Upregulation of epidermal growth factor receptor induced by alpha-interferon in human epidermoid cancer cells

Unregulated or increased expression of epidermal growth factor receptor (EGF-R) is a common event in neoplastic transformation; modulation of such a receptor by physiological agents could be, therefore, of clinical interest. We have studied the binding ability, the availability at cell surface, and the synthesis of EGF-R in the A431 and KB human epidermoid cancer cell lines after treatment with recombinant alpha-interferon (IFN-alpha). After 48 h of treatment, IFN-alpha induces, in both cell lines, growth inhibition and enhances class I major histocompatibility HLA complex expression, which is a common marker of IFN action. [125I]EGF total binding assessed after 48 h of treatment with IFN-alpha shows a dose-dependent upregulation of EGF-R binding capacity. Saturation plots of the binding data show that IFN-alpha treatment does not dramatically alter the affinity of the EGF-R and indicate that IFN-alpha only increases the number of low affinity receptors. We show that this effect is due to a specific increase in the synthesis of the receptor protein, as assessed by immunoprecipitation of [35S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed an increase of EGF-R proteins at cell surface without major changes in the morphology of the cells. Taken together, these results indicate that IFN-alpha consistently induces both the binding capacity and the synthesis of EGF-R in human epidermoid cancer cells and suggest the use of such a mechanism for new anticancer therapies.     

Prevalence, clinical characteristics, quality of life, and prognosis of patients with congestive heart failure and isolated left ventricular diastolic dysfunction.

Prevalence of isolated left ventricular (LV) diastolic dysfunction has been reported to be as high as one-third of all heart failure (HF) cases, with an increasing prevalence in the elderly population. However, there is a paucity of prospective data about the prevalence and prognosis of isolated LV diastolic dysfunction in an unselected population of patients hospitalized with HF. Therefore, we prospectively evaluated 179 consecutive patients discharged from our hospital with HF to assess the prevalence of systolic versus diastolic LV dysfunction among patients hospitalized with HF and to compare their demographics, clinical features, self-perceived quality of life (QOL), and 6-month readmission rate and mortality. Among them, 133 (59% men, median age 74 years) showed in sinus rhythm and had no significant primary valvular disease. LV diastolic dysfunction was diagnosed on the basis of the European Study Group on Diastolic HF echocardiographic criteria. QOL was assessed at hospital discharge and 6-month follow-up visit using the Minnesota Living with HF questionnaire. Survival of patients with HF was compared with that of age- and sex-matched general population. In all, 29 patients (22%) had isolated LV diastolic dysfunction and 102 (78%) had prevalent LV systolic dysfunction (ie, LV ejection fraction 相似文献   

Efficacy of a short-term psychoeducational intervention for persistent non-organic insomnia in severely mentally ill patients. A pilot study.

Insomnia in psychiatric patients is frequently underestimated in clinical practice. Usually drugs are prescribed for the treatment of this disorder but non-pharmacological intervention can be successfully used. The present study aimed at evaluating the efficacy of a two-session psychoeducational intervention in improving persistent non-organic insomnia and reducing the administration of PRN therapy in severely mentally ill patients. A pre-post study was performed on 36 psychiatric patients admitted to a residential psychiatric unit. The Nocturnal Sleep Onset Scale (NSOS) and Daytime Sleepiness Scale (DSS), the sleep onset latency, the time awake after sleep onset and the numbers of awakenings were gathered 2 weeks before the intervention (T0), immediately prior the intervention (T1), 2 weeks after the last session of the intervention (T2) and a 3-month follow-up (T3). The total number of administrations of PRN therapy from T0 to T1 and from T1 to T2 were also examined. A significant reduction was shown on the NSOS, the sleep onset latency and in the time awake after sleep onset from T1 to T2 and from T1 to T3, while no significant difference was found between T0 and T1. A significant decrease on the mean number of administrations of PRN therapy was also found between 15 days before the intervention (T0-T1) and 15 days after intervention (T1-T2). The initial results of this study seems to suggest the possible efficacy of a short-term psychoeducational intervention on improving persistent non-organic insomnia in severely mentally ill patients. Further control studies are necessary to confirm these findings.     

Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats.

Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption.     

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

Empty Sella and Headache

SYNOPSIS
Empty sella is an anatomical condition caused by herniation of the subarachnoid space into the pituitary fossa through an incompetent seller diaphragm. Headache seems to be one of the most frequently reported symptoms. We studied 13 headache patients (12 females, 1 male) presenting with primary empty sella (PES) on CT scan. The characteristics of the headache were analyzed and plasma levels of pituitary hormones or cortisol assessed. We confirmed the nonspecific nature of the headache in PES even though the majority of our patients complained of daily headache, mostly localized anteriorly. Hormone plasma levels were within normal range in all the patients assessed. However, four patients reported earlier endocrine disorders and more than half of the patients presented with obesity.
In our opinion, PES should be suspected in middle-aged overweight women with daily headache even in the absence of endocrine symptomatology.     

A comparison between the Regnauld arthroplasty and osteotomies of the first ray for the treatment of hallux valgus

This article is a retrospective study comparing the efficacy of Regnauld arthroplasty to first ray osteotomies for the treatment of hallux valgus. One hundred consecutive cases of Regnauld arthroplasties were compared with 100 consecutive first ray osteotomies. One hundred fourty-one patients were available for follow-up, and based on clinical/radiographic examinations, 72 were treated with the osteotomy protocol (group A) and 69 with Regnauld arthroplasty (group B). Age at surgery, clinical symptoms, and preoperative radiologic findings were similar for the 2 groups; there was a preponderance of female patients (90%). The average follow-up was 49 months in group A and 51 months in group B. Clinical evaluation showed in the osteotomy group a more stable correction (79% v 49%), greater pain reduction (measured in a visual analog scale from 0 = pain free to 10 = deep intolerable pain), increased residual articular excursion of the first metatarsophalangeal joint (27 degrees of active dorsiflexion from neutral position v 8 degrees ), and less presence of central metatarsalgia (15% v 34%) (P <.05). The radiographic evaluation expressed more stable correction values in group A for the following parameters: joint preservation, sesamoid position, intermetatarsal angle (7 degrees v 12 degrees ), abduction angle of the hallux (14 degrees v 20 degrees ), and proximal articular set angle (8 degrees v 18 degrees ) (P <.05).     

Discriminant analysis in diagnosing carcinoma of the pancreas and of the papilla of Vater

The clinical and biochemical presentation of carcinoma of the pancreas (PC) and of the papilla of Vater (CPV) are very similar, and, consequently, detailed investigations are required to correctly distinguish between them. The aim of the present study was to select the clinical and biochemical variables that would most efficiently discriminate the precise site of tumor origin. The study group consisted of 72 patients with PC and 22 patients with CPV consecutively hospitalized in our department. The following clinical parameters were considered: age, asthenia, anorexia, vomiting, weight loss, pain, fever, pruritis, and constipation; the biochemical parameters considered were total, direct, and indirect bilirubin, glucose, alkaline phosphatase, gamma glutamy transferase, transaminase, total protein, amylase, and occult blood in stools. The results indicated that in the initial phase of PC the most frequent clinical parameters were weight loss (P<0.0001), anorexia (P<0.02), constipation (P<0.001), and pruritus (P<0.01). In contrast, in CPV, fever (P<0.003) was most frequent in the same phase. There was a statistically significant difference in occult blood in stools (P<0.0001), total (P<0.03) and direct bilirubin (P<0.02), alkaline phosphatase (P<0.05), and transaminase (P<0.002) values in the two groups. On discriminant analysis, weight loss, constipation, pruritus, nausea, anorexia, and fever were the variables which best discriminated between the two types of tumors. In fact, the presence of weight loss, anorexia, asthenia, constipation, and pruritus correctly classified 87.5% of the patients with PC, while the presence of fever and nausea correctly classified 72.7% of the patients with CPV.     

Chronic peritoneal dialysis in paediatrics: Experience of a national registry

The results of the first 3 year' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986–1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.