Search

Background: DSM-5 separates bipolar (BD) from depressive disorders, but some experts consider BD as part of a spectrum of mood disorders. The interpretation of numerous false positives of BD screened by the Mood Disorders Questionnaire (MDQ) is part of this debate. Recent study results suggest that the worsening of health-related quality of life (H-Qol) associated with MDQ positivity does not depend solely on mood disorders. This study aims to clarify whether the impairment may be due to other concomitant disorders, unrelated to mood disorders, leading to a worsening of H-Qol. Additionally, the study aims to explore if MDQ positivity itself observe clinical significance., Design and Methods: The study involved pairs of cases (MDQ+) and controls (MDQ-) matched for sex, age, and absence of DSM-IV psychiatric comorbidity. The impact of MDQ positivity on the quality of life in a sample of MDQ+ comorbid with MDD was measured and compared to impact of MDD in other chronic disorders., Results: The H-Qol was significantly worse in MDQ+ than in controls (both groups without any psychiatric co-morbidity). The worsening was similar to severe chronic disorders The burden of worsening quality of life due to MDD was mild in another sample of MDQ positives with comorbid MDD., Conclusion: The study hypothesizes that MDQ positivity may be related to hyperactivation and dysregulation of rhythms typical of stress disorders. In fact, MDQ+ was found strongly related to sleep disturbances. Future studies could verify if a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), causes worsening the H-Qol in MDQ+., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

To verify if lethality and diffusivity of Covid-19 correlated with percentage of people vaccinated in different countries and whether results on these indicators were comparable under different types of vaccines. A linear regression analysis was conducted between vaccines/inhabitant, new cases/inhabitants and ratio deaths/cases. A comparison between the three indicators was carried out in countries subdivided by kind of vaccine. The proportion of vaccinations/inhabitants correlates negatively with proportion of deaths × 100 cases ( R  = -3.90, p  < 0.0001), but didn't on incidence of new cases. Countries with prevalence of mRNA vaccines were similar to others on incidence of new cases; but a lower lethality of Sars-Cov2 was found than in countries with prevalence of viral vehicle vaccines ( F  = 6.064, p  = 0.0174) but didn't against countries with prevalence of inactivated vaccines. The higher is the proportion of vaccine/inhabitant in a given country, the less is the fraction of infected people who die., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: The aim was to outline a methodology to monitor the impact of vaccinations in different countries comparing at two different times within countries and between countries the frequency of new cases and Covid-19 related deaths and the percentage of vaccinations conducted., Design and Methods: The 25 countries with the largest increase in SARS-CoV-2 cases on 8 August 2021 were evaluated. In each nation was calculated the proportion of Covid-19 deaths divided per new cases x 100 and the proportion of new cases per 1.000 inhabitants on 10 January 2021 (before vaccinations' distribution) and 8 August 2021 (when large percentage of the population had been vaccinated in many countries)., Results: The study shows that in the countries with the highest number of cases as of 8 August 2021, the proportion of vaccinations carried out in the population correlates negatively with both the proportion between Covid-19 dead people x100 infected people and with the rate of new cases. However, the proportion of vaccinations does not correlate with the differences in the two same indicators considered in the weeks observed, thus additional factors seem to play an important role., Conclusions: This work indicates that mass vaccination is associated with a lower spread of the pandemic and, to greater extent, with a lowering of mortality in infected people.

Background: Functioning of Social Behavioral Rhythms (SBRs) may affect resilience toward stressful events across different age groups. However, the impact of SBRs on the coronavirus disease of 2019 (COVID-19) in elder people is yet to ascertain, representing the aim of the present report., Design and Methods: Follow-up of a peer-reviewed randomized controlled trial on exercise on old adults (³65 years), concurrent to the onset of the pandemic-related lockdown. Post-RCT evaluations occurred after further 12 and 36 weeks since the beginning of the lockdown phase. People with Major Depressive Episode (MDE) at week-48 (follow-up endpoint) were deemed as cases, people without such condition were considered controls. MDE was ascertained using the Patient Health Questionnaire-9 (PHQ-9); SBRs functioning at week 12 onward, through the Brief Symptom Rating Scale (BSRS)., Results: Seventy-nine individuals (53.2%, females) entered the RCT-follow-up phase. The frequency of MDE did not significantly change before versus during lockdown (OR 2.60, CI95%=0.87-9.13). People with BSRS>1 standard deviation of the whole sample score at week-12 had an inflated risk of DE during lockdown (OR=5.6, 95%CI: 1.5-21.4) compared to those with lower BSRS scores. Such odd hold after excluding individuals with MDD at week-12. The post-hoc analysis could be potentially affected by selection bias., Conclusions: Overall, older adults were resilient during the first phase of the pandemic when functioning of pre-lockdown was still preserved, in contrast to the subsequent evaluations when the impairment of daily rhythms was associated with impaired reliance.

Background: Changes in social and behavioral rhythms (SBR) in the elderly are related to health status. Nevertheless, there is no data on factor analysis of the Brief Social Rhythm Scale (BSRS) an internationally well-known tool in this field. The aim was to analyze, in the elderly, the factorial structure of the Italian version of BSRS.  Design and methods: Principal Component Analysis of the BSRS carried out in elderly living at home., Results: Sample of 141 participants (83 Females, 58,9%), aged 72.3±4.8. All the items of the questionnaire were related and could compose a single factor, explaining 56% of variance. A solution adopting two factors, the first (including items 1,2,3,4,9,10), the second (including items 5,6,7,8), covered cumulatively 78.8% of the variance., Conclusions: The study confirms that the BSRS is consistent with the idea for which it was built and can be useful for the study of the regularity of SBR in old adults.

The study aimed to verify whether exercise training in older adults can improve social behavioral rhythms (SBR) and if any modification is maintained over time. Older adults (n=120) from a previous randomized controlled trial, were randomly allocated to either a moderate-intensity exercise group or a control group. SBR was evaluated at t0, t26, and t48 weeks (during the COVID-19 lockdown), using the brief social rhythms scale (BSRS). Seventy-nine participants completed the follow-up (age 72.3±4.7, women 55.3%). An improvement in the BSRS score was found in the exercise group at 26 weeks (p=0.035) when the exercise program was concluded, and it was maintained at 48 weeks (p=0.013). No improvements were observed in the control group. To conclude, SBR, previously found as a resilience factor in older adults during COVID-19, appear to improve after a moderate 12 weeks exercise program, and the improvement persisted even after stopping exercise during the COVID-19 lockdown.

Background: A substantial coronal plane deformity is common in the context of end-stage ankle osteoarthritis. Recent literature shows a trend toward extending the indication of total ankle arthroplasty in increasingly severe coronal deformities, showing promising results when correct alignment is achieved. Nevertheless, the results of lateral transfibular total ankle replacement (LTTAR) in valgus has not been extensively studied. We aimed to evaluate if the outcomes of LTTAR in ankles with valgus deformity were similar to those with no major deformity at short-term follow-up., Methods: This retrospective cohort study included 228 LTTARs. Patients were classified into 2 groups according to the preoperative coronal plane tibiotalar angle (TTS): neutral (less than 10 degrees of coronal deformity, 209 patients) and valgus (above 10 degrees of valgus, 19 patients). Clinical evaluation was performed using the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analog scale (VAS), 12-Item Short Form Health Survey 12 (SF-12) regarding its Physical and Mental Component Summary items. The radiographic evaluation considered anteroposterior and lateral ankle radiographs. Complications were also registered and classified as major or minor. The minimum follow-up was 2 years., Results: The average AOFAS, VAS, and SF-12 scores improved significantly postoperatively ( P < .001), without differences between groups. At final radiographic follow-up, the valgus alignment group did not show significant differences with the neutral alignment group regarding TTS, lateral distal tibial angle, or anterior distal tibial angle ( P > .05)., Conclusion: LTTAR in cases with valgus deformity achieved and maintained correction at short-term follow-up, as obtained in neutral alignment ankles. Clinical outcomes improved significantly regardless of preoperative valgus deformity., Level of Evidence: Prognostic Level III, retrospective cohort study.

Background: The aim was to verify whether the density of particulate matter (PM10), the climate, and the mobility of people can influence the pandemic in the 19 regions and in the two autonomous Italian provinces as incidence rate and lethality., Design and Methods: The incidence rates per 100,000 inhabitants and the case fatality ratio (CFR) (dependent variables) in all Italian regions were calculated in January 2021 at John Hopkins University Coronavirus Center. The independent variables were: Minimum average temperatures in the same month (January) of 2020; average pollution of PM10 in the air in each region in the last year available reported on a 0-10 scale to 0 = total absence of PM10 to 10 maximum pollutions; number of places in hotels occupied per inhabitants in 2020. Linear regression and Multiple Regression Analysis were carried out., Results: The spread of the COVID-19 in the Italian regions seems to be related to pollution of PM10, the number of beds occupied in hotels (as an index of mobility and temperature (indirect correlation). On the contrary, the CFR correlates inversely with temperature but not with pollution. Measuring the concomitant effect of two independent variables by means of Multiple Regression Analysis, temperature and pollution show a synergistic effect on COVID-19 incidence., Conclusions: The study seems to confirm the literature on the influence of temperature on the lethality of COVID-19 but adds the new results of an inverse relationship between the spread of the virus and low temperature in regions between the Mediterranean area (which includes southern Italy and Sicily and Sardinia islands) and the cold European temperate zone which includes the northern regions under the Alps. A new date also concerns the summation effect of the risk between cold weather and PM10 air pollution was found. Due to several methodic weaknesses, the study has an exploratory than conclusive relevance.

Introduction: Bromelain is a complex mixture of thiol proteases and other non-proteolytic constituents, commercially extracted primarily from the pineapple stem. Evidence from several in vitro and in vivo studies highlights its excellent bioavailability, lack of side effects, and broad spectrum of medical efficacies, of which the antiphlogistic properties are among the most valuable ones. Bromelain has indeed been employed for the efficient treatment of many inflammatory disorders, ranging from osteoarthritis and inflammatory bowel diseases to cancer-related inflammation., Methods: The aim of the current study was to assess the anti-inflammatory effects of bromelain after gastrointestinal digestion simulated in vitro using stomach, intestinal, and chondrocyte human cellular models (AGS, Caco-2, and SW1353, respectively)., Results: We successfully demonstrated the capability of bromelain to reduce an inflammatory stimulus by reproducing its exposure to the gastro-enteric environment in vitro and assaying its effect in human cell lines derived from stomach, intestinal, and chondrocytes., Conclusion: Consistently with the previously published data, our work underpins the relevance of bromelain in the development of safer and more effective anti-inflammatory therapies.

Background: End-stage ankle arthritis can involve malalignment of the ankle in both the coronal and sagittal planes. Up to 33% to 44% of patients who present for total ankle replacement (TAR) have greater than 10° of coronal plane deformity. Normalization of the sagittal and coronal alignment is key in improving survivorship and functional outcomes in TAR. In the present study, we analyzed how both the ankle and hindfoot alignment for both a fixed-bearing and mobile-bearing TAR system changed over time. Specifically, we measured coronal and sagittal alignment of both the ankle and hindfoot complex., Methods: A retrospective study was performed on 2 independent groups of patients undergoing 2 different systems for total ankle replacement: Zimmer (lateral approach, fixed-bearing) and Hintegra (anterior approach, mobile bearing). Specific demographic data and radiographic data were measured. Within-group comparisons were performed using 1-way repeated measures ANOVA, analyzing the temporal course of clinical data within the Hintegra and Zimmer groups., Results: At the ankle joint, as measured by the α and β angles ( P > .05), the position of the components remained relatively similar in both the fixed- and mobile-bearing TAR at 24-month follow-up. The sagittal alignment, as measured by the TT (tibiotalar) ratio, demonstrated a posterior shifting of the talus in the mobile bearing group ( P = .036). Although the fixed- and mobile-bearing TAR had both significant hindfoot alignment improvement between the preoperative radiographs and at 24 months, over time, the fixed-bearing ankle had a significant increase in both the hindfoot alignment view angle and hindfoot alignment distance ( P < .001), suggesting a possible dynamism of the hindfoot in the fixed-bearing TAR., Conclusion: The lateral-approach fixed and anterior approach mobile-bearing implants maintained coronal and sagittal alignment in the short term; the temporal course of the lateral approach fixed-bearing ankle showed an increase in the valgus positioning of the hindfoot. The anterior approach mobile-bearing implant maintained its hindfoot alignment over the course of the study., Level of Evidence: Level III, case-control study.

Background:: The aim is to measure the association between fibromyalgia syndrome (FMS) and post-traumatic stress disorder (PTSD), mood and anxiety disorders using reliable psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) and with a case-control design., Methods:: Case-control study with cases (71 consecutive female patients with FMS) and controls (284 subjects without FMS), randomly drawn after a gender- and age-matching technique from the database of an epidemiological survey. Psychiatric diagnoses were conducted according to DSM-IV and carried out by clinical staff using a structured interview (Advanced Neuropsychiatric Tools and Assessment Schedule). QoL was measured by Short Form Health Survey (SF-12)., Results:: The lifetime prevalence of major depressive disorder (MDD; 43.7% vs 8.1%, p < .0001), bipolar disorder (BD; 21.1% vs 0.7%, p  < .0001), PTSD (8.4% vs 1.4%, p < .0001) and panic disorder (28.2% vs 5.6%, p < .001) was higher in people with FMS than in controls. People with FMS showed a poorer QoL than controls on the SF-12 (26.43 ± 6.04 vs 37.45 ± 5.80, p < .0001). Those with comorbidity with MDD and BD showed a mean SF-12 score of 24.75 ± 6.31 versus 29.52 ± 4.84 ( N = 25) of people with FMS without any mood disorder ( p = .002). The attributable burden of FMS in worsening QoL was found comparable to that of serious chronic diseases such as multiple sclerosis., Conclusion:: FMS is a disorder that 'in itself' can have a devastating impact on an individual's life. The frequency of the association with major depressive and bipolar disorders increases the impact on the QoL of people with FMS. One of the causes of this association appears to be the extreme vulnerability to chronic stress that this disorder involves. The findings have important clinical significance: the physician must interpret in the right dimension and with dignity the suffering of the people with FMS.

Colorectal liver metastases with intrabiliary growth are uncommon and difficult to characterize by radiology alone. We present the case of a 61-year-old woman previously operated on for a left colon cancer who developed a metacronous lesion at liver segment II-III. Radiologic workup was indicative for cholangiocarcinoma. Thus, the patient underwent an anatomical left lateral hepatectomy. Pathology showed instead a colorectal metastases with intrabiliary growth. We suggest that in cases of radiological uncertainty between an intrabiliary growth metastasis and a cholangiocarcinoma, the correct surgical strategy should always be an anatomical liver resection without preoperative biopsy because it would not change the operative planning and instead it may increase the risk of dissemination.

Spinal epidural abscess (SEA) is a rare condition that can be fatal if untreated. Risk factors are immunocompromised states as well as spinal procedures including epidural anesthesia and spinal surgery. The signs and symptoms of SEA are nonspecific and can range from low back pain to sepsis. The treatment of choice is surgical decompression followed by four to six weeks of antibiotic therapy. The most common causative organism in SEA is staphylococcus aureus and spread is usually haematogenous or contiguous from psoas, paraspinal or retropharyngeal abscesses. The exact mechanism by which an epidural abscess causes spinal cord damage is unclear. In fact, the damage is often out of proportion to the degree of compression demonstrated radiologically. There is only a report of a patient with syrinx formation secondary to epidural abscess. We describe the case of a 48-year-old woman with a two-week history of thoracic back pain and evidence of dorsal SEA probably from contiguous psoas abscess. Neurological examination revealed flaccid paraplegia and loss of sphincter control. A spinal MRI scan with Gd-enhancement revealed focal high intensity signal in the T2-weighted and FLAIR images at the level of the vertebral bodies in segments D3-D11. The patient was treated with posterior decompression and drainage of the SEA, but with a poor outcome. Six weeks after the onset of symptoms, an MRI scan showed a newly-formed hydromyelia formation from D4 to D8. The case reported is the second to describe hydromyelia formation secondary to epidural abscess and a poor outcome, experiencing partial improvement without recovery. For this reason, we confirmed that the essential problem of SEA lies in the need for early diagnosis, because the early signs and symptoms may be vague and the "classic" triad of back pain, fever and variable neurological deficits occur in only 13% of patients by the time of diagnosis. Only timely treatment will avoid or reduce permanent neurological deficits before massive neurological symptoms occur. The clear message is that a high index of suspicion and modern imaging techniques are essential.

We report a case of a patient observed in emergency condition for recurrent episodes of massive obscure gastrointestinal bleeding that required surgical control. At laparotomy we found an ileal mass with the characteristics of a gastrointestinal stromal tumor (GIST) at histopathological analysis. GISTs should always be considered as a possible cause of obscure gastrointestinal bleeding, although they are often difficult to diagnose preoperatively. Laparotomy is sometimes the only way to obtain a diagnosis. Starting from this case, we reviewed the literature about GISTs, focusing our attention on their diagnosis and the possible surgical and nonsurgical therapies.

Several studies have shown that there is a paucity of immune cells within the stroma of pancreatic adenocarcinoma, a very aggressive cancer with a median survival of about 18 months. A 65-year-old man presented with jaundice. Abdominal ultrasound revealed intra- and extrahepatic bile duct dilatation and a 45-mm diameter hypoechoic solid mass within the pancreatic head; a computed tomography scan excluded vascular infiltration and metastatic lesions. The patient received immunotherapy consisting of 6,000,000 IU human recombinant interleukin-2 administered subcutaneously twice a day for 3 consecutive days. Thirty-six hours after the last dose, he underwent a pylorus-preserving pancreatoduodenectomy. Because of the presence of high-grade dysplasia detected by intraoperative histological examination of a distal section, a spleen preserving total pancreatectomy was performed. The postoperative course was uneventful. The patient died 32 months after surgery because of local recurrence. Histopathology showed G3 pancreatic ductal adenocarcinoma infiltrating the anterior and posterior peripancreatic tissue, duodenal wall and intrapancreatic common bile duct, with sarcoma-like foci and a component of intraductal tumor involving the common bile duct. In the distal pancreas, widespread foci of pancreatic intraepithelial neoplasia (PanI2-3) were found. The Ki-67 proliferation index was 16%. TNM staging was pT3 pN1 R1. Sections were immunostained for the T-lymphocyte marker CD3 and for the dendritic cell marker CD1a. Intratumoral infiltration was high for CD1a+ cells and mild for CD3+ cells. Preoperative immunotherapy with interleukin-2 may contribute to massive stromal infiltration of immune cells in pancreatic adenocarcinoma. This may prolong the survival even in the presence of negative prognostic factors (age >65 years, tumor diameter >20 mm, R1, tumor grade G3).

We report a case of the contemporaneous presence of two histologically different pancreatic neoplasms, one renal cancer and one embryogenic duodenal anomaly in a single patient. A 66-year-old man underwent ultrasound examination because of urinary disorders; a solid neoformation within the inferior pole of the left kidney was observed. Computed tomography confirmed the renal lesion, but also a heterogeneous mass within the pancreatic head appeared without bile ducts dilatation. Abdominal magnetic resonance revealed a multiloculated cystic component of the pancreatic mass. A second CT scan confirmed the renal and biliary findings, but it revealed a modest enlargement of the pancreatic asymptomatic mass. A resection of the left kidney inferior pole and a pylorus-preserving pancreaticoduodenectomy were performed. Histopathologic analysis of the surgical specimen revealed mild differentiated papillary renal carcinoma, intraductal papillary mucinous adenoma of the pancreatic head, foci of intraepithelial pancreatic neoplasm and pancreatic heterotopy of duodenal muscular and submucosal layers. The coexistence of several primaries and anomalies in one patient led us to suppose a genetic predisposition to different lesions, even in the absence of known familial genetic syndromes. The study of such cases may help to improve the investigation of molecular correlations and etiological factors of different solid tumors. Nowadays, surgery is the only effective cure.

Carcinoma showing thymic-like elements (CASTLE) is a rare tumor affecting thyroid and neck soft tissues, which has to be distinguished from squamous cell and anaplastic thyroid carcinoma, because it has a better prognosis. We report a new case of CASTLE which occurred in a patient submitted to total thyroidectomy with central neck dissection. The tumor stained positively for CD5, which seems to be the most useful marker in the differential diagnosis. By the analysis of the 18 cases reported in literature, total thyroidectomy with selective modified neck dissection should be the treatment of choice and radiotherapy should be considered for patients with positive nodal status.

Heterotopic ossification has been reported only rarely within the abdominal cavity, specifically in a mesenteric location (heterotopic mesenteric ossification). We describe the case of a 76-year-old man with no history of previous surgery who developed small bowel obstruction associated with multiple foci of heterotopic bone formation within the small bowel mesentery. He underwent small bowel and mesentery resection and is disease-free 9 months later.

Cystic hepatic metastases arising from lung cancer are rare. We herein describe a case of a 71-year-old women admitted to our hospital for abdominal pain 6 months after the resection of a lung adenocarcinoma. Two cystic lesions of the liver were discovered at abdominal ultrasonography and computerized tomography scan. An ERCP excluded a biliary adenoma or adenocarcinoma, and an ultrasound-guided liver biopsy was negative for malignant cells. For persistence of symptoms and lack of a diagnosis, the patient underwent an exploratory laparotomy, a surgical biopsy with a diagnosis of adenocarcinoma, and a consequent right hepatectomy. After 2 years of follow-up, the patient is well and disease free. Although cystic liver metastasis are rare and a differential diagnosis difficult, the malignant nature should always be considered in the differential diagnosis of hepatic cysts to offer the patient the best treatment.

Angiomyolipoma (AML) is a benign mesenchymal tumor that has been frequently reported in the kidney but rarely in the liver. Hepatic AML may be clinically, radiologically and morphologically difficult to distinguish from hepatocellular carcinoma or other hepatic lesions, even though the number of cases has been increasing recently due to improved imaging techniques. Histologically it consists of smooth muscle cells, adipose cells and abnormal blood vessels. It is commonly diagnosed following abdominal pain but may also be asymptomatic, has a predominant female predilection, highly variable size and occurs in subjects with a wide age range. The right lobe is the most common site, and multicentricity has been reported. Here we report a case of the myomatous variant of AML, accidentally discovered in a young woman with no clear features on radiographic examination, which was diagnosed by means of fine needle aspiration biopsy (FNAB) and then surgically removed. Although careful observation with serial radiological follow-up is an option in these cases, we chose the surgical approach because of the risk of rupture due to the large size of the lesion and the risk of malignant behavior or transformation. In case of the myomatous variant composed of irregular cells with epithelioid appearance, hepatocellular carcinoma with fatty changes or the possibility of other malignant tumors must be ruled out by immunohistochemistry (HMB-45), even in biopsy specimens.

Meckel's diverticulum is an uncommon gastrointestinal congenital anomaly that occurs in 1-3% of the population. It is sometimes associated with complications related to the presence of ectopic tissue (obstruction, ulceration, hemmorhage, inflammation, perforation, fistula and tumors). Neoplastic degeneration of Meckel's diverticulum mucosa is rare, developing in only 1-5% of all diverticula, usually asymptomatic and occasionally discovered. Disease is metastatic, usually to the liver, in 25% of cases. We report a case of asymptomatic unsuspected carcinoid of Meckel's diverticulum with ileal, hepatic and mesenteric metastasis discovered during a gastrectomy performed for gastric adenocarcinoma. The patient underwent ileal and Meckel diverticulum resection, excision of mesenterial metastasis and liver bisegmentectomy. Furthermore, total gastrectomy with esophago-jejunal anastomosis was performed. After an 18-month follow-up period, the patient is alive and disease free. Owing to possible neoplastic degeneration, Meckel's diverticulum should be resected when occasionally discovered. In the presence of a carcinoid tumor, even if associated with metastatic disease, extended resection is recommended.

Aims: To evaluate the efficacy and treatment compliance in elderly patients with advanced non-small cell lung cancer (NSCLC) of two chemotherapeutic agents with mild toxicity, 153 previously untreated patients aged over 70 years were randomized to receive lonidamine (450 mg daily p.o. until progression), vindesine (3 mg/m2/daily i.v. weekly for 4 weeks and then every 2 weeks until progression), the combination of the two drugs at the same dose and schedule, or supportive therapy only in a four-arm factorial randomized trial., Methods: 126 patients were included in the final analysis. Their median age was 75 years. Forty percent had stage IV disease and 60% stage III. Most patients were males (85%) and the majority had squamous histology (68%)., Results: Among 104 patients evaluable for response there were only 3 PRs (1/30 in the lonidamine arm and 2/33 in the lonidamine + vindesine arm). Overall, 8.7% and 9.5% of the patients, respectively, progressed or died early, before response evaluation; another 9.4% refused treatment continuation because of poor compliance with the study protocol. Eighty-five patients were fully evaluable for toxicity, which was generally mild. Leukopenia grade 1-3 was found in less than 30% of patients treated with vindesine or vindesine + lonidamine. The most common complaints associated with lonidamine treatment were myalgia (70% of patients), fatigue (55% and 83% of patients treated with lonidamine or lonidamine + vindesine, respectively) and testicular pain in nearly 40% of cases. The overall median survival was 170 days, with no significant impact on survival of either lonidamine or vindesine., Conclusions: The low response rate and survival together with the poor treatment compliance, even in the presence of mild toxicity, do not support the usefulness of these "gentle" chemotherapies in elderly NSCLC patients. The standard management of advanced NSCLC in elderly patients remains to be defined. Specifically designed studies to address this issue are warranted.

The activities of sisomicin and of fourteen other antibiotics have been compared for their inhibitory activity on all the different strains of bacteria isolated from a 3,000 bed hospital. The antibiotic sensitivity tests were performed in liquid medium and expressed as minimum inhibitory concentrations. The tests were performed over a period of four months. The results are discussed.

A single exposure to a low concentration (10(-10) mol/L) of several tumor promoters, namely 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital (PB), nafenopin, saccharin, teleocidin, benzoyl peroxide, butylated hydroxytoluene (BHT), dichlorodiphenyltrichloroethane (DDT), lindane, clofibrate, and melittin significantly stimulated DNA synthesis of neonatal rat hepatocytes in 4-day-old primary cultures. These cultures were kept in low-calcium (0.01 mmol/L) HiWoBa2000 synthetic medium, thereby evoking a neoplastic phenotype in otherwise normal (i.e., non-initiated) cells. The simultaneous addition of a single dose of alpha-tocopherol (10(-4) mol/L) or selenous acid (10(-5) mol/L), just as that of exogenous superoxide dismutase (SOD) (4), together with each of the above agents fully suppressed the stimulation of hepatocytic DNA synthesis by the xenobiotics. Hence, these findings strengthen the view that superoxide anions (or some other oxidizing compounds) act as the common mediators of the mitogenic effects of various tumor promoters in hepatocytes. Inhibition kinetics studies, in which TPA in a single dose (10(-10) mol/L) was used as the paradigmatic compound together with several kinds of inhibitors of its activity showed that the early mitogenic effects of TPA, i.e., the commitment of quiescent (G0) hepatocytes and the reentry into active cycling of hepatocytes spontaneously poised at the G1/S boundary, required oxidizing compounds, arachidonate metabolism derivatives, and plasmalemmal calcium-binding sites and transmembrane calcium fluxes. Instead, a later TPAs effect, the flow into DNA synthesis of hepatocytes previously committed to cycle, was shown to be controlled by retinoid-modulable activities, by some product(s) of the lipoxygenase pathway, and again by plasmalemmal calcium-binding sites and transmembrane calcium fluxes. Such results reveal that in the neonatal rat hepatocyte the ability to answer to a single mitogenic stimulus and the metabolic pathways by which this answer is enacted depend upon the mitotic cycle setting of the hepatocytes at the moment of the experimental treatment.

Sisomicin, gentamicin and aminosidine sulphate were compared for their antibiotic activity against Pseudomonas strains freshly isolated from clinical material. The activity of the three agents, expressed as a minimum inhibitory concentration, was determined using the same automatized system.