Active Therapeutic Intervention Research Articles

An analysis of pregnancy outcome in dichorionic and monochorionic twins given special antenatal and intranatal care: a four-year survey.

The present study aims to analyze perinatal outcomes in twins given special care during pregnancy and labor and to compare fetal and neonatal outcomes in dichorionic twins with monochorionic twins. Eighty eight (88) twin pregnancies booked for care at a tertiary care Fetal Medicine centre were included in this study. The maternal demographic variables, course of pregnancy, fetal problems, and specialized fetal therapeutic and diagnostic interventions were noted. The above parameters were compared in the sub-groups of dichorionic and monochorionic twin pregnancies and related to the perinatal outcome. Statistical analysis was done using the student's t test and the two-tailed chi sqaure tests with Yate's continuity correction. A p value <0.05 was considered as significant. Mean maternal age was 30.34+4.81years (range 19-48). 81% of the twins were DCDA, and 19% were MCDA. The mean gestational age at delivery was 34.4±3.5weeks, and this was not significantly different in MCDA and DCDA groups. Serious fetal problems warranting intervention at the time of initial referral were significantly higher in MCDA twins although overall perinatal outcome in both groups were not different. Specialized care during pregnancy and labor including active fetal surveillance and therapeutic intervention when indicated improves the perinatal outcome in twin pregnancies and ensured at least one healthy live birth in over 90% cases, although with an increase in late prematurity.

Features of massive hepatocellular carcinomas

Massive hepatocellular carcinomas (HCCs) are uncommon and poorly characterized. To characterize a large cohort of HCC patients with massive tumors, with documented baseline characteristics and survival data. Records were examined of a cohort of 344 biopsy-proven and randomly presenting unresectable HCC patients with tumors of at least 10 cm diameter (massive), which were analyzed for their clinical characteristics and survival. Massive HCC patients were significantly different from others, in having less severe cirrhosis and higher blood platelet counts, α-fetoprotein (AFP), alkaline phosphatase (ALKP), and γ-glutamyl transpeptidase (GGTP) levels. Platelets, ALKP, and GGTP correlated with tumor size. Within massive HCCs, ALKP levels related to tumor number, whereas platelet counts related to tumor size. AFP and GGTP related to neither. All four parameters related to survival. A multivariate Cox proportional hazard model showed that ALKP and AFP were significant for overall survival. Survival of massive tumors was not significantly worse than for other larger tumors. Massive HCCs were characterized by high blood platelets, AFP, ALKP, and GGTP levels. AFP levels were important for survival, but did not directly relate to tumor size or number, suggesting that AFP represents some other property of massive HCC biology. Patients with massive HCC should thus be considered for active therapeutic intervention, just as for other sizes of HCC.

Transarterial (chemo)embolisation versus no intervention or placebo intervention for liver metastases

Primary liver tumours and liver metastases from colorectal carcinoma are the two most common malignant tumours to affect the liver. The liver is second only to the lymph nodes as the most common site for metastatic disease. More than half of the patients with metastatic liver disease will die from metastatic complications. Chemoembolisation is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Therefore, embolisation of the hepatic artery can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. To study the beneficial and harmful effects of transarterial (chemo)embolisation compared with no intervention or placebo intervention in patients with liver metastases. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to December 2012. We included all randomised clinical trials assessing beneficial and harmful effects of transarterial (chemo)embolisation compared with no intervention or placebo intervention in patients with liver metastases, no matter the location of the primary tumour. We extracted relevant information on participant characteristics, interventions, study outcome measures, and data on the outcome measures for our review as well as information on the design and methodology of the studies. Bias risk assessment of the trials, fulfilling the inclusion criteria, and data extraction from the retrieved final evaluation trials were done by one author and checked by a second author. One randomised clinical trial fulfilled the inclusion criteria of the review. Sixty-one patients with colorectal liver metastases were randomised into three intervention groups: 22 received hepatic artery embolisation, 19 received hepatic artery infusion chemotherapy, and 20 were randomised to control, described as "no active therapeutic intervention, although symptomatic treatment was provided whenever necessary". As hepatic artery infusion chemotherapy is not in the scope of this review, we have not included the data from this intervention group. In the remaining two groups that were of interest to the review, 43 of the participants were men and 18 women. Most tumours were synchronous metastases involving up to 75% of the liver and non-resectable. The risk of bias in the trial was judged to be high.Patients were followed-up for a minimum of seven months. Mortality at last follow-up was 86% (19/22) in the hepatic artery embolisation group versus 95% (19/20) in the control group (RR 0.91; 95% CI 0.75 to 1.1), that is, no statistically significant difference was observed. Median survival after trial entry was 7.0 months (range 2 to 44) in the hepatic artery embolisation group and 7.9 months (range 1 to 26) in the control group. Nine out of 22 (41%) in the hepatic artery embolisation group and five out of 20 (25%) in the control group developed evidence of extrahepatic disease (RR 1.64; 95% CI 0.60 to 4.07). Local recurrence was reported for 10 patients in the trial without details about the trial group. Most patients in the embolisation group experienced post-embolic syndrome (82%), and one patient had local haematoma. No other adverse events were reported.The authors did not report if there were any adverse events in the control group. On the basis of one small randomised trial that did not describe sequence generation, allocation concealment or blinding, it can be concluded that in patients with liver metastases no significant survival benefit or benefit on extrahepatic recurrence was found in the embolisation group in comparison with the palliation group. The probability for selective outcome reporting bias in the trial is high. At present, transarterial (chemo)embolisation cannot be recommended outside randomised clinical trials.

Hepatitis B in the spotlight

In the context of recent developments in the area of antiviral therapy, accurate selection of patients into treatment groups and timely initiation of therapy has become crucial. As infectious diseases practitioners, it is important to use all available tools for identifying those patients which have the potential of responding to the therapeutic options at hand. Given the fact that hepatitis B virus (HBV) infection is a leading cause of chronic liver disease and of hepatocellular carcinoma, the decision-making process behind the clinical management of the infection needs to take into account all parameters known to play a role in patients’ response to treatment. Bearing in mind the four stages of disease and given the fact that each patient may respond differently to the presence of the virus, it is vital to choose who to treat, when to start treatment, what to start with and when to stop. It has been postulated that who to treat is no longer an issue, the real question being rather when to switch from watch-and-wait to active therapeutic intervention for each patient. When talking about therapy in HBV hepatitis, one might automatically think about chronic HBV infection. But what about severe acute hepatitis? Can we spare those initial 6 months watching and waiting only to eventually start therapy for chronic hepatitis? Or should we customize the clinical judgment early to apply a treatment protocol individualized for each patient? Field literature describes a wide range of options, from lamivudine treatment to entecavir, pegylated interferon and back to the watch-and-wait approach. Which option best suits our patient? This remains an open question. It might be time to learn from the management of HIV infection, where therapy is tailored for each patient. Looking back at our experience with managing patients with HBV infection, we should focus more on acting in the acute phase of the disease for the symptomatic patients, and treat more actively at that time point in order to limit the integration of HBV into the hepatic cell and the subsequent evolution towards chronic hepatopathy, and as we browse through field literature, we notice some interesting results for these patients. We should also focus on better vaccination implementing programs and test for response to vaccine in order to minimize the responsive mass for HBV infection, as HBV is a chronic disease with lifelong complications. ‘As for the future, your task is not to foresee it, but to enable it.’-- Antoine de Saint-Exupery

Cardiovascular risk factors in women and the role of sex hormones

Despite certain success in the recent years, the problem of cardiovascular disease (CVD) in women remains one of the greatest challenges of the 21st century. Its social and economic burden will continue to increase, due to increasing proportion of older women in the population. Recently, cardiologists have been focusing on menopause as a specific CVD risk factor in women. At the same time, other conditions, also increasing CVD risk, such as certain pregnancy complications and premature menopause, have not received enough attention. Hormone replacement therapy (HRT) remains the first-line treatment and the most effective strategy in young women with estrogen deficiency and postmenopausal women with menopausal symptoms. HRT effectiveness and safety is based on its timely start, low dose, and individually appropriate combination of estrogens and progestins. Interdisciplinary approach is essential for early identification of high-risk women, since lifestyle modification recommendations, diagnostic procedures, and, if needed, an active therapeutic intervention could reduce future CVD incidence in these women.

Pecularities of Prolonged Use of Moxonidine in Patients with Hypertension Associated with Metabolic Syndrome

A 6-month clinical study with active therapeutic intervention was carried out to evaluate the efficacy of moxonidine for the correction of arterial hypertension in 30 patients with metabolic syndrome. Along with the metabolic neutrality for the lipid and purine metabolism, the drug demonstrated a distinct antihypertensive effect, which against the background of pronounced sympatholytic action after 3 months of therapy tends to disappear, which can be prevented by dosage correction. It was shown that the efficacy of moxonidine in reducing insulin resistance in patients with metabolic syndrome directly depends on the severity of hypersympathicotonia manifesting in heart rate over 80 bpm at rest.

Bile leakage after hepatobiliary and pancreatic surgery: A definition and grading of severity by the International Study Group of Liver Surgery

Despite the potentially severe impact of bile leakage on patients' perioperative and long-term outcome, a commonly used definition of this complication after hepatobiliary and pancreatic operations has not yet been established. The aim of the present article is to propose a uniform definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. An international study group of hepatobiliary and pancreatic surgeons was convened. A consensus definition of bile leakage after hepatobiliary and pancreatic operative therapy was developed based on the postoperative course of bilirubin concentrations in patients' serum and drain fluid. After evaluation of the postoperative course of bilirubin levels in the drain fluid of patients who underwent hepatobiliary and pancreatic operations, bile leakage was defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis. Using this criterion severity of bile leakage was classified according to its impact on patients' clinical management. Grade A bile leakage causes no change in patients' clinical management. A Grade B bile leakage requires active therapeutic intervention but is manageable without relaparotomy, whereas in Grade C, bile leakage relaparotomy is required. We propose a simple definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. The application of the present proposal will enable a standardized comparison of the results of different clinical trials and may facilitate an objective evaluation of diagnostic and therapeutic modalities in the field of hepatobiliary and pancreatic operative therapy.

An Analysis of Outcomes in twin Pregnancies With Active Fetal Surveillance and Intervention: A Four Year Survey

The present study aims to highlight the prospects of improving fetal and perinatal outcomes in twin pregnancies with active fetal surveillance and effective fetal therapeutic interventions. 88 twin pregnancies booked for care at this centre were included in this study. The maternal demographic variables, course of pregnancy, fetal problems and specialised fetal therapeutic and diagnostic interventions were noted. The above parameters were also compared in dichorionic and monochorionic twin pregnancies and related to the perinatal outcome. Statistical analysis was done using the student's t test and two-tailed chi sqaure tests with Yate's continuity correction. A p value <0.05 was considered as significant. Mean maternal age was 30.34 ± 4.81 years (Range 19–48). 81% of the twins were DCDA and 19% were MCDA. The mean gestaional age at delivery was 34.4±3.5 weeks and this was not significantly different in MCDA and DCDA groups. Serious fetal problems warranting intervention at thetime of initial referral were significantly higher in MCDA twins although overall perinatal outcome in both groups were not different. Active fetal surveillanve and therapeutic intervention improves the perinatal outcome to over 90% of at least one take home baby rate but with an increase in late prematurity.

Definition and grading of anastomotic leakage following anterior resection of the rectum: A proposal by the International Study Group of Rectal Cancer

Anastomotic leakage represents a major complication after anterior resection of the rectum. The incidence of anastomotic leakage varies considerably among clinical studies in part owing to the lack of a standardized definition of this complication. The aim of the present article was to propose a definition and severity grading of anastomotic leakage after anterior rectal resection. After a literature review a consensus definition and severity grading of anastomotic leakage was developed within the International Study Group of Rectal Cancer. Anastomotic leakage should be defined as a defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- and extraluminal compartments. Severity of anastomotic leakage should be graded according to the impact on clinical management. Grade A anastomotic leakage results in no change in patients' management, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy. The proposed definition and clinical grading is applicable easily in the setting of clinical studies. It should be applied in future reports to facilitate valid comparison of the results of different studies.

Current Prostate Cancer Treatments: Effect on Quality of Life

Patients with prostate cancer (PCa) are presented with multiple therapeutic options. However, the evidence supporting a survival benefit with current PCa therapies is often limited and data directly comparing the available options are lacking. Although dramatic improvements have been made in the treatment methods available for PCa and there has been a decline in death rates for the disease, each active intervention has potential side effects and long-term complications that can adversely affect quality of life (QOL). The cancer diagnosis and management strategies can also negatively affect the QOL of patients and their families. The healthcare costs associated with cancer treatment are another factor to consider. When determining treatment options, patients and physicians should consider the efficacy of the therapy, as well as the safety, effect on QOL, and cost. As a part of a risk reduction strategy, effective screening programs, along with possible therapeutic agents, could have a positive effect on QOL and offer a preemptive benefit to patients at increased risk of PCa.

What is the best way to feed patients with pancreatitis?

Patients with acute pancreatitis have traditionally been treated with 'bowel rest'. Recent data, however, suggest that this approach may be associated with increased morbidity and mortality. This paper reviews evolving concepts in the nutritional management of patients with acute pancreatitis. Both experimental and clinical data strongly support the concept that enteral nutrition started within 24 h of admission to hospital reduces complications, length of hospital stay and mortality in patients with acute pancreatitis. Clinical trials suggest that both gastric and jejunal tube feeding is well tolerated in patients with severe pancreatitis. Although there is limited data for the optimal type of enteral feed, a semielemental formula with omega-3 fatty acids is recommended. On the basis of current evidence, immune modulating formulas with added arginine and probiotics are not recommended. Nutritional support should be viewed as an active therapeutic intervention that improves the outcome of patients with acute pancreatitis. Enteral nutrition should begin within 24 h after admission and following the initial period of volume resuscitation and control of nausea and pain. Patients with mild acute pancreatitis should be started on a low-fat oral diet. In patients with severe acute pancreatitis, enteral nutrition may be provided by the gastric or jejunal route.

Storage behavior of immune-enhancing enteral formulation from natural sources

Nutrition support has become an important therapeutic intervention for improving outcomes in hospitalized patients. The present study was carried out with the objective of studying appropriate packaging and storage studies of enteral formulation from natural sources comprising finger millet (Eleusine coracana), soyprotein isolate, tomato powder, carrot powder, anne greens (Celosia argentea), groundnut oil and fish oil. Two type of packages—namely, polypropylene pouches and metallized polyester/polyethylene pouches—were used. The storage conditions were 27°C and 42°C at 65% relative humidity. The chemical, microbiological and sensory qualities of the formulation were assessed at regular intervals. The moisture sorption studies revealed that the formulation had an initial moisture content of 3.59%, which equilibrated to 13%. The product was acceptable at 64% relative humidity, after which it tend to become soggy. Analysis of peroxide value and free fatty acid content of the equilibrated samples revealed that moisture content of 4–5% was ideal for the storage of the formulation. An increase in the peroxide value and free fatty acid content was observed during 90-day storage period but the formulation was organoleptically acceptable. The microbial analysis of the formulation revealed an initial total bacterial count of 1.5×102 colony-forming units and increased to 7.9×102 colony-forming units (polypropylene) and 5.0×102 colony-forming units (metallized polyester/polyethylene). No fungal and coliform was detected at 90 days of storage. Thus it was concluded that the formulation can be stored for a period of 3 months at 27°C and 65% relative humidity. Such formulations can be primarily a supportive strategy to an active therapeutic intervention.

Telephone-Delivered, Interpersonal Psychotherapy for HIV-Infected Rural Persons With Depression: A Pilot Trial

Telephone-Delivered, Interpersonal Psychotherapy for HIV-Infected Rural Persons With Depression: A Pilot Trial

Primary liver cancers with nonalcoholic steatohepatitis

Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH.

Predictive risk factors for coronary artery abnormalities in Kawasaki disease

Clinical characteristics to predict the development of coronary artery abnormalities (CAA) in Kawasaki disease (KD) were assessed by reviewing medical records of patients diagnosed with KD at Korea University Medical Center from March 2001 to February 2005. Of the 285 patients diagnosed with KD, 19 developed CAA (6.7%). Compared with the CAA(-) group, the CAA(+) group had a longer duration of fever after intravenous gamma-globulin (IVGG) injection (2.4+/-2.9 vs. 1.5+/-1.2 days, p=0.008) and higher C-reactive protein (CRP)(12.3+/-7.8 vs. 8.7+/-7.1 mg/dL, p=0.038). In particular, the CAA(+) group tended to have more than 7 days of fever before IVGG and more than 3 days of fever after IVGG (26.3 vs. 5.3%, p<0.001; 26.3 vs. 6.4%, p=0.002). When the IVGG responsiveness was defined by the presence of defervescence within 3 days after IVGG, IVGG-non-responders showed a higher incidence of CAA (22.7 vs. 5.3%, p=0.002). Non-responders had a longer duration of fever after IVGG (5.5+/-1.9 vs. 1.2+/-0.6 days, p<0.001) and a significantly increased CRP, AST, ALT and total bilirubin. Multivariate regression analysis for CAA showed that the only factor significantly associated with the development of CAA was total fever that lasted for longer than 8 days (OR=4.052, 95% CI=1.151-14.263, p=0.0293). Conclusively, the most important predictor of CAA in KD is total duration of fever longer than 8 days. Early identification of IVGG non-responders and active therapeutic intervention for fever in KD cases might decrease the incidence of CAA.

Thyrotropin Receptor Autoantibodies in differential diagnosis of hyperthyroidism in children

There was investigation carried out in group of 54 children (42 females and 12 males) aged between 10.3 and 17.2 years (median - 13. years) for the purpose of the estimation of the clinical significance determination of the general autoantibodies to the TSH recepetor (TBII) in differential diagnostics hyperthyroidism. In 45 from 54 cases (83.3 %) there was Graves’ disease (GD) diagnosis set, while high level of TBII was detected amongst 44 from those children (97.8%). Amongst patients with subacute thyroiditis and uninodal toxic goiter together with 7 children, initially estimated by us as “AIT, hyperthyroidism” the values TBII were in limit of reference interval. But for all of that unexpectedly there was detected normal level of Ab-TPO amongst all patients in this group, and - normal echogenic in 6 from 7 cases. From the one hand, high level of Ab-TG and heterogeneous structure may be estimated as particular qualities of hyperthyroidism clinical course during AIT by amongst children. However, absence of the row of diagnostic signs with long-lasting euthyroid condition do not allow us to estimate that cases as hyperthyroidism phase of AIT. From the other hand, we can suppose that we observe the diagnostic of natural clinical course of GD cases in phase of immunological remission. The detection of normal level of TBII in absence of typical clinical signs of GD amongst children with manifestation of hyperthyroidism let us retreat from active therapeutic intervention and choose the method of dynamic observation.

Role of a follow-up in puberty children with diffuse euthyroid goiter

То identify patients with autoimmune thyroiditis (AIT) in a random sample of children, a stepwise clinical examination was conducted among 427 ninth-form pupils (aged 14-15 years) from 4 Yekaterinburg districts. Among 58 children with goiter as shown by ultrasonography, 18 were initially diagnosed as having hypertrophic AIT; 38patients had diffuse euthyroid goiter; one patient had diffuse toxic goiter; and mixed euthyroid goiter was detected in one case. At one-year follow-up, re-examination rejected the diagnosis of AIT in 13 of the 18 patients. It was concluded that: (1) the follow-up of children with a presumptive diagnosis of AIT suggests that the latter plays a much less role in the etiological pattern of diffuse euthyroid goiter as compared with the data of the primary examination; (2) most changes originally interpreted as manifestations of AIT are reversible, which suggests that it is preferable to follow-up children with a presumptive diagnosis of AIT in the phase of euthyrosis under active therapeutic intervention.

Lack of interference between ribavirin and nucleosidic analogues in HIV/HCV co-infected individuals undergoing concomitant antiretroviral and anti-HCV combination therapy.

HIV and hepatitis C virus (HCV) share parenteral routes of transmission through exposure to contaminated blood. The prevalence of HCV seropositivity among HIV-infected homosexual/bisexual men and intravenous drug users has been reported to be 10 and 80%, respectively [1]. Co-infection with HIV alters the clinical course of hepatitis C by inducing a more rapid progression to fibrosis and cirrhosis [2]. The morbidity and mortality rate from liver disease is thus higher in co-infected patients than in immunocompetent patients infected with HCV alone [3], emphasizing the need for active therapeutic intervention to treat HCV infection in co-infected patients [4]. On the basis of the promising results of combination therapy with IFN-α and ribavirin for chronic hepatitis C in immunocompetent individuals [5], we have recently engaged in an open prospective trial of this combination therapy in patients co-infected with HCV and HIV [6]. As ribavirin, zidovudine (ZDV) and stavudine (D4T) are metabolized to their triphosphate active forms by thymidine kinase, ribavirin has been suggested to reduce the intracellular phosphorylation of nucleosidic reverse transcriptase inhibitors [7]. No data are, however, available at this time on the clinical relevance of this putative antagonistic interaction. We have investigated the changes in plasma HIV-RNA levels during and after combination therapy with IFN and ribavirin in the first 38 HIV/HCV co-infected patients of our cohort undergoing stable antiretroviral therapy to reach 6 months of follow-up after discontinuation of a 6 or 12 month course of IFN and ribavirin. Nineteen of the 38 patients had been treated with a combination of two nucleosidic analogues, D4T and lamivudine (3TC) (n = 15) or ZDV and 3TC (n = 4) for a mean duration of 20 ± 10 months before the initiation of IFN and ribavirin. The remaining 19 patients had been treated with a triple combination antiretroviral regimen including a protease inhibitor with D4T and 3TC (n = 13) or ZDV and 3TC (n = 6) for a mean duration of 24 ± 8 months. The patients did not change their antiretroviral regimen throughout the period of the study. Seven patients received IFN (3 MU three times a week) and ribavirin (1000 mg per day) combination therapy for 6 months and 31 patients were treated for 12 months, depending on the severity of histological lesions in the pretreatment liver biopsy. The mean duration of HIV and HCV-targeted therapies was similar in the group of patients treated with double combination nucleosidic antiretroviral therapy and in the group receiving triple combination antiretroviral therapy. The plasma levels of HIV RNA were measured using the Quantiplex HIV-RNA 2.0 assay (Chiron, Emeryville, CA, USA.) with a threshold of detection of 500 copies/ml. The number of CD4 T cells was assessed by conventional cytofluorometric methods. Statistical evaluation was performed using the Wilcoxon signed-rank test. As shown in Table 1, the mean plasma HIV-RNA levels did not differ between baseline (before initiation of IFN and ribavirin), the time at which IFN and ribavirin were discontinued and at 6 monrths after discontinuation of IFN and ribavirin. As described previously by others in patients receiving IFN alone, the absolute number of CD4 cells decreased significantly during IFN treatment and returned to baseline values thereafter, suggesting that CD4 cells are trapped in extravascular sites during therapy with IFN [8]. Our observations strongly argue against the in-vivo relevance of the in-vitro competition between ribavirin, D4T and ZDV for intracellular phosphorylation. Ribavirin may thus be initiated in HIV/HCV co-infected patients receiving ZDV or D4T without switching reverse transcriptase inhibitors.Table 1: Changes in CD4 cell counts and plasma HIV viral load in HIV/hepatitis C virus co-infected patients treated with antiretroviral drugs and IFN in combination with ribavirina. Alain Landaua Dominique Batisse Christophe Piketty Raymond Jiana Michel D. Kazatchkine

Diffusion MRI detects early events in the response of a glioma model to the yeast cytosine deaminase gene therapy strategy.

Detection of a therapeutic response early in the course of cancer treatment, before tumor growth delay or regression, is not currently possible in experimental models or clinical medicine. New interim measures of therapeutic response would be particularly useful in the development of cancer chemosensitization gene therapy by facilitating optimization of gene transfer protocols and prodrug dosing schedules. Diffusion MRI is a sensitive technique producing quantitative and noninvasive images of the apparent mobility of water within a tissue. We investigated the utility of diffusion MRI for detecting early changes associated with a refined cytosine deaminase (CD)/5-fluorocytosine (5FC) chemosensitization gene therapy paradigm in orthotopic 9L gliomas stably expressing the recently cloned S. cerevisiae CD gene. Mean tumor diffusion increased 31% within 8 days of initiating 5-FC treatment, preceding tumor growth arrest and regression. Complete regression of the intracranial tumor was observed in four of five treated animals, and recurrent tumor in the remaining animal exhibited water diffusion behavior similar to primary, untreated tumors. These results demonstrate the efficacy of the yCD/5FC strategy for glioma and suggest that increased tumor water diffusion is an indicator of active therapeutic intervention.

Treatment of Critical Illness in the Elderly

There are conflicting signals about benefits and burdens of invasive therapies for elderly with life-threatening illness. On one hand there are those concerned that routine application of cardiopulmonary resuscitation and intensive care for elderly patients in acute crises may serve only to prolong dying process and deprive patient of a dignified death. An editorial in New England Journal of Medicine recently claimed that the very high suicide rate in older Americans is due partly to concern that they may be unable to stop treatment if hospitalized. Some people now fear living more than dying, because they dread becoming prisoners of technology.[1] Others are more concerned that elderly patients may be deprived of access to therapies that could both extend and enhance their lives because of failure to recognize benefits that such treatment can bring.[2] These advocates for elderly emphasize that although fewer of an unselected group of elderly patients may respond well to treatment than would younger patients, many suitably selected elderly patients do well. It has been suggested that absolute benefit to these patients is more relevant than whether such benefit is statistically less probable than for younger patients.[3] Such advocates counsel against age as a selection factor per se, pointing out that proper influence of age is as a marker for factors that may adversely affect outcome, such as reduced physiological reserve and comorbidity. It is these factors that should affect decision as to whether treatment is likely to be worth while, not age itself. Moreover, expectation of life in patients who have already reached age of sixty-five years or more is considerably greater than is often realized, making extension of life resulting from active therapeutic intervention often well worth while. Therapeutic technologies fall into three categories: lifesaving (cardiopulmonary resuscitation, emergency surgery, intensive care), life-sustaining (dialysis, mechanical ventilation, tube feeding), and life-enhancing (mostly surgical interventions that improve quality of life). Decisions about whether to employ interventions that aim to save or sustain life are affected by way in which patients are categorized. There are those who, being previously well, have a sudden unexpected crisis--a heart attack, stroke, or head injury. In such instances an initial trial of treatment will almost always be justified before any decision is made about whether to continue treatment. Quite different are patients with progressive disorders in whom a predictable crisis or relapse occurs and about whom some prior discussion about limiting future treatment may have been held with patient and family. These will include patients with progressive organ failure--of heart, lungs, brain, kidneys, or liver--and those with advanced cancer or dementia. A third category are those already disabled by progressive disease who fall victim to an unpredictable accident or acute illness unrelated to their existing disease (such as severely demented or vegetative patients). In each of these categories there will be patients who are competent and can participate in decisions about their treatment, and others who cannot. Decisions to initiate or continue with technologies that save or sustain life in patients of any age should depend on patient's preference, once expected benefits of intervention have been balanced against possible burdens. This preference can be properly exercised only if patient is fully informed about implications of various treatment options. Intervention may be deemed inappropriate if, after explanation about its likely effect, it is unwanted by patient or surrogate. If severity of illness is such that there is unlikely to be a favorable response to treatment, or if at best it will only briefly postpone a fatal outcome, it may be unfair even to offer such treatment as an option. …