurts in both sexes: in the first year of life OC values (mean +/- SD) were 82.6 +/- 34.3 and 60.2 +/- 32.9 OC ng/ml in males and females, respectively; during puberty, peak values occurred at the age of 10-12 yrs in girls (76.6 +/- 25.8) and at the age of 12-14 yrs in boys (113 +/- 48.3). Furthermore, significant positive correlations with age were found for males from 2 to 14 yrs (p < 0.00001) and for females from 2 to 12 yrs (p < 0.001). Elevated levels of BAP occurred in the first year, 70.4 +/- 28.2 and 71.8 +/- 28.5, and in the second year, 69.4 +/- 26.7 and 67.4 +/- 33.8 ng/ml, for males and females, respectively. For children older than 2 yrs, a positive correlation with age (p < 0.01) was found for females only, with a peak value of 67.2 +/- 13.9 at the age of 10-12 yrs. For ages 2-14 yrs the reference values (mean +/- 2SD) were 15.5 - 90.3 and 17.2 - 95.2 ng/ml for males and females, respectively. The highest PICP levels (1354 +/- 680 ng/ml in males and 1041 +/- 766 in females) were observed in infants less than 1 year of age, decreasing by about 60% at the age of 2. There was no significant change in serum PICP for children older than 2 yrs with values covering a range (mean +/- 2SD) of 52 - 544 and 18 - 546 ng/ml in males and females, respectively. Similarly, the highest ICTP values were seen in infants younger than 1 year (29.7 +/- 11.7 and 29.5 +/- 20.1 ng/ml in males and females, respectively). In the ages from 2 to 14 yrs there did not seem to be any systematic age-correlated changes, with values covering a range (mean +/- 2SD) of 6.06 - 24.5 in boys and 6.84 - 22.9 ng/ml in girls. Serum PTH concentrations (mean +/- SD) in infancy were 27.2 +/- 19.3 pg/ml for males and 25.8 +/- 10.8 for females. Normal ranges (mean +/- 2SD) in the older group were 5.77 - 53.1 and 6.71 - 57.3 pg/ml for males and females, respectively. Serum 1,25(OH)2D presented values of 47.3 +/- 28.1 and 38.7 +/- 18.2 pg/ml under 2 yrs for males and females, respectively. The ranges (mean +/- 2SD) in children above 2 yrs were 9.5 - 101 pg/ml in boys and 10.9 - 88.4 in girls. The results of this study contribute to the establishment of reference values in normal children for these biochemical assays; these reference values are needed when the above biological markers will be applied in the monitoring of metabolic bone diseases.

Thyroxine-binding globulin in elderly patients with hepatocellular carcinoma.

In order to evaluate the possible relevance of the increased serum levels of thyroxine binding globulin (TBG) in elderly patients with cirrhosis and hepatocellular carcinoma (HCC), TBG and alpha-fetoprotein (AFP) levels were measured in 3 groups: (i) 14 healthy subjects (mean age: 74 +/- 2 years); (ii) 15 patients with cirrhosis of the liver (mean age: 70 +/- 1 years); (iii) 17 patients with cirrhosis and HCC (mean age: 71 +/- 1 years). Both TBG and AFP levels were significantly higher (p < 0.01) in the patients with HCC, as compared to the healthy subjects or to the cirrhotic ones without HCC. The increased plasma TBG levels in cirrhotic patients with HCC is probably due to a derepression of the TBG gene in hepatocytes undergoing neoplastic transformation. The results suggest that TBG together with AFP may be of diagnostic value for the presence of HCC in aging patients with liver cirrhosis.

How alternative are immunoassay systems employing non-radioisotopic labels? A comparative appraisal of their main analytical characteristics.

The immunoassay is one of the most sensitive and reliable analytical techniques available in the clinical laboratory. The original label for immunoassays was radioisotopes, and these methods, radioimmunoassay (RIA) and immunoradiometric assay (IRMA) are still the reference methods, because of invulnerability of the radioactive emission with respect to environmental interference. Labels other than radioisotopes have been tested for use in immunoassay to improve the sensitivity and reliability and to avoid some of the disadvantages of radioisotopic techniques. New labels have continued to be developed (Horseradish peroxidase-HPR-, pyrophosphatase, luciferases, pyrodopirazines, europium cryptates, porphirins, phosphors) and new label detection methods have been set up (e.g. chemiluminescence assay, thermometric assay, NADP+ and FADP- based coupled assay). New immunoassay strategies such as simultaneous multianalyte automated test have been developed and the reliability of the assays has in some cases caused division among researchers about the choice between the radioisotopic immunoassay or the non-radioisotopic immunoassay, as considerable effort and investment had been devoted to the search for more sensitive and practicable tests than the classic RIA-IRMA methods. The evolution of immunoassays (Monoclonal Antibodies, non-radioactive tracers, automation) has produced systems which allow a large number of laboratories to determine a great number of analytes with very good practicability. The availability of fully automated systems has generated the opinion that analytical performance of immunoassays can be considered similar to that of many traditional parameters of clinical chemistry. This conclusion seems however too optimistic, in fact data collected from interlaboratory studies demonstrate that problems concerning the analytical reliability of the measurements still remain not completely solved. In the authors' opinion, this opposition between immunological assay based on isotopic or non-isotopic labels is misleading, because each assay (whether it uses isotopic, enzymatic, fluorimetric or luminescent labels) has its own analytical characteristics and performance. For this reason the term "alternative", used to indicate all non-isotopic assays as a unique class of tests, should be abandoned. From a theoretical point of view the choice should not be between isotopic and non isotopic techniques. For each analyte to be tested, it is advisable to use the immunological assay that suits the requirements of the laboratory, irrespective of type of label. From a practical point of view, the choice should be based on the analytical performance and on the characteristics of each assay, on its cost and the type of instrumentation available in the laboratory, and on the experience and the knowledge of the laboratory personnel.

Intraoperative fall in plasma levels of intact parathyroid hormone in patients undergoing parathyroid adenomectomy.

Intraoperative measurement of intact parathyroid hormone (PTH) can be used to evaluate the success of parathyroid surgery in primary hyperparathyroidism associated with parathyroid adenoma. To evaluate this approach we used a modified immunoradiometric assay (IRMA) to study the kinetic patterns of circulating PTH disappearance in 13 patients undergoing adenomectomy for single adenoma. The rapid and the standard assay for PTH measurement in plasma were used and compared. The two methods showed a highly significant correlation (r = 0.995; p < 0.0001). We reported a decrease in PTH to 18.2 +/- 2.30 (mean +/- SEM) from baseline values at 15 minutes after successful parathyroid adenomectomy in the 13 patients. The biphasic pattern of serum PTH clearance was calculated in 8 of the studied patients with a fast phase showing a half-life (T1/2) of 3.99 (SEM 0.464) minutes and a slow phase with a T1/2 of 91.0 (SEM 33.6) minutes. Half the amount of the basal values was reached between 4 and 9 minutes. Our study concludes that the modified IRMA for intraoperative measurement is feasible, reliable and sufficiently precise for low hormone values. Since it may yield information on the half-life of PTH in the circulation, it may play a role in the surgical guidance for total exeresis of hyperfunctioning tissue.

Effects of melatonin administration on cytokine production in patients with advanced solid tumors.

There is growing evidence that the pineal gland has antineoplastic properties, which include the action of melatonin (MLT) on the immune system through the release of cytokines by activated T-cells and monocytes. Despite these intriguing preliminary findings, only few studies have been undertaken to date on MLT's action in cancer patients. The present study was carried out on 23 patients (15 males and 8 females, range 48-71 years), with advanced solid tumors, who received MLT (10 mg/day orally for a month) after conventional therapy. Blood was assayed for tumor necrosis factor alpha (TNF-alpha), Interleukin-2 (IL-2) and human interferon gamma (IFN-gamma). Blood samples were taken immediately before the start of MLT administration and 30 days after therapy. Plasma was collected in EDTA tubes on ice, centrifuged immediately at 4-degrees-C and stored frozen at -80-degrees-C until assayed. Cytokines were quantified by immunoradiometric assays. Circulating levels of TNF-alpha, IL-2 and IFN-gamma increased by 28%, 51% and 41% respectively after MLT administration. These increments were statistically significant (paired Student's t-test, p<0.01). These findings are consistent with the hypothesis that MLT modulates immune functions in cancer patients by activating the cytokine system.

Coenzyme Q10 in essential hypertension.

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty-six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24-hour automatic blood pressure monitoring were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification, characterization, and biological activity of somatostatin receptors in human neuroblastoma cell lines.

To investigate the presence of biologically active somatostatin (SS) receptors in neural crest-derived tumors, radioligand binding studies, cyclic AMP accumulation, intracellular calcium, and growth assays were performed in eight human neuroblastoma (NB) cell lines. Mathematical modeling of binding experiments strongly indicates the presence of heterogeneity of sites. The first site (SSR1) is present in 40% of the NB cell lines and binds with low capacity (0.5 pmol/mg protein) and high affinity (0.1-1 nM) SS14, SS28, and analogues. The second site (SSR2) is a high capacity site (200 pmol/mg protein), widely distributed in all of the cell lines investigated, that shows relative selectivity yet low affinity (100 nM) for SS14, SS28, and [D-Trp8]SS14 without any apparent biological activity. SSR1 is coupled to a pertussis toxin-sensitive G protein, inhibits forskolin- or VIP-stimulated adenylate cyclase activity, decreases intracellular free calcium, and mediates inhibition (30%) of both DNA synthesis and cell growth. Analysis of cell cycle distribution in aphidicolin-synchronized SSR1-positive NB cells indicated that this inhibitory effect is partially mediated by a transient accumulation in G0-G1. Our data indicate high affinity binding sites for SS14, and analogues are present and biologically active in a subset of NB cells.

Circulating growth hormone and insulin-like growth factor-I in nonalcoholic liver cirrhosis with or without superimposed hepatocarcinoma: evidence of an altered circadian rhythm.

Adult liver is considered the major source of circulating insulin-like growth factor-I (IGF-I). Growth hormone (GH) exerts its effects by stimulating IGF-I release from the liver, which then mediates the somatogenic actions in target tissues. In turn, circulating IGF-I levels operate a negative feedback mechanism on GH release. In cirrhotic patients, single daily determinations, performed after an overnight fast, indicated that serum IGF-I are decreased, whereas GH levels are increased. To verify whether this phenomenon occurs through the 24-h period, we have studied the profiles of GH and IGF-I in cirrhotic patients with or without superimposed hepatocellular carcinoma (HCC) and in a group of control subjects. The results of the present studies suggest that in cirrhotic patients, the above changes are constantly present through the 24-h period, and are associated with a loss of circadian rhythm for both GH and IGF-I. These data are consistent with a failure of the liver to synthesize and release IGF-I in response to GH. In addition, the presence of constantly higher IGF-I levels in cirrhotic patients with superimposed HCC, compared with cirrhotic patients without HCC, raises the hypothesis of a causal relationship between IGF-I and the development of HCC.

Radioimmunoassay of epidermal growth factor in human saliva and gastric juice.

A sensitive radioimmunoassay was developed for human epidermal growth factor (hEGF) in saliva and gastric juice. This method was sufficiently sensitive for an accurate measurement of hEGF in these biological fluids. The minimal detectable concentration of EGF was 30 ng/L. The imprecision profile of EGF standard curve had a CV less than 10% in the range of 0.1-3.0 micrograms/L. Serial dilution curves of saliva and gastric juice paralleled that of standard EGF. The antibody to hEGF showed no cross-reactivity with a large excess of growth factors, such as human transforming growth factor alpha, human insulin-like growth factor I, and platelet-derived growth factor (c-sis). No detectable cross-reactivity was observed with some biological gut peptides: somatostatin, gastrin, secretin or pancreatic polypeptide. The intra-assay CV for saliva and gastric juice was less than 10%, and the recoveries were 93.9 +/- 8.7% and 93.7 +/- 11.3%, respectively for saliva and gastric juice. Gel exclusion chromatography revealed hEGF-like substances, heterogeneous in size in saliva and gastric juice, the origins and physiological functions of which are unknown.

Circadian variations of plasma somatostatin levels in healthy subjects.

The plasma levels of somatostatin-like immunoreactivity, growth hormone and insulin were measured using a RIA method in healthy volunteers every 4h during the day and every 2h at night, without waking the subjects. In the waking state the fluctuation of plasma somatostatin-like immunoreactivity level only occurred near to meal time. A marked episodic surge of plasma SLI (peak value, 127.25 +/- 4.40 pg/ml (mean +/- ES)) was noted at 0200 in the initial period of slow wave sleep (SWS) 2h after the peak of GH. Insulin showed no sharp peak and its pattern was unrelated to other two hormones studied. A positive correlation was observed between SLI and GH in plasma using the mean cosinor method: the acrophase of SLI was at 0018 about 1h later than GH (at 2315). The acrophase of insulin occurred at 1525, significantly different as compared with the previous two. From these findings, it is concluded that SLI in peripheral plasma fluctuates with a significant circadian rhythm and a nychthemeral maxima as GH and that, whatever its source, that it is related to plasma GH and not to plasma insulin.

Gastric juice immunoreactive epidermal growth factor levels in patients with peptic ulcer disease.

Immunoreactive epidermal growth factor (IR-EGF) was measured by a highly sensitive and specific radioimmunoassay in gastric juice samples obtained during endoscopy from 26 control subjects, 44 patients with duodenal ulcers, and 18 with benign gastric ulcers. In the active stage, the concentrations of the peptide were consistently reduced, compared with those found in control subjects (592.7 +/- 55.8 pg/ml), in both duodenal (262.6 +/- 21.4 pg/ml) and gastric ulcer patients (320.2 +/- 34.1 pg/ml) (p less than 0.001 and 0.01, respectively). Mean IR-EGF values distinctly lower than in the controls were still present in the gastric juice of patients with inactive duodenal ulcers (349.7 +/- 35.9 pg/ml; p less than 0.001), whereas no difference was observed in patients with healed gastric ulcers (502.2 +/- 132.3 pg/ml). Although these findings suggest a possible role for EGF deficiency in the pathogenesis of peptic ulcer disease, the pathophysiological significance of our results (if any) remains to be elucidated.

[Use of antimyosin monoclonal antibodies in the diagnosis of acute myocardial infarct. Comparison with other imaging technics and in vivo kinetics study]. / Impiego degli anticorpi monoclonali antimiosina nella diagnosi di infarto miocardico acuto. Confronto con altre tecniche di imaging e studio della cinetica in-vivo.

Labelled monoclonal antimyosin antibodies have been proposed for the diagnostic imaging of acute myocardial infarction (AMI). In order to verify in the clinical practice the theoretical advantages of this new approach, we performed planar imaging with a commercial kit of 111In-antimyosin (111In-AM) in 17 patients admitted to our Coronary Care Unit with the diagnosis of AMI. The results were compared with the echocardiographic assessment of AMI and, in 9 subjects, also with 99mTc-pyrophosphate (99mTc-PYP) scintigraphy. Furthermore, the in-vivo kinetics of 111In-AM was investigated in 11 patients (blood pool activity curve; column gel-chromatography of the injected compound and patient serum). 111In-AM images showed a myocardial uptake in 16/17; 99mTc-PYP scintigraphy in 7/9. The site of AMI was correctly identified by 111In-AM in 14/17, was mistaken in one and impossible to evaluate in another (diffuse uptake pattern). AMI extent, qualitatively assessed in 111In-AM images was consonant with echocardiography in 8/17 and with 99mTc-PYP in 5 of 9 subjects studied also with this method. An apparent underestimation, in comparison with echocardiography was found in 2 cases, whilst an overestimation was seen in 5 cases. One patient was also underestimated in comparison with 99mTc-PYP. 111In-AM images showed a poor quality, with considerable liver, bone marrow, kidney and blood pool activity and therefore low target to background ratio. In-vivo kinetics was characterized by a slow clearance from the blood pool.(ABSTRACT TRUNCATED AT 250 WORDS)