Lower White Cell Count Research Articles

Demographic and Clinical Features of Dengue Fever in Pakistan from 2003–2007: A Retrospective Cross-Sectional Study

BackgroundDemographic features of dengue fever have changed tremendously in Pakistan over the past two decades. Small scale studies from all over the country have reported different aspects of individual outbreaks during this time. However, there is scarcity of data looking at the overall trend of dengue virus infection in the country. In this study, we examined annual trends, seasonality, and clinical features of dengue fever in the Pakistani population.MethodsDemographic information and dengue IgM status of all patients tested for dengue IgM antibody at Aga Khan University Hospital from January 2003 to December 2007 were analyzed to look for trends of IgM-positive cases in Pakistan. In addition, clinical and biochemical parameters were abstracted retrospectively from medical records of all patients hospitalized with IgM-proven dengue fever between January 2006 and December 2007. These patients were categorized into dengue fever and dengue hemorrhagic fever according to the WHO severity grading scale.ResultsOut of a total of 15040 patients (63.2% male and 36.8% female), 3952 (26.3%) tested positive for dengue IgM antibody. 209 IgM proven dengue patients were hospitalized during the study period. During 2003, IgM positive cases were seen only during the months of July-December. In contrast, such cases were detected throughout the year from the 2004–2007. The median age of IgM positive patients decreased every year from 32.0 years in 2003 to 24.0 years in 2007 (p<0.001). Among hospitalized patients, nausea was the most common presenting feature found in 124/209 (59.3%) patients. Children presented with a higher median body temperature than adults (p = 0.010). In addition, neutropenia was seen more commonly in children while raised serum ALT levels were seen more commonly in adults (both p = 0.006). While a low total white cell count was more common in patients with dengue fever as compared to Dengue Hemorrhagic Fever (p = 0.020), neutropenia (p = 0.019), monocytosis (p = 0.001) and raised serum ALT level (p = 0.005) were observed more commonly in the latter group.ConclusionsDengue virus is now endemic in Pakistan, circulating throughout the year with a peak incidence in the post monsoon period. Median age of dengue patients has decreased and younger patients may be more susceptible. Total and differential leukocyte counts may help identify patients at risk of hemorrhage.

Lower white blood cell counts in elite athletes training for highly aerobic sports

White cell counts at rest might be lower in athletes participating in selected endurance-type sports. Here, we analysed blood tests of elite athletes collected over a 10-year period. Reference ranges were established for 14 female and 14 male sports involving 3,679 samples from 937 females and 4,654 samples from 1,310 males. Total white blood cell counts and counts of neutrophils, lymphocytes and monocytes were quantified. Each sport was scaled (1-5) for its perceived metabolic stress (aerobic-anaerobic) and mechanical stress (concentric-eccentric) by 13 sports physiologists. Substantially lower total white cell and neutrophil counts were observed in aerobic sports of cycling and triathlon (~16% of test results below the normal reference range) compared with team or skill-based sports such as water polo, cricket and volleyball. Mechanical stress of sports had less effect on the distribution of cell counts. The lower white cell counts in athletes in aerobic sports probably represent an adaptive response, not underlying pathology.

Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension

Portal venous thrombosis (PVT) is a potentially fatal complication following splenectomy. Its mechanisms and risk factors are poorly understood, especially in patients with cirrhosis and portal hypertension. This study investigated risk factors for PVT following splenectomy in such patients. All consecutive patients with cirrhosis who underwent splenectomy in Kyushu University Hospital between 1998 and 2004 were included in this retrospective study. They were divided into two groups based on the presence or absence of postoperative PVT. Preoperative and operative factors were compared, and the relationships between formation of PVT and its independent variables were analysed. In some cases, portal venous flow was measured before and after splenectomy using duplex Doppler ultrasonography. PVT developed after surgery in 17 (24 per cent) of 70 patients studied. Multivariable analysis showed that increased splenic vein diameter and low white cell count were significant independent risk factors for PVT. Portal venous flow after splenectomy was greatly reduced in the PVT group, but not in patients without PVT. Large splenic vein diameter and low white cell count are independent risk factors for PVT after splenectomy in patients with cirrhosis and portal hypertension.

Procalcitonin and C-reactive protein in severe 2009 H1N1 influenza infection

PurposeTo examine whether, in an adult intensive care unit (ICU), procalcitonin or C-reactive protein (CRP) levels discriminated between 2009 H1N1 influenza infection and community-acquired pneumonia of bacterial origin.MethodsA retrospective observational study performed at an Australian hospital over a 4-month winter period during the 2009 H1N1 influenza pandemic. Levels on admission of procalcitonin and CRP were compared between patients admitted to the ICU with community-acquired pneumonia of bacterial and 2009 H1N1 origin.ResultsCompared to those with bacterial or mixed infection (n = 9), patients with 2009 H1N1 infection (n = 16) were significantly more likely to have bilateral chest X-ray infiltrates, lower APACHE scores, more prolonged lengths of stay in ICU and lower white cell count, procalcitonin and CRP levels. Using a cutoff of >0.8 ng/ml, the sensitivity and specificity of procalcitonin for detection of patients with bacterial/mixed infection were 100 and 62%, respectively. A CRP cutoff of >200 mg/l best identified patients with bacterial/mixed infection (sensitivity 100%, specificity 87.5%). In combination, procalcitonin levels >0.8 ng/ml and CRP >200 mg/l had optimal sensitivity (100%), specificity (94%), negative predictive value (100%) and positive predictive value (90%). Receiver-operating characteristic curve analysis suggested the diagnostic accuracy of procalcitonin may be inferior to CRP in this setting.ConclusionsProcalcitonin measurement potentially assists in the discrimination between severe lower respiratory tract infections of bacterial and 2009 H1N1 origin, although less effectively than CRP. Low values, particularly when combined with low CRP levels, suggested bacterial infection, alone or in combination with influenza, was unlikely.

口腔内に初発症状を呈した急性骨髄性白血病の3例

The initial symptoms of leukemia include oral manifestations such as gingival hemorrhage and swelling. In patients with these symptoms, attention should be paid to the early diagnosis of acute leukemia. This report describes three cases of acute myelogenous leukemia (AML) with initial manifestations in the oral cavity.Patient 1: A 32-year-old woman. Ulcer lesions of the oral mucosa were diagnosed as decubital ulcers, and symptoms did not respond to the application of steroid ointment. She also had appetite loss, general malaise, and bloody stools. Blood examination showed a low white-cell count (1,600/μl).Patient 2: A 52-year-old man. He received anti-inflammatory treatment and had pain at the mandibular third molar region and gingival swelling, but the symptoms did not improve. At the initial visit, pericoronitis of the mandibular third molar with fever and general malaise were observed. Blood examination showed a low white-cell count (2,300/μl) and remarkably increased myeloblasts (20 %) .Patient 3: A 54-year-old woman. She received medication to treat full-mouth gingival swelling. However, fever and general malaise persisted. Blood examination showed a high white-cell count (47,000/μl).All three patients were given a diagnosis of AML on bone marrow biopsy.When the patients present with oral symptoms such as gingival swelling and ulcers accompanied by fever and general malaise, blood examinations should be promptly performed for the differential diagnosis of acute leukemia.

A Rare Case of Spontaneous Cryptococcal Peritonitis

Purpose: Cryptococcus neoformans is an encapsulated yeast, most commonly affecting the immunocompromised including patients with HIV/AIDS, hematological malignancies, prolonged steroid use, or organ transplantation. The typical forms of Cryptococcal infection consist of meningoencephalitis, pulmonary infiltration, skin lesions, and osteomyelitis. Cryptococcal infection of ascites is a rare and fatal infection that is often unrecognized due to vague presenting symptoms that resemble spontaneous bacterial peritonitis (SBP). Here, we present a case of Cryptococcal peritonitis in a patient with hepatitis C (HCV) related cirrhosis. Methods: A 63 y/o HIV-negative Latino male with decompensated cirrhosis due to HCV, undergoing evaluation for liver transplantation, presented to the ED with a 10 day history of increasing confusion. On admission, he was obtunded and unable to communicate clearly. His wife reported a decrease in frequency of his bowel movements. She denied any fevers, chills, nausea, vomiting, abdominal pain, melena, or hematechezia. She reported that the patient was compliant with his Ciprofloxacin prescribed for SBP prophylaxis. Physical exam revealed a somnolent, thin male with bitemporal wasting, scleral icterus, spider angiomas, diffuse abdominal tenderness, and clonus. Results: Lab results included a normal WBC (6.8), elevated INR (2.8), reduced complement level, venous ammonia level of 52, hypoalbuminemia (1.6), alkaline phosphatase of 87, total bilirubin of 11.3, AST 111, and ALT 46. Urine drug screen was negative. A CT abdomen illustrated cirrhosis and massive ascites. Ascites fluid contained only 67 WBC/mm3 with only 2% neutrophils. On hospital day 4, blood cultures and ascites fluid grew yeast that was later identified as Cryptococcus neoformans. Treatment with IV Fluconazole was initiated and changed to Liposomal Amphotericin B and 5-fluorocytosine once the organism was identified. On hospital day 8 he became acutely hypoxic and hypotensive. In light of the patient's wishes, the family declined mechanical ventilation, and comfort care was initiated. Conclusion: Cryptococcal peritonitis is a rare but usually fatal infection of ascites. It is often acquired through hematogenous dissemination from subclinical pulmonary infection. Patients with cirrhosis have impaired opsonization, phagocytic dysfunction, and complement deficiency, making them more susceptible to Cryptococcal infection. The mortality rate for Cryptococcal peritonitis with antifungal therapy has been reported to be 73%. Although a rapid antigen test is available, on average, it takes six days for the detection of Cryptococcus in ascites by culture. A low ascites white cell count and fungemia should lead to a heightened suspicion of Cryptococcal peritonitis.

Sensitivity and specificity of an index for the diagnosis of TB meningitis in patients in an urban teaching hospital in Malawi

Tuberculous (TB) meningitis is difficult to diagnose and has a high mortality rate, particularly when presentation is delayed. A diagnostic index developed in Vietnam, an area of low-HIV seroprevalence, has been proposed as a means to differentiate TB meningitis from acute bacterial meningitis using clinical and laboratory features. We applied this index over a 4-month period to adults presenting with meningitis to an urban teaching hospital in Malawi, where HIV seroprevalence is 70% among medical inpatients. Eighty-five consecutive eligible patients were studied. Nine had TB meningitis, 64 bacterial meningitis and 12 cryptococcal meningitis. The sensitivity of the diagnostic index for predicting TB meningitis was 78%, with a specificity of 43%, too low to be used in the diagnosis of TB meningitis in this setting. This finding is likely to be generalizable to other southern African countries with similarly high-HIV seroprevalences.

Inferior response of Asian vs non‐Asian hepatitis C genotype 3 infection to combination antiviral therapy

Racial differences in response to treatment of hepatitis C virus (HCV) have been noted in several trials. In this study, we compared the response rate to treatment of Asian patients infected by genotype 3 HCV with non-Asians treated for the same genotype. Sixteen of 38 (42.1%) Asians achieved a sustained virological response (SVR), compared with 41 of 66 (62.1%) Caucasians (P = 0.063). At baseline prior to treatment, Asians had a higher histological fibrosis stage (P = 0.0014), indicating more advanced disease at presentation. In univariable analysis of baseline factors predicting failure to achieve an SVR, Asian ethnicity, fibrosis stage, higher serum aspartate transaminase, bilirubin and alkaline phosphatase, as well as lower white cell count, haemoglobin and platelet count were statistically significant. None of these factors achieved significance in multivariate analysis, possibly because of the relatively small number of patients studied. We have observed an inferior response to treatment of Asian vs Caucasian patients. The poor response probably reflects the more advanced liver disease at baseline observed for Asian British patients.

Role of laparoscopic surgery in the etiologic diagnosis of exsudative ascites: a prospective study of 90 cases

Peritoneal tuberculosis and carcinomatosis are the most frequent etiologies of exsudative ascitis and require rapid diagnosis and treatment. The purpose of this study has been to evaluate the predictive value of clinical and complementary data for the etiologic diagnosis of exsudative ascites and to assess the results of laparoscopic surgery. We report a prospective long-term study conducted over 10 years, having included all cases of exsudative ascites of unidentified etiology. We excluded patients with a history of anterior laparotomy and patients having a contraindication for laparoscopic surgery. Clinical signs, results of the cytochemical and bacteriological exam of the ascetic liquid and findings from radiological exams and endoscopic investigations were noted. Open laparoscopic exploration noted the macroscopic aspect and many peritoneal biopsies were obtained as well as a liver biopsy when possible. Statistical analysis was performed with SPSS10.0 software. The degree of statistical significance was set for P<0.05. We included 90 cases of isolated exsudative ascites. There were 59 cases of tuberculosis and 31 of carcinomatosis. Mean patient age was 47 years with a sex ratio of 0.5. Bowel transit disorders were significantly in favor of a carcinomatosis (P=0.04) while fever and nocturnal sweats were suggestive of tuberculosis (P=0.04) but in both instances, the positive predictive value (PPV) of these two signs was weak, respectively 29% and 43%. Relative to chemical and cytologic study of ascitic fluid, hemorrhagic fluid, low white cell count, low lymphocyte differential and presence of atypical cells were significantly linked with the carcinomatosis (P=0.01) but with a PPV<85%. Radiological exams were not very contributive for the etiologic diagnosis. The laparoscopic peritoneal aspect was typical of tuberculosis in 90% of proved cases and in 29% of carcinomatosis cases, underlying the importance of peritoneal biopsies for histological study. Hepatic tuberculosis was associated with peritoneal localisation in 48% of cases. We had no surgical mortality and the morbidity was about 1%. Etiological diagnosis of exsudative ascitis remains difficult to establish. Peritoneal biopsies under videolaparoscopy are currently the "gold standard" for diagnosis.

Identical Outcome Following Autologous or Allogeneic Genoidentical Hematopoietic Stem Cell Transplantation in First Complete Remission for Good Risk Acute Myelocytic Leukemia Carrying INV 16 or t(8;21): A Retrospective Comparison from the Acute Leukemia Working Party (ALWP) of the European Cooperative Group for Blood and Marrow Transplantation (EBMT).

Patients with acute myelocytic leukaemia (AML) with core binding factor mutations (CBF), bearing abnormalities of chromosome 16 or t(8;21) are classified as good risk with chemotherapy regimens including high dose cytosine arabinoside and are not subjected to hemopoietic stem cell transplantation (HSC) front line. However there are limited data from old studies indicating good outcome following HSC, autografting in particular, and there has been recently some concern about higher than expected relapse incidence following conventional chemotherapy in this patient population. From January 1990 to December 2004, a total of 325 adult patients were reported to the EBMT Acute Leukemia registry as receiving a transplant in first remission (CR1). Of these, 159 had an inversion 16, including 124 with no additional chromosome abnormality and 35 with other abnormalities. 166 had a t(8;21) translocation, as the only chromosome abnormality in 106 and associated to other abnormalities in 60. 64 patients with inv 16 and 81 patients with t(8;21) received a geno-identical allograft. 95 patients with inv 16 and 85 patients with t(8;21) translocation received an autograft. In patients with inv 16, following allogeneic and autologous transplantation respectively, the LFS were 59 ± 7% and 66 ± 5% (p=0.5), the RI 27 ± 6% and 32 ± 4% (p=0.45) and the TRM 14 ± 4% and 2 ± 2% (p=0.003). The LFS was significantly higher after January 2001. Female patients had a significantly lower incidence of relapse and a higher LFS. The existence of additional chromosome abnormalities not only did not worsen the prognosis but was associated with less relapses (12±5% vs 34 ± 4%, p= 0.01), and a better LFS (78 ± 7% vs 59 ± 5%, p=0.04). In patients with t(8;21), following allogeneic and autologous transplantation respectively, the LFS were 60 ± 5% and 66 ± 5% (p=0.69), the RI 15 ± 2% and 28 ± 3% (p=0.03) and the TRM 24 ± 3% and 6 ± 1% (p=0.003). Younger age and a lower white cell count at diagnosis were associated with a lower TRM and a better LFS.There was no difference in outcome between female and male patients. Following autologous transplantation as compared to allogeneic, the TRM was significantly lower and the relapse incidence significantly higher. For all adult CBF AML, the LFS did not differ between autologous and allogeneic transplants. Although the reasons why these patients were transplanted are unclear, considering the low TRM of autologous stem cell transplantation and the possibility to monitor in vivo purging by molecular biology, the data support the inclusion of ASCT in the front line treatment of CBF AML and suggest that a randomized prospective trial comparing high dose ARA-C and ASCT would be of interest.

A case of breast carcinoma, chemotherapy, and acute appendicitis

In May 2006 a 51-year-old woman with a history of infiltrating ductal carcinoma of the breast presented with atypical symptoms of acute appendicitis. She had undergone a modified radical mastectomy 4 months earlier and had received four courses of chemotherapy (cyclophosphamide doxorubicin and fluorouracil). After the fourth course of chemotherapy she developed a dull low abdominal pain lasting 3 days. She initially visited our gastroenterology clinic where physical examination and laboratory studies were unremarkable; persistent symptoms led her to present to our emergency department 2 days later. Physical examination showed mild tenderness without rebound in the lower abdomen especially on the right side. Laboratory test results showed a low white cell count of 3.1 × 10/--3/L with a normal differential cell count. Abdominal ultrasonography showed a hypoechoic soft-tissue mass about 3 cm in diameter adjacent to the terminal ileum. Acute appendicitis was diagnosed and our patient underwent an appendectomy. Pathology results showed acute suppurative inflammation with periappendiceal abscess formation consistent with perforation. Her postoperative course was uneventful and she was discharged 4 days after the procedure. When last seen in June 2006 the patient was well. (excerpt)

Hepatobiliary and pancreatic: Spontaneous splenorenal shunts in portal hypertension

Why do some patients with cirrhosis show spontaneous improvement in features of portal hypertension? The answer is the development of increasing numbers of collateral channels that decompress the portal system and lower portal pressures. Common sites for these collaterals include the gastric cardia, rectum, retroperitoneum and umbilicus. Less commonly, collaterals may involve the left renal vein and, if large, can function as significant portosystemic shunts. Two patients with spontaneous splenorenal shunts are illustrated below. The patient whose image is shown in Fig. 1 was a woman, aged 31 years, who was diagnosed with autoimmune hepatitis at the age of 4 years. She had been taking prednisolone, 5 mg per day, for at least 10 years. On examination, she had a large spleen. Blood tests revealed a low white cell count and platelet count, abnormal coagulation studies and a low plasma albumin (19 g/L). Upper gastrointestinal endoscopy was normal. An abdominal ultrasound study showed splenomegaly and numerous dilated vessels in the splenic hilum but no ascites. She had antegrade portal blood flow (velocity 2.3 cm/s) and a hepatic venous pressure gradient of 8 mmHg. Selective catheterization of the superior mesenteric artery showed the mesenteric vein, a small portal vein, back flow to the splenic vein (black arrow) and a large shunt between the splenic and left renal vein (red arrow). The patient illustrated in Fig. 2 was a male, aged 31, who had portal hypertension because of portal vein thrombosis associated with factor V Leiden mutation. Over a period of 5 years, esophageal varices were treated by endoscopic ligation on several occasions. Subsequently, however, varices appeared to regress spontaneously. Abdominal gray-scale and color-Doppler sonography showed a large splenorenal shunt and this was confirmed by magnetic resonance imaging (arrows). Spontaneous splenorenal shunts appear to be uncommon in adults but may be more common when portal hypertension occurs in children.

An unusual case of Candida tropicalis and Candida krusei arthritis in a patient with acute myelogenous leukemia before chemotherapy

A 79-year-old male with acute myelogenous leukemia developed acute right knee arthritis during admission, after the use of broad-spectrum antibiotics before chemotherapy. The initial synovial fluid sample appeared to be mildly inflammatory with a low white cell count. The fungal septic arthritis was not diagnosed until Candida tropicalis, a rare species of Candida, was isolated in the synovial fluid. Although fluconazole is effective in treating the microorganism, the untreated leukemia rendered the infection incurable and led to the growth of fluconazole-resistant Candida krusei. We reported the unusual case of fungal arthritis and reviewed the literature.

The physiological and production effects of increased dietary intake of vitamins E and C in feedlot cattle challenged with bovine herpesvirus 11

The physiological and production effects of feeding additional vitamin E and ruminally protected vitamin C were examined in cattle challenged with bovine herpesvirus 1 (BHV 1). Forty-eight individually penned 6-mo-old Angus and Angus crossbred heifer calves with a mean BW of 151 kg were allocated randomly to four diets in a 2 x 2 factorial arrangement of treatments. Pelleted diets provided either 15 or 185 IU/kg of DM of vitamin E, with or without 3.7 g of ruminally protected vitamin C/kg of DM. Blood samples were taken at start of the experiment and at wk 4, 5, and 6. At the start of wk 5, half of each of the dietary groups was challenged with BHV 1. Feeding additional vitamin E was associated with greater (P < 0.001) mean plasma alpha-tocopherol. In contrast, feeding ruminally protected vitamin C was not associated with greater (P = 0.59) mean plasma ascorbate concentration; however, feeding ruminally protected vitamin C was associated with lower (P = 0.03) mean blood total superoxide dismutase (Cu/Zn SOD and Mn SOD) concentration. Calves fed additional vitamin E had greater (P = 0.05) mean plasma beta-carotene concentrations. There were interactions between dietary intake of vitamins E and C with respect to serum ceruloplasmin concentration (P = 0.01) and G:F (P = 0.05). Bovine herpesvirus 1 challenge was associated with lower white cell count (P = 0.007), lymphocyte count (P < 0.001), and DMI (P = 0.03). Feeding additional vitamin E to calves challenged with BHV 1 was associated with a lower (P = 0.03) serum ceruloplasmin concentration. There was a non-significant trend towards an interaction (P = 0.06) between the feeding of vitamins E and C, with virus-challenged calves fed additional vitamin E alone having greater plasma retinol concentrations. The feeding of vitamins E and/or C in calves challenged with BHV 1 was associated with alterations in the concentrations of other antioxidants. More severe disease may have translated these cellular effects to changes in health and performance.

Secondary effects of immunosuppressive drugs after simultaneous pancreas–kidney transplantation

This report examines the early and late secondary effects of tacrolimus, cyclosporin microemulsion (ME), mycophenolate mofetil (MMF) and rabbit anti-thymocyte globulin (rATG) in simultaneous pancreas-kidney (SPK) recipients. Of the 205 patients participating in the Euro-SPK 001 study, 103 were randomized to tacrolimus (0.2 mg/kg) and 102 to cyclosporin-ME (7 mg/kg). All patients received rATG for 4 days [ATG-Fresenius (ATG-F) 4 mg/kg/day or Thymoglobulin (Thymo-S) 1.25 mg/kg/day] plus MMF and short-term corticosteroids. Thymo-S induction therapy was associated with a lower white cell count in the first 3 months than was seen with ATG-F, while ATG-F caused a lower initial nadir in platelet count. Both polyclonal preparations were well tolerated and no clinically relevant differences were observed with respect to side effects such as infections and malignancies. High cyclosporin-ME trough levels were associated with pancreas graft thrombosis, and concentrations >150 ng/ml were associated with poor renal allograft function. Treatment discontinuation was higher with cyclosporin-ME (57.8%) than with tacrolimus-based therapy (36.9%) due to more frequent toxicity, graft loss and lack of efficacy requiring a switch to tacrolimus. The main reason for withdrawal in the tacrolimus group was MMF discontinuation; MMF-related side effects resulted in more frequent dose reductions to <2 g/day and discontinuations in the tacrolimus group, and indirectly indicate a higher dose-corrected exposure to mycophenolic acid, as previously observed in kidney transplant patients. Short-term induction therapy is effective and well tolerated in patients undergoing SPK transplantation. Tacrolimus was the preferred immunosuppressive agent, resulting in fewer cases of pancreas graft loss and drug discontinuation compared with cyclosporin-ME.

Procalcitonin and C-reactive protein levels in HIV-positive subjects with tuberculosis and pneumonia

Pulmonary tuberculosis (PTB) and pneumococcal community-acquired pneumonia (PCAP) are common causes of lower respiratory tract infections in HIV-seropositive patients and may have similar clinical and radiological features. This study aimed to assess the value of serum procalcitonin (PCT) and C-reactive protein (CRP) levels in HIV-seropositive patients with pneumonia, and to investigate their potential role in differentiating pneumococcal from mycobacterial infections. HIV-seropositive patients admitted with pneumonia were evaluated prospectively, 34 with PTB and 33 with PCAP. All 33 patients in the PCAP group and 20 of 34 patients in the PTB group had elevated PCT levels (>0.1 ng x mL(-1)). All patients in both groups had elevated CRP levels (>10 mg x L(-1)). The PTB group had significantly lower CD4 T-lymphocyte counts, lower CRP levels, lower white cell counts, and lower PCT levels than the PCAP group. Receiver operating characteristic analysis showed that optimal discrimination between PTB and PCAP could be performed at a cut-off point of 3 ng x mL(-1) for PCT (sensitivity 81.8%; specificity 82.35%) and 246 mg x L(-1) for CRP (sensitivity 78.8%; specificity 82.3%). In conclusion, HIV-seropositive patients with pneumococcal community-acquired pneumonia had significantly higher procalcitonin and C-reactive protein levels than those with pulmonary tuberculosis. A procalcitonin level >3 ng x mL(-1) and a C-reactive protein level >246 mg x L(-1) were both highly predictive of pneumococcal infection.

Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis

BACKGROUND: We conducted a nationwide study in the Netherlands to determine cl inical features and prognostic factors in adults with community acquired acute bacterial meningitis. METHODS: From October 1998 to April 2002, all Dutch patien ts with community acquired acute bacterial meningitis, confirmed by cerebrospin al fluid cultures, were prospectively evaluated. All patients underwent a neurol ogic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discha rge) or favorable (a score of 5). Predictors of an unfavorable outcome were iden tified through logis tic regression analysis. RESULTS: We evaluated 696 episod es of community acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of pisodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in menta l status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered m ental status. On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities. The overall mortality rate was 21 percent. T he mortality rate was higher among patients with pneumococcal meningitis than am ong those with meningococcal meningitis (30 percent vs. 7 percent, P 0.001). Th e outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavor able outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission , tachycardia, a positive blood culture, an elevated erythrocyte sedimentation r ate, thrombocytopenia, and a low cerebrospinal fluid white cell count. In adult s presenting with community acquired acute bacterial meningitis, the sensitivit y of the classic triad of fever, neck stiffness, and altered mental status is lo w, but almost all present with at least two of the four symptoms of headache, fe ver, neck stiffness, and altered mental status. The mortality associated with ba cterial meningitis remains high, and the strongest risk factors for an unfavorab le outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae.

A Low Peripheral Blood White Blood Cell Count in Infants Younger than 90 Days Increases the Odds of Acute Bacterial Meningitis Relative to Bacteremia

A Low Peripheral Blood White Blood Cell Count in Infants Younger than 90 Days Increases the Odds of Acute Bacterial Meningitis Relative to Bacteremia

P-Glycoprotein Overexpresion and Internal Tandem Duplications of FLT3 Are Characteristic of Discrete Populations of Elderly AML Patients.

Poor outcome in elderly patients with AML has been linked to an increased incidence of p-glycoprotein (pgp) expression, poor risk cytogenetics and secondary AML. Internal tandem duplication of the FLT3 gene is prognostic for poor outcome in younger patients with AML, but has not been analysed alongside other poor risk variables in the elderly. The ongoing AML14 trial for patients of 60 years or older is conducted by the UK National Cancer Research Institute Haematological Oncology Study Group, and is sponsored by the Leukaemia Research Fund. Patients could enter randomisations to intensive (daunorubicin- and ara-C-based) or non-intensive chemotherapy regimens. Using flow cytometry, we measured functional and phenotypic p-glycoprotein as well as MRP, LRP, bcl-2 and bax in CD45-gated blasts from 274 AML 14 patients. FLT3 ITDs were measured by PCR in the same cohort.We found that pgp protein and function were associated with a lower presenting white blood count (median WBC 27.0 × 109/l in non-functional cases, 6.0 × 109/l in functional cases, p<0.0001; p=0.0002 for protein). Conversely, FLT3 ITDs were associated with a high presenting white count (wildtype median WBC 18.2 × 109/l, ITD median 58.5 × 109/l). Moreover FLT3 ITDs were strongly associated with the absence of functional p-glycoprotein (P=0.0005): 18% patients had FLT3 ITDs, 45% patients had functional pgp, but only 4% patients had both. There was also a suggestion that pgp is associated with poor risk cytogenetics (P=0.02 for pgp protein expression, P=0.01 for functional pgp).Of the 274 patients analysed, 235 had intensive chemotherapy and 39 non-intensive treatment. Of the factors investigated, only pgp was associated with lower remission rates in univariate analysis adjusted for type of chemotherapy (functional pgp, p=0.01 for trend, protein p<0.0001), largely due to increases in the incidence of resistant disease (overall p=0.0008 for functional pgp, p<0.0001 for protein). In multivariate analysis, allowing for the effects of age, cytogenetics, WBC and performance status, only pgp protein proved significant in predicting CR or resistant disease.For overall survival, none of the variables proved significant in univariate or multivariate analyses adjusted for part of trial (intensive or non-intensive). However, this finding should be construed as lack of evidence of effect, rather than lack of effect: the confidence intervals for the hazard ratio for pgp protein range from 0.92 to 1.62, so the results are still consistent with a moderate adverse effect of pgp protein. Among the cohort, 154 patients were randomised to receive the pgp inhibitor PSC-833 (n=62) or not (n=92). PSC-833 has been previously reported as conferring worse overall survival, mainly arising from early deaths. There is evidence that higher levels of pgp protein mitigate the adverse effects of PSC 833 (p=0.005 for heterogeneity) in remission rates. In conclusion, pgp over-expression was associated with a low white cell count and with increased levels of resistant disease in elderly patients with AML. We suggest that pgp positive (slow-growing) and growth-factor receptor mutated (fast-growing) AML clones form distinct subsets which may merit distinct therapeutic approaches in future trials.

Molecular Characterization of AML1 (RUNX1) Amplification: A Poor Risk Chromosomal Marker in Acute Lymphoblastic Leukaemia (ALL).

We have recently defined a new recurrent chromosomal abnormality in patients with acute lymphoblastic leukemia (ALL) involving the duplication of chromosomal band 21q22 and amplification of the AML1 (RUNX1) gene. Currently, fluorescence in situ hybridization (FISH) with probes directed to the AML1 gene is the only reliable detection method. AML1 signals are seen as clusters in interphase cells and in tandem duplication on the long arm of chromosome 21 in metaphase. To date, we have identified 46 patients with this abnormality: 26 males and 20 females. The median age of the 44 children was 9 years (range 4–16 years): two adults were 20 and 30 years old. Their median white cell count was 3.7x109/L (range 1−80x109/L) and all had a common/pre-B immunophenotype. The 3 year event free survival for the 24 children treated on MRC ALL97 was 51% (95% confidence interval 27%–71%). Hence, this abnormality has been associated with older children with a low white cell count and, most significantly, a poor prognosis. The NCRI UK Childhood Leukaemia Working Party has categorized these children into a high-risk group and recommended that they be treated on a more intensive protocol, making their accurate detection vital. To achieve this goal, we have attempted to define the amplified region on chromosome 21 and to identify the genes involved, employing a range of molecular techniques. Microarray analysis (genomic and expression) in conjunction with FISH and quantitative PCR were used to investigate DNA and/or RNA samples from 11 patients. Comparative genomic hybridization (Spectral Genomics 1Mb) (aCGH) showed variable regions of amplification (common minimal region ~10Mb DNA).Complementary FISH, using a range of specific probes corresponding to the aCGH clones, confirmed the extent of the amplified region on chromosome 21, while indicating the precise copy number changes for each clone. FISH also revealed unexpected chromosomal rearrangements of the amplified chromosome, including loss of the 21q telomeric region. These observations confirm the chromosomal instability associated with this abnormality, as previously indicated from the variable chromosome morphology seen by cytogenetic analysis. Expression profiling (Affymetrix HG-U133) detected 60 over-expressed genes in these patients, of which six were located within the chromosome 21 amplicon. This study has defined the extent of the chromosome 21 amplified region surrounding AML1, and highlighted the over-expression of specific genes within the amplicon. This combined molecular approach will help to identify the most appropriate test for the detection of this high-risk abnormality.