Use of carbon dioxide versus normal saline for diagnostic hysteroscopy

OBJECTIVE: To compare CO2 and normal saline as distention medium in diagnostic hysteroscopy. DESIGN: Prospective randomized study. SETTING: University-based artificial insemination and sterility center in Italy. PATIENT(S): Seventy-four women who underwent hysteroscopy. INTERVENTION(S): Hysteroscopy was performed with CO2 or normal saline. MAIN OUTCOME MEASURE(S): Quality of intrauterine images, cervical dilatation, local anesthesia, and duration of the test. In addition, each patient evaluated pain during and after the examination, irritation of the phrenic plexus, analgesic use, and side effects. RESULT(S): The quality of the hysteroscopic image was statistically similar for both media. Dilatation of the cervical canal and use of local anesthesia was more often necessary in the CO2 group. The procedure time was 5.96 +/- 1.55 minutes in the CO2 group and 3.12 +/- 0.96 in the normal saline group. The CO2 group reported pain more frequently during and after the examination, shoulder pain, greater analgesic use, and more side effects. CONCLUSION(S): For hysteroscopy, normal saline is technically equal to CO2 in terms of image quality and ease of use but offers more advantages. Hysteroscopy with normal saline is more acceptable to patients, quicker to perform, and entails fewer additional procedures.     

Serum human glandular kallikrein (hK2) and insulin-like growth factor 1 (IGF-1) improve the discrimination between prostate cancer and benign prostatic hyperplasia in combination with total and %free PSA

BACKGROUND: There is growing evidence describing an association of hK2 and IGFs with cancer. The aim of this study is to investigate the differences in serum levels of hK2 and IGFs in a large group of patients with benign prostatic hyperplasia (BPH) or prostatic carcinoma (CaP) and to examine the value of these variables, as well as their various combinations with PSA, for discriminating between these two clinical entities. METHODS: Human glandular kallikrein 2 (hK2), insulin-like growth factor-1 (IGF-1), free and total PSA concentrations were measured with non-competitive immunological procedures. Receiver operating characteristic (ROC) analysis as well as univariate and multivariate logistic regression analysis were performed to investigate the potential utility of the various markers and their combinations for discriminating between BPH and CaP. RESULTS: hK2 and IGF-1 concentrations were increased in CaP patients, in comparison to BPH patients. hK2/free PSA and free/total PSA ratios (area under the curve, AUC = 0.70) were stronger predictors of prostate cancer than the IGF-1/total PSA ratio (AUC = 0.56) in the group of patients with total PSA <4 microg/L. The hK2/free PSA ratio (AUC = 0.74) was found to have significant discriminatory value in patients with total PSA within the "gray zone" (4-10 microg/L). Multivariate logistic regression models confirmed the observed relationships and identified IGF-1/free PSA and hK2/free PSA as independent predictors of CaP. CONCLUSIONS: hK2/free PSA and IGF-1/free PSA ratios may be useful adjuncts in improving patient selection for prostate biopsy.     

Coarse nodular US pattern in hepatic cirrhosis: risk for hepatocellular carcinoma

PURPOSE: To determine the prevalence of the coarse nodular ultrasonographic (US) pattern and its prognostic importance in terms of hepatocellular carcinoma (HCC) risk in hepatic cirrhosis caused by hepatitis B virus (HBV); HBV with hepatitis D virus (HDV), formerly known as hepatitis delta virus; hepatitis C virus (HCV); and alcoholic cirrhosis (ALC) or primary biliary disease (primary biliary cirrhosis [PBC]). MATERIALS AND METHODS: Four hundred two cases of hepatic cirrhosis caused by HBV (94 patients), HDV (100 patients), HCV (100 patients), ALC (63 patients), or PBC (45 patients) were retrospectively reviewed to identify the US pattern present at diagnosis and its possible association with the cause of the disease and subsequent development of HCC during a mean follow-up of 43.9 months +/- 29.9 (SD). Data were analyzed with the chi2, Fisher exact, and log-rank tests and with the Kaplan-Meier method (all two-tailed). RESULTS: The coarse nodular pattern was found in a significantly higher percentage of patients with HDV-related cirrhosis (51%) compared with those with HBV (9%), HCV (9%), ALC (11%), or PBC (9%) (P <.001). This pattern was associated with a significantly increased risk for HCC in patients with cirrhosis and HBV-, HCV-, and ALC-related disease but not in those with HDV-related disease and PBC. CONCLUSION: The coarse nodular pattern is more often seen in patients with HDV-related cirrhosis, and, in this setting (in contrast to HBV-, HCV-, and ALC-related cirrhosis, as well as in PBC), it does not represent an added risk factor for HCC.     

Effects of hypoxia on the circadian patterns in men

We tested the hypothesis that acute hypoxia may alter the circadian pattern of body temperature in adult humans. Six healthy subjects were studied in normoxia, hypoxia (approximately 13% inspired O(2)), and again normoxia, each session lasting >24 h and spaced a few days apart, with a constant routine protocol of sustained wakefulness and minimal activity. Some parameters (e.g., tympanic and abdominal temperatures, heart rate) were recorded continuously; others (e.g., oxygen consumption and pulmonary ventilation) were monitored for approximately 10 min every 2 h. The amplitudes of the circadian oscillation of tympanic, abdominal, and calf skin temperatures were reduced in hypoxia, averaging, respectively, 61%, 80% and 50% of the normoxic amplitude. Oxygen consumption and pulmonary ventilation, which presented a circadian pattern in normoxia, had no longer significant oscillations during hypoxia, whereas the opposite was the case for heart rate and diastolic pressure. Therefore, acute hypoxia can disturb the normal circadian patterns and, specifically, depress those of body temperature. These effects, qualitatively similar to those observed in chronically hypoxic animals and humans, could contribute to sleep disturbances at high altitude.     

Pamidronate reduces skeletal events but does not improve progression-free survival in early-stage untreated myeloma: results of a randomized trial

Ninety patients with untreated, stage I-II A myeloma, were randomised to receive or not monthly infusions of pamidronate (PMD) for 1 year, without additional therapies. Follow-up ranged from 36 to 72 months (median 51 months). Three years after the start of the treatment, the disease had progressed in 25% of PMD treated patients and in 26.8% of controls (p n.s). Median time-to-progression was 16 and 17.4 months, respectively (p n.s). Among the 21 patients who required chemo-radiotherapy, skeletal events (osteolytic lesions, pathological fractures and/or hypercalcemia) developed in 9/11 (81.8%) controls and in 4/10 (40%) of treated patients (p < 0.01). "Prophylactic" administration of PMD may decrease the development of skeletal events, but does not reduce the rate and the time of disease progression in early-stage myeloma.     

The role of free radicals and plasmatic antioxidant in Ménière's syndrome

The objective of this study was verification, through suitable hematochemical tests, of the supposition that central-systemic microtoxicosis plays a role either in the etiopathogenesis of Ménière's syndrome or in labyrinthine pathological processes or hypoacusis. We did not, therefore, exclude other well-known hypotheses in the causality of these pathologies. Nonetheless, one finds, particularly in the Ménière's cases, a constant homogeneous distribution of the metabolic products of this microtoxicosis, such as a high concentration of free radicals and low natural defenses (e.g., antioxidant plasmatic capacity). Therefore, there exists a kind of dangerous central and systemic presence of reactive molecules, aimed toward the polyunsaturated fatty acids and homeostatic complex enzymes, that is not compensated for by the natural antioxidant defense. The presence of this lack of balance, verified by suitable tests, has shown the rationality of use of a product made from reduced glutathione, thioctic acid, cysteine, and other antioxidants as a multipurpose antidote to this element of etiopathogenesis. Patients were divided into three groups (control, conventional therapy, and antioxidant treatment), and those in the antioxidant treatment group, especially those with Ménière's syndrome, demonstrated a net and more significant improvement. Also, parallel clinical and instrument evaluations of this new therapeutic solution, the efficacy of which has already been positively demonstrated, are expected to provide further evidence to support the primary hypothesis.     

Retinoblastoma-related p107 and pRb2/p130 proteins in malignant lymphomas: distinct mechanisms of cell growth control.

pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of proteins and regulate cellular growth and differentiation. Because recent functional studies have indicated that the expression of the RB-related proteins p107 and pRb2/p130 are tightly cell cycle regulated, we were interested in investigating their expression along with cellular kinetic characteristics and proliferative features of non-Hodgkin's lymphomas (NHLs). p107 and pRb2/ p130 expression was determined immunohistochemically in biopsy specimens from 83 untreated patients with NHLs of various histiotypes. The expression of these two RB-related proteins was correlated with the mitotic index, apoptotic index, and percentages of Ki-67(+), cyclin A(+), p34(+), and cyclin B(+) cells. The overall survival rate was evaluated according to the Kaplan-Meier method and the log-rank test. We found a positive correlation between the percentages of cells positive for p107 and proliferative features such as mitotic index and percentage of Ki-67(+) and cyclin A(+) cells, whereas such correlation could not be demonstrated for the percentages of pRb2/p130 positive cells. Low immunohistochemical levels of pRb2/p130 detected in untreated patients with NHLs of various histiotypes inversely correlated with a large fraction of cells expressing high levels of p107 and proliferation-associated proteins. Such a pattern of protein expression is normally observed in continuously cycling cells. Interestingly, such cases showed the highest survival percentage (82.5%) after the observation period of 10 years. Thus, down-regulation of the RB-related pRb2/p130 protein could be one of the reasons why these cases display such a high rate of proliferation and why they respond so well to therapy.     

Histone deacetylase inhibitors as a new weapon in the arsenal of differentiation therapies of cancer

Absent or altered differentiation is one of the major features of cancer cells. Histone deacetylases (HDACs) play a central role in the epigenetic regulation of gene expression. Aberrant activity of HDACs has been documented in several types of cancers, leading to the development of HDAC inhibitors (HDACi) as anti-tumor drugs. In vitro and in vivo experimental evidences show that HDACi are able to resume the process of maturation in undifferentiated cancer cells, justifying their introduction as differentiating agents in several clinical trials. Modulation of cell fate by HDACi is observed at several levels, including the stem cell compartment: HDACi can act both on cancer stem cells, and with the rest of the tumor cell mass, leading to complex biological outputs. As a note of caution, when used as single agent, HDACi show only a moderate and limited biological response, which is augmented in combinatorial therapies with drugs designed against other epigenetic targets. The optimal employment of these molecules may be therefore in combination with other epigenetic drugs acting against the set of enzymes responsible for the set-up and maintenance of epigenetic information.     

Enhanced production of interferon-gamma by T lymphocytes cloned from rejected kidney grafts.

Seventy-seven T cell clones were generated from cell blasts infiltrating rejected kidney allografts. All clones, either CD4 or CD8, displayed cytolytic activity evaluated by lectin-dependent cell-mediated cytotoxicity (LDCC) and natural killer activities. Furthermore, both types of clones were able to produce IFN-gamma following PHA stimulation. These data suggest that the graft infiltrate is characterized by T cell clones with cytolytic potential responsible for the killing of graft cells. The production of IFN-gamma, enhancing the class II MHC expression, may amplify the recipient immune response.