Maintenance therapy with intravenous iron in hemodialysis patients receiving erythropoietin.
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The occurrence of carcinoma in chronic alcoholics exceeds that of the general population. Cytoplasmic alkalinization, due to the influence of different factors on the transmembrane Na+/H+ exchange (NHE), has been put forward as a triggering event in cell growth and division. In accordance with these findings, the carcinogenic potential of NHE deficient cell types is reported to be diminished. The aim of this study was to investigate whether the intracellular pH and the NHE activity is altered in chronic alcoholics. Seventy-two Caucasian males were assigned to one of four groups: non-alcoholics without carcinoma, chronic alcoholics without carcinoma, non-alcoholics with carcinoma and chronic alcoholics with carcinoma. Alcoholism was diagnosed according to DSM-III-R. The groups did not differ in relation to basic patient characteristics, such as age and blood pressure. Intracellular calcium, pH and NHE in platelets were determined by spectrofluorometry before and after thrombin stimulation. In chronic alcoholics with carcinoma, the intracellular pH was significantly more alkaline and the NHE activity was elevated. In contrast, a decrease in intracellular pH associated with an increased activity of NHE and a more acidic set point was found in chronic alcoholics without carcinoma. Basal and thrombin stimulated intracellular Ca2+ did not differ between groups except in chronic alcoholics with carcinoma in whom a thrombin-induced increase of Ca2+ due to liberation of Ca2+ from intracellular stores was demonstrated. In chronic alcoholics with carcinoma, cytoplasmic alkalinization was observed and this may be an indication of an increase in cell proliferation. The possibility that the increased incidence of carcinomas in chronic alcoholics is related to the increased activity of NHE and whether this may be prevented by NHE inhibitors requires further investigation.
Dioxolides, a novel class of secondary metabolites were detected by a HPLC-diode array screening technique in the culture filtrate of Streptomyces tendae Tu 4042. The compounds show no biological activity against Gram-positive and Gram-negative bacteria, yeasts and fungi. Besides dioxolides, which consist of an unusual substituted dioxolane ring, anhydroshikimate and para-hydrobenzamide were detected by this technique. Both compounds were not yet described as natural products.
OBJECTIVE: A chronic alcoholic group following trauma was investigated to determine whether their ICU stay was longer than that of a non-alcoholic group and whether their intercurrent complication rate was increased. DESIGN: Prospective study. SETTING: An intensive care unit. PATIENTS: A total of 102 polytraumatized patients were transferred to the ICU after admission to the emergency room and after surgical treatment. Of these patients 69 were chronic alcoholics and 33 were allocated to the non-alcoholic group. The chronic-alcoholic group. met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in these patients was > or = 60 g. Diagnostic indicators included an alcoholism-related questionnaire (CAGE), conventional laboratory markers and carbohydrate-deficient transferrin. MEASUREMENT AND RESULTS: Major intercurrent complications such as alcohol withdrawal syndrome (AWS), pneumonia, cardiac complications and bleeding disorders were documented and defined according to internationally accepted criteria. Patients did not differ significantly between groups regarding age, TRISS and APACHE score on admission. The rate of major intercurrent complications was 196% in the chronic alcoholic vs 70% in the non-alcoholic group (p = 0.0001). Because of the increased intercurrent complication rate, the ICU stay was significantly prolonged in the chronic-alcoholic group by a median period of 9 days. CONCLUSIONS: Chronic alcoholics are reported to have an increased risk of morbidity and mortality. However, to our knowledge, nothing is known about the morbidity and mortality of chronic alcoholics in intensive care units following trauma. Since chronic alcoholics in the ICU develop more major complications with a significantly prolonged ICU stay following trauma than non-alcoholics, it seems reasonable to intensify research to identify chronic alcoholics and to prevent alcohol-related complications.
The yield of TTE and TEE in identifying cardiac sources of embolism in patients with TIA or stroke was calculated from data from the Berlin Stroke Data Bank. High risk sources of embolism were detected by TTE in 4.2% with and in 1.6% of patients without evidence of cardiac disease from case history, clinical symptomatology, and ECG respectively. TEE yielded high risk sources of embolism in 10.6% of patients with and in 4.2% of patients without evidence of cardiac disease from case history, clinical symptomatology, ECG, and TTE respectively. Pathological findings were 12 atrial thrombi, 4 ventricular thrombi, and 1 atrial myxoma. 12 out of 14 atrial thrombi were only detected by TEE and not by TTE. There was a significant association of high risk cardiac sources of embolism with pial artery infarct pattern in CCT compared with lacunes. The yield of TEE in detecting high risk sources was not significantly associated with CCT infarct pattern probably due to the small numbers of investigations.
In our society every second polytraumatized patient is a chronic alcoholic. A patient's alcohol-related history is often unavailable and laboratory markers are not sensitive or specific enough to detect alcohol-dependent patients who are at risk of developing alcohol withdrawal syndrome (AWS) during their post-traumatic intensive care unit (ICU) stay. Previously, it has been found that plasma levels of norharman are elevated in chronic alcoholics. We investigated whether beta-carbolines, i.e. harman and norharman levels, could identify chronic alcoholics following trauma and whether possible changes during ICU stay could serve as a predictor of deterioration of clinical status. Sixty polytraumatized patients were transferred to the ICU following admission to the emergency room and subsequent surgery. Chronic alcoholics were included only if they met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use and their daily ethanol intake was > or =60 g. Harman and norharman levels were assayed on admission and on days 2, 4, 7 and 14 in the ICU. Harman and norharman levels were determined by high pressure liquid chromatography. Elevated norharman levels were found in chronic alcoholics (n = 35) on admission to the hospital and remained significantly elevated during their ICU stay. The area under the curves (AUC) showed that norharman was comparable to carbohydrate-deficient transferrin (CDT) and superior to conventional laboratory markers in detecting chronic alcoholics. Seventeen chronic alcoholics developed AWS; 16 of these patients experienced hallucinations or delirium. Norharman levels were significantly increased on days 2 and 4 in the ICU in patients who developed AWS compared with those who did not. An increase in norharman levels preceded hallucinations or delirium with a median period of approximately 3 days. The findings that elevated norharman levels are found in chronic alcoholics, that the AUC was in the range of CDT on admission and that norharman levels remained elevated during the ICU stay, support the view that norharman is a specific marker for alcoholism in traumatized patients. Since norharman levels increased prior to the onset of hallucinations and delirium it seems reasonable to investigate further the potential role of norharman as a possible substance which triggers AWS.
The number of patients with methicillin-resistant Staphylococcus aureus (MRSA) before and after discontinuing placement of patients into private rooms was determined. The mean monthly number of patients with MRSA decreased from 34 to 22, and the proportion of S aureus isolates that were MRSA decreased from 34% to 20%. We found no evidence that failure to isolate patients with MRSA resulted in an increased prevalence of MRSA.
OBJECTIVES: To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay. DESIGN: A prospective, randomized, blinded, controlled clinical trial. SETTING: A university hospital ICU. PATIENTS: Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment. INTERVENTIONS: Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale). MEASUREMENTS AND MAIN RESULTS: The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group. CONCLUSIONS: There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.
OBJECTIVE: To determine patterns of autopsy findings among persons with acquired immunodeficiency syndrome (AIDS) during a 12-year period. DESIGN AND SETTING: All 168 autopsies performed on adult AIDS patients at the Bronx-Lebanon Hospital Center in New York City between 1982 and 1993 were analyzed. The Center is a 725-bed, acute-care facility in the south Bronx, which serves a population of approximately half a million people. High poverty levels, tuberculosis and AIDS incidence, and intravenous drug abuse are common in this population. Subjects were predominantly Hispanic and black. MAIN OUTCOME MEASURES: Changes in the frequency of single and multiple opportunistic infections in general and frequencies of specific infections during the 12-year period. RESULTS: Through 1986, 75% of AIDS autopsies demonstrated single infections, particularly Pneumocystis carinii pneumonia. Since 1987, 72% of autopsies demonstrated multiple infections related to P carinii pneumonia, mycobacteriosis, cytomegalovirus, and various fungi. During the last 3 years, the prevalence of mycobacterial infections was higher than in the previous 9 years combined. In contrast, P carinii pneumonia decreased from 52% in 1988 to 14% in 1993. CONCLUSIONS: We note the recent emergence of multiple infections by multiple organisms, a significant decrease in the prevalence of P carinii pneumonia, and a slight increase in mycobacterial tuberculosis. Awareness of these changing patterns of infection may be useful in treating persons with AIDS.
BACKGROUND: Investigations of outbreaks of multidrug-resistant tuberculosis have found low rates of treatment response and very high mortality, and they have mainly involved patients with advanced human immunodeficiency virus (HIV) infection. For patients without HIV infection, one study reported an overall rate of response to treatment of 56 percent, and the mortality from tuberculosis was 22 percent. We investigated treatment response and mortality rates in 26 HIV-negative patients in New York with multidrug-resistant tuberculosis. METHODS: We obtained detailed data from seven teaching hospitals in New York City on patients with multidrug-resistant tuberculosis--defined as tuberculosis resistant at least to isoniazid and rifampin--who were HIV-negative on serologic testing. Lengths of times from diagnosis to the initiation of appropriate therapy and from the initiation of appropriate therapy to conversion to negative cultures were assessed. Therapeutic responses were evaluated by both microbiologic and clinical criteria. RESULTS: Between March 1991 and September 1994, 26 HIV-negative patients were identified and treated. Of the 25 patients for whom adequate data were available for analysis, 24 (96 percent) had clinical responses; all 17 patients for whom data on microbiologic response were available had such a response. The median times from diagnosis to the initiation of appropriate therapy and from the initiation of therapy to culture conversion were 44 days (range, 0 to 181) and 69 days (range, 2 to 705), respectively. Side effects requiring the discontinuation of medication occurred in 4 of 23 patients (17 percent) who were treated with second-line antituberculosis medications. The median follow-up for the 23 patients who responded and who received appropriate therapy was 91 weeks (range, 41 to 225). CONCLUSIONS: In this report from New York City, HIV-negative patients with multidrug-resistant tuberculosis, contrary to previous reports, responded well to appropriate chemotherapy, both clinically and microbiologically.
OBJECTIVE: To evaluate the impact of a coordinated approach for the isolation, diagnosis, and treatment of patients with tuberculosis. DESIGN: Retrospective cohort study. SETTING: Bronx-Lebanon Hospital Center, an inner-city hospital in the South Bronx, New York City. PATIENTS: Patients with smear-positive, culture-confirmed pulmonary tuberculosis. INTERVENTIONS: Institution of a coordinated tuberculosis team. RESULTS: Admissions of 46 patients before and 39 patients after the formation of a tuberculosis team were reviewed. Before institution of the tuberculosis team, 35% of patients were isolated within 24 hours of presentation, 41% never were isolated, and the mean number of days patients were not isolated was 19. After implementation of the tuberculosis team, 59% of patients were isolated within 24 hours, only 5% were never isolated, and the mean number of days patients were not isolated was 3.5. These differences were statistically significant. There also was a corresponding decrease in length of hospitalization. In addition, there were noticeable improvements in patient and staff morale and attitudes. CONCLUSIONS: The tuberculosis team likely has decreased the risk of nosocomial tuberculosis transmission by increasing the proportion of infectious tuberculosis patients admitted into AFB isolation and by reducing (by 780) the number of days out of isolation while smear positive. There also were concomitant financial savings.
Prophylaxis of alcohol withdrawal syndrome (AWS) in alcohol-dependent patients shortens the duration of stay in the intensive care unit (ICU). The objective of this study was to assess the effect of four different prophylactic regimens on the duration of ICU stay, prevention of AWS and rate of major intercurrent complications in alcohol-dependent patients admitted to the ICU after tumour resection. A total of 197 alcohol-dependent patients, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (third revised edition) with a daily ethanol intake of 60 g, were allocated randomly to one of the following regimens which were commenced on admission to the ICU: flunitrazepam-clonidine, chlormethiazole-haloperidol, flunitrazepam-haloperidol or ethanol. The duration of ICU stay, prevention of AWS, incidence of tracheobronchitis and major intercurrent complications such as pneumonia, sepsis, cardiac disorders, bleeding disorders and death were documented. On admission, patients did not differ significantly in age, APACHE II and multiple organ failure scores. ICU stay, incidence of AWS, severity of AWS (revised clinical institute withdrawal assessment for alcohol scale > 20) and major intercurrent complication rate did not differ significantly between groups. Although there was no advantage in any of the four regimens with respect to the primary outcome measures, pulmonary and cardiac patients were not included in the study. Patients in the chlormethiazole-haloperidol group had a significantly increased incidence of tracheobronchitis (P = 0.0023), probably because of an increased incidence of hypersecretion.
We conducted a retrospective study of patients with culture-confirmed multidrug-resistant tuberculosis (MDR-TB) at Bronx-Lebanon Hospital Center (South Bronx, NY) to determine what factors affected clinical and microbiological responses and survival. For the 38 patients with MDR-TB, reporting of first-line drug susceptibilities was relatively rapid (median time, 30 days). Thirty-four patients (89%) were infected with human immunodeficiency virus (HIV), and initial and overall response rates were 59% and 50%, respectively; the median survival was 315 days; and 50% of these patients died of tuberculosis. Bivariate analysis revealed that the following factors had a positive impact on response and survival: receiving > or = 2 consecutive weeks of appropriate therapy with at least two drugs to which the isolate was susceptible in vitro; starting appropriate therapy within 4 weeks of the diagnosis; and having tuberculosis that was limited to the lungs. Multivariate analysis revealed that the only variable associated with response was receipt of appropriate therapy for > or = 2 consecutive weeks. In contrast to findings in the published literature, our results indicate the outcome of MDR-TB can be improved, particularly for severely immunosuppressed HIV-infected patients. Rapid reporting of susceptibilities and prompt initiation and continuation of appropriate antituberculous therapy improved response and survival.
Every second traumatized patient is a chronic alcoholic. Chronic alcoholics are at risk due to an increased morbidity and mortality. Reliable and precise diagnostic methods for detecting alcoholism are mandatory to prevent posttraumatic complications by adequate prophylaxis. The patient's history, however, is often not reliable, and conventional laboratory markers are not sensitive or specific enough. The aim of this study was to investigate whether carbohydrate-deficient transferrin (CDT) is a sensitive and specific marker to detect alcoholism in traumatized patients. One hundred and five male traumatized patients or their relatives gave their written informed consent to participate in this institutionally approved study. All patients were transferred to the intensive care unit after admission to the emergency room, followed by surgical treatment. Diagnostics included an alcoholism-related questionnaire, conventional laboratory markers (mean corpuscular volume, gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase), and CDT sampling (microanion-exchange chromatography, turbidimetry, and radioimmunoassay, respectively). Only patients in whom a reliable history could be obtained were included. Alcoholism was diagnosed if the patients met the Diagnostic and Statistical Manual of Mental Disorders criteria for chronic alcohol abuse or dependence. The administration of fluids before CDT sampling was carefully documented. Patients did not differ significantly regarding age, Trauma and Injury Severity Score, and Acute Physiology and Chronic Health Evaluation score. The sensitivity of the CDT research kit was 70% and of the commercially available kit CDTect was 65%. Early sampling in the emergency room and before administration of large volumes of fluid increased the sensitivity to 83% for the CDT research kit and 74% for CDTect, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
The prevalence of chronic alcoholism in patients with carcinomas of the upper digestive tract exceeds 60%. The patient's history and laboratory markers, preoperatively, are often not sensitive or specific enough to detect alcohol-dependent patients, preoperatively, who are at risk of developing alcohol withdrawal syndrome (AWS) during their postoperative intensive care unit (ICU) stay. Previously, it was found that plasma norharman was elevated in chronic alcoholics, suggesting marker characteristics for chronic ethanol misuse and possibly alcohol dependence. We investigated whether beta-carbolines (i.e., harman and norharman) were different between chronic alcoholics and nonalcoholics with carcinoma, and how the levels change in alcohol-dependent patients during their hospital stay. Ninety-seven patients with oral, pharyngeal, laryngeal, or esophageal carcinomas were evaluated regarding their drinking habits. Sixty patients were transferred to the ICU following tumor resection. Chronic alcoholics met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in chronic alcoholics was > or = 60 g. Blood samples were collected on admission to the hospital, preoperatively, on admission to the ICU and on days 2, 4, and 7 in the ICU. Harman and norharman were determined by HPLC. Elevated norharman was found in chronic alcoholics on admission to the hospital, whereas harman did not differ between groups. On admission, the area under the receiver operating characteristics curve was significantly larger for carbohydrate-deficient transferrin and preoperatively for norharman. The preoperative norharman levels were significantly correlated with the period of mechanical ventilation and the length of ICU stay. Postoperatively, norharman decreased in all patients, except a group of 11 alcohol-dependent patients who developed AWS during their ICU stay. The finding that elevated norharman levels were found in chronic alcoholics on admission to the hospital and preoperatively supports the view of a specific marker for alcoholism. Preoperative norharman was superior to carbohydrate-deficient transferrin and was associated with a prolonged ICU stay and a prolonged period of mechanical ventilation. Further studies are required to determine whether norharman aids in the preoperative diagnosis of chronic alcohol misuse with respect to the prevention of postoperative complications.
A new member of the quinoxaline group antibiotics has been detected by HPLC-diode-array screening. The main compound produced by Streptomyces tendae strain Tü 4031 showed a high degree of similarity in the UV-visible spectral region with echinomycin and their structural similarity was confirmed by structure elucidation using electron tandem mass spectrometry and 2D nuclear magnetic resonance. The new compound, named echinoserine, is a non-cyclic form of echinomycin, but it is not a biosynthetic precursor. Echinoserine is less antibiotically active than echinomycin.
OBJECTIVE: To describe and quantify changing AIDS incidence trends in New York City. METHODS: Data on 44,400 AIDS cases diagnosed and reported between 1981 and 1992 were analyzed among demographic and HIV transmission categories. Data were grouped into 10-year birth cohorts by sex, race/ethnicity, and mode of HIV transmission. AIDS incidence and rates of change, as well as changes in median age at diagnosis, were analyzed for persons born between 1920 and 1969. RESULTS: Declining AIDS incidence between 1989 and 1992 was only observed among white men who have sex with men (MSM) born prior to 1960 and among minority MSM born prior to 1940. Between 1989 and 1992 the highest rate of increase in AIDS incidence was observed among female injecting drug users (IDU) and persons born after 1960. Median age at diagnosis increased during the study period by 1 year among white MSM, by 2 years among minority MSM, by 7 and 6 years among male and female IDU, respectively, and by 5 years among women infected through heterosexual contact. CONCLUSIONS: These findings suggest that early HIV infection dynamics of the AIDS epidemic were differentially related to age, sex, and transmission category, which resulted in the diffusion of infection from older to younger cohorts and from men to women. The continuing increase in AIDS incidence among the 1960s cohort suggests that the future growth of the epidemic will be dependent upon infection patterns of younger birth cohorts.
This study examined survival trends among the 23,324 cases of acquired immunodeficiency syndrome (AIDS) meeting the Centers for Disease Control (CDC) definition that were diagnosed and reported to the New York City Department of Health from the beginning of the epidemic in 1980 through June 1989. The survival patterns of 20,760 individuals who survived for at least 1 calendar month beyond diagnosis were analyzed; all survival analyses were truncated at December 1, 1990, 17 months after the last diagnosis. Persons who died during the same month in which they were diagnosed ("zero" survivors) were excluded. Cases were examined by race/ethnicity, sex, age at diagnosis, calendar period of diagnosis, transmission category, CDC AIDS case definition (prior to and after the 1987 change in the AIDS case definition), and nature of diagnosis. Results of two- and three-way categorical analysis and logistic regression analysis are reported. Overall median survival time was 13.7 months (14.0 for males and 12.0 for females). Survival was better for whites than for blacks and Hispanics and was better for men who had sex with men than for injecting drug users. Each of the seven demographic and risk behavior factors was independently associated with survival. Trends in survival during three time periods indicated that survival is improving among all groups examined.