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CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression.

BACKGROUND: Sustained suppression of the human immunodeficiency virus (HIV) type 1 RNA load with the use of highly active antiretroviral therapy (HAART) results in immunologic improvement, but it is not clear whether the CD4(+) cell count increases to normal levels or whether it reaches a less-than-normal plateau. We characterized the increase in the CD4(+) cell count in patients in clinical practice who maintained sustained viral suppression for up to 6 years. METHODS: All patients were from the Johns Hopkins HIV Clinical Cohort, a longitudinal observational study of patients receiving primary HIV care in Baltimore, Maryland, who were observed for >1 year while receiving HAART and who had sustained suppression of the HIV RNA load at <400 copies/mL. We analyzed annual change in the CD4(+) cell count for up to 6 years after the start of HAART, stratified by baseline CD4(+) cell counts of < or =200, 201-350, >350 cells/microL, and we assessed the development of clinical events (death and new acquired immunodeficiency syndrome-defining illness) by Kaplan-Meier analysis. RESULTS: A total of 655 patients were observed for a median of 46 months (range, 13-72 months). The median change from baseline to most recent CD4(+) cell count was +274 cells/microL, with 92% of patients having an increase in CD4(+) cell count. By 6 years, the median CD4(+) cell count was 493 cells/microL among patients with baseline CD4(+) cell counts < or =200 cells/microL, 508 cells/microL among those with baseline CD4(+) cell counts of 201-350 cells/microL, and 829 cells/microL among those with baseline CD4(+) cell counts >350 cells/microL. In addition to baseline CD4(+) cell count, injection drug use and older age were associated with a lesser CD4(+) cell count response, and duration of therapy was associated with a greater CD4(+) cell count response. CONCLUSION: Only patients with baseline CD4(+) cell counts >350 cells/microL returned to nearly normal CD4(+) cell counts after 6 years of follow-up. Significant increases were observed in all CD4(+) cell count strata during the first year, but there was a lower plateau CD4(+) cell count at lower baseline CD4(+) cell strata. These data suggest that waiting to start HAART at lower CD4(+) cell counts will result in the CD4(+) cell count not returning to normal levels.

Adult↗

Grading of superficial antral gastritis: comparison of cell-counting and photographic-based methods.

A cell-counting technique and a photographic-based scoring system for assessing inflammatory cell infiltration were compared for agreement in 275 endoscopic gastric antral biopsies from 55 dyspeptic patients. Each biopsy was independently scored 0-5 for polymorphs and mononuclear cells using both methods, and a mean score was derived for each patient. There was a highly significant correlation between the mean patient scores obtained using each method (P less than 0.001). Agreement statistics showed that the mean score difference (cell-counting minus photographic score) was negative for polymorphonuclear and mononuclear cells, indicating that the photographic method yielded higher mean patient scores. Scatterplots of difference versus mean by the two methods showed that only 3.6 per cent of scores fell outside +/- 2 SD of the mean difference. The use of standard photomicrographs to grade superficial antral gastritis therefore provides accurate results, comparable to those obtained by cell counting, yet is a faster and much cheaper technique.

Biopsy↗

Herd incidence of bovine mastitis in four danish dairy districts. III. Relation between frequency of mastitis and cell counts on bulk molk samples.

The correlations between monthly bulk milk cell counts and the actual frequency of mastitis was investigated in 399 Danish dairy farms with a total of about 7000 cows. The correlation coefficients varied from 0.3 to 0.5. Correlations were improved by using more than one cell count, but not further improved by using more than two cell counts. The correlations were higher for large than for small herds. It was not possible by combining cell counts in different ways, as indicated in (Table IV, to point out every heavily mastitis-affected herd without also pointing out some not so heavily affected ones. Table IV shows what infection levels can be expected when different criteria based on bulk milk cell counts are applied. The figures cannot be transferred directly from Danish conditions to conditions in other countries, but similar tendencies can probably be found anywhere.

Animals↗

Correlation of circulating natural killer cell count with prognosis in large cell lymphoma.

A monoclonal antibody recognizing a natural killer (NK) cell-associated antigen was used to sequentially quantify numbers of peripheral blood NK cells in a small group of patients with large cell lymphoma. Patients with active disease had low numbers (less than 100/mm3) of NK cells. Patients in complete remission after therapy had normal numbers of NK cells, but those patients who relapsed had a fall of NK cell number to less than 100/mm3 preceding or concurrent with clinical relapse. A role for NK cells in the surveillance and control of abnormal lymphoproliferation is suggested, as is the possible prognostic utility of sequential peripheral blood NK cell quantification in patients with large cell lymphoma.

Antibodies, Monoclonal↗

Neonatal nucleated red blood cell counts in growth-restricted fetuses: relationship to arterial and venous Doppler studies.

OBJECTIVE: Elevated nucleated red blood cell count in neonatal blood and Doppler-detected circulatory decompensation in fetuses with intrauterine growth restriction are associated with hypoxemia. We sought to determine the relationship between the nucleated red blood cell count at birth and the circulatory status of fetuses with intrauterine growth restriction. STUDY DESIGN: Eighty-four fetuses with elevated umbilical artery pulsatility index values >2 SD above the gestational age mean and a subsequent birth weight <10th percentile were examined serially. Umbilical and middle cerebral artery pulsatility index, inferior vena cava and ductus venosus peak velocity index, and flow pattern in the umbilical vein (umbilical vein constant vs pulsatile) were recorded. Fetuses were grouped as follows, on the basis of the last examination before delivery: 1, elevated umbilical artery pulsatility index only; 2, middle cerebral artery pulsatility index >2 SD below the gestational age mean in addition to abnormal umbilical artery pulsatility index; 3, either peak velocity index >2 SD above the gestational age mean in the inferior vena cava and ductus venosus or pulsatile flow in the umbilical vein, or both. Nucleated red blood cells per 100 white blood cells were ascertained in a peripheral blood sample obtained within 1 hour of delivery with daily follow-up samples until the nucleated red blood cell count was <5/100 white blood cells. RESULTS: Groups 2 (median 38.5, range 1-273) and 3 (median 145, range 2-3180) had higher nucleated red blood cell counts than group 1 (median 8.5, range 1-270) (P <.05 and P <.005, respectively). The persistence of the nucleated red blood cell count elevation was also longer in groups 3 (median 4 days, range 1-19 days) and 2 (median 2. 5 days, range 1-7 days) than in group 1 (median 1 day, range 1-8 days). Neonates in group 3 also had lower platelet count, hemoglobin value, hematocrit value, and white blood cell count. The umbilical cord artery bicarbonate level was the strongest independent determinant of the peak nucleated red blood cell count and persistence of nucleated red blood cell elevation (r (2) = 0.27, P <. 001 and r (2) = 0.47, P <.0001). CONCLUSION: Increasing abnormality of arterial and venous flows in fetuses with intrauterine growth restriction is associated with increasing nucleated red blood cell count at birth. Metabolic acidemia rather than altered PO (2 ) associated with this circulatory state appears to be the main determinant of the rise in nucleated red blood cells.

Adult↗

The effects of cytocentrifugation on differential cell counts in samples obtained by bronchoalveolar lavage.

Quantification of the differential cell count and total number of cells recovered from the lower respiratory tract by bronchoalveolar lavage is a valuable technique for the diagnostic study of interstitial lung diseases. To examine the effect on the cell counts of different methods of processing the lavage fluid, two comparisons were performed. First, two methods of differential cell counting were compared using 28 fluids. One count was performed in a Malassez hemocytometer after incubation of the living cells with neutral red for five minutes at room temperature; large cells and some small cells that had incorporated neutral red were identified as macrophages. Another count was performed on cytocentrifuge preparations made using the Shandon Cytospin I and Cytospin II and stained by the May-Grünwald-Giemsa method. The percentage of cells identified as lymphocytes was significantly lower on the cytocentrifuge preparations than with the Malassez hemocytometer. In the second study, the differential cell counts on smears prepared by the two types of cytocentrifuge (Cytospin I and Cytospin II) were compared for 32 bronchoalveolar lavage fluids. The percentage of small cells (especially lymphocytes) was lower on preparations made with the Cytospin I than on those made with the Cytospin II, but the difference was not significant. The results indicate that (1) cytocentrifugation of bronchoalveolar lavage fluids does result in a significant loss of small cells, especially lymphocytes, and (2) this loss is not significantly lessened by the use of the Cytospin II.

Bronchoalveolar Lavage Fluid↗

Blasts in CSF with a normal cell count do not justify alteration of therapy for acute lymphoblastic leukemia in remission: a Childrens Cancer Group study.

PURPOSE: The Childrens Cancer Group (CCG) requires both a CSF WBC count of more than five cells per microliter and demonstration of blast cells in the cytocentrifuge specimen to support a diagnosis of CNS relapse. We reviewed the CSF examinations of patients with intermediate-risk acute lymphoblastic leukemia (ALL) to determine the clinical significance of blast cells reported in the cytocentrifuge when the total CSF cell count was normal. PATIENTS AND METHODS: Children treated on CCG-105 for ALL had CSF examinations every 12 weeks during maintenance therapy. The outcome of children who had a positive CSF cytocentrifuge examination without an elevated CSF WBC count was compared with that of children who did not have any CSF blast cells observed. RESULTS: Sixty-four patients had 81 CSF examinations with blast cells and a normal cell count. By Cox life-table regression analysis, patients with blasts had a different disease-free survival (DFS) distribution, with relapses tending to occur earlier (P = .008). However, the DFS for these patients was 63% +/- 9.6% at 5 years from the time of the abnormal cytocentrifuge result as compared with 69% +/- 1.5% for 1,490 children who did not have blasts in their CSF. This difference is not significant. CONCLUSION: Blast cells were infrequently identified in cytocentrifuge preparations of CSF when the cell count was normal. The majority of patients in whom such an event was observed have not experienced a subsequent relapse as measured by life-table analysis at 5 years. The data do not justify changing or augmenting therapy based on cytocentrifuge results alone.

Adolescent↗

Somatic cell counts in relation to infection status of the goat udder.

Bacteriological analyses, cell counts using the Fossomatic method and California Mastitis Test were performed on 1523 goat milk samples taken aseptically at monthly intervals throughout lactation from three goat herds. Of the goat udders, 81.4% were infected, minor pathogens being the most frequent isolates (65.7%). Differences in the level of infection by minor pathogens were found between herds. Cell counts were influenced by stage of lactation and intramammary infection. Cell counts greater than 10(6) cells/ml were found in 80% of milk samples infected by major pathogens and in 45% infected by minor pathogens. About 81% of udders infected with major pathogens gave California Mastitis Test scores of 2 and 3, compared with 20% for uninfected goats. A high proportion (65%) of udders infected with minor pathogens also produced scores of 2 and 3. A significant positive correlation was found between the California Mastitis Test and cell counts. The use of cell counts for the detection of abnormal goat milk is discussed.

Animals↗

Increase and plateau of CD4 T-cell counts in the 3(1/2) years after initiation of potent antiretroviral therapy.

We evaluated CD4 cell counts over a 3(1/2) year period following the initiation of potent antiretroviral therapy (ART) in the Multicenter AIDS Cohort Study. The study population included 314 HIV-infected gay men who provided CD4 cell counts for at least 2 years after the initiation of potent ART. Trends in CD4 cell counts and plasma HIV-RNA were analyzed by regression methods that incorporated the statistical dependencies of outcomes measured over time within individuals. Regardless of CD4 cell count at initiation of potent ART, CD4 cell counts increased significantly (p <.05) in the first 2 years after initiation. However, between 2 and 3(1/2) years after initiation, these counts neither increased nor decreased. The pattern of the proportion with plasma HIV-RNA <400 copies/ml was similar to CD4 cell count (i.e., increased significantly after initiation and plateau in the subsequent 1(1/2) years). The single most important predictor of the steady state CD4 cell count that was maintained between 2 and 3(1/2) years after initiation was the change in plasma HIV-RNA in the first year after initiation of potent ART.

Anti-HIV Agents↗

[Densitometry and fetal superficial cell count in the amniotic fluid for the determination of fetal lung maturity].

It was shown that a spectrophotometric investigation of the amniotic fluid for the determination of fetal lung maturity can be achieved with a photometer of the wave length 644 nm (CD) and 623 nm (HG) in conjunction with a count of superficial cells. In a small number of investigations the combination of spectrophotometry and fetal cell count is a sufficiently accurate method to determine fetal lung maturity.

Amniotic Fluid↗

The prognostic importance of changes in CD4+ cell count and HIV-1 RNA level in women after initiating highly active antiretroviral therapy.

BACKGROUND: The prognostic value of CD4+ cell counts and HIV-1 RNA levels attained after the initiation of highly active antiretroviral therapy (HAART) compared with before the initiation of HAART has not been well defined. OBJECTIVE: To determine the prognostic value for clinical outcomes of CD4+ cell counts and HIV-1 RNA levels attained after initiating therapy. DESIGN: Prospective cohort study. SETTING: Women's Interagency HIV Study. PATIENTS: 1132 participants in the Women's Interagency HIV Study. MEASUREMENTS: HIV-1 RNA level, CD+ cell counts, AIDS-defining illness, and death. RESULTS: In multivariate analyses with a median follow-up of 3.9 years, women with CD4+ cell counts of less than 0.200 x 10(9) cells/L compared with women with CD4+ cell counts of greater than 0.350 x 10(9) cells/L after HAART initiation had a relative hazard of death from all causes of 2.66 (95% CI, 1.42 to 4.99) and a relative hazard of death from AIDS of 47.61 (CI, 5.69 to 398.40). The relative hazard of all-cause death was 3.44 (CI, 1.67 to 7.09) in women with RNA levels of more than 10 000 copies/mL compared with women with attained RNA levels of less than 80 copies/mL. The relative hazard of AIDS-related or all-cause death did not increase for women with post-HAART CD4+ cell counts between 0.200 and 0.350 x 10(9) cells/L compared with women with CD4+ cell counts of greater than 0.350 x 10(9) cells/L. Also, the relative hazard did not increase in women with post-HAART HIV-1 RNA levels between 80 and 10 000 copies/mL compared with women with post-HAART HIV-1 RNA levels of less than 80 copies/mL. Of the laboratory markers, only the post-HAART CD4+ cell count and HIV-1 RNA level were predictive of new AIDS-defining illness. CONCLUSION: Post-HAART laboratory markers predicted death and new AIDS-defining illness. Pre-HAART CD4+ cell count and HIV-1 RNA level were not predictive of clinical outcomes if adjusted for values attained after HAART initiation, suggesting that even advanced immune suppression can be overcome with HAART that results in CD4+ cell counts of greater than 0.200 x 10(9) cells/L and RNA levels of less than 10 000 copies/mL.

Acquired Immunodeficiency Syndrome↗

Reduction in preterm delivery and neonatal mortality after the introduction of antenatal cotrimoxazole prophylaxis among HIV-infected women with low CD4 cell counts.

BACKGROUND: Cotrimoxazole prophylaxis is recommended for subgroups of human immunodeficiency virus (HIV)-infected adults and children to reduce all-cause morbidity and mortality. We investigated whether antenatal cotrimoxazole prophylaxis begun during pregnancy for HIV-infected pregnant women with low CD4 cell counts would affect birth outcomes. METHODS: Cotrimoxazole prophylaxis was introduced as a routine component of antenatal care for HIV-infected women with CD4 cell counts <200 cells/ micro L during the course of a trial of mother-to-child HIV transmission in Lusaka, Zambia. Rates of preterm delivery, low birth weight, and neonatal mortality were compared for women with low CD4 cell counts before and after its introduction. RESULTS: Among 255 women with CD4 cell counts <200 cells/ micro L, the percentage of preterm births (< or =34 weeks of gestation) was lower (odds ratio [OR], 0.49 [95% confidence interval {CI}, 0.24-0.98]) after cotrimoxazole prophylaxis was introduced than before; there was a significant decrease in neonatal mortality (9% to 0%; P=.01) and a trend toward increased birth weight ( beta =114 g [95% CI, -42 to 271 g]). In contrast, there were no significant changes in these parameters over the same time interval among women with CD4 cell counts > or =200 cells/ micro L.Conclusion. Antenatal provision of cotrimoxazole for HIV-infected pregnant women with low CD4 cell counts may have indirect benefits for neonatal health.

AIDS-Related Opportunistic Infections↗

The use of sputum cell counts to evaluate asthma medications.

Total and differential cell counts from hypertonic-induced, dithiothreitol-dispersed sputum provide reproducible measurements of airway inflammatory cell counts, which are responsive to treatment with anti-inflammatory drugs. They have helped to understand the kinetics of inflammatory cell changes in asthma after the reduction of corticosteroids and the subsequent re-introduction of treatment. They have identified that the presence of sputum eosinophilia in asthma, chronic cough and chronic airflow limitation is a predictor of steroid-responsiveness and of lack of 'asthma control'. They can be used to study the dose-response effect of inhaled corticosteroids and may be useful to establish the relative potency of different corticosteroid formulations and delivery devices. Sputum cell counts are also useful to study the potential anti-inflammatory effects of drugs like theophylline, long-acting beta-adrenoceptor agonists, leukotriene antagonists and newer drugs in development. They may be helpful to select add-on therapy to corticosteroids in 'difficult-to-control' asthma.

Adrenal Cortex Hormones↗

Somatic cell counts of ewes' milk.

The somatic cell counts of ewes' milk were determined by an electronic particle counter (Coulter Counter). Of 1408 apparently normal milk samples, 98.2% had a somatic cell count lower than 1.0 x 10(6) cells/ml and 85.8% of 254 bacteriologically positive samples had a count higher than 1.0 x 10(6) cells/ml. Values exceeding 1.0 x 10(6) cells/ml are indicative of subclinical mastitis, if samples were collected from clinically healthy mammary glands.

Animals↗

Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4+ cell count is 0.200 to 0.350 x 10(9) cells/L.

BACKGROUND: The safety of delaying highly active antiretroviral therapy (HAART) in HIV-infected patients is uncertain when the CD4+ cell count declines below 0.350 x 10(9) cells/L. OBJECTIVE: To evaluate the effect of baseline CD4+ cell count and adherence to HAART on survival rates. DESIGN: Prospective observational study. SETTING: Province-wide Canadian HIV/AIDS treatment program. PATIENTS: 1422 HIV-infected persons initiating HAART between 1 August 1996 and 31 July 2000 and followed through 31 March 2002. MEASUREMENTS: Patients were stratified by baseline CD4+ cell count and adherence level. Cumulative mortality rates were evaluated by using Kaplan-Meier methods and Cox regression-estimated adjusted relative hazards. RESULTS: Kaplan-Meier analyses showed no survival benefit of starting HAART at a CD4+ count of 0.200 x 10(9) cells/L or greater among adherent patients. Adjusted analysis showed that compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, nonadherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically elevated mortality rates (adjusted relative hazard, 2.56 [95% CI, 1.36 to 4.84]; P = 0.004). However, compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, adherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically similar mortality rates (adjusted relative hazard, 0.82 [CI, 0.45 to 1.49]; P > 0.2). CONCLUSIONS: Delaying HAART until the CD4+ cell count falls to 0.200 x 109 cells/L does not increase the mortality rate in HIV-infected patients with good medication adherence. Mortality rates increase if HAART is initiated below 0.200 x 10(9) cells/L. Also, nonadherent patients have higher mortality rates than adherent patients with similar CD4+ cell counts. Above a CD4+ cell count of 0.200 x 10(9) cells/L, medication adherence is the critical determinant of survival, not the CD4+ cell count at which HAART is begun.

Adult↗

Cell count ratio: new criterion of diagnostic peritoneal lavage for detection of hollow organ perforation.

OBJECTIVES: Diagnostic peritoneal lavage (DPL) had been widely used in evaluating patients with suspected intraperitoneal injuries due to its high sensitivity. If the positive criteria are strictly followed, however, the incidence of nontherapeutic laparotomies will be unacceptably high. This realization has become more important recently with the popularization of nonoperative treatment for blunt solid organ injuries. For these patients, the early diagnosis of an associated hollow organ perforation is mandatory. METHODS: Three hundred and twenty patients undergoing DPL over an 18-month period were retrospectively reviewed to evaluate the usefulness of "cell count ratio" in diagnosing hollow organ perforation. The cell count ratio was defined as the ratio between white blood cell count and red blood cell count in the lavage fluid divided by the ratio of the same parameters in the peripheral blood. RESULTS: Two hundred twelve patients were diagnosed as having a positive DPL according to the classic criteria. Forty-four patients (21%) had a cell count ratio of greater than or equal to 1. The diagnosis at laparotomy was small bowel perforation in 31 patients, colon perforation in eight patients, diaphragmatic hernia in one patient, pancreatic transection in two patients, and liver laceration in two patients. None of the patients with a cell count ratio of less than I sustained hollow organ perforation. The average interval from injury to DPL was 5 hours, with the shortest being 1.5 hours. CONCLUSION: A cell count ratio of greater than or equal to 1 predicted hollow organ perforation with a specificity of 97% and a sensitivity of 100%. The selective use of the cell count ratio has improved the probability of early diagnosis of bowel perforation without increasing the cost of care. Nonoperative management can be applied more confidently to those patients sustaining a blunt solid viscus injury of the abdomen if the cell count ratio is low. We conclude that the cell count ratio of DPL effluent is a very sensitive and specific indicator of hollow organ perforation. In the treatment of blunt abdominal injuries, if the cell count ratio is positive, nonoperative treatment should be abandoned and a laparotomy undertaken.

Abdominal Injuries↗

The impact of cirrhosis on CD4+ T cell counts in HIV-seronegative patients.

BACKGROUND: Studies of the progression liver fibrosis in human immunodeficiency virus (HIV) and hepatitis C virus-coinfected patients suggest that cirrhosis is associated with immunosuppression, as measured by low absolute CD4(+) T cell counts. However, we hypothesized that, in patients with advanced liver disease, low CD4(+) T cell counts may occur secondary to portal hypertension and splenic sequestration, regardless of the presence or absence of HIV infection. METHODS: Sixty HIV-seronegative outpatients with cirrhosis were enrolled during the period 2001-2003 in a prospective, cross-sectional study of the association between liver disease and CD4(+) T cell counts and percentages. Demographic characteristics, liver disease-related characteristics, and laboratory results--including CD4(+) T cell parameters--were collected. RESULTS: A total of 39 patients (65%) had a low CD4(+) T cell count; 26 patients (43%) and 4 patients (7%) had CD4(+) T cell counts <350 and <200 cells/mm(3), respectively. Abnormal CD4(+) T cell counts were associated with splenomegaly (P=.03), thrombocytopenia (P=.002), and leukopenia (P<.001). The percentage of CD4(+) T cells was normal in 95% of patients who had a low absolute CD4(+) T cell count. CD4(+) T cell counts were significantly lower among cirrhotic patients than among 7638 HIV-seronegative historic control subjects without liver disease. CONCLUSIONS: Cirrhosis is associated with low CD4(+) T cell counts in the absence of HIV infection. Discordance between low absolute CD4(+) T cell counts and normal CD4(+) T cell percentages may be attributable to portal hypertension and splenic sequestration. Our findings have significant implications for the use and interpretation of absolute CD4(+) T cell counts in HIV-infected patients with advanced liver disease.

Adult↗