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Biomedical subjects

F Giannini

Publications and source records attributed to F Giannini.

At least 19 recordsLinked to original sources

All-trans, 13-cis and 9-cis retinoic acids induce a fully reversible growth inhibition in HNSCC cell lines: implications for in vivo retinoic acid use.

Retinoids are a group of vitamin A analogues that have shown promise as chemopreventive and therapeutic agents in many types of malignancy and have been entered in clinical trials with some successful results. To better understand the mechanism that mediates retinoid action and the anti-proliferative effects, we treated 7 human oral squamous-cell carcinoma (SCC) cell lines (FADU, HEp-2, CCL-17, SCC-9, SCC-15, SCC-25 and HN-212) with 10(-6) M of all-trans retinoic acid (ATRA), 9-cis and 13-cis retinoic acid (RA) in continuous for different periods of time. We assessed the extent of growth inhibition, the stability of the anti-proliferative effect and the mRNA expression levels (by RT-PCR) of RA receptors (RARs), retinoid X receptors alpha (RXR alpha) and cytosolic RA-binding proteins (CRBP I and CRABP II) in treated cells compared with controls. The data obtained showed that all 3 RAs were able to inhibit the cellular growth of the tested cell lines, although to a different extent. The cis compounds were able to inhibit the proliferation of all cell lines, whereas ATRA was ineffective in inhibiting the proliferation of the CCL-17 cell line, which was naturally resistant to ATRA concentrations in the range between 10(-5) and 10(-6) M. All inhibitory effects were completely reversible since all cell lines restored their normal growth proliferation within few days after drug removal. RT-PCR analysis of the receptor and cell binding protein status of control and treated cells showed a good correlation between growth inhibition and induction of, or increase in, the expression levels of RAR beta in RA-treated cells. No differences were observed in RAR alpha and RXR alpha mRNA expression levels between control and treated cells. CRBP I, CRABP II and RAR gamma mRNA levels increased in some treated cell lines but not in all.

Alitretinoin

Role of antepartum computerized fetal heart rate analysis in the prediction of fetal distress during labor.

OBJECTIVE: To ascertain the diagnostic ability of a computerized fetal heart rate (FHR) analysis system in the identification of patients at risk of fetal distress in labor. STUDY DESIGN: Five-hundred and seventy-seven healthy term pregnancies were enrolled in a prospective, cross-sectional study and subdivided into two groups, with (n = 90) or without (n = 487) fetal distress in labor. Computerized FHR recordings were performed periodically and regression analysis was performed in a univariate and multivariate way to assess the ability of the last FHR recordings in the prediction of subsequent fetal distress. RESULTS: The two groups showed a significant difference in almost all of the FHR parameters studied. The multivariate analysis showed that only the FHR baseline and the percentage of small acceleration were independently and significantly related to the labor outcome. The combination of these two parameters reaches a sensitivity of 45%, specificity of 91%, positive predictive value of 48% and negative predictive value of 90%, with an overall accuracy of 84%. CONCLUSIONS: The increase in FHR baseline and in small FHR accelerations can be major factors in the prediction of subsequent fetal distress in healthy term fetuses.

Computers

Cervical and scalp recorded short latency somatosensory evoked potentials in response to epidural spinal cord stimulation in patients with peripheral vascular disease.

Somatosensory evoked potential (SEP) studies were performed in 14 patients with peripheral vascular disease who received epidural spinal cord stimulation (SCS) for chronic pain relief of the lower limbs. Signals were amplified and filtered between 20-2000 Hz and 200-2000 Hz to better identify activities in the high frequency range. In 7 patients bit-colour maps were also computed. In all the patients a homogeneous short-latency scalp evoked potential with a prevalent diphasic shape (P1-N1) was recorded. In all our scalp records, even with the wide bandpass, small short-latency positive deflections were observed on the descending front of the first major positive wave and they were better defined as a series of up to 6 wavelets, preceding the major negative scalp wave in the tracings filtered through the narrow bandpass. They appeared in an interval ranging from 5.5 to 15.6 msec. Bit-colour maps showed consistent positive fields, with a maximum at the vertex, starting mainly at about 5.5 msec; in 3 patients, a prominent positivity between 8.5 and 10.5 msec was recorded followed by smaller components preceding the major positive-negative (P1-N1) complex. More synchronous volleys during direct SCS produced clear short-latency SEPs. Although they were of larger amplitude, we regarded them as corresponding to those described by previous authors obtained by stimulation of nerves of the lower limbs, and probably arising from subcortical structures.

Adult

Molecular mechanisms possibly affecting WT1 function in human ovarian tumors.

The frequent allelic deletions observed on the short arm of chromosome 11 in ovarian tumors suggest that the WT1 gene, a proposed tumor-suppressor gene located on chromosome 11p13 and expressed in the human fetal genitourinary system, may contribute to the development of ovarian neoplasms. Structural and sequence analysis of the entire coding portions of the WT1 gene did not reveal any abnormalities in the 20 ovarian tumor specimens (13 of which showed 11p13 allelic deletions) and 5 cell lines which we analyzed. These findings invalidate the hypothesis that the WT1 gene functions as a classical tumor-suppressor gene in ovarian tumorigenesis and suggest that a different recessive oncogene may be "exposed" by the observed 11p13 allelic deletions. Expression analysis showed that the WT1 gene was transcriptionally active in all the tumors tested, but considerable variations in the mRNA levels were found. This apparent variability, which should be confirmed at the cellular level in the tumor specimens, was also observed in the ovarian tumor-cell lines. Finally, WT1 expression data were evaluated in conjunction with immunohistochemical data on p53. The possible functional effects of altered WT1 mRNA expression in ovarian tumors are discussed, taking into account the potential WT1/p53 protein interaction.

Adenocarcinoma

Sensory neural conduction of median nerve from digits and palm stimulation in carpal tunnel syndrome.

The median sensory nerve conduction between ring finger and wrist is a suitable parameter for early detection of carpal tunnel syndrome (CTS), although shorter segments of median nerve have also been proposed for the same goal. In order to assess the relative diagnostic value of the sensory nerve conduction velocity (SNCV) of the third palmar branch versus the SNCV of the second palmar branch, generally performed until now, we studied 62 patients with typical signs and symptoms of CTS. The following parameters were evaluated by surface recording: orthodromic SNCVs in digit-wrist segments for median (index = M2, third = M3 and ring = M4 fingers), ulnar (fourth = U4 finger) and radial (thumb = R1) nerves; SNCVs in palm-wrist segments by surface bipolar stimulation at each metacarpo-phalangeal interspace (second = P2 and third = P3 for the median nerve and fourth = P4 for the ulnar nerve); and distal motor latencies of the median and ulnar nerves. No responses at the wrist were recorded in 22.6% of patients after digital stimulation of M4, whereas the SNCV of P3, the palmar nerve branch arising from digital nerves of the medial side of M3 and the lateral side of M4, was measurable in 93.5% of patients. As significantly expressed (P < 0.001) by the increased ratio of the mean values of P2 and P3 in CTS patients, the SNCV of P3 decreased more frequently and to a greater extent than the SNCV of P2.

Action Potentials

Diagnosis of thoracic outlet syndrome. Relative value of electrophysiological studies.

The diagnostic utility of various electrophysiological techniques was evaluated in patients with thoracic outlet compression syndrome (TOCS). Our results suggest that in true neurogenic TOCS, there is no standard electrophysiological picture, but that this evolves with the severity of the syndrome. The first changes observed are electromyographic, followed by changes in F-wave and SEPs, followed finally by changes in nerve conduction parameters. EMG study was certainly more informative, showing neurogenic damage not only in limbs with neurological signs but also in about 1/4 of limbs with only subjective symptoms. The study of F-wave and SEPs does not seem to be particularly helpful, however, in view of the peculiar changes found in these patients, SEPs may be a useful complement to EMG. Nerve conduction studies were of little utility since changes in these parameters are only found in patients with long-standing anomalies and severe atrophy.

Adult

Sex differences in surface EMG interference pattern power spectrum.

Sex differences in the spectral parameters of the surface electromyogram (EMG) power spectrum were studied during voluntary muscle contractions of different strength with rest in between. The influence of two different types of leads (unipolar and bipolar) on the values of the spectral parameters was also investigated under the same experimental conditions. The subjects were 15 healthy female and 15 healthy male volunteers. The relationship between the amplitude (root mean square) of the EMG and the force developed was not linear. The mean values of the median power frequency were lower in women than in men. With both types of lead, the increase in force was accompanied by a progressive increase in median power frequency in male and female subjects. The significant differences in spectral parameters observed in the two sexes are probably correlated with anatomic differences.

Adult

Effects of Braxton-Hicks contractions on fetal heart rate variations in normal and growth-retarded fetuses.

The objective of this study was to evaluate whether Braxton-Hicks contractions induce changes in fetal heart rate variation in normal and growth-retarded fetuses. 110 uncomplicated singleton pregnancies were cross-sectionally studied as well as 16 pregnancies complicated by fetal growth retardation secondary to uteroplacental insufficiency. Fetal heart rate variability was analyzed by a commercially available computerized system (2CTG Hewlett Packard, Italy) 10 min before and 10 min after the Braxton-Hicks contraction. All the included fetal heart rate tracings fulfilled the following criteria: (1) presence of a single Braxton-Hicks contraction in the 20 min considered; (2) absence of fetal heart rate decelerations after the contraction, and (3) stable fetal heart rate behavioral pattern in the period analyzed. 82 tracings of normal fetuses were analyzed during an active fetal heart rate pattern (type B) and the remaining 28 during a quiet pattern (type A). In both patterns no significant differences in delta value, long-term irregularity, short-term variability and interval index were found before and after the contraction. All the tracings of growth-retarded fetuses were analyzed during the fetal heart rate pattern A. Short-term variation and interval index significantly decreased during the first 5 min after the contraction while no significant differences were found in the other indices investigated. The decrease in these indices was significantly more marked in those fetuses developing fetal distress within 7 days. In conclusion, Braxton-Hicks contractions induce a significant decrease of short-term variation and interval index only in growth-retarded fetuses. This can be useful in the early identification of fetal compromise in such fetuses.

Cross-Sectional Studies

An electromyographic evaluation of motor complications in thoracic herpes zoster.

Motor complications in thoracic herpes zoster were evaluated in 52 patients by electromyographic examination of the paraspinal muscles. At the initial EMG examination, abnormal findings were observed in 18 patients (35%). In 8 patients the myomers involved coincided in location with affected dermatomes, while in 10 patients, in addition to the involvement of myomers corresponding to affected dermatomes, there also appeared an involvement of one or more contiguous myomers not corresponding to affected dermatomes. Our study demonstrated that motor involvement in thoracic HZ is much more common than previously suggested and its incidence (35%) appears to be greater than that reported in both cervical and lumbosacral HZ.

Adult

P-glycoprotein but not topoisomerase II and glutathione-S-transferase-pi accounts for enhanced intracellular drug-resistance in LoVo MDR human cell lines.

The biochemical bases of the multidrug-resistant (MDR) phenotype were investigated in drug-resistant sublines derived from LoVo human colon carcinoma cell lines by doxorubicin (DOX) and teniposide (VM26) selection. In addition to P-glycoprotein-mediated drug extrusion through the plasma-membrane, LoVo MDR cells display a further drug-resistance mechanism. That is, to achieve equitoxic effects, LoVo MDR sublines require much higher intracellular drug concentrations than those required by LoVo drug-sensitive parent cell line. Involvement of mdr1, topoisomerase II and glutathione-S-transferase-pi (GST-pi) drug-resistance systems in intracellular drug resistance was investigated. Pharmacologic and biochemical data indicated that intracellular drug resistance in LoVo MDR sublines is uniquely consequent to the drug-transporting property of intracytoplasmic membrane-bound P-glycoprotein molecules which compartment drugs in vacuole-like structures.

ATP Binding Cassette Transporter, Subfamily B, Mem

Expression of glutathione-S-transferase-pi in human tumours.

Expression of glutathione-S-transferase-pi (GST-pi) gene was quantitatively analysed on various human tumours (renal cell, colorectal, head and neck, ovarian carcinomas, soft tissue sarcomas; non-Hodgkin lymphomas) and on the corresponding normal tissues when available (kidney, colorectum and head and neck). GST-pi mRNA expression level was found to be significantly higher in tumours (P less than 0.01) than in the normal counterparts (mainly 7.3, 3.5- and 3.0-fold in colorectal, head and neck, and renal carcinomas, respectively). Most tumours displayed a significant relationship between higher GST-pi expression level and poor differentiation grade of tumour cells, thus suggesting a relationship between GST-pi activity, neoplastic transformation and cellular differentiation grade. The high requirement of GST-pi activity neoplastic cells displayed was not singularly related to cellular replication rate. Finally, GST-pi gene expression levels were not affected by chemotherapeutic treatments.

Adolescent

Chromosomal localisation of two putative 11p oncosuppressor genes involved in human ovarian tumours.

In this study, 44 primary or metastatic human ovarian tumours were tested for allelic deletions on the short arm of chromosome 11. Analysis of 12 polymorphic loci by Southern blotting evidenced loss of heterozygosity (LOH) in at least one locus in 41% of cases. Moreover, two hot spots of deletions were tentatively mapped on 11p13 and 11p15.5. Our results demonstrated that LOH at 11p is a common event in ovarian carcinomas and were indicative of the possible existence in 11p of two oncosuppressor genes involved in ovarian carcinogenesis. The similarity observed with 11p allelic losses in Wilms tumours, clustered in 11p13 and 11p15.5 too, suggests that deletion and possibly inactivation of the same growth regulatory genes (WT genes) could also contribute to development of the malignant phenotype in ovarian carcinomas. Finally, a statistically significant association (P = 0.005) between 11p deletions and hepatic involvement was suggested by the analysis of distribution of 11p LOH relative to different clinical and pathological parameters of the tumour patients.

Adult

Electrophysiologic evaluation of local steroid injection in carpal tunnel syndrome.

Extensive sensory and motor nerve conduction studies were performed in a series of patients with electrophysiologically proven, idiopathic carpal tunnel syndrome who were treated by a single steroid injection (40 mg of triamcinolone acetonide). Electrophysiologic studies, which included evaluation of median, ulnar, and radial orthodromic sensory action potentials, median and ulnar motor action potentials, and electromyography of two intrinsic muscles of the hand, were done before and at 45 days and six months after the treatment. By the end of the follow-up period, the symptoms had remitted completely in 11 hands (35%), 18 (58%) benefitted from partial relief, and two did not improve. In addition to the relief of symptoms, abnormalities of motor nerve conduction improved in 65% of cases, and abnormalities of sensory nerve conduction improved in 73% of all the individual digital branches of the median nerve examined. Recovery of function of the median nerve continued for a long period, even after the pharmacologic effect of the steroid agent had presumably ceased.

Action Potentials

Diagnostic specificity of sensory and motor nerve conduction variables in early detection of carpal tunnel syndrome.

In the carpal tunnel syndrome (CTS) sensory nerve conduction is more sensitive than motor conduction. However, 8%-25% of the sensory distal latencies in symptomatic hands may still be normal. A systematic study was made of the median, ulnar and radial orthodromic nerve conduction velocities (SNCV) stimulating each of the fingers separately. Four SNCVs from the median nerve, two SNCVs from the ulnar nerve and one from the radial nerve were obtained, and the ratio of the median to radial SNCV and the ratios of the median and ulnar SNCVs were estimated. The significance of these parameters in the diagnosis of the CTS was studied, and a rapid technique for the screening of nerve entrapment in the initial stages of the disease is proposed. Three hundred and seventy-five symptomatic hands were examined. Seventy-five hands showed normal distal latency, in which cases, however, the SNCV of the ring finger was always outside the normal range, while the SNCVs of the thumb, index and middle fingers were abnormal in 64%, 80% and 92% of cases respectively. The amplitudes of the sensory responses were the least sensitive of the parameters studied. Our results suggest that a study of the median nerve digital branch to the ring finger may be of value in providing an easily performed and rapid technique for screening an early median nerve entrapment at the wrist.

Adolescent

Differences between surface EMG in male and female subjects evidenced by automatic analysis.

40 healthy volunteers (20 males and 20 females) have been studied by an automatic analysis of their surface EMG. The power density spectrum (PDS) of the electromyographic signal, derived from the tibialis anterior muscle, was used to evaluate the RMS values of the EMG developed during maximal voluntary (Vc) and evoked (Vm) contractions. The ratios between Vc, calculated over each of 5 frequency bands (5-15, 20-40, 45-70, 75-110, 115-160 Hz), and the total Vc have also been calculated. No significant differences emerge in the Vm values for males and females, whereas the Vc values for female subjects are found to be significantly reduced (P less than 0.001) with respect to the corresponding values for males. Significant differences have also been found concerning the percentage distribution of power in the above mentioned frequency bands for men and women (P less than 0.001). It can thus, be hypothesized that there are two different modalities of motor unit recruitment and that different sociological and cultural traditions may be more important in producing these differences than sexually determined physiological differences.

Adult

Altered CSF protein pattern in a case of mycosis fungoides with nervous system involvement.

We report the clinical, neurophysiological and CSF study in a case of mycosis fungoides with nervous system involvement. The CSF contained an abnormal protein of molecular weight 22000 that was not in the patient's serum or in the CSF of control subjects and that disappeared after intrathecal immunosuppressive therapy. The nature of this protein is discussed in the light of hypothesis regarding the pathogenesis of the disease.

Cerebrospinal Fluid Proteins

Aperiodic alternating nystagmus: report of two cases and treatment by baclofen.

We report two cases of non periodic alternating nystagmus, one of vascular origin (ischemia of the vertebrobasilar territory) and a second of traumatic origin (whiplash injury) with otoneurological signs, typical of lesions in posterior cranial fossa and in particular of vestibulum-cerebellum and brainstem: gaze paretic nystagmus, rebound nystagmus, saccadic dysmetria, vestibular hyperreflexia and impaired visual suppression test. In one case it was possible to give baclofen therapy, which yielded positive results. Suspension of drug administration resulted in the worsening of clinical signs. The mechanism of action of the drug will be discussed.

Aged

Exercise-induced bilateral anterior tibial compartment syndrome without pain.

We report the case of a 41 year old man who complained of a severe bilateral deficit of the anterior tibial compartment two hours after prolonged exercise. On admission there was no spontaneous or evoked pain, no objective sensory deficit but total loss of dorsiflexion of feet and toes. Electrophysiological investigation showed no voluntary or evoked electrical activity in tibial and extensor digitorum muscles; while peroneus longus and gastrocnemius muscles showed a near-normal pattern. On the other hand a weak motor response was obtained by direct stimulation of the anterior tibial muscle belly. An early bilateral fasciotomy was followed by almost complete recovery of the spontaneous and evoked motor activities of the tibial anterior muscles. On the basis of these findings we discuss the possible pathogenetic role of a neuroapraxic block of the deep peroneal nerve where it crosses the anterior fibular septum and supply a possible interpretation of the absence of pain.

Adult