Paradoxical embolism with thrombus stuck in a patent foramen ovale: a review of treatment strategies.

OBJECTIVE: Paradoxical embolism represents a rare condition occurring when a thrombus originating from venous system produces pulmonary embolism and systemic embolization through an intracardiac or pulmonary shunt. The evidence of a thrombus entrapped in a patent foramen ovale (PFO) is an even more rare condition. There is uncertainty about the optimal treatment strategy. PATIENTS AND METHODS: A 58-year-old male patient was admitted to our Internal Medicine Unit with the diagnosis of bilateral bronchopneumonia. During hospitalization, the co-occurrence of chest pain and amaurosis led us to hypothesize a paradoxical embolism. RESULTS: Transthoracic echocardiography showed the presence of a thrombus stuck over the interatrial septum. A contrast-enhanced chest CT scan showed multiple pulmonary embolisms and brain CT scan documented a hypodense area, of ischemic significance, in the left occipital lobe near tentorium. In order to prevent further embolization, emergency cardiac surgery (right atriotomy, removal of thrombus and closure of the PFO, pulmonary thrombectomy) was performed without complications. CONCLUSIONS: Although rare, the evidence of a thrombus stuck in a patent foramen ovale represents a clinical emergency. The optimal therapeutic approach is still debated. The surgical correction seems to be a safe and effective option for these patients.

Circadian variations of cortisol, melatonin and lymphocyte subpopulations in geriatric age.

A number of age-related changes in the 24-hour hormonal and non-hormonal rhythms have been found in older human beings. Lymphocyte subpopulations present circadian variation of some of their subsets and this variation may influence magnitude and expression of the immune responses. Numerous interactions exist among the nervous, endocrine and immune systems, mediated by neurotransmitters, hormones and cytokines. The aim of this study is to evaluate circadian variations of some endocrine and immune factors in older adults. Cortisol and melatonin serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from ten healthy young and middle-aged subjects and from ten healthy elderly subjects. There was a statistically significant difference between the groups in the observed values of CD20 (higher in young and middle-aged subjects) and CD25 and DR+ T cells (higher in elderly subjects). In the group of young and middle-aged subjects a clear circadian rhythm was validated for the time-qualified changes of all the factors studied. In the group of elderly subjects a number of rhythms were absent or altered. The results of the current study show that aging is associated with enhanced responsiveness of T cell compartment and alterations of circadian rhythmicity.

The hypothalamic-pituitary-thyroid axis and melatonin in humans: possible interactions in the control of body temperature.

OBJECTIVE: Melatonin plays a role in the regulation of biological rhythms, body temperature presents circadian variations with lower levels during nighttime, when melatonin levels are very high, and thyroid hormones influence shiver independent thermogenesis. We have investigated on possible interactions between the hypothalamic-pituitary-thyroid axis and melatonin in the control of body temperature in humans. METHODS: Peripheral blood samples for thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free-thyroxine (FT4), melatonin levels determination and body temperature measurements were obtained every four hours for 24-hours starting at 0600 h in a controlled temperature and light-dark environment from ten healthy males, aged 38-65 (mean age +/-s.e. 57.4+/-3.03, mean body mass index +/-s.e. 25.5+/-0.75). We calculated fractional variation and correlation on single time point hormone serum levels and tested whether the time-qualified data series showed consistent pattern of circadian variation. RESULTS: A statistically significant difference was evidenced for the fractional variation of daytime TSH serum levels (0600 h-1000 h vs. 1000 h-1400 h, p=0.01, 1000 h-1400 h vs. 1400 h-1800 h, p=0.0001, 1400 h-1800 h vs. 1800 h-2200 h, p=0.001) and for the fractional variation of FT4 serum levels at 1800 h-2200 h vs. 2200 h-0200 h (p=0.02). FT4 serum levels correlated positively with TRH serum levels at 1000 h (r=0.67, P=0.03) and at 1400 h (r=0.63, p=0.04), negatively with TSH serum levels at 2200 h (r=-0.67, p=0.03), negatively with melatonin serum levels at 2200 h (r=-0.64, p=0.04) and at 0200 h (r=-0.73, p=0.01). TRH serum levels correlated positively with TSH serum levels at 0200 h (r=0.65, p=0.04) and at 0600 h (r=0.64, p=0.04). Body temperature correlated positively with FT4 serum levels at 1000 h (r=0.63, p=0.04) and negatively with melatonin serum levels at 0200 h (r=-0.64, p=0.04). A clear circadian rhythm was validated for body temperature (with acrophase in the morning) and melatonin, TRH and TSH secretion (with acrophase at night), while FT4 serum level changes presented ultradian periodicity (with acrophase in the morning). CONCLUSION: Changes of TSH serum levels are smaller and those of FT4 are greater at night, when melatonin levels are higher, so that the response of anterior pituitary to hypothalamic TRH and of thyroid to hypophyseal TSH may be influenced by the pineal hormone that may modulate the hypothalamic-pituitary-thyroid axis function and influence the circadian rhythm of body temperature.

Immune system alterations in lung cancer patients.

The immune system plays an important role in the defense against neoplastic disease and immune responses show temporal changes related to circadian variations of antibodies, total lymphocytes in the peripheral blood and cell mediated immune responses. In this study we evaluate. lymphocyte subpopulations and interleukin-2 (IL-2) serum levels in peripheral blood samples collected at four-hour intervals for 24-hours starting at 06.00 h from ten healthy subjects aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.81). Areas under the curve, mean diurnal levels (mean of 06.00-10.00-14.00 h) and mean nocturnal levels (mean of 18.00-22.00-02.00 h) were calculated, and the presence of circadian rhythmicity was evaluate. When we compared AUC values there was a decrease in CD8bright (T suppressor subset) and an increase in CD16 (natural killer cells) and of IL-2 serum levels in cancer patients. When we compared mean diurnal levels, CD8 (T suppressor/cytotoxic subset) and CD8bright levels were lower, and CD16 levels were higher in cancer patients. When we compared mean nocturnal levels, CD16 and CD25 (T and B activated lymphocytes with expression of the a chain of IL-2 receptor) levels were higher, while CD8, CD8bright, CD20 (total B-cells), TcRd1 (epitope of the constant domain of d chain of T-cell receptor 1) and dTcS1 (epitope of the variable domain of d chain of T-cell receptor1) levels were lower in cancer patients. A clear circadian rhythm was validated for the time-qualified changes in CD4, CD20, HLA-DR with acrophase at night, and CD8, CD8 bright, CD8 dim, CD16, TcRd1 and dTcS1 with acrophase in the morning in the control group. A clear circadian rhythm was validated for the time-qualified changes in CD4 with acrophase at night, in the group of cancer patients. Results obtained in our study show that lung cancer is associated with anomalies of proportion and circadian variations of lymphocyte subsets that must be considered when adoptive immunotherapy has to be planned.

[Transrectal ultrasonography in the early diagnosis of prostate carcinoma: use of a new ultrasonography technique with endorectal probe]. / L'ecografia transrettale nella diagnosi precoce del carcinoma prostatico: utilizzo di una nuova manovra ecografica con sonda endorettale.

Seventy-80% of prostatic carcinoma develops in the peripheral gland. Transrectal ultrasound (TRUS) has the capacity to identify nodules or hypoechogenic areas in the peripheral zone, suspected to be carcinoma. We describe a new echographic technic with endorectal probe (target compression test), to study hypoechogenic areas or nodules in the peripheral gland, during TRUS examination. Thirty-three patients, aged 49-77 years, with prostatic peripheral hypoechoic lesion at transrectal ultrasound, were studied. All patients underwent prostatic biopsy. Ten of the 11 positive patients (non compressible lesion) at the target compression test resulted to be affected by adenocarcinoma. Only 3 of the 22 negative patients (compressible lesion) at the target compression test resulted to be affected by adenocarcinoma. Even if our data have to be confirmed by further studies, they suggest that the target compression test may be a useful complementary test, during TRUS, in the evaluation of hypoechogenic areas in the peripheral gland.

Lymphocyte subpopulations anomalies in lung cancer patients and relationship to the stage of disease.

BACKGROUND: The host immune response is important in the natural history of neoplastic disease. In order to evaluate alterations of immune function associated with cancer we analyzed the nyctohemeral profile of lymphocyte subpopulations in peripheral blood of cancer patients. The study was carried out on seven healthy volunteers (mean age +/- s.e. 68.8 +/- 1.92), seven patients with I and II stage lung cancer (mean age +/- s.e. 67.2 +/- 0.80), seven patients with III and IV stage lung cancer (mean age +/- s.e. 69.5 +/- 2.26). The area under the curve (AUC) and the presence of circadian rhythmicity were evaluated. RESULTS: The most striking differences were a statistically significant decrease of CD8 (T suppressor/cytotoxic subset) and CD8bright (T suppressor subset) in cancer patients, with a loss of normal circadian rhythmicity, and a statistically significant increase of CD16 (natural killer cells) in cancer patients, especially with I and II stage disease, with a clear circadian rhythm present in all the groups. A statistically significant decrease of delta TcS1 (epitope of the variable domain of delta chain of T-cell receptor 1) was observed in the subjects with I and II stage lung cancer, with a loss of circadian rhythmicity in the two groups of cancer patients. TcR delta 1 (epitope of the constant domain of delta chain of T-cell receptor 1) was significantly decreased in cancer patients, but a clear circadian rhythm was present in these subjects. No significant differences among the groups were found in the values of CD2 (total T cells), CD4 (T helper/inducer subset), CD8dim (T cytotoxic subset), CD4/CD8 ratio, HLA-DR (B cells and activated T cells), CD20 (total B cells) and CD25 (T activated lymphocytes with expression of the alpha chain of interleukin-2 receptor). Nyctohemeral variations of CD2 in control subjects and in I-II stage cancer patients and of CD4 and CD20 in III-IV stage cancer patients presented circadian rhythmicity. CONCLUSIONS: The results suggest that lung cancer is associated with alterations in the proportions and nyctohemeral profiles of various lymphocyte subsets, related to the stage of disease and probably the expression of an altered immune function.

Decreased serum levels of insulin-like growth factor (IGF)-I in patients with lung cancer: temporal relationship with growth hormone (GH) levels.

AIMS AND BACKGROUND: Several studies have evidenced that IGF-1 may play a role in the growth regulation of many cancer cell lines, and recently GH and IGF-1 have been recognized as stimulators of lymphopoiesis and immune function. We investigated whether there are differences among health- old people and old people suffering from lung cancer at different stages of disease in the 24-hour secretory profiles of GH und IGF-1. METHODS: The study was carried out on seven healthy volunteers (mean age +/- s.e. 68.8 + 1.92), seven patients with I and II stage lung cancer (mean age +/- s.e. 67.2 +/- 0.80) and seven patients with III and IV stage lung cancer (mean age +/- s.e. 69.5 +/- 2.26). GH and IGF-1 serum levels were measured on blood samples collected every four hours for 24 hours; the area under the curve (AUC) and the presence of circadian rhythmicity were evaluated. RESULTS: A normal circadian rhythmicity was recognizable only for GH secretion in healthy subjects. A progressive increase of GH serum levels and a steady decrease of IGF-1 serum levels were observed in cancer patients in relation to advancing stage of neoplastic disease. CONCLUSIONS: Lung cancer is associated with an altered regulation of GH-IGF-1 system, that might play a role in the clinical course of neoplastic disease.