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Mantle zone lymphoma. A clinicopathologic study of 22 cases.

A clinicopathologic analysis of 22 cases of mantle zone lymphoma (MZL) was performed. In lymph node sections, MZL was characterized by the proliferation of neoplastic small lymphoid cells in wide mantles around benign germinal centers. Eighteen cases were of the intermediate lymphocytic type and four cases were of the small lymphocytic type. Immunohistologic analysis of paraffin sections revealed the following characteristic immunophenotype of MZL: L26, LN2, NUB1 and T2/48 positive, and LN5, LN1, AF6 and UCHL1 negative. The immunophenotype of MZL was identical to that of normal primary lymphoid follicles and the mantle zones of secondary follicles, except for the absence of staining with LN5 in MZL. The median age of the patients was 63 years, and the male-to-female ratio was 1.2:1. B symptoms were present in 55% of the patients, and 81% had splenomegaly. An absolute lymphocytosis was present at the time of initial diagnosis in 13% of the patients, and 67% had bone marrow involvement by lymphoma. Thirteen percent of the patients had Stage II disease, 23% had Stage III disease, and 64% had Stage IV disease. All 22 patients received some form of therapy, with 73% receiving multiagent chemotherapy. Eleven patients achieved a complete remission at some time during their course. The overall median survival of the entire group was 88 months. Clinical features which appeared to influence survival adversely included an absolute lymphocyte count above 4000/microliters, a platelet count less than 100,000/microliters, and male sex. Achievement of a complete remission at any time favorably influenced survival. Pathologic features which appeared to influence survival adversely were a mitotic rate of 10 or more per 10 high-power fields (HPF) and the presence of 40 or more large lymphoid cells per 10 HPF. These findings lead the authors to conclude that MZL is a distinctive form of low-grade non-Hodgkin's lymphoma.

Adult↗

Peripheral lymphocytes and intracellular cytokines in C282Y homozygous hemochromatosis patients.

BACKGROUND/AIMS: Several abnormalities in the immune status of hereditary hemochromatosis patients have been reported. We evaluated the peripheral blood lymphocytes phenotype and cytokine profile of CD8(+) and CD4(+) T cells in C282Y homozygous hereditary hemochromatosis patients compared to control subjects. METHODS: Peripheral blood lymphocytes from 17 asymptomatic patients and 14 control subjects were analyzed. We determined the distribution of lymphocyte subsets and investigated at single-cell level by flow-cytometry the potential of cytokines production. The frequency of cytokine (interferon gamma, tumor necrosis factor alpha, interleukin 2 (IL-2), IL-4, IL-5, IL-10 and IL-13) producing cells was assessed in total T-lymphocytes, CD3(+)CD8(+) and CD3(+)CD4(+) subsets. RESULTS: The patients studied showed a significant decrease of total lymphocyte count, T CD4(+)CD3(+), CD28(+), CD8(+)CD28(+) lymphocytes and natural killer (NK) CD56(+)CD16(+)CD3(-) cells. The reduction of CD28(+) and CD8(+)CD28(+) lymphocyte count was inversely related to transferrin saturation index. An increase in the ability of T-cells to produce all the cytokines studied and a major increase in IL-4 and IL-10 production in the CD3(+)CD8(+) subset was found. Our results demonstrate that activated Th1 and Th2 lymphocytes coexist in the peripheral blood of hereditary hemochromatosis patients and that T-cytotoxic (Tc) 2 subset is more expanded than in control population. CONCLUSIONS: The association of a decreased number of T CD8(+) cytotoxic lymphocytes and NK cells, and the development of Tc2 cells in asymptomatic C282Y homozygous patients represents an imbalance in their immune function that might contribute to the high incidence of hepatocarcinoma.

Adult↗

Long-term survival following cladribine (2-chlorodeoxyadenosine) therapy in previously treated patients with chronic lymphocytic leukemia.

PURPOSE: To assess long-term survival following cladribine salvage treatment for previously treated patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: Fifty-two patients aged 39-84 years with previously treated CLL received cladribine 0.12 mg/kg/day in 2-hour infusions for 5 days in monthly courses. Two-thirds were refractory to previous therapy, and 8 had prior fludarabine. RESULTS: Sixteen (31%) patients achieved complete response (CR) and 14 (27%) partial remission (PR) according to consensus criteria. Response correlated with clinical stage, number of previous treatment regimes, blood lymphocyte count, and lymphocyte halflife following the first cladribine course. Toxicity included pneumonia (n = 9), herpes zoster (n = 7), and septicemia (n = 2). Four patients in CR underwent high-dose chemotherapy with autologous blood stem cell support, and 2 remain in CR 48 and 60 months from start of cladribine, and 2 had relapse at 42 and 48 months, respectively. Median progression-free survival (Kaplan-Meier analysis) for CR patients was 23 months from start of cladribine treatment, and for PR patients 16 months. The projected overall survival was 80% at 3 years for CR patients, and the median survival 28 months for PR patients and 4 months for non-responding patients. CONCLUSIONS: Our previous finding of durable CRs from cladribine in advanced CLL is thus confirmed in a larger patient material, and follow-up indicate that long-term survival may be achieved.

Adult↗

Cross-sectional study of immunologic abnormalities in intravenous drug abusers on methadone maintenance in New York City.

One hundred and ninety-nine patients with a history of intravenous drug abuse, and enrolled on the St Luke's-Roosevelt Hospital Center Methadone Program, had baseline evaluations performed from September 1984 to April 1987. The study was designed to examine immunologic parameters associated with HIV seropositivity and those predictive of progression to AIDS-related complex (ARC) and AIDS. Sixty-four patients (32%) had antibodies to HIV by enzyme-linked immunosorbent assay (ELISA), with confirmation by Western blot and none of these patients had ARC or AIDS at the time of initial evaluation. The mean values for white blood-cell count, absolute lymphocyte count, proportion and absolute CD4, and CD4/CD8 ratio were decreased significantly in the HIV-seropositive group compared with the HIV-seronegative group. On the other hand, levels of circulating beta 2-microglobulin, SCD8, SIL-2R, and HIV p24 antigen were significantly elevated in the HIV-seropositive group compared with the HIV-seronegative group.

AIDS-Related Complex↗

Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging.

The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11 cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal at entry for these 3 variables had a theoretical 36 times as high hazard of developing symptoms within the observation period as had individuals with normal parameters. There was no significant covariation between HIV antigenemia on the one hand and CD4 count and response to PWM on the other. Although, the latter 2 variables covaried, each of them provided independent information, and both were used to classify the degree of the immunodeficiency in 3 stages: Im-0 with normal values, Im-1 with one, and Im-2 with both tests abnormal. Individuals in stage Im-2 had a 10 times increased risk of developing symptoms. The immunologic staging correlated significantly with the clinical grouping (CDC criteria). This staging improved in only 1, but deteriorated in half of 36 individuals observed for at least 18 months. Thus, the staging is likely to prove useful when attempts to arrest the immunodeficiency of HIV-infected individuals has to be monitored.

Biomarkers↗

Treatment history and baseline viral load, but not viral tropism or CCR-5 genotype, influence prolonged antiviral efficacy of highly active antiretroviral treatment.

BACKGROUND: The efficacy of highly active antiretroviral treatment (HAART) in HIV-1 disease may vary between nucleoside-naive and experienced patients as well as between patients with different viral phenotypes and in different stages of disease. OBJECTIVE: To investigate variables of importance for successful long-term viral suppression by analysing virological, clinical and immunological characteristics at initiation of protease inhibitor treatment on suppression of HIV RNA over 1 year. DESIGN: An open, non-randomized, observational clinical study. SETTING: Venhälsan, Department of Dermatovenereology, Söder Hospital, Stockholm, Sweden. PATIENTS: A total of 147 unselected advanced patients with known HIV-1 infection for a mean of 7 years, of whom 37% had AIDS and who started treatment with a protease inhibitor during 1996. INTERVENTIONS: All patients received HAART with at least two nucleoside analogues in combination with either indinavir (81%) or ritonavir (19%). The majority (77%) had been previously treated with nucleoside analogues for a mean of 39 months. MEASUREMENTS: CD4+ lymphocyte count, plasma HIV-1 RNA, viral phenotype and HIV-1 coreceptor CCR-5 genotype at baseline. Viral load and CD4+ lymphocyte count were determined every 3 months. RESULTS: Patients were analysed on an intention-to-treat basis. The mean CD4+ lymphocyte count at baseline was 170 x 10(6)/l and the median viral load was 68 600 copies/ml. Heterozygosity for the delta32 deletion of the CCR-5 gene (delta32/wt) was found in 27%. MT-2 positive virus (syncytium-inducing) was isolated in 46%. Logistic regression revealed that nucleoside analogue experience and baseline log10 HIV-1 RNA were the only factors independently related to plasma HIV-1 RNA levels below 500 copies/ml after 1 year of treatment, which was found in 69%. CONCLUSION: The virological outcome after 1 year of HAART was strongly correlated to prior treatment history and baseline viral load, whereas CD4+ lymphocyte count, CCR-5 genotype and viral biological phenotype had less influence. The long-term antiviral efficacy of HAART was lowest in individuals with previous nucleoside analogue treatment and a high baseline viral load. In these individuals an even more aggressive treatment should be considered.

Adult↗

Clinical experience with adding delavirdine to combination therapy in patients in whom multiple antiretroviral treatment including protease inhibitors has failed.

OBJECTIVE: To determine the effectiveness and safety of adding delavirdine mesylate to a treatment regimen that included indinavir and nucleoside analog reverse transcriptase inhibitors in patients in whom combination therapy had failed. DESIGN: Observational study. SETTING: Private practice. PATIENTS: HIV-1-positive patients with peripheral blood CD4+ lymphocyte counts < 300 x 10(6)/l in whom antiretroviral therapy had failed or whose condition was deteriorating. Of the 53 patients who were eligible for the study, 47 took part; for the majority of these patients indinavir combination therapy had been unsuccessful. the majority of the patients were male (98%), white (92%) and homo/bisexuals (96%). INTERVENTIONS: Delavirdine added to current therapy (usually zidovudine, indinavir and lamivudine); in approximately half of the patients zidovudine was replaced with stavudine. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA levels; peripheral blood CD4+ and CD8+ lymphocyte counts. Safety of the therapy was assessed by monitoring side-effects. RESULTS: Mean baseline CD4+ lymphocyte count was 127 x 10(6)/l and mean baseline HIV-1 plasma RNA was 5 log10 copies/ml. Adding delavirdine to the therapeutic regimen produced a rapid and sustained decrease in the mean plasma HIV-1 RNA of 1.1 log10 copies/ml over 6 months; 18-21% of patients showed decreases of 2-3 log10 copies/ml. Viral burden in 33% of subjects declined below the assay's limit of detection (2.6 log10 copies/ml) after 6 months. CD4+ lymphocyte counts increased by 66-90% in each group between 1 and 9 months (mean increase approximately 60 x 10(6)/l after 6 months). Adding delavirdine to current therapy was well tolerated. Side-effects reported were: skin rash, 28%; nausea, 9%; kidney stones, 9%; diarrhea, 6%; flank pain, 2%; proteinuria, 2%. Three patients reported serious medical events all of which resolved and none of which were attributed to delavirdine. CONCLUSIONS: Adding delavirdine to the combination regimen of patients in whom protease inhibitor therapy had failed often resulted in a rapid and remarkable decrease in viral load, sustained improvement in CD4+ lymphocyte counts and viral load, and clinical improvement with minimal toxicity.

Adult↗

Serological and haematological diagnosis of enzootic bovine leukosis in cattle in Turkey.

A serological study of enzootic bovine leukosis in the Bursa Region of Turkey showed that of 459 cattle (282 Holstein, 127 Brown-Swiss and 50 native Boz breed) 42 (9.15 per cent) were seropositive. The seropositive cattle had higher IgG1 (P < 0.001) and lower IgM (P < 0.01) levels than the seronegative cattle. In addition, the seropositive cattle with persistent lymphocytosis had higher IgG1 levels (P < 0.001), total leucocyte counts (P < 0.001) and lymphocyte counts (P < 0.001), than the cattle in the seropositive group without persistent lymphocytosis and the cattle in the seronegative group. There was a positive correlation (P < 0.05) between the IgG1 levels and the lymphocyte counts of the seropositive cattle with persistent lymphocytosis.

Animals↗

Human immunodeficiency virus status and delayed-type hypersensitivity skin testing in Ugandan children.

BACKGROUND: In previous studies, delayed-type hypersensitivity (DTH) skin testing has been shown to be affected by several factors including nutritional status, intercurrent infection, host immune status, and previous exposure to the antigen being used. OBJECTIVE: To determine the effect of human immunodeficiency virus type 1 (HIV-1) status on DTH skin testing in a cohort of HIV-1-infected and noninfected Ugandan children followed prospectively from birth. DESIGN: Nested case-control study. SETTING: Primary care clinic serving study participants at Mulago Hospital, Makerere University, Kampala, Uganda. PARTICIPANTS: Thirty HIV-1-infected children and 30 age-matched, HIV-1-noninfected children. METHODS: After completion of history and physical, each child underwent Mantoux skin testing with both Candida and purified protein derivative (PPD). Results of skin testing were read in 48 to 72 hours. Complete chart reviews were performed on all children. CD4 lymphocyte counts were obtained on all HIV-1-infected children at the time the skin testing was read. RESULTS: The average age of participants was 67 months (range, 51-92 months). HIV-1-infected children (mean CD4 lymphocyte count, 1069 mL-1; range, 86-3378 mL-1), compared with noninfected, age-matched peers, developed significantly smaller PPD reaction size (mean, 1.18 mm +/- 4.3 vs 3.6 mm +/- 7.6, respectively). Candida responses were not different between the two groups of children. Among HIV-1-infected children, there was a larger Candida reaction size in children who had recently received chloroquine treatment. There was no significant correlation between Candida reactivity and PPD reactivity, progressive HIV-1 disease, or CD4 lymphocyte count. The six children diagnosed clinically with active tuberculosis had lower absolute CD4 lymphocyte counts than children without tuberculosis. Lack of reaction to PPD was associated with lower CD4 lymphocyte counts and progressive HIV-1 disease. CONCLUSIONS: In HIV-1-infected Ugandan children, DTH skin testing was influenced by the choice of antigen selected, HIV-1 infection, and recent treatment with chloroquine. Based on these findings, we believe that further prospective, longitudinal investigation into the role of chloroquine in HIV-1-infected children is needed. We emphasize the limitations of DTH skin testing in HIV-infected children as an adjunct in the diagnosis of active tuberculosis.

Antigens, Fungal↗

Metabolic and functional results after laparoscopic colorectal surgery: a randomized, controlled trial.

PURPOSE: This study was designed to compare metabolic and functional results after laparoscopic and open colorectal resection. METHODS: Seventy-nine patients were randomly assigned to laparoscopic (n = 40) or open (n = 39) colorectal resection. Before and after operation, the following parameters were determined: respiratory function (spirography and blood gas); serum level of cortisol, lactate, and C-reactive protein; total lymphocyte count; and CD4 and CD8 lymphocyte subsets. Intraoperative core temperature was measured by a bladder probe. Postoperative pain and analgesic consumption were also monitored. RESULTS: Mild operative hypothermia, a trend to postoperative reduction of total lymphocyte count, and significant impairment of respiratory function early after surgery were found in both groups. Laparoscopy showed a higher CD4/CD8 ratio (P = 0.01) on postoperative Day 1 and a faster return of C-reactive protein to preoperative values (P = 0.01) than in the open colorectal resection group. Morphine consumption in the first 48 hours after surgery was lower in the laparoscopic than in the open group (P = 0.02). CONCLUSIONS: Laparoscopy was associated with a less pronounced immunosuppression and inflammatory response and a lower consumption of analgesic drugs than open surgery. Moreover, our data did not show any additional detrimental effect of laparoscopy on either operative core temperature or early postoperative respiratory function.

C-Reactive Protein↗

Nutritional assessment of drug addicts.

OBJECTIVE: To discern if factors such as organic pathology, sex, duration and/or intensity of drug addiction, alcohol abuse, hepatitis B infection, anorexia with poor food and drink consumption, or disturbance of social and familial networks, are related to an impaired nutritional status in hospitalized drug addicts. DESIGN: Cross-sectional prospective study. SETTING: Detoxication unit and internal medicine unit of a university hospital. PATIENTS: 140 drug addicts without acute organic pathology and 18 with acute organic pathology related to drug addiction. The immunological study was compared with a control group composed of 50 healthy and well-nourished individuals (26 women and 24 men), age-matched with our patients. RESULTS: Drug addicts without organic pathology were under-nourished: 92.4% weighed under the mean weight for the population and 55.7% had had a weight loss above 5%. The distribution of mid-upper arm circumference (MUAC), triceps skinfold (TSF) measurement and mid-arm muscle area (MAMA) compared with the percentiles for the population showed a shift towards lower values. We found a high percentage of patients with a high lymphocyte count (55%). Despite the high lymphocyte count, delayed hypersensitivity was depressed in our patients. Of our patients, 66.4% exhibited anorexia at admission. The mean calorific intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. However, in most cases, malnutrition (usually marasmus-like malnutrition) was not very severe; only 30% of the drug addicts weighed less than 80% of the mean weight for the population, or admitted to a weight loss above 10%, and by subjective nutritional assessment, only 18% were deeply malnourished. Otherwise, the nutritional status was very poor in drug addicts with acute organic pathology. We also found a worse nutritional status in our patients related to female sex, intensity of drug addiction, anorexia with poor food and drink consumption, and disturbance of the social and familial networks. CONCLUSIONS: Many drug addicts suffer from calorie and protein malnutrition. This mainutrition is related to female sex, intensity of drug addiction, anorexia and poor food and drink consumption, and disturbance of the social and familial links. Acute organic pathology leads to a significant worsening of the nutritional status of drug addicts.

Adult↗

Reduced dose Thymoglobulin, tacrolimus, and mofetil mycophenolate results in excellent solitary pancreas transplantation outcomes.

BACKGROUND: Graft survival following solitary pancreas transplantation has traditionally lagged behind that of simultaneous pancreas-kidney transplants. Thymoglobulin (TMG), a polyclonal rabbit-derived antilymphocyte antibody was originally introduced as treatment for acute rejection of renal allografts. However, data regarding the efficacy of TMG induction in solitary pancreas transplants is lacking. We present the 1-yr graft survival and acute rejection rate of 22 solitary pancreas transplants performed at the McGill University Health Centre using reduced dose TMG induction with lower dose tacrolimus and mophetil mycophenolate. PATIENTS AND METHODS: Eighteen pancreas after kidney and four pancreas transplants alone were performed between January 1998 and October 2000 at McGill University. Induction therapy with TMG at a starting dose of 1.5 mg/kg/d was started 12 h post-operatively. The daily dose of TMG was held if the total leukocyte count was <2,500/mm3 or if the lymphocyte count was <100/mm3. Maintenance therapy was initiated with steroids (tapered to 20 mg prednisone orally once a day) tacrolimus (2 mg twice a day), and mofetil mycophenolate (1 g daily). RESULTS: Patients received three to seven doses of TMG over the first seven post-operative days at a dose of 0.85 +/- 0.27 mg/kg/d (mean +/- SD). The mean follow-up was 1.28 +/- 0.14 yr. The 1-yr patient and graft survival was 100% (22 of 22) and 96% (21 of 22), respectively. The 1 yr acute rejection rate was 27.3% (six of 22). Five of the six rejections responded to steroid boluses. One was refractory to steroids and TMG resulting in graft loss. Presumed rejections were diagnosed on the basis of decreasing urine amylase and/or hyperglycemia. DISCUSSION: Monitoring the total leukocyte and lymphocyte count resulted in a 43% reduction in the amount of TMG used compared with the recommended dosing. Despite the reduced amounts, patient and graft survival were excellent with acute rejection rates comparing favorably to other published series.

Adult↗

Heat-denatured human immunodeficiency virus type 1 protein 24 antigen: prognostic value in adults with early-stage disease.

CD4(+) lymphocyte count and human immunodeficiency virus (HIV) type 1 RNA level are useful for determining when to initiate antiretroviral therapy but are not used widely in developing countries due to the high cost. Heat-denatured protein 24 (p24) antigen is an inexpensive assay that predicts disease progression among persons with advanced disease but has not been assessed among persons with early-stage disease. Plasma levels of heat-denatured p24 antigen were quantified in baseline study-visit specimens obtained from injection drug users enrolled in a longitudinal cohort study of HIV-1 infection. Of the 494 study participants (median initial CD4(+) lymphocyte count, 518 lymphocytes/mm(3)), 90 (18%) progressed to acquired immunodeficiency syndrome within 5 years. p24 antigen level correlated with both CD4(+) lymphocyte count (r=-0.34; P<.0001) and HIV-1 RNA level (r=0.55; P<.0001). p24 antigen level >5 pg/mL predicted disease progression, comparable with that of cutoff CD4(+) lymphocyte count <350 lymphocytes/mm(3) and HIV-1 RNA level >30,000 copies/mL. Heat-denatured p24 antigen level predicted subsequent clinical disease progression in early-stage HIV-1 infection and correlated with both CD4(+) lymphocyte count and HIV-1 RNA level.

Acquired Immunodeficiency Syndrome↗

The predictive value of several markers in the progression to acquired immunodeficiency syndrome.

Serum beta 2-microglobulin, neopterin, immunoglobulins A, G and M, adenosine deaminase and CD4+ lymphocyte count were evaluated as predictors of progression of HIV-1 infection to AIDS. A population of HIV-1 seropositive, initially asymptomatic men (n = 213) and women (n = 101) was followed up quarterly. We estimated the AIDS-free time using the actuarial method (median survival time 47.2 months). Cox proportional hazard analysis revealed that all markers studied were significant (p < 0.05) in relation to progression to AIDS. The best markers for predicting progression to AIDS were, in descending order, CD4+ lymphocyte count, beta 2-microglobulin, IgA, neopterin, IgG, IgM and adenosine deaminase. On stratifying population into four groups (divided at percentiles 25, 50 and 75--from group 1, with values nearest to reference ranges, to group 4, with most abnormal values) we observed statistically significant differences (p < 0.05) for all markers except for adenosine deaminase. The relative risk from the Cox proportional hazards model were used to quantify the effects of the best markers and compared to the risk obtained in group 1. CD4+ lymphocyte count was the best predictor of progression to AIDS. When considering beta 2-microglobulin and CD4+ together, the relative risk in the group with lowest CD4+ cell count (group 4) ranged from 25.6% (with lower beta 2-microglobulin values) to 41.1% (with higher beta 2-microglobulin values). Similar results were obtained when considering neopterin and CD4+ together. The addition of beta 2-microglobulin or neopterin values to CD4+ lymphocyte count improved the predictive value of CD4+ lymphocyte count.

Acquired Immunodeficiency Syndrome↗

Lymphopenia: a bad prognostic factor in Hodgkin's disease.

Pretreatment peripheral blood lymphocyte counts have been recorded in 181 consecutive untreated patients with histologically proven Hodgkin's disease and the patients followed prospectively to determine the relationship of lymphopenia to survival. Lymphocyte counts at presentation did not correspond with histology type but were lower in stage 4 disease. Survival in the 77 patients with lymphocyte counts of less than 1.5 X 10(9)/l was 49.7% which was significantly worse (P less than 0.0001) than the 74.2% survival of those with 'normal' counts. This difference was maintained even after adjustment for other acknowledged prognostic variables including sex, age, stage, symptom status, histology type, and response to treatment. The study provides evidence that the lymphocyte count can be used as a meaningful marker in the clinical staging of Hodgkin's disease.

Adult↗

Leukocytosis of exercise: role of cardiac output and catecholamines.

The effect of propranolol (5 mg iv) on the leukocytosis of exercise was studied in seven normal young males. Leukocyte counts, plasma norepinephrine (NE), epinephrine (E), and cardiac output were measured at rest and in the steady state of several submaximal work loads when subjects exercised on a cycle ergometer. The results in control experiments were compared with those obtained on a different day with propranolol. Propranolol decreased heart rate at all work loads (P less than 0.001) but had no effect on the increase in cardiac output at increasing work loads. Plasma NE and E levels were similar at rest and in exercise in control and propranolol studies. There was no effect of propranolol on the increase in leukocyte counts with increasing work loads. Although propranolol did not affect the increase in total leukocyte count, the increase in lymphocyte count at higher work loads was less with propranolol. We conclude that the demargination of leukocytes from the pulmonary circulation in exercise is probably a mechanical effect of the increase in cardiac output. However, we have not excluded a contribution from a humoral event that would decrease the adherence of leukocytes to endothelium during exercise. The smaller increase in lymphocytes at higher work loads in the presence of propranolol suggests that catecholamines affect the lymphocyte count over and above their effect on cardiac output.

Adult↗

The effects of nutritional status on outcome after hip fracture.

OBJECTIVE: To determine the effect of nutrition on patient outcome after hip fracture. STUDY DESIGN: Retrospective review of prospectively collected data. METHODS: Four hundred ninety hip fracture patients had albumin and total lymphocyte count levels determined at the time of admission and constituted the study population. These variables were examined as predictors for outcomes, including: in-hospital mortality, postoperative complications, hospital length of stay, hospital discharge status, one-year mortality rate, ambulatory ability, and independence in basic and instrumental activities of daily living twelve months after surgery. RESULTS: Eighty-seven patients (18 percent) were found to be malnourished on hospital admission based on a preoperative albumin level of < 3.5 grams/deciliter, and 280 patients (57 percent) based on a total lymphocyte count of < 1,500 cells/milliliter. An albumin level of < 3.5 grams/deciliter was predictive for increased length of stay (p = 0.03) and for in-hospital mortality (p = 0.03). A total lymphocyte count < 1,500 cells/milliliter was predictive for one-year mortality (p < 0.01). Patients with abnormal albumin and total lymphocyte count were 2.9 times more likely to have a length of stay greater than two weeks (p = 0.03), 3.9 times more likely to die within one year after surgery (p = 0.02), and 4.6 times less likely to recover their prefracture level of independence in basic activities of daily living (p < 0.01). Neither parameter was predictive for patients developing a postoperative complication, hospital discharge status (home versus nursing home), recovery of prefracture ambulatory ability, or independence in instrumental activities of daily living at twelve-month follow-up. CONCLUSION: Patients at risk for poor outcomes after hip fracture can be identified using relatively inexpensive laboratory tests such as albumin and total lymphocyte count.

Age Distribution↗

Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on growth and immunological parameters of broiler chickens.

An experiment was conducted to investigate the effects of feeding grains naturally contaminated with Fusarium mycotoxins on growth and immunological parameters of broiler chickens. Three hundred sixty, 1-d-old male broiler chicks were fed 1 of 4 diets containing grains naturally contaminated with Fusarium mycotoxins for 56 d. The diets included (1) control; (2) low level of contaminated grains (5.9 mg/kg deoxynivalenol (DON), 19.1 mg/kg fusaric acid (FA), 0.4 mg/kg zearalenone, and 0.3 mg/kg 15-acetyldeoxynivalenol; (3) high level of contaminated grains (9.5 mg/kg DON, 21.4 mg/kg FA, 0.7 mg/kg zearalenone, and 0.5 mg/kg 15-acetyldeoxynivalenol); and (4) high level of contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent (GM polymer). Body weight gains and feed consumption of chickens fed contaminated grains decreased linearly with the inclusion of contaminated grains during the grower phase (d 21 to 42). Efficiency of feed utilization, however, was not affected by diet. Production parameters were not significantly affected by the supplementation of GM polymer to the contaminated grains. Peripheral blood monocytes decreased linearly in birds fed contaminated grains. The feeding of contaminated diets linearly reduced the B-cell count at the end of the experiment, whereas the T-cell count on d 28 responded quadratically to the contaminated diets. The feeding of contaminated diets did not significantly alter serum or bile immunoglobulin concentrations, contact hypersensitivity to dinitrochlorobenzene, or antibody response to SRBC. Supplementation with GM polymer in the contaminated diet nonspecifically increased white blood cell count and lymphocyte count, while preventing mycotoxin-induced decreases in B-cell counts. It was concluded that broiler chickens are susceptible during extended feeding of grains naturally contaminated with Fusarium mycotoxins.

Animal Feed↗