West Nile virus neuroinvasive disease associated with rituximab therapy.

West Nile virus neuroinvasive disease (WNVND) manifests with meningitis, encephalitis, and/or acute flaccid paralysis. It represents less than 1% of the clinical syndromes associated with West Nile virus (WNV) infection in immunocompetent patients. Immunosuppressive therapy is associated with increased risk of WNVND and worse prognosis. We present a patient with WNVND during therapy with rituximab, and a review of the literature for previous similar cases with the goal to describe the clinical spectrum of WNVND in patients treated specifically with rituximab. Our review indicates that the most common initial complaints are fever and altered mental status, brain magnetic resonance imaging often shows bilateral thalamic hyperintensities, and cerebrospinal analysis consistently reveals mild lymphocytic pleocytosis with elevated protein, positive WNV polymerase chain reaction, and negative WNV antibodies. Treatment is usually supportive care, with intravenous immunoglobulins (IVIG) plus corticosteroids and WNV-specific IVIG also used. The disease is usually fatal despite intervention. Our patient's presentation was very similar to prior reports, however demonstrated spontaneous improvement with supportive management only. WNVND is a rare and serious infection with poor prognosis when associated with rituximab therapy. Diagnosis is complicated by absent or delayed development of antibodies. The presence of bilateral thalamic involvement is a diagnostic clue for WNVND. There is insufficient evidence to recommend the use of corticosteroids or IVIG.

Mercuric chloride induced hepatotoxic and hematologic changes in rats: The protective effects of sodium selenite and vitamin E.

This study focuses on investigating the possible protective effect of sodium selenite (Na2SeO3) and/or vitamin E against mercuric chloride (HgCl2)-induced hepatotoxicity in rat. Male rats were given HgCl2 (1 mg/kg body weight (bw)) and HgCl2 plus Na2SeO3 (0.25 mg/kg bw) and/or vitamin E (100 mg/kg bw) daily via gavage for 4 weeks. HgCl2-treated groups had significantly higher white blood cell and thrombocyte counts than the control group. Serum activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl-transferase, and lactate dehydrogenase significantly increased and serum levels of total protein, albumin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly decreased in the HgCl2-treated groups compared with control group. Malondialdehyde level significantly increased and superoxide dismutase, catalase, and glutathione peroxidase activities decreased in liver tissue of HgCl2-treated rats. Also, HgCl2 exposure resulted in histopathological changes. Supplementation of Na2SeO3 and/or vitamin E provided partial protection in hematological and biochemical parameters that were altered by HgCl2 As a result, Na2SeO3 and/or vitamin E significantly reduced HgCl2-induced hepatotoxicity, but not protected completely.

Bilateral thalamic bleed and cerebral venous sinus thrombosis in Japanese encephalitis.

Japanese encephalitis (JE) is a potentially serious form of viral encephalitis with varied clinicoradiological manifestations. We report the case of a 19-year-old girl admitted with headache, vomiting and altered sensorium in the absence of fever, whose cerebrospinal fluid analysis showed lymphocytic pleocytosis with significant protein content and positive serum IgM JE antibodies. MRI with venography revealed bilateral thalamic haemorrhage and cerebral venous sinus thrombosis. Although thalamic hypodensities are a well-described feature, thalamic haemorrhage and cerebral venous thrombosis are distinctly rare in JE. This report highlights the role of imaging in cases of encephalitis in general and JE in particular, in the early detection of uncommon manifestations that may complicate these diseases.

Prevalence and severity of vitamin D deficiency in patients with diabetic foot infection.

The aim of the present research was to study the prevalence and severity of vitamin D deficiency in patients with diabetic foot infection. Patients were enrolled in two groups: diabetic patients with foot infection (n 125) as cases and diabetic patients without the infection as controls (n 164). Serum 25-hydroxyvitamin D (25(OH)D) was measured by RIA. Data were presented as means and standard deviations unless otherwise indicated and were analysed by SPSS. Results revealed that 25(OH)D (nmol/l) was significantly lower (40·25 (sd 38·35) v. 50·75 (sd 33·00); P < 0·001) in cases than in controls. Vitamin D inadequacy (25(OH)D < 75 nmol/l) was equally common in cases and controls (OR 1·45, 95 % CI 0·8, 3·0; P = 0·32), but cases had a greater risk of vitamin D deficiency (25(OH)D < 50 nmol/l) than controls (OR 1·8, 95 % CI 1·1, 3·0; P = 0·02). Risk of severe vitamin D deficiency (25(OH)D < 25 nmol/l) was significantly higher in cases than in controls (OR 4·0, 95 % CI 2·4, 6·9; P < 0·0001). Age, duration of diabetes and HbA1c were significantly higher in cases than in controls and therefore adjusted to nullify the effect of these variables, if any, on study outcome. The study concluded that vitamin D deficiency was more prevalent and severe in patients with diabetic foot infection. This study opens up the issue of recognising severe vitamin D deficiency (< 25 nmol/l) as a possible risk factor for diabetic foot infections and the need for vitamin D supplementation in such patients for a better clinical outcome. This could be substantiated by similar data from future studies.

Antihistaminic and antiallergic actions of extracts of Solanum nigrum berries: possible role in the treatment of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Berries of the plant Solanum nigrum Linn (Solanaceae) are used for the treatment of asthma in folk medicine and ancient books. AIM OF STUDY: To evaluate potential of the plant berries in the treatment of asthma. MATERIALS AND METHODS: Petroleum ether, ethanol and aqueous extracts of S. nigrum berries (50, 100 and 200mg/kg, i.p.) were screened for the treatment of asthma by the various methods viz. effect on clonidine and haloperidol induced catalepsy, milk-induced leucocytosis and eosinophilia, mast cell stabilizing activity in mice and studies on smooth muscle preparation of guinea pig ileum (in vitro). Active petroleum ether extract was standardized by HPTLC. RESULTS: The petroleum ether extract of S. nigrum berries inhibited clonidine-induced catalepsy significantly but not haloperidol-induced catalepsy. Petroleum ether extract significantly inhibited increased leukocyte and eosinophil count due to milk allergen and showed maximum protection against mast cell degranulation by clonidine. Petroleum ether extract resisted contraction induced by histamine better than other extracts. All the results are dose dependant. Active petroleum ether extract showed presence of antiasthmatic compound, ß-sitosterol. CONCLUSION: The petroleum ether extract of S. nigrum berries can inhibits parameters linked to the asthma disease.

Suppression of the postoperative neutrophil leucocytosis following neoadjuvant chemoradiotherapy for rectal cancer and implications for surgical morbidity.

OBJECTIVE: The extent to which neoadjuvant chemoradiotherapy for rectal cancer influences postoperative morbidity is controversial. This study investigated whether this treatment suppresses the normal perioperative inflammatory response and explored the clinical implications. METHOD: Prospective databases were queried to identify 37 consecutive study patients undergoing definitive surgery following 5-FU/capecitabine-based chemoradiotherapy and 34 consecutive untreated control patients operated upon for rectal or rectosigmoid cancer. Preoperative (< 10 days) and postoperative (< 24 h) neutrophil counts, along with morbidity data, were confirmed retrospectively. Univariate and multivariate analyses assessed the apparent effect of chemoradiotherapy on change in neutrophil count. The latter's association with postoperative morbidity was then examined. RESULTS: Sufficient data were available for 34 study and 27 control patients. Repeated-measures ANCOVA revealed significant differences between their perioperative neutrophil counts (P = 0.02). Of the other characteristics which differed between the groups, only age and tumour location were prognostically significant regarding perioperative change in neutrophil count. Accounting for relevant covariates, chemoradiotherapy was significantly associated with a suppressed perioperative neutrophil leucocytosis. Local postoperative complications affected 25 of 61 patients, who had lower perioperative neutrophil increases than their counterparts (P = 0.016). CONCLUSION: Chemoradiotherapy appears to suppress the perioperative inflammatory response, thereby increasing susceptibility to local postoperative complications.

[Safety and efficiency of ambulatory treatment of acute diverticulitis]. / Eficiencia y seguridad del tratamiento ambulatorio de la diverticulitis aguda.

INTRODUCTION: The treatment of acute diverticulitis is currently being modified, showing a tendency to limit surgical treatment and favor conservative management. OBJECTIVE: To analyze the safety and efficiency of ambulatory treatment of acute diverticulitis in a selected group of patients. METHODS: We performed a prospective study of domiciliary oral antibiotic therapy for acute diverticulitis in a cohort of patients in the Emergency Surgery Section of our hospital. Seventy-four patients (44 men and 30 women) were included between 2000 and 2006. Patients with Hinchey stage 1 diverticulitis and those with Hinchey stage 2 diverticulitis and abscesses of less than 3cm, who were clinically and biochemically stable, were selected. The patients were treated with oral ciprofloxacin and metronidazole for 7-10 days. Follow-up was performed in the outpatients unit with clinical evaluation at 10 days and an imaging test at 1 month. RESULTS: The mean age of the patients was 55 years. The most frequent clinical presentation was spontaneous abdominal pain associated with leukocytosis. The mean duration of treatment was 8.8 days. Four patients (5.4%) required subsequent hospital admission for intravenous antibiotic administration and 70 (94.6%) completed treatment without complications. During follow-up, two cases of colonic adenocarcinoma and six cases of polyposis were diagnosed. Only 13 patients underwent elective surgery. CONCLUSIONS: In most of the patients studied, ambulatory conservative management was safe and effective in the treatment of uncomplicated acute diverticulitis. Moreover, this approach reduces length of hospital stay and lowers costs.

Transfusion-related acute lung injury (TRALI) during remission induction course of acute myeloid leukemia: a possible role for all-transretinoic-acid (ATRA)?

Transfusion-related acute lung injury (TRALI) is a clinical syndrome characterized by sudden onset of respiratory distress due to pulmonary edema during or following transfusion. Two proposed pathophysiologic mechanisms for TRALI were proposed: the antibody hypothesis and the two-event hypothesis. The two-event hypothesis postulates that a pathway to neutrophil activation and aggregation can occur without leukocyte antibodies. We report a case of TRALI occurring during remission induction course of acute myeloid leukemia in a 27-year-old woman who received All-transretinoic-acid (ATRA). We postulate that ATRA may have played a role in this life-threatening complication by priming neutrophil and enhancing their adherence and their activation in the pulmonary endothelium. TRALI improved with non-invasive ventilation support and use of high dose corticosteroids.

[Severe thrombocytosis and leukocytosis associated with iron deficiency anaemia: a case-report]. / Thrombocytose et hyperleucocytose sévères au cours d'une anémie par carence martiale: à propos d'un cas.

Reactive thrombocytosis (secondary thrombocytosis) is frequent and typically moderate. We report a case of extreme thrombocytosis and leukocytosis secondary to an iron deficiency anemia. A 21-year-old woman is admitted in emergency department for acute headache. Biological assessment reveals a severe microcytic anaemia (5.4 g/dL) with thrombocytosis (2500 giga/L) and leukocytosis (35 giga/L) leading to multiple diagnosis hypotheses. Finally, biological evaluation concludes to a diagnosis of iron deficiency anaemia related to insufficient oral intake and menorrhagia. Reactive hyperleukocytosis and thrombocytosis rapidly resolved with iron supplementation. This case is a reminder that iron deficiency-related thrombocytosis can sometimes be severe. However, the associated reactive leukocytosis is quite exceptional.

Antistress and antiallergic effects of Ficus bengalensis bark in asthma.

Various extracts of Ficus bengalensis bark was screened for it's antiallergic and antistress potential in asthma by milk-induced leucocytosis and milk-induced eosinophilia. Aqueous, ethanol, and ethyl acetate extracts showed significant decrease in leucocytes and eosinophils in the order given while petroleum ether and chloroform extracts were inactive. This shows the application of polar constituents of F. bengalensis bark as antistress and antiallergic agents in asthma.

Hypersensitivity to progesterone-in-oil after in vitro fertilization and embryo transfer.

OBJECTIVE: To report the occurrence and management of pulmonary compromise, marked leukocytosis, and eosinophilia in a patient receiving P-in-oil after IVF and embryo transfer. DESIGN: Case report.A tertiary referral reproductive medicine unit. PATIENT(S): A 29-year-old patient receiving P-in-oil supplementation after IVF embryo transfer. INTERVENTION(S): Extensive diagnostic testing and surveillance for hypersensitivity to P in sesame oil; development of an alternative oil-based P-in-oil suspension. MAIN OUTCOME MEASURE(S): Tolerance of alternative P vehicle; clinical pregnancy. RESULT(S): The patient tolerated an alternative P oil vehicle and successfully achieved a clinical pregnancy after frozen embryo transfer. CONCLUSION(S): Although rare, hypersensitivity reactions may occur in patients receiving P-in-oil supplementation after IVF embryo transfer. Testing for tolerance and subsequent use of alternative P vehicles may be an effective strategy in managing patients with sensitivity to P-in-oil.

Effects of three different types of exercise on blood leukocyte count during and following exercise.

CONTEXT: High-intensity exercise causes tissue damage, production of stress hormones, and alterations in the function and quantity of various immune cells. Many clinical-physical stressors such as surgery, trauma, burns and sepsis induce a pattern of hormonal and immunological response similar to that of exercise. It has thus been suggested that heavy exercise might be used to cause graded and well-defined amounts of muscle trauma, thereby serving as an experimental model for inflammation and sepsis. OBJECTIVE: In order to explore whether some form of strenuous exercise might provide an useful model for the inflammatory process, we studied the effects of three different exercise protocols on blood leukocyte count during and following exercise. DESIGN: Four different experimental conditions, using a randomized-block design. SETTING: Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada. PARTICIPANTS: Eight healthy and moderately fit males. PROCEDURES: Participants were each assigned to four experimental conditions. Subjects performed 5 minutes of cycle-ergometry exercise at 90%, 2 hours of cycle-ergometry exercise at 60%, a standard circuit of resistance exercises with 3 sets of 10 repetitions at 60 to 70% of one-repetition maximum (1-RM) force at each of 5 different stations; or they remained seated for 5 hours. DIAGNOSTIC TEST USED: Flow cytometric analysis. MAIN MEASUREMENTS: Blood samples were analyzed for total leukocyte counts, total T cells, T helper/inducer cells, T suppressor/cytotoxic cells, B cells, cytolytic T cells, and natural killer cells. RESULTS: The peak aerobic and prolonged submaximal exercise induced similar alterations in cell counts. These changes were generally larger than those produced by the resistance exercise, although both resistance and peak aerobic exercise resulted in a significantly longer-lasting decrease in the CD4+/CD8+ ratio than the submaximal exercise bout did. CONCLUSION: The data suggest that, of the three exercise patterns tested, prolonged aerobic exercise induced the largest and most readily measured patterns of immune response. Nevertheless, the changes provided only a partial model for the clinical inflammatory process.

Potential complications of intralesional laser photocoagulation for extensive vascular malformations.

Vascular anomalies remain a challenge for both patients and plastic surgeons. Recently, promising results have been reported using intralesional photocoagulation (ILP) to treat extensive vascular lesions. At the authors' center, they have treated more than 300 patients with vascular anomalies in different parts of the body between 1996 and 1999. They describe their operative techniques of ILP. Laser pulses of a 1,064-nm wavelength from the Nd:YAG laser were delivered to the target tissues with a 600-microm optical fiber. They report 2 patients who developed complications after a single session of ILP therapy for their extensive vascular malformations. The first patient had Klippel-Trenaunay syndrome (capillary-lymphaticovenous malformations) with widespread involvement of her buttocks and left lower limb. She had severe leukocytosis, thrombocytosis, and hyperkalemia that resolved with intravenous hydration, antibiotics, and sodium bicarbonate. In their second patient, the entire left upper limb was affected. Her total red cell count diminished by a quarter and her hemoglobin concentration dropped by more than 3 g%. This was corrected gradually with supplemental oral hematinics. Although these complications resolved uneventfully in their patients, they hope that their possible development will caution anyone who may wish to attempt this new method of therapy.

Doce casos de absceso pulmonar en pediatría: revisión clínica / 12 cases of lung abscesses in paediatrics: clinical review

El absceso pulmonar (AP) se define como un área de supuración que desarrolla necrosis central y cavitación del parénquima pulmonar, rodeado por una pared gruesa de tejido inflamatorio. Con el objeto de describir las características clínicas, tratamiento y evolución de los pacientes con AP, revisamos los 12 pacientes con AP egresados del Servicio de Pediatría del Hos. Clínico de la U. Católica, durante un período de 10 años (1990 a 1999) cinco pacientes eran hombres; tenían una edad promedio de 4,3 años (5 meses a 8 años); los síntomas principales fueron fiebre, tos, dificultad respiratoria y compromiso del estado general, 7 habían usado antibióticos previo al ingreso. En 10/12 se observó leucocitosis (promedio: 20 136 cel/mmü), aumento de la VHS (promedio: 78 mm/h) y elevación de la PCR (promedio: 31 mg/di). La localización más frecuente fue el LSD (7 casos), LID (2 pacientes), LII (2 casos) y 1 tenía compromiso de LSD y LID. En 7 casos se observó concomitantemente derrame pleural, 4 presentaron atelectasia y 2 neumotórax. Se aisló germen en 4 pacientes, Streptococcus pneumoniae en 3/4 (uno asociado a Stafilococcus aureus) y Streptococcus beta hemolítico grupo A en 1 caso. Todos recibieron tratamiento con 1 o más antibióticos, 2 requirieron lobectomía por alteración anatómica predisponente (secuestro pulmonar o quiste pulmonar simple). La evolución fue hacia la mejoría en todos, con una estadía hospitalaria promedio de 14,8 días y desaparición de las imágenes cavitarias entre la cuarta semana y tercer mes posterior al alta. En nuestro estudio encontramos que el AP es poco frecuente, que tiene una evolución favorable con resolución clínica y radiológica, requiriendo la gran mayoría de las veces solo tratamiento médico

Catecholamine-induced leukocytosis: early observations, current research, and future directions.

Recent studies demonstrate that acute psychological stress in man affects lymphocyte circulation. It has been suggested that catecholamines are responsible for these changes. The present review summarizes findings regarding catecholamine-induced lympho- and leukocytosis, starting with observations dating back to the beginning of this century. Particular attention is given to the mechanisms of this phenomenon and the potential site of origin of newly appearing leukocytes. Characteristically, two phases are recognized after catecholamine administration: a quick (<30 min) mobilization of lymphocytes, followed by an increase in granulocyte numbers with decreasing lymphocyte numbers. Many studies have shown that catecholamines predominantly affect natural killer (NK) cell and granulocyte circulation, whereas T- and B-cell numbers remain relatively unaffected. The changes in lymphocyte circulation seem to be mainly mediated via activation of beta2-adrenoceptors, whereas granulocyte increases involve alpha-adrenoceptor stimulation. Results further indicate that the marginal pool and the spleen are the major sources for freshly recruited lymphocytes, whereas granulocytes are predominantly released from the marginal pool and the lung. Results from acute psychological stress or physical exercise models corroborate the results obtained with catecholamine administration. Together, the data demonstrate that components of the innate immune system participate in the classical fight/flight response.

Is acute promyelocytic leukemia a curable disease? Treatment strategy for a long-term survival.

The major cause of early death in acute promyelocytic leukemia (APL), the high risk of a bleeding diathesis is now successfully counteracted within a few days by differentiation therapy using ATRA. Moreover, no resistance to this drug has been recorded during induction when the usual presence of PML/RAR alpha was confirmed by molecular study (some M3 cases do lack rearrangement of PML/RAR alpha). Paradoxically, a hypercoagulable clotting tendency may occur in these patients during the first month of ATRA treatment. Leucocyte activation (retinoic acid syndrome), often secondary to hyperleukocytosis, is prevented by early addition of chemotherapy when WBCs exceed defined limits, and is successfully treated by high dose corticosteroids. Routine acquired progressive in vivo resistance to all trans retinoic acid (ATRA) requires consolidation of ATRA-induced complete remission (CR) with intensive chemotherapy. Prevention of relapses using maintenance therapy is questionable and has not been tested in randomized trials. Actually the event-free survival of APL patients treated by the combination of ATRA and chemotherapy is 80% at 1 year, and the cure of 50% of patients is within our reach.

Venous blood platelets decrease during allergen-induced asthmatic reactions.

To determine whether circulating platelets alter during asthmatic reactions induced by allergens, we studied nine subjects previously shown to develop an early or dual asthmatic reaction after inhalation challenge with extracts of house dust mite or grass pollen. In each subject, FEV1, circulating platelets and leucocytes were measured before, 15, 30 and 60 min, and 2, 4, 6 and 8 hr after inhalation of allergen and diluent control administered in a single-blind, randomized fashion. The same procedure was repeated in six of the nine subjects after bronchoconstriction induced by methacholine. Each subject developed an early asthmatic reaction after allergen inhalation challenge, which was followed by a late asthmatic reaction in six subjects and by an equivocal late asthmatic reaction in two of them (fall in FEV1 of 15 and 17% respectively). Compared with the control day, circulating platelets significantly decreased during the allergen-induced early asthmatic reaction (P less than 0.025, at 30 min). Platelet counts returned to baseline values within 4 hr and remained steady thereafter both in subjects who did and did not develop a late asthmatic reaction. No changes in platelet counts occurred after bronchoconstriction induced by methacholine. Diurnal increase of leucocyte numbers occurred after challenge with both allergen and diluent control. These results suggest that platelets may be involved in the pathogenesis of allergen-induced asthmatic reactions.

ADP-ribosyltransferase activity of pertussis toxin and immunomodulation by Bordetella pertussis.

Pertussis toxin is produced by the causative agent of whooping cough, Bordetella pertussis, and is an adenosine diphosphate (ADP)-ribosyltransferase capable of covalently modifying and thereby inactivating many eukaryotic G proteins involved in cellular metabolism. The toxin is a principal determinant of virulence in whooping cough and is a primary candidate for an acellular pertussis vaccine, yet it is unclear whether the ADP-ribosyltransferase activity is required for both pathogenic and immunoprotective activities. A B. pertussis strain that produced an assembled pertussis holotoxin with only 1 percent of the ADP-ribosyltransferase activity of the native toxin was constructed and was found to be deficient in pathogenic activities associated with B. pertussis including induction of leukocytosis, potentiation of anaphylaxis, and stimulation of histamine sensitivity. Moreover, this mutant strain failed to function as an adjuvant and was less effective in protecting mice from intracerebral challenge infection. These data suggest that the ADP-ribosyltransferase activity is necessary for both pathogenicity and optimum immunoprotection. These findings bear directly on the design of a nontoxic pertussis vaccine.