Total White Blood Count Research Articles

Severe Combined Immunodeficiency Signalized by Eosinophilia and Lymphopenia in Rotavirus Infected Infants

Severe combined immunodeficiency (SCID) is a heterogeneous disease consisting of several different subtypes. Most subtypes present during infancy and without treatment, infections usually lead to early death. Diagnosis of SCID can be difficult as new subtypes are expected to be discovered soon. Late diagnosis is associated with a poorer outcome. Infections like rotavirus enteritis cannot be cleared in children with SCID due to impaired immunity. The aim of our study was to identify clues in children with rotavirus enteritis that aid to diagnose SCID early. Total white blood counts in a cohort of SCID patients with persistent rotavirus infection at diagnosis (n=18) were compared to total white blood counts in matched control patients without SCID but with rotavirus infection. Relative and absolute lymphopenia and eosinophilia were more common in SCID patients (p<0.005). In infants with rotavirus infection, a full blood count should be performed: Eosinophilia and/or lymphopenia raise a high suspicion of SCID.

Clinical and laboratory features of disseminated histoplasmosis in HIV patients from Brazil

To identify the main clinical and laboratory features of disseminated histoplasmosis (DH) in human immunodeficiency virus (HIV) patients and compare them with those of HIV patients with other opportunistic diseases. Retrospective study of HIV patients comparing the clinical and laboratory data of patients with and without DH. Univariate and multivariate analyses were performed to verify the risk factors related to DH. In total, 378 HIV patients were included, 164 with DH and 214 with other opportunistic diseases. Acute renal failure, respiratory insufficiency and septic shock were more frequent in DH patients, who also had a higher mortality (32%vs. 14%, P < 0.001). Independent risk factors for DH were: acute renal failure [odds ratio (OR) 5.2; 95% confidence interval (CI) 3.2-8.5; P < 0.001], splenomegaly (OR 3.4; 95% CI 1.19-9.9; P < 0.001), respiratory insufficiency (OR 2.7 95% CI 1.5-5.0; P < 0.001), proteinuria (OR 2.7; 95% CI 1.3-5.2; P = 0.03), hypotension (OR 2.5; 95% CI 1.2-5.0; P = 0.008), hepatomegaly (OR 2.4; 95% CI 1.2-4.8; P = 0.01), cutaneous lesions (OR, 1.9; 95% CI 1.0-3.3; P = 0.02) and weight loss (OR 1.8; 95% CI 1.0-3.1; P = 0.03). Our results suggest that DH is a severe opportunistic disease with high mortality rate, which should be promptly recognized in order to provide early specific treatment.

Rheumatoid arthritis, periodontal disease and coronary artery disease

Rheumatoid arthritis (RA), periodontal disease (PD), and coronary artery disease (CAD) are common chronic inflammatory diseases. RA is associated with accelerated vascular risk resulting in an increased prevalence of CAD with attendant early mortality and excess morbidity. RA and PD have a common pathobiology. Accordingly, the aim of this study was to evaluate the association between RA, PD, and CAD and the influence of systemic inflammatory factors. A total of 100 active RA patients of which 50 had established CAD and 50 had no CAD were assessed for PD. All subjects underwent a clinical, cardiac, dental, laboratory, and radiological evaluation. Blood samples were obtained, and the level of high sensitivity C-reactive protein (hs-CRP), total white blood counts (WBC), erythrocyte sedimentation rate (ESR), fibrinogen and tumor necrosis factor (TNF) alpha, total cholesterol (TC), and high density lipoprotein (HDL) were assayed. The findings of this study demonstrated an association between RA, PD, and CAD. The RA patients with CAD had significantly more PD than RA patients without CAD. The inflammatory markers, hsCRP, ESR, WBC, fibrinogen, and TNF-alpha, were raised in all patients but were significantly higher in RA patients with CAD who also had PD. HDL levels were lower in RA patients with CAD when compared to RA patients without CAD. Evidence from this study shows an association between RA, PD, CAD, and systemic levels of the inflammatory mediators. The implication is that inflammation may be the central link between the chronic inflammatory, autoimmune disorders, and atherosclerosis.

Chronic Inflammatory Autoimmune Disorders and Atherosclerosis

Rheumatoid arthritis (RA), periodontal disease (PD), and coronary artery disease (CAD) are common chronic inflammatory diseases. RA is associated with accelerated vascular risk resulting in an increased prevalence of CAD with attendant early mortality and excess morbidity. RA and PD have a common pathobiology. Accordingly, the aim of this study was to evaluate the association between RA, PD, and CAD and the influence of systemic inflammatory factors. A total of 100 active RA patients of which 50 had established CAD and 50 had no CAD were assessed for PD. All subjects underwent a clinical, cardiac, dental, laboratory, and radiological evaluation. Blood samples were obtained and the level of high-sensitivity C-reactive protein (hs-CRP), total white blood counts (WBC), erythrocyte sedimentation rate (ESR), fibrinogen and tumor necrosis alpha (TNF-alpha), total cholesterol (TC), and high-density lipoprotein (HDL) were assayed. The findings of this study demonstrated an association between RA, PD, and CAD. The RA patients with CAD had significantly more PD than RA patients without CAD, P < 0.001. The inflammatory markers hs-CRP, ESR, WBC, fibrinogen, and TNF-alpha were raised in all patients but were significantly higher in RA patients with CAD who also had PD, that is, in those with more inflammatory disease burden. HDL levels were lower in RA patients with CAD when compared to RA patients without CAD, P < 0.005. Evidence from this study shows an association between RA, PD, CAD, and systemic levels of the inflammatory mediators. The implication is that inflammation may be the central link between the chronic inflammatory autoimmune disorders and atherosclerosis.

Low-dose Metronomic Combined with Intermittent Bolus-dose Cyclophosphamide Is an Effective Long-term Chemotherapy Treatment Strategy

Metronomic chemotherapy refers to the close, regular administration of comparatively low doses of cytotoxic drugs, with minimal or no drug-free breaks, over prolonged periods. It is thought to have an antiangiogenic basis. However, whereas surprisingly durable and potent tumor responses have been observed in a number of preclinical tumor models, relapses usually eventually occur using this type of treatment strategy. We therefore decided to test modified metronomic chemotherapy regimens that might significantly delay such relapses, but still maintain modest and acceptable toxicity profiles. Here, we show that repeated administration of bolus doses (BDs) of cyclophosphamide every 3 or 6 weeks, combined with a daily oral low-dose metronomic (LDM) regimen (20 mg/kg/d cyclophosphamide), improves efficacy and significantly delays progression of transplanted PC-3 human prostate cancer xenografts, syngeneic transplanted EMT-6 breast tumors, and "spontaneous" murine erythroleukemia. Efficacy was superior whereas toxicity was mild and comparable to the LDM regimen, the latter assessed by body weight, neutrophil, lymphocyte, and total white blood counts. Antiangiogenic activity, measured by reduction in circulating endothelial precursor cells, revealed that the greatest degree of suppression occurred using the combination treatment. Overall, our results indicate that the administration of intermittent BD combined with chronic oral LDM cyclophosphamide is a potent treatment regimen for controlling tumor growth, which has a low toxicity profile, over prolonged periods of time.

Genetic Modeling of Chemical Antagonists: Genome Scale Validation of Hematopoietic Disease Drug Targets by In Vivo Functional Analysis.

Clinical management remains elusive for a large number of patients with hematological and other disorders necessitating the development of new, more effective pharmaceutical agents. While the sequencing of the human genome has provided a list of all drug targets that will ever exist, in order to improve the speed and cost of drug development there is a critical need to identify the small subset of these targets whose modulation will lead to therapeutic outcomes. As a genetic model of a perfectly selective and potent chemical antagonist, the analysis of the phenotypes of knockout mice allows one to predict the mechanism based efficacy and side effect profile of modulators of a particular target in a physiologic mammalian setting without having to first develop a candidate drug with which to validate the target. The power of this approach has been demonstrated by studies examining the targets of the best-selling drugs and current pharmaceutical pipelines. These analyses have confirmed a strong (~85%) correlation between the target's knockout phenotype and the efficacy and/or side effects of drugs that modulate them. We have implemented this target validation approach by developing systems and infrastructure to generate and comprehensively phenotype mutant mice at a rate of more than fifteen novel lines per week. The battery of tests encompassed by our analysis have been specifically selected to reveal those genes that encode key control points in mammalian physiology whose modulation may be used to treat major disease processes including hematologic disorders. Tests to detect hematologic phenotypes include complete blood count; immunophenotyping; blood chemistry; analysis of soluble factors (immunoglobulins, cytokines and inflammatory mediators); full histopathologic examination, and various in vivo and in vitro immune challenge and cell activation assays. In addition, selected lines are subjected to more extensive analyses including additional challenge assays, gene expression profiling, and bone marrow transplantation. Data will be presented describing one of the lines analyzed in this screen, the Abl2 knockout, which has an increased mean total white blood count relative to wild-type littermates, as well as smaller body size (decreased length and weight). In parallel with the identification of therapeutically relevant proteins, we are actively exploring pharmacologic methods, both with small molecules and therapeutic antibodies, to modify the function of these novel gene targets, and ultimately to treat human disease.

Sealing effect of fibrin glue on the healing of gastrointestinal anastomoses: implications for the endoscopic treatment of leaks

The adoption of advanced laparoscopic techniques for complex surgical procedures has raised the concern that the leak rate might be higher than for open surgery, particularly in the surgeon's early experience or in difficult cases. In this study, the sealing effect of fibrin glue on leaking gastrointestinal anastomoses was evaluated in an experimental swine model. A standardized gastrojejunostomy was performed on 20 female pigs (mean weight, 47.7 +/- 5.7 kg). A leak was created on the anterior surface of the anastomosis. The animals were randomized to either fibrin glue or no treatment of the leak. Clinical conditions and vital signs, including body temperature, heart rate and, respiratory rate, were collected three times a day. Preoperative and postoperative complete and differential blood count and lactate dehydrogenase levels were determined. Postmortem analysis was performed when the animals were killed. Clinical signs of peritonitis developed in the control animals by the second or third postoperative day. Findings that confirmed the presence of an anastomotic leak at the postmortem examination were the presence of food or gastrojejunal juices in the abdominal cavity, a localized abscess, or a positive air leak test. Fibrin glue treatment prevented the development of peritonitis in all the animals. Complete sealing of the leak was observed on postoperative day 7 in all treated animals, except one in which an asymptomatic contained leak developed. The postoperative total white blood count was significantly increased in the untreated group (24.69 +/- 5.5 vs 12.74 +/- 3.7 10(3)/ul p < 0.001, paired t-test), as compared with the treated group (15. 55 +/- 2.4 vs 14.89 +/- 2.7 10(3)/ul; p = 0.24). In this study, fibrin glue showed reproducible sealing effects on leaking gastrojejunal anastomoses. Fibrin glue application may be a valuable approach for the treatment of gastrointestinal anastomotic leaks.

CD4T Lymphocyte subsets and disease manifestation in children with and without HIV born to HIV-1 infected mothers

To understand the natural history of HIV-1 infection in children in terms of evolution of childhood clinical manifestations versus the immune status, we prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 for two years between March 1998 and March 2000. A prospective cohort study. An institutional children's home. Fifty nine children (26 males and 33 females) with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 and adopted in institutional children home. HIV-1 status of children under nine months was confirmed by polymerase chain reaction(PCR). ELISA for HIV-1 antibody in serum/plasma was used to confirm HIV-infection status for children aged < or = 18 months. Children were visited every three months between March and June 2000. At every visit blood was collected for total white cell count, haemoglobin and CD4+ and CD8+ T cell counts. The institutional doctor routinely examined children and treated all ailments. Clinical data were recorded. HIV-DNA, anti-HIV antibodies, total white blood count, total T cell counts, CD4 and CD8 T cell subset counts, frequency of childhood manifestations of infection. The children were aged between 4.5 and 13 years. The baseline haematological and immunological profiles (mean, mode) were: HIV-1 sero-converters (WBC 7151,7150; HB 11.6, 12.0; CD4+ 686, 795; CD8+ 2168, 1507) and HIV-1 de-seroconverters (mean, mode) were: (WBC 8386, 7150; HB 11.7, 12.8; CD4+ 735, 795; CD8+ 2168, 1507). The commonest causes of illnesses among the HIV-1 children were URTI (85.3%), TB(56.1 %), pneumonia (56.2%), tonsillitis (34.1%), parotiditis (28%) and acute otitis media (25%). The distribution of clinical manifestations was similar between the two categories of children, except URTI, whose prevalence was significantly increased among HIV-1 infected children (p-value=0.006). Among the HIV-1 infected children, only TB, parotiditis, and acute otitis media (AOM) were significantly associated with decreased CD4+ T cell count (p<0.05) resulting from HIV infection. HIV infection in children predisposes them to common childhood infections that can be used as markers of immune decline. TB, AOM, URTI may be early indicators of suspicion that would enable selective screening for HIV infection in children.

Coexisting Neurofibromatosis-II And Sarcoidosis: A Case Report

We report about a young woman who had various biopsies in the cervical region because of cervical swelling. Histology showed neurofibromas as well as sarcoidosis. MRI revealed bilateral schwannoma. CASE REPORT We report about a 30-year-old woman who had burning pain in the cervical region. There were enlarged and tender lymph nodes especially in the submandibular angle bilaterally. The patient had a history of prior lung sarcoidosis two years ago which was successfully treated with steroids. This time chest-CT showed no pathological changes. The total white blood count was in normal range (6150/ L) but showed increased neutrophiles (4630/ L), increased monocytes (590/ L), decreased lymphocytes (1060/ L) and decreased eosinophiles. Red blood count and platelets were in normal range. Serum ACE was slightly elevated (56 IU/L). Blood chemistry showed low total iron of 33/ g. Three specimens, which were clinically suspected to be lymph nodes (two from the neck and one from the upper arm) were taken. The Histology showed Schwannomma with no signs of malignancy and no signs of sarcoidosis (fig.2). However, histology of submandibular lymph nodes a few months before showed typical histomorphology of sarcoid granulomas (figure 1). Figure 1 Figure 1: Non necrotizing granuloma formation in Sarcoidosis (hemotoxylin-eosin stain) Coexisting Neurofibromatosis-II And Sarcoidosis: A Case Report 2 of 3 Figure 2 Figure 2: Palisading of fibroblast like cells in Schwannoma (hemotoxylin-eosin stain) On MRI the patient had bilateral lymph node enlargement (figure 4) and bilateral Schwannoma (dumbell-tumor) of the nerve roots C7 (figure 3 arrow). Figure 3 Figure 3: CM-enhanced coronal T1w image shows bilateral Schwannoma with slight contrast enhancement at the level of C7 Figure 4 Figure 4: CM-enhanced and fatsaturated axial T1w image shows bilateral lymph node enlargement of sarcoidosis DISCUSSION Bilateral Schwannoma is one of the typical features of NF-2 [1]. In addition the patient had sparse manifestations of cutaneous neurofibromas. Other typical signs of Neurofibromatosis-2 such as acoustic schwannomas, meningeomas or other intracranial tumours (especially schwannomas of the cranial nerves) were rouled out by MRI. Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin. Theprevalence of sarcoidosis in Europe is 19/100,000 and involvement of lymph nodes is common (75-90%) [2]. To our knowledge coincidence of NF-2 and sarcoidosis has not been described yet (Medline search).

The influence of stress from transport and handling on hematologic and clinical chemistry blood parameters of racing pigeons (Columba livia domestica).

In the present study, the influence of stress from handling and transport on some frequently examined blood parameters of racing pigeons was evaluated. After 3 hr, there was a highly significant (P < 0.01) increase in the number as well as in the percentage of heterophils and decrease of lymphocytes. In clinical chemistries, increases of creatine kinase and glucose and a decrease of uric acid were observed. There was a mean decrease of the total white blood count of >15% that was less significant (P < 0.05). Changes in lactate dehydrogenase, basophils, and monocytes did not prove to be significant; eosinophils, aspartate aminotransferase, total protein, and the packed cell volume were not influenced by stress.

EFFECTS OF 6 MONTHS OF MODERATE AEROBIC EXERCISE TRAINING ON IMMUNE FUNCTION IN THE ELDERLY

The purpose of this study was to determine the effects of 6 months of moderate aerobic exercise on age-dysregulated measures of T lymphocyte and natural killer (NK) cell number and function. Previously sedentary elderly (age = 65 +/- 0.8 years) subjects were randomly assigned to supervised 3 time/week exercise intervention group (EXC, n = 14) or flexibility/toning control group (FT-CON, n = 15). Fasting resting blood samples were drawn prior to and after the 6 month intervention. The EXC group exhibited a significant (P < 0.05) 20% increase in VO2 max, whereas the FT-CON group had a smaller non-significant (P = 0.07) increase (9%). Immune results revealed that, in general, changes in immune function in response to 6 months of exercise training at an average intensity of 52% heart rate reserve (HRR) were similar when compared to FT-CON who exercised at approximately 21% HRR. There were no intervention-induced changes in total white blood cell, neutrophil, lymphocyte, monocyte, eosinophil, or basophil blood counts. Furthermore, the percentage and number of CD3+, CD4+ and CD8+ T cells in the blood remained unchanged. There was a tendency for the percentage and number of CD4+ and CD8+ naive cells (CD45RA+) to increase and for CD4+ memory cells (CD45RO+) to decrease post-intervention, especially in FT-CON. Both groups exhibited a small intervention-induced increase in the T-cell proliferative response to mitogenic stimulation: the percentage change of which was higher in the EXC group at several doses of Con A. Unstimulated NK cell cytolysis versus K562 cells tended to increase (P < 0.1) in the EXC group with little change in FT-CON. We conclude that 6 months of supervised exercise training can lead to nominal increases in some measures of immune function, while not affecting others, in previously sedentary elderly.

Successful Validation of the Palliative Prognostic Score in Terminally Ill Cancer Patients

The aim of this work was to validate a previously constructed prognostic score for terminally ill cancer patients in order to determine its value in clinical practice. The Palliative Prognostic Score (PaP Score) was tested on a population of 451 evaluable patients consecutively entered in the hospice programs of 14 Italian Palliative Care Centers. The score subdivided patients into three specific risk classes based on the following six predictive factors of death: dyspnea, anorexia, Karnofsky Performance Status (KPS), Clinical Prediction of Survival (CPS), total white blood count (WBC), and lymphocyte percentage. The performance of the PaP Score index in the training and testing sets was evaluated by comparing mortality rates in the 3 prognostic risk categories. The score was able to subdivide the validation-independent case series into three risk groups. Median survival was 76 days in group A (with a 86.6% probability of 30-day survival), 32 days in group B (with a 51.6% probability of 30-day survival), and 14 days in group C (with a 16.9% probability of 30-day survival). Survival medians were remarkably similar to those of the training set (64 days in group A, 32 days in group B, and 11 days in group C). In the complex process of staging terminally ill patients, the PaP Score is a simple instrument which permits a more accurate quantification of expected survival. It has been validated on an independent case series and is thus suitable for use in clinical practice.

A New Palliative Prognostic Score: A First Step for the Staging of Terminally Ill Cancer Patients

In recent years, extensive research has been performed to identify prognostic factors that predict survival in terminally ill cancer patients. This study describes the construction of a simple prognostic score based on factors identified in a prospective multicenter study of 519 patients with a median survival of 32 days. An exponential multiple regression model was adopted to evaluate the joint effect of some clinico-biological variables on survival. From an initial model containing 36 variables, a final parsimonious model was obtained by means of a backward selection procedure. The Palliative Prognostic Score (PaP Score) is based on the final model and includes the following variables: Clinical Prediction of Survival (CPS), Karnofsky Performance Status (KPS), anorexia, dyspnea, total white blood count (WBC) and lymphocyte percentage. A numerical score was given to each variable, based on the relative weight of the independent prognostic significance shown by each single category in the multivariate analysis. The sum of the single scores gives the overall PaP Score for each patient and was used to subdivide the study population into three groups, each with a different probability of survival at 30 days: (1) group A: probability of survival at 30 days >70%, with patient score ≤5.5; (2) group B: probability of survival at 30 days 30–70%, with patient score 5.6–11.0; and (3) group C: probability of survival at 30 days <30%, with patient score >11.0. Using this method, 178/519 (34.3%) patients were classified in risk group A, 205 (39.5%) patients were in risk group B, and 136 (26.2%) patients were in risk group C. The patients classified in the three risk groups had a very different survival experience (logrank = 294.8, P < 0.001), with a median survival of 64 days for group A, 32 days for group B, and 11 days for group C. The PaP Score based on simple clinical and biohumoral variables proved to be statistically significant in a multivariate analysis. The score is valid in this population (training set). An independent validation on another patient series (testing set) is required and is the object of a companion paper. J. Pain Symptom Manage 1999;17:231–239.

Use of Erythropoietin in Stable Preterm Infants (1000-1500 grams) to Reduce Erythrocyte Transfusions † 1374

Objective: Earlier studies have shown that erythropoietin (Epo) is beneficial in reducing erythrocyte transfusions given for symptomatic anemia among very low birth weight infants. The objective of this study was to determine if blood transfusions could be reduced using erythropoietin among stable preterm infants who are still at risk of donor blood exposure.Methods: A randomized, non-placebo controlled clinical trial was conducted on 28 preterm infants with birth weights ranging from 1000 to 1500 grams. Inclusion criteria also included being appropriately sized for gestational age and having an hematocrit ≥30% at study entry. Study infants were randomly assigned to receive Epo, 300 units/kg/day 3 times a week subcutaneously (n=13) or no treatment (n=15) starting at less than 2 weeks of age for 6 weeks. Criteria for transfusion was set by a standard protocol for both the treatment group and controls. Infants in both groups were supplemented with iron (Fer-In-Sol 0.3ml/day) beginning at 2 weeks of age. The dose of Fer-In-Sol was increased weekly by 0.3ml/day if serum ferritin level was noted to be less than 65.0ng/ml. The primary outcome variable was the total number and volume of transfusions given per group during the entire hospitalization. Results: Two infants required transfusions among the 13 Epo treated infants compared to 9 infants among the 15 control infants(p=0.02). The total number of transfusions given was 2 in the Epo group versus 18 in the controls (89% reduction, p=0.01). The total volume of transfusions given to the Epo group was 39 ml compared to 487 ml in the control group (92% reduction, p=0.007). We found no differences in the total white blood count, neutrophil count, platelet count, incidence of sepsis, necrotizing enterocolitis, seizures and hypertension between the groups. The mean hematocrit for the Epo group at 2 weeks into the study was 34.5±2.8 compared to 29.2±4.7 among controls (p=0.003). The mean hematocrit values at other study periods could not be meaningfully analysed because of transfusions given to control infants. Conclusions: These data suggest that use of Epo in stable preterm infants with birth weights of 1000 to 1500 grams is an effective means of reducing the need for transfusions.

Do worker's chronically exposed to lead have leukocytosis?

In the following study, we examined the possible relationship between acute and chronic measures of lead exposure and total white cell blood counts in 94 workers in a lead-battery plant who were followed-up from 1980 to 1993. Acute measures of lead exposure included blood lead (PbB), and zinc protoporphyrin levels (ZPP) measured concomitantly with the total white blood count, and a measure of chronic exposure was represented by average blood lead levels over the follow-up period. Of the 947 white blood cell counts, leukocytosis was found in 92 (9.7%), but there was no higher proportion of leukocytosis in the groups with higher PbB or ZPP results. Of those where a smoking history was recorded, none of the 188 non-smokers had leukocytosis, compared to 78 of 590 smokers (0 vs. 13.2%, respectively, P < 0.05). The white count was not significantly correlated with ZPP, PbB or the average PbB of the workers. We conclude that lead exposure does not influence the white blood cell count in battery workers, and that the cause of an elevated white count in such worker's is probably due entirely to a history of smoking. Further studies are warranted to substantiate our findings.

Haemolytic uraemic syndrome complicated by disseminated extraneural cryptococcosis.

Case report (Dr R F Miller) A 33 year unemployed white man was admitted to hospital in January 1994 complaining of a 1 week history of diarrhoea, passing up to...

HIV infection in women

To describe the influence of pregnancy on immunological marker paths and progression of HIV-infected women. Analysis of prospectively collected immunological and clinical data collected on 145 women reviewed at the City Hospital, Edinburgh, between 1985 and 1992 using a two-level random-effects model that allows for within- and between-patient variance. There were differences between the marker paths of women according to risk activity; women who had acquired HIV via injecting drug use (in addition to heterosexual intercourse) had a higher level of absolute CD4 cells, CD4% and total lymphocytes at seroconversion than those who had acquired HIV via heterosexual intercourse alone; however, immunological markers declined more steeply after seroconversion. There was no evidence that pregnancy, either before or after HIV seroconversion had an adverse effect on marker paths of HIV disease. There was a significant association between pregnancy after HIV seroconversion and post-pregnancy changes in immunological markers: an increase in the CD4% and a decrease in CD8%. However, causality cannot be implied as pregnancy itself may be associated with considerable lifestyle changes. During pregnancy the total white blood count rose due to an increase in the number of granulocytes, whereas the total lymphocyte numbers fell. The absolute CD4 lymphocyte subset counts fell progressively but the effect was due to the fall in the total lymphocyte counts, there being no influence of pregnancy on either CD4% or CD8%. In asymptomatic HIV infection, changes in the absolute levels of CD4 and CD8 lymphocyte counts are primarily related to changes in the other components of the white cell count because there were no changes in CD4% and CD8%. Pregnancy itself has no adverse effect on immunological markers of HIV.

Anti-CD4 monoclonal antibody treatment combined with total lymphoid irradiation and cyclosporin A in hamster-to-rat cardiac transplantation: Analysis of lymphocyte subsets and anti-donor xenoantibodies

Combined treatment with total lymphoid irradiation and cyclosporin A results in prolonged graft survival in concordant xenogeneic cardiac transplantation, but reproducible long-term graft acceptance has proved to be difficult. Anti-CD4 monoclonal antibody treatment has been successful in inhibiting heart graft rejection in allogeneic models. Used as monotherapy in a concordant xenogeneic model for pancreatic islet transplantation, prolonged graft survival has been reported; however, no beneficial effect on primarily vascularized heart grafts was noted. The object of this investigation was to combine these treatment strategies with respect to reproducible long-term hamster heart graft survival in rats, to monitor the effect on lymphocyte subpopulations, and to determine possible anti-donor antibody formation correlated to time of rejection. Graft survival after combined preoperative total lymphoid irradiation and postoperative cyclosporin A + anti-CD4 monoclonal antibody treatment was prolonged from 14 to > 100 days (compared to spontaneous graft survival of three to four days), with long-term graft function in four of 19 recipients. Total white blood counts in the postoperative course were characterized by an unproportional increase of Ig+ cells and an incomplete recovery of CD4+ cells. Flow-cytometric analysis of anti-donor antibodies showed low levels of performed antibodies and increasing amounts of strain-, but not donor-specific antibodies, correlated to the time of rejection. Long-term survivors with functioning grafts at the time of sacrifice had an initially moderate antibody increase with subsequent decrease to baseline levels. Our results indicate that total lymphoid irradiation combined with cyclosporin A and anti-CD4 monoclonal antibodies can prolong graft survival significantly in concordant hamster-to-rat cardiac xenotransplantation. Graft rejection seems to be of a delayed antibody-mediated type, where the inhibition of T cell help for antibody formation may play a significant role.

Endocarditis in the 80s in a General Hospital in Auckland, New Zealand

The clinical and investigative features of 102 episodes of infective endocarditis were analysed retrospectively. The most frequent presenting symptoms (malaise, fever, sweats, myalgia, weight loss) were non-specific. Fever, cardiac murmur, tachycardia, vascular phenomena and a change in mental state were the most common physical signs at admission. Anaemia was present in half the episodes and renal and liver dysfunction in about one-third. Streptococci (61) and staphylococci (31) were the causative organisms in all but 10 episodes. The commonest predisposing factors were underlying cardiac disease (52 per cent) and a preceding focus of infection (14.6 per cent). Left ventricular failure (33 per cent) and focal neurological disease (29 per cent) occurred frequently. Valvular surgery was performed in 20 episodes, with two in-hospital deaths. Overall hospital mortality was 27.5 per cent and death was most commonly neurological (11/28). A higher mortality was associated with elevated total white blood count, microscopic haematuria, renal or liver dysfunction at admission, S. aureus endocarditis, the development of left ventricular failure or focal neurological disease, age greater than or equal to 60 years and persistence of fever after one week of antibiotic therapy. The absence of both renal dysfunction at admission and subsequent microscopic haematuria identified a group with a very low hospital mortality (4.7 per cent). The three-year mortality of the entire group was 43.5 per cent.

Quantitative buffy coat analysis in haematological patients compared to standard laboratory methods

We have tested a Quantitative Buffy Coat (QBC) instrument (Becton Dickinson, USA), and compared results obtained with this instrument to results obtained with standard methods in a haematology clinic. The basic principle of the method is a classical haematocrit centrifuge. The analysis provides a haematocrit value, platelet count, a total white blood count, and separates the white blood cells in granulocytes and mononuclear cells (lymphocytes plus monocytes). The instrument is easy to use but requires a trained observer. All results are available in 15 min. We have found the accuracy of the method good for all parameters. The precision of the instrument is good but for estimation of granulocytes and lymphocytes plus monocytes we did not find the high sensitivity claimed by the manufacturer (manufacturer's lower limit 0.02 x 10(9)/l; standard deviation for low levels of granulocytes: 0.300 x 10(9)/l and lymphocytes plus monocytes: 0.235 x 10(9)/l). A large fraction of samples (leukocytes 27%, platelets 40%) from a haematological clinic falls beyond the limits for reliable results set by the manufacturer, which reduces the utility of the instrument in such patients. Furthermore, in 21% and 10% of samples within the recommended range for leukocytes and platelets, respectively, QBC results could not be read owing to ill-defined boundaries. For granulocytes and lymphocytes plus monocytes 25% and 34% of the samples, respectively, could not be read owing to ill-defined boundaries. The instrument is not constructed to protect against blood contamination of the centrifuge and, therefore, the safety of the instrument is not satisfactory.