Lower White Cell Count Research Articles

Immunological evaluation of four arc welders exposed to fumes from ignited polyurethane (isocyanate) foam: antibodies and immune profiles.

Four arc welders having a flu-like illness with multiple health complaints following an exposure to high concentrations of isocyanate fumes from ignited polyurethane foam underwent immunological tests as follows: ELISA antibody assays, activated lymphocyte profiles, and lymphocyte blastogenesis. ELISA procedures revealed the presence of antibodies to hexamethylene diisocyanate (HDI) and formaldehyde (F) conjugated to human serum albumin (HDI-SA and F-SA). The results from the activated lymphocyte profiles showed deviations from the norm as follows: three welders had elevated helper/suppressor (H/S) ratios; all four had elevated percentages of Tal positive cells; two had decreases in B cells; and one had low total white cell and lymphocyte counts. In contrast, the percentage and absolute numbers of ILS receptor cells were normal in the four subjects. T cell blastogenesis to PHA, Con A and PWM resulted in the following: T-cells from one subject responded normally; in another, a high response (212% of controls) to PHA occurred with normal mitogenesis to Con A and PWM. In the remaining two welders, the T cells responded abnormally low (50 to 75% of controls) to the three mitogens. In conclusion, the existence of IgG antibodies to HDI-SA and F-SA, the altered activated immune profiles, the elevated Tal cells, and the abnormal blastogenesis are interpreted as being linked with the episode of HDI and F exposure and the subsequent flu-like illness of the four welders.

Comparative clinical and laboratory features of legionella with pneumococcal and mycoplasma pneumonias

The clinical and laboratory features of 83 cases of community-acquired pneumococcal pneumonia (PP), 79 cases of legionella pneumonia (LP) and 62 cases of mycoplasma pneumonia (MP) have been compared. No unique features have been found in any group. Patients with MP were younger, were more likely to have had prior antibiotics before hospital referral, had a predominance of upper respiratory tract symptoms, low total white cell counts and lacked features of multisystem involvement. Multisystem features were common in both PP and LP with confusion, high fever, hyponatraemia, hypoalbuminaemia and abnormalities of liver function occurring more often in LP. A high leucocyte count was especially common in PP. Antibiotic therapy in community-acquired pneumonia must remain empirical until a definite microbiological diagnosis is made.

Cyclosporin-A treatment of experimental allergic encephalomyelitis: Changes in immunological regulation and blood-CSF barrier function

Strain 13 guinea pigs at 18–21 days of age were sensitised with spinal cord and Freund's complete adjuvant to induce experimental allergic encephalomyelitis (EAE). Treatment with cyclosporin-A (CS-A) from one day before sensitisation until from 12 to 39 days after sensitisation resulted in a suppression of the disease. Suppression was indicated by an absence or reduction in severity of clinical signs together with a lack of increase in blood-cerebrospinal fluid (CSF) barrier permeability to proteins and a lower white cell count in the CSF from treated animals. When CS-A treatment was withdrawn, clinical disease reappeared but changes in IgG concentration in the CSF indicated that intrathecal synthesis of IgG had occurred, which was not the case in the untreated disease. Modification by CS-A of the immunoregulatory processes involved in the development of EAE, provides a model to study the special conditions which operate in neuroimmunological disorders.

Adult acute lymphoblastic leukaemia: a study of prognostic features and response to treatment over a ten year period.

Between 1974 and 1984 69 adults with acute lymphoblastic leukaemia (ALL) were treated with two different protocols. Fifty-four (78%) of the patients entered complete remission (CR); 27 of these then received a consolidation protocol consisting of daunorubicin, cytosine arabinoside and 6-thioguanine, followed by two courses of intravenous methotrexate 500 mg m-2 with folinic acid rescue. All patients received intrathecal methotrexate and cranial irradiation (24 Gy) followed by maintenance therapy with 6-mercaptopurine and methotrexate for at least 2 years. The median survival for all patients was 23 months from the time of presentation with an actuarial 5-year survival of 21%. The actuarial chance of surviving 5 years in CR for patients receiving the consolidation protocol was 38% compared to 19% for patients receiving no consolidation (P = NS). Only patient age and white cell count at presentation were found to influence the chance of achieving CR and the chance of overall survival. The presence or absence of c-ALL antigen did not influence prognosis. Patients younger than 35 years with low white cell counts at presentation (less than 10 X 10(9)1(-1] had a particularly good prognosis but no patient with T-ALL and no patient older than 50 years old at diagnosis survived more than 18 months.

Cardioplegic solution: A contamination crisis

Eleven patients were given varying doses of cardioplegic solution contaminated with Enterobacter cloacae. Five patients died. Early bleeding, necessitating reoperation, occurred in eight patients and a total of 126 units of blood and 203 units of platelets were given (range 2 to 19 and 15 to 47 units, respectively). Mycotic aneurysms developed in four patients, rupturing between the ninth and eleventh postoperative day. Only one of these patients survived. Other complications included adult respiratory distress syndrome (three patients), renal failure (four patients), sternal infections (six patients), and organic brain syndrome (five patients). Although some factors of gram-negative septicemia were identified in retrospect, others were masked by the clinical setting in which it occurred. We recommend that each dose of cardioplegic solution be prepared on an individual basis and used immediately. We also recommend that "sternal blood" be cultured on all patients. The subtle features of "gram-negative septicemia" necessitate urgent investigation and treatment. The combination of low white cell count, high cardiac output, and low peripheral vascular resistance should be assumed to indicate septicemia until proved otherwise. A full coagulation screen including platelet function and fibrin degradation products should be performed in any and all patients with these findings. Mycotic aneurysms mandate urgent reoperation with interposition of a saphenous vein segment of these patients are to survive.

Appendicitis Perforata in CAPD Patients -Report of Two Cases

Two patients on CAPD had peritonitis due to perforated appendicitis. Both presented with diffuse painful peritonitis with nausea, fever and prostration. There was blood leukocytosis with a shift to the left. The peritonitis did not respond to antibiotic therapy. The diagnosis was made after 8 and 18 days respectively by exploratory laparotomy. Both patients had a gangrenous perforated appendix surrounded by abscess. Both patients had uncomplicated recovery after appendectomy, drainage, removal of the Tenckhoff catheter with discontinuation of CAPD and change to hemodialysis. Our experience suggests that a perforated appendix might be recognized early in a patient with apparent fecal peritonitis in whom other more common causes (e.g. diverticulosis/ diverticulitis) have been ruled out, or when he presents with severe symptoms and a low peritoneal white cell count. Perforated appendicitis leading to fecal peritonitis is a rare complication of continuous ambulatory peritoneal dialysis (CAPD). Among 85 patients treated with CAPD since 1978 for a total of 1062 patient months, we observed two such cases. Although CAPD now is established as a kidney replacement treatment and appendicitis is a common condition, we know of no other report of perforated appendicitis during CAPD. Therefore we describe our experience with two such patients, treated with CAPD for 14 and 5 months, respectively. The diagnostic and therapeutic implications are discussed in the context of other forms of fecal peritonitis, mainly due to colonic perforation, secondary to diverticular disease. This report emphasizes the need for a high level of suspicion that the peritonitis may be related to bowel disease, especially when it does not respond quickly to standard treatment.

Preparation of Buffy Coats From Blood Samples With Extremely Low White Cell Counts

Preparation of Buffy Coats From Blood Samples With Extremely Low White Cell Counts

The role of azathioprine reduction in late renal allograft failure.

A group of 123 patients who had functioning renal transplants for more than 5 years were studied to discover whether prolonged reduction of azathioprine could predispose to late allograft failure. From the point of entry into the study (5 years after transplantation), the 5-year cumulative graft survival among living-related-donor recipients was 91.7%, and among non-living-related-donor recipients it was 84.8%. The azathioprine dose was reduced in 21 patients, for medical reasons, below 100 mg/day for more than one year when serum creatinine was stable and less than 2 mg/dl. Eight patients subsequently required dialysis. In the control group of 35 patients (transplanted in the same years, with serum creatinine that was similar at the same time posttransplantation to that of those who had azathioprine reduced) only 1 patient required dialysis. The likelihood of dialysis was significantly greater in those who had azathioprine reduced compared with those who did not (chi 2 = 12.0, P less than 0.001). No patient who had azathioprine reduced because of low white cell counts or chronic hepatitis subsequently required dialysis. It was concluded that a prolonged reduction of the azathioprine dose may predispose to late allograft failure.

Translocation 1;19—A new cytogenetic abnormality in acute lymphocytic leukemia

A study of the chromosomes of 125 consecutive patients with acute lymphocytic leukemia (ALL) showed the same translocation between chromosomes #1 and #19 in 5 patients. In 4 of the 5, the t(1;19) (q21;q13) was present at diagnosis. The fifth patient, who had Philadelphia chromosome positive (Ph 1+) ALL, developed t(1;19) in first relapse. Trisomy 1q was involved in 2 of the 5 patients; 3 patients had additional abnormalities. All patients had low white cell counts at presentation (<35 × 10 9/L), and the 4 patients tested had common ALL antigen (CALLA) positive leukemic blast cells. All achieved complete remission, including the Ph 1+ ALL patient in first relapse, and survival times ranged from 4 to 21+ mo from the time the t(1;19) first appeared. Our data suggest that t(1;19) is a previously unrecognized nonrandom structural abnormality in ALL that is also found in other lymphoid malignancies. Unlike the other specific translocations, it is not associated with a poor prognosis.

A good prognosis group in childhood acute lymphoblastic leukaemia.

The records of 121 children presenting with acute lymphoblastic leukaemia between 1969 and 1982 were reviewed. The overall relapse free survival rate was 50%. However, girls presenting with a total white blood cell count of 20 X 10(9)/l or less (35% of all patients) had a particularly favourable prognosis with an 80% relapse-free survival rate at 12 years. The difference in prognosis between the sexes is confirmed but this difference is confined to the low initial white cell count group. We suggest that girls in this group should be excluded from the more intensive arms of new treatment protocols.

Risikofaktoren bei eitriger Meningitis im Kindesalter

Retrospective studies of the case histories of 237 children suffering from bacterial meningitis at the department of pediatrics, university of Graz, show the significant difference between cured, deceased and children with permanent sequels. The risk factors for the fatal outcome of meningitis were: age (less than 1 year), bacteria (pneumococcus), concomitant disease (pneumonia), low initial white cell count in the blood (less than or equal to 5000/cmm) as well as in cerebrospinal fluid (less than or equal to 4000/cmm), high cerebrospinal fluid protein (greater than or equal to 336 mg%) and a high bacterial inoculum (greater than or equal to 10(7) CFU/cmm). With all these risk factors at the time of diagnosis of purulent meningitis the chance for recovery is poor.

Results of cessation of treatment in childhood acute lymphocytic leukaemia.

From 1972 to 1977, 55 of 161 children with acute lymphocytic leukaemia discontinued treatment after being in continuous complete remission for three years. A low total white cell count as diagnosis (less than 10 X 10(9)/L) was significantly associated with cessation of therapy, but there was no significant association with age or sex. Nine patients have relapsed, all but one within 50 weeks of cessation of treatment. Testicular relapse occurred only in one patient. Actuarial complete remission rate with a median duration of follow-up 140 weeks was 76%, and there was no significant sex difference. It is proposed that the relatively good prognosis in boys after cessation of therapy may be related to limited use of steroids during induction chemotherapy.

Association of monocytic leukemia in patients with extreme leukocytosis

Fifteen of 73 newly diagnosed patients with acute myeloid leukemia (AML), admitted to Mount Sinai Hospital between July 1977 and October 1979, presented with leukocyte counts greater than 100,000/μl. Eleven of these 15 patients with hyperleukocytosis had myelomonocytic (AMML-M4) or monocytic (AMOL-M5) leukemia compared to 14 of 58 patients with lower white cell counts (p < 0.001). Identification of type of leukemia, using the FAB classification, was based on morphology and special stains, including myeloperoxidase, Sudan black B, periodic acid-Schiff and nonspecific esterase with and without inhibition by fluoride. The proportion of patients with splenomegaly is higher in those with hyperleukocytosis (73 percent) than in those with lower white blood cell counts (p < 0.001) regardless of cell type. Leukemic infiltration of the skin, gums and central nervous system was seen exclusively in patients with AMML and AMOL. The serum lysozyme levels were significantly higher for all patients with AMML and AMOL regardless of the white blood cell count. The mean serum lysozyme for M-4, M-5 patients was 59.7 μg/ml compared to 18.9 μg/ml in patients with other cell types (p < 0.0001). Patients with a white blood cell count ≤100,000/μl had a complete remission rate of 69 percent compared to 47 percent for patients with higher white blood cell counts.

Long-term treatment with clozapine on aging mice

To further clarify the relationship between central neurotransmitter systems, organ function and aging, we used mice to study the effects of long-term administration of the antipsychotic agent clozapine (10 and 20 mg/kg) on some age-related behavioral and organ-function tests. Compared to controls, clozapine-treated mice weighed less, had lower white-cell counts in peripheral blood, and had a shorter lifespan. Hexobarbital sleeping time of the clozapine-treated mice was elevated at 12, 16, and 20 months and decreased at 24, 28, and 32 months of age. Clozapine-treated mice had higher locomotor-activity scores (behavioral supersensitivity) at varying intervals from 12 to 24 months of age, but not at 28 and 32 months. A significant change in the total white-cell number in drug-treated mice compared to controls was also first noted at 24 months and the difference progressively increased at 28 and 32 months. These observations indicate that age may be a major factor in the level and even direction of responsiveness to longterm administration of antipsychotic agents like clozapine.

The Pathogenesis of Trypanosoma congolense Infection in Calves

Calves infected with Trypanosoma congolense TREU 112 had, at the onset of anemia, a very low total white cell count and neutropenia but with chronicity there was lymphocytosis. Infected calves had a marked reduction in granulocyte mobilization for the first 14 weeks of infection and there was reduced ability to mount an inflammatory response during the onset of anemia. Bone marrow aspiration biopsies showed marked erythroid hyperplasia in response to the anemia with a relative and likely absolute reduction in myeloid precursors and marrow granulocyte reserves.

Pneumococcal Meningitis: A Clinical and Laboratory Study

Forty-two patients who were admitted consecutively with pneumococcal meningitis during an 18-month period were studied in Ahmadu Bello University Hospital, Zaria, Nigeria. The disease was seen most frequently in older children and young adults. A predisposing condition was found in only four patients. Counter-current immunoelectrophoresis was found to be a rapid and effective method of diagnosis: pneumococcal polysaccharide antigen was found in the initial cerebrospinal fluid (CSF) sample from all but one of the patients. Detailed physiological studies carried out in two patients showed profound disturbances of cerebral carbohydrate metabolism and an increase in cerebral vascular resistance. Twenty patients died (48 per cent) in spite of treatment with large doses of penicillin. A fatal outcome was associated with impairment of consciousness on admission, a low CSF white cell count and a high CSF antigen titre. It is suggested that marked changes in cerebral carbohydrate metabolism, and perhaps vascular damage, play important roles in producing severe brain damage in patients with pneumococcal meningitis and that defective CSF polymorphoneutrophil leukocyte function may contribute to the failure of the infection to respond satisfactorily to antibiotic therapy.

Heterogeneous nuclear rna from lymphocytes of chronic lymphocytic leukaemia: adenylate-rich and double-stranded regions.

Rapidly labelled high molecular weight nuclear RNA from lymphocytes of chronic lymphocytic leukaemia was analysed for ribonuclease-stable adenylate-rich and double-stranded regions. The polyadenylate content corresponds to 0.4-0.5 percent and the content of double-stranded sequences to 2-4 percent of the total nucleotides. Partial association of polyadenylate segments with double-stranded regions was found by comparative analysis of (3H)-adenosine and (3H)-uridine labelled ribonuclease-stable RNA before and after thermal denaturation. Comparison with normal lymphocytes shows lower proportions of polyadenylate-containing RNA binding to poly(U)-Sepharose in leukaemia cells than in normals. Partial degradation of rapidly labelled high molecular weight RNA was found in leukaemia cases with low white cell counts.

Ribonuclease--ribonuclease inhibitor patterns in lymphocytes of chronic lymphocytic leukaemia.

Lymphocytes of chronic lymphocytic leukaemia were analysed for acid ribonuclease (pH 5.8), alkaline ribonuclease (pH 7.8) and alkaline ribonuclease inhibitor. At the same time, responsiveness of the lymphocytes to phytohaemagglutinin was measured by determination of the incorporation of 3H‐thymidine in culture. Lymphocytes responsive to phytohaemagglutinin showed higher levels of total acid and alkaline ribonuclease than lymphocytes with low or no response to phytohaemagglutinin. In addition, large proportions of free alkaline ribonuclease were formed and all ribonuclease inhibitor inactivated in lymphocytes isolated from patients with low white cell counts. In contrast, low free ribonuclease and relatively high free inhibitor levels were found in lymphocytes from patients with high white cell counts.

The effects of centralization in haematology.

<b>Objective:</b> To examine prospectively whether irritable bowel syndrome (IBS) or other variables—that is, psychiatric profiles, health-related quality of life (HRQoL) and clinical features—are associated with negative appendectomy (NA). <b>Design:</b> Longitudinal study. <b>Setting:</b> Inpatient and emergency service in a university-affiliated teaching hospital. <b>Patients:</b> 430 consecutive patients underwent emergent surgery for suspected appendicitis. <b>Main outcome measures:</b> Rome-II IBS questionnaire; the Hospital Anxiety and Depression Scale; the Short-Form 36 survey; the clinical, pathological and CT findings. <b>Results:</b> The NA group (n = 68, 15.8%) was younger, with female predominance, higher prevalence of Rome-II IBS, higher anxiety/depression scores and lower levels of HRQoL than the positive appendectomy group. The patients with NA tended to have atypical presentations (absence of migration pain/fever/muscle guarding), lower white cell count and percentage of polymorphonuclear cells (PMNC) and lower rate of CT scan usage than the positive group. After multiple logistic regression, IBS (OR 2.17; 95% CI 1.14 to 4.24), degree of anxiety (OR 1.12; 95% CI 1.02 to 1.49), absence of migrating pain (OR 3.43; 95% CI 1.90 to 5.95)/muscle guarding (OR 3.72; 95% CI 2.07 to 6.70), a lower PMNC percentage (&lt;75%; OR 3.05; 95% CI 1.69 to 5.51) and no CT scan usage (OR 2.32; 95% CI 1.27 to 4.26) were found to be the independent factors in predicting NA. <b>Conclusion:</b> Both patient (IBS, anxiety, atypical presentation) and physician (low CT scan usage) factors are the independent determinants predicting NA. Physicians should be cautious before operating on or referring patients with IBS for appendectomy. CT scan should be considered in patients with suspected appendicitis, particularly in those with IBS and atypical clinical presentations.

Recovery of Delayed-Type Hypersensitivity in Mice Following Suppressive Doses of X-Radiation

Summary A study was made of the effects of sub-lethal whole body x-radiation on an established state of delayed hypersensitivity induced by the intravenous infection of mice with M. bovis (BCG) or S. gallinarum. The level of delayed sensitivity was determined by measuring the foot-thickness 24 hr after the injection of a suitable eliciting antigen into the footpad. In appropriately sensitized mice the delayed reactivity to both PPD and the Salmonella antigen was largely suppressed by 400 rad of whole body x-radiation. No recovery of reactivity was detected in the 8 days following irradiation of tuberculin sensitive mice. On the other hand, in mice sensitized to S. gallinarum there was a gradual recovery in footpad reactivity. X-radiation resulted in an abrupt decline in the absolute numbers of circulating lymphocytes, monocytes but not granulocytes. Low white cell counts were sustained throughout the remainder of the experiment. Concurrent autoradiographic labeling studies showed a fall in the labeling index of mononuclear exudate cells at the reaction site coincident with minimal footpad reactivity. The subsequent return of a normal labeling index in the cells of the infiltrate was associated with the recovery of a significant degree of specific footpad reactivity. These results were interpreted to favor the concept that delayed hypersensitivity is mediated by two cell populations. The first is relatively radioresistant and endowed with the specific sensitivity necessary to initiate a delayed reaction. The second, which is necessary for its ultimate expression, is derived from radiosensitive precursors that are capable of rapid regeneration.